Spirocyclic KRAS inhibitors for treating disease

Abstract

The present disclosure relates to spirocyclic compounds targeting KRAS, pharmaceutical compositions containing the compounds, and methods of using such compounds to treat disease, such as cancer.

Description

SPIROCYCLIC KRAS INHIBITORS FOR TREATING DISEASE RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 762,529, filed February 24, 2025, U.S. Provisional Application No.63 / 683,447, filed August 15, 2024, and U.S. Provisional Application No.63 / 657,561, filed June 7, 2024, the entire disclosure of each of which is incorporated herein by reference. TECHNICAL FIELD

[0002] The present disclosure relates to spirocyclic compounds targeting KRAS, pharmaceutical compositions containing the compounds, and methods of using such compounds to treat disease, such as cancer. BACKGROUND

[0003] Ras is a GTP-binding protein and regulates many important physiologic processes within a cell, such as cell cycle progression, survival, apoptosis, etc. H-Ras, K-Ras, and N- Ras are the main members of Ras superfamily, which are tightly regulated by factors that switch on / off the GTPase activity. Somatic mutations at codons 12, 13, and 61 in the RAS genes are associated with about 16% of all human cancers and KRAS is the most frequently mutated RAS isoform, accounting for 85% of all RAS-related cancers (Prior I. A. et al, A comprehensive survey of Ras mutations in cancer. Cancer Res. 2012, 72, 2457−2467), including 86-96% in pancreatic cancers, 40-50% in colorectal cancers, and 27-39% in lung adenocarcinomas (Kessler D. et al. Drugging an undruggable pocket on KRAS Proc Natl Acad Sci U S A.2019, 116(32):15823-15829). Mutated RAS is locked in the constitutively activated GTP bound state and facilitates enhanced Ras signaling in cancer cells.

[0004] Direct targeting of mutant KRAS has previously proven challenging because of its high affinity for nucleotide and the lack of tractable binding pockets for small-molecule inhibitors. Recent successful inhibition of the KRAS G12C mutant by covalent chemical modifiers sotorasib and adagrasib (Stower K, KRAS inhibitors at last, Nature Medicine 2020, 26, 1804) in KRAS G12C mutated lung cancer patients has shed lights on targeting KRAS mutants for therapeutic invention. However, inhibitors targeting KRAS mutants without covalent formation at KRAS G12C are still absent. The increased understanding of structural elements of the KRAS switch II pocket made it possible to design KRAS inhibitors selective for different mutant variants. MRTX1133 has been reported as potent and highly selective noncovalent KRAS G12D inhibitor (Wang X. et al, Identification of MRTX1133, anoncovalent, potent, and selective KRASG12Dinhibitor, J. Med. Chem.2022, 65: 3123–3133). However, intraperitoneal injection of MRTX1133 was required to achieve sufficient plasma exposure and demonstrate drug efficacy in mice. This suggests MRTX1133 may have poor bioavailability.

[0005] Therefore, there is unmet medical need to develop noncovalent KRAS inhibitors that can selectively target KRAS mutants such as KRAS G12C, KRAS G12D, KRAS G12V, KRAS G12R, KRAS G12S, KRAS G13C, and KRAS G13D with good in vivo efficacy, safety, and predicted human oral pharmacokinetic profile for treating patients with KRAS mutant cancers. SUMMARY

[0006] In one aspect, the disclosure relates to a compound of the formula I,

[0007] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is 5- or 6-membered heteroaryl;

[0008] ring B is phenyl or 5- or 6-membered heteroaryl having at least one nitrogen atom;

[0009] ring C is C6-C10aryl or 5- to 10-membered heteroaryl;

[0010] X is a -O-, -S-, or -NR8-;

[0011] each of X1, X2, and X3is independently an -O-, -S-, -S(O)2-, -CHR3-, -C(R3)2-, or -CH2- , provided that no more than one of X1, X2, and X3is a -O-, -S-, or -S(O)2-;

[0012] each R1, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10- membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2, or an R1and R8, when present, taken together with the atoms to which they are attached,combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10- membered heteroaryl), and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkyl-ORe, C1-C6alkyl-SRe, C1-C6 alkyl-NReRf, C1-C6 alkyl-C(O)Re, C1-C6 alkyl-C(O)ORe, C1-C6 alkyl- C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0013] each R2, when present, is independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2, or two R2, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0014] each R3and R4, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -ORc, -OC(O)Rc, -OC(O)NRcRd, -OC(=NRc)NRcRd, -OS(O)Rc, -OS(O)2Rc, -OS(O)NRcRd, -OS(O)2NRcRd, -SRc, -S(O)Rc, -S(O)2Rc, -S(O)NRcRd, -S(O)2NRcRd, -NRcRd, -NRcC(O)Rd, -NRcC(O)ORd, -NRcC(O)NRcRd, -NRcC(=NRd)NRcRd, -NRcS(O)Rd, -NRcS(O)2Rd, -NRcS(O)NRcRd, -NRcS(O)2NRcRd, -C(O)Rc, -C(O)ORc, -C(O)NRcRd, -C(=NRc)NRcRd, -PRcRd, -P(O)RcRd, -P(O)2RcRd, -P(O)NRcRd, -P(O)2NRcRd,-P(O)ORc, -P(O)2ORc, -CN, or -NO2; or two R3or two R4, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6 cycloalkyl or a 4- to 10-membered heterocycloalkyl; or two R3or two R4, when present, taken together with the carbon atom to which they are attached combine to form an oxo group or a C2-C6alkenyl group; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, C1-C6 haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0015] each R5, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2; or two R5, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0016] R6is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, or -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl,and -C1-C6 alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6 alkyl, -C1-C6 alkylene-(O-C1-C6 alkyl), -OC1-C6 alkylene-(O-C1-C6 alkyl), -C1-C6 alkylene-(O-Re), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), haloalkyl, C3-C6 cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6 alkylene-(5- to 10- membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0017] R7, when present, is H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, and 5- to 10-membered heteroaryl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, C1-C6haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0018] each Ra, Rb, Rc, Rd, Re, and Rfis independently selected from the group consisting of H, deuterium, C1-C6 alkyl, C1-C6 alkyl-(O-C1-C6 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6alkylene-(C3-C6cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, C1-C6 alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, and C1-C6 alkylene-(5- to 10-membered heteroaryl); or two of Raand Rb, or Rcand Rd, or Reand Rf, taken together with the atom or atoms to which they are attached, combine to form a C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl; or -Reand -Rftaken together with the carbon atom to which they are attached form an oxo groups or a C2-C6 alkenyl; wherein each hydrogen atom in C1-C6alkyl, C1-C6alkyl-(O-C1-C6alkyl), C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6 alkylene-(C3-C6 cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and C1-C6 alkylene-(5- to 10-membered heteroaryl) is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, 4- to 10- membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -OH, -OC1-C6 alkyl, -OC(O)C1-C6 alkyl, -OC(O)N(H or C1-C6 alkyl)2, -OS(O)C1-C6 alkyl, -OS(O)2C1-C6 alkyl,-OS(O)N(H or C1-C6 alkyl)2, -OS(O)2N(H or C1-C6 alkyl)2, -SC1-C6 alkyl, -S(O)C1-C6 alkyl, -S(O)2C1-C6 alkyl, -S(O)N(H or C1-C6 alkyl)2, -S(O)2N(H or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)C(O)-C1-C6 alkyl, -N(C1-C6 alkyl)C(O)OC1-C6 alkyl, -N(C1-C6 alkyl)C(O)N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)S(O)C1-C6 alkyl, -N(C1-C6 alkyl)S(O)2C1-C6 alkyl, -N(C1-C6alkyl)S(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)2N(H or C1-C6alkyl)2, -C(O)C1-C6 alkyl, -C(O)OC1-C6 alkyl, -C(O)N(H or C1-C6 alkyl)2, -P(H or C1-C6 alkyl)2, -P(O)(H or C1-C6alkyl)2, -P(O)2(H or C1-C6alkyl)2, -P(O)N(H or C1-C6alkyl)2, -P(O)2N(H or C1-C6 alkyl)2, -P(O)OC1-C6 alkyl, -P(O)2OC1-C6 alkyl, -CN, or -NO2, wherein each hydrogen atom in C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl, is optionally substituted with one or more deuterium, halogen, or Rg;

[0019] each Rgis independently C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, 4- to 10- membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, -OH, -OC1-C6alkyl, -OC(O)C1-C6alkyl, -OC(O)N(H or C1-C6alkyl)2, -OS(O)C1-C6alkyl, -OS(O)2C1-C6alkyl, -OS(O)N(H or C1-C6 alkyl)2, -OS(O)2N(H or C1-C6 alkyl)2, -SC1-C6 alkyl, -S(O)C1-C6 alkyl, -S(O)2C1-C6alkyl, -S(O)N(H or C1-C6alkyl)2, -S(O)2N(H or C1-C6alkyl)2, -N(H or C1-C6alkyl)2, -N(C1-C6 alkyl)C(O)-C1-C6 alkyl, -N(C1-C6 alkyl)C(O)OC1-C6 alkyl, -N(C1-C6 alkyl)C(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)C1-C6alkyl, -N(C1-C6alkyl)S(O)2C1-C6alkyl, -N(C1-C6 alkyl)S(O)N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)S(O)2N(H or C1-C6 alkyl)2, -C(O)C1-C6alkyl, -C(O)OC1-C6alkyl, -C(O)N(H or C1-C6alkyl)2, -P(H or C1-C6alkyl)2, -P(O)(H or C1-C6 alkyl)2, -P(O)2(H or C1-C6 alkyl)2, -P(O)N(H or C1-C6 alkyl)2, -P(O)2N(H or C1-C6alkyl)2, -P(O)OC1-C6alkyl, -P(O)2OC1-C6alkyl, -CN, or -NO2;

[0020] m1 is 0, 1, or 2;

[0021] m2 is 0, 1, or 2;

[0022] m3 is 0, 1, 2, or 3;

[0023] m4 is 0 or 1;

[0024] n1 is 0, 1, 2, 3, or 4;

[0025] n2 is 0, 1, 2, 3, or 4;

[0026] p is 0 or 1;

[0027] q1 is 0, 1 or 2; and

[0028] q2 is 1 or 2.

[0029] In another aspect, the disclosure provides a compound of the formula II,

[0030] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, ring C, R1, R2, R3, R4, R5, R6, R7, X, m1, m2, m3, m4, n1, n2, p, q1, and q2 are as described herein.

[0031] In another aspect, the disclosure provides a compound of the formula III

[0032] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, ring C, R1, R2, R3, R4, R5, R6, R7, X, m1, m2, m3, m4, n1, n2, p, q1, and q2 are as described herein.

[0033] In another aspect, the disclosure provides a compound of the formula IV,

[0034] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5a, R6, R7, X, Z1, Z2, m1, m2, m4, n1, n2, p, q1, and q2 are as described herein.

[0035] In another aspect, the disclosure provides a compound of the formula V,

[0036] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5a, R6, R7, X, Z1, Z2, m1, m2, m4, n1, n2, p, q1, and q2 are as described herein.

[0037] In another aspect, the disclosure provides a compound of the formula VI,

[0038] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5a, R6, X, Z1, Z2, Y1, Y2, m1, m2, n1, n2, p, q1, and q2 are as described herein.

[0039] In another aspect, the disclosure provides a compound of the formula VII,

[0040] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5a, R6, X, Z1, Z2, Y1, Y2, m1, m2, n1, n2, p, q1, and q2 are as described herein.

[0041] In another aspect, the disclosure provides a compound of the formula VIII,

[0042] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R3, R4, R5a, R6, X, Z1, Z2, Z3, Z4, Z5, Y1, Y2, n1, n2, p, q1, and q2 are as described herein.

[0043] In another aspect, the disclosure provides a compound of the formula IX,

[0044] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R3, R4, R5a, R6, X, Z1, Z2, Z3, Z4, Z5, Y1, Y2, n1, n2, p, q1, and q2 are as described herein.

[0045] In another aspect, the disclosure provides a compound of the formula X,

[0046] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5, R6, R7, X, Z1, Z2, m1, m2, m4, n1, n2, p, q1, and q2 are as described herein.

[0047] In another aspect, the disclosure provides a compound of the formula XI,

[0048] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5, R6, R7, X, Z1, Z2, m1, m2, m4, n1, n2, p, q1, and q2 are as described herein.

[0049] In another aspect, the disclosure provides a compound of the formula XII,

[0050] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5, R6, X, Y1, Y2, Z1, Z2, m1, m2, n1, n2, p, q1, and q2 are as described herein.

[0051] In another aspect, the disclosure provides a compound of the formula XIII,

[0052] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5, R6, X, Y1, Y2, Z1, Z2, m1, m2, n1, n2, p, q1, and q2 are as described herein.

[0053] In another aspect, the disclosure provides a compound of the formula XIV,

[0054] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R3, R4, R5, R6, X, Y1, Y2, Z1, Z2, Z3, Z4, Z5, n1, n2, p, q1, and q2 are as described herein.

[0055] In another aspect, the disclosure provides a compound of the formula XV,

[0056] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R3, R4, R5, R6, X, Y1, Y2, Z1, Z2, Z3, Z4, Z5, n1, n2, p, q1, and q2 are as described herein.

[0057] In certain embodiments, ring C is of the formula

[0058] wherein,

[0059] “ ” is a point of covalent attachment to ring A;

[0060] R1ais H or R1;

[0061] R1bis H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkyl-ORe, C1-C6 alkyl-SRe, C1-C6 alkyl-NReRf, C1-C6 alkyl-C(O)Re, C1-C6 alkyl-C(O)ORe, C1-C6 alkyl- C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; and

[0062] R2ais H or R2.

[0063] In certain embodiments, the compound, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprises a portion of the formula

[0064] wherein “” is a point of covalent attachment to ring A.

[0065] In certain embodiments of the above aspects, the compound of Formula (I)-(XV) is a compound selected from those species described or exemplified in the detailed description below.

[0066] In further aspects, the disclosure relates to a pharmaceutical composition comprising at least one compound of Formula (I)-(XV) an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof. Pharmaceutical compositions according to the disclosure may further comprise a pharmaceutically acceptable excipient.

[0067] In further aspects, the disclosure relates to a compound of Formula (I)-(XV), an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, for use as a medicament.

[0068] In further aspects, the disclosure relates to a method of treating disease, such as cancer comprising administering to a subject in need of such treatment an effective amount of at least one compound of Formula (I)-(XV), an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0069] In further aspects, the disclosure relates to use of a compound of Formula (I)-(XV), an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, in thepreparation of a medicament for the treatment of disease, such as cancer, and the use of such compounds and salts for treatment of such diseases.

[0070] In further aspects, the disclosure relates to a method of inhibiting a Ras, such as K-Ras, comprising contacting a cell comprising one or more of Ras with an effective amount of at least one compound of Formula (I)-(XV), an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, and / or with at least one pharmaceutical composition of the disclosure, wherein the contacting is in vitro, ex vivo, or in vivo.

[0071] Additional embodiments, features, and advantages of the disclosure will be apparent from the following detailed description and through practice of the disclosure. The compounds of the present disclosure can be described as embodiments in any of the following enumerated clauses. It will be understood that any of the embodiments described herein can be used in connection with any other embodiments described herein to the extent that the embodiments do not contradict one another.

[0072] 1. A compound of the formula I, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof,

[0073] wherein

[0074] ring A is 5- or 6-membered heteroaryl;

[0075] ring B is phenyl or 5- or 6-membered heteroaryl having at least one nitrogen atom;

[0076] ring C is C6-C10 aryl or 5- to 10-membered heteroaryl;

[0077] X is a -O-, -S-, or -NR8-;

[0078] each of X1, X2, and X3is independently an -O-, -S-, -S(O)2-, -CHR3-, -C(R3)2-, or -CH2- , provided that no more than one of X1, X2, and X3is a -O-, -S-, or -S(O)2-;

[0079] each R1, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10- membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb,-NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, - PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or - NO2, or an R1and R8, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10- membered heteroaryl), and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-ORe, C1-C6 alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl- C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0080] each R2, when present, is independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2, or two R2, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0081] each R3and R4, when present, is independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, -ORc, -OC(O)Rc, -OC(O)NRcRd, -OC(=NRc)NRcRd, -OS(O)Rc, -OS(O)2Rc, -OS(O)NRcRd, -OS(O)2NRcRd, -SRc, -S(O)Rc, -S(O)2Rc, -S(O)NRcRd,-S(O)2NRcRd, -NRcRd, -NRcC(O)Rd, -NRcC(O)ORd, -NRcC(O)NRcRd, -NRcC(=NRd)NRcRd, -NRcS(O)Rd, -NRcS(O)2Rd, -NRcS(O)NRcRd, -NRcS(O)2NRcRd, -C(O)Rc, -C(O)ORc, -C(O)NRcRd, -C(=NRc)NRcRd, -PRcRd, -P(O)RcRd, -P(O)2RcRd, -P(O)NRcRd, -P(O)2NRcRd, -P(O)ORc, -P(O)2ORc, -CN, or -NO2; or two R3or two R4, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6cycloalkyl or a 4- to 10-membered heterocycloalkyl; or two R3or two R4, when present, taken together with the carbon atom to which they are attached combine to form an oxo group or a C2-C6 alkenyl group; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1- C6alkyl, C1-C6haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, - NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0082] each R5, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10- membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2; or two R5, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6 haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0083] R6is C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, or -C1-C6 alkylene-(4- to 10-memberedheterocycloalkyl), wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, and -C1-C6 alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6 alkyl), -C1-C6 alkylene-(O-Re), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10- membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0084] R7, when present, is H, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, and 5- to 10-membered heteroaryl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6 alkyl, C1-C6 haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, - NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0085] R8, when present, is H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl; or an R1and R8, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6 alkyl-ORe, C1-C6 alkyl-SRe, C1-C6 alkyl-NReRf, C1-C6 alkyl-C(O)Re, C1-C6 alkyl-C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe,-C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0086] each Ra, Rb, Rc, Rd, Re, and Rfis independently selected from the group consisting of H, deuterium, C1-C6 alkyl, C1-C6 alkyl-(O-C1-C6 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6alkylene-(C3-C6cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, C1-C6 alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, and C1-C6alkylene-(5- to 10-membered heteroaryl); or two of Raand Rb, or Rcand Rd, or Reand Rf, taken together with the atom or atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl; or -Reand -Rftaken together with the carbon atom to which they are attached form an oxo groups or a C2-C6alkenyl; wherein each hydrogen atom in C1-C6 alkyl, C1-C6 alkyl-(O-C1-C6 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6alkylene-(C3-C6cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and C1-C6 alkylene-(5- to 10-membered heteroaryl) is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, 4- to 10- membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -OH, -OC1-C6 alkyl, -OC(O)C1-C6alkyl, -OC(O)N(H or C1-C6alkyl)2, -OS(O)C1-C6alkyl, -OS(O)2C1-C6alkyl, -OS(O)N(H or C1-C6 alkyl)2, -OS(O)2N(H or C1-C6 alkyl)2, -SC1-C6 alkyl, -S(O)C1-C6 alkyl, -S(O)2C1-C6alkyl, -S(O)N(H or C1-C6alkyl)2, -S(O)2N(H or C1-C6alkyl)2, -N(H or C1-C6alkyl)2, -N(C1-C6 alkyl)C(O)-C1-C6 alkyl, -N(C1-C6 alkyl)C(O)OC1-C6 alkyl, -N(C1-C6 alkyl)C(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)C1-C6alkyl, -N(C1-C6alkyl)S(O)2C1-C6alkyl, -N(C1-C6 alkyl)S(O)N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)S(O)2N(H or C1-C6 alkyl)2, - C(O)C1-C6 alkyl, -C(O)OC1-C6 alkyl, -C(O)N(H or C1-C6 alkyl)2, -P(H or C1-C6 alkyl)2, - P(O)(H or C1-C6 alkyl)2, -P(O)2(H or C1-C6 alkyl)2, -P(O)N(H or C1-C6 alkyl)2, -P(O)2N(H or C1-C6 alkyl)2, -P(O)OC1-C6 alkyl, -P(O)2OC1-C6 alkyl, -CN, or -NO2, wherein each hydrogen atom in C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl, is optionally substituted with one or more deuterium, halogen, or Rg;

[0087] each Rgis independently C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, 4- to 10- membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, -OH, -OC1-C6alkyl, -OC(O)C1-C6 alkyl, -OC(O)N(H or C1-C6 alkyl)2, -OS(O)C1-C6 alkyl, -OS(O)2C1-C6 alkyl, -OS(O)N(H or C1-C6alkyl)2, -OS(O)2N(H or C1-C6alkyl)2, -SC1-C6alkyl, -S(O)C1-C6alkyl, -S(O)2C1-C6 alkyl, -S(O)N(H or C1-C6 alkyl)2, -S(O)2N(H or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)C(O)-C1-C6 alkyl, -N(C1-C6 alkyl)C(O)OC1-C6 alkyl, -N(C1-C6alkyl)C(O)N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)S(O)C1-C6 alkyl, -N(C1-C6 alkyl)S(O)2C1-C6 alkyl, -N(C1-C6 alkyl)S(O)N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)S(O)2N(H or C1-C6 alkyl)2, -C(O)C1-C6 alkyl, -C(O)OC1-C6 alkyl, -C(O)N(H or C1-C6 alkyl)2, -P(H or C1-C6 alkyl)2, -P(O)(H or C1-C6 alkyl)2, -P(O)2(H or C1-C6 alkyl)2, -P(O)N(H or C1-C6 alkyl)2, -P(O)2N(H or C1-C6alkyl)2, -P(O)OC1-C6alkyl, -P(O)2OC1-C6alkyl, -CN, or -NO2;

[0088] m1 is 0, 1, or 2;

[0089] m2 is 0, 1, or 2;

[0090] m3 is 0, 1, 2, or 3;

[0091] m4 is 0 or 1;

[0092] n1 is 0, 1, 2, 3, or 4;

[0093] n2 is 0, 1, 2, 3, or 4;

[0094] p is 0 or 1;

[0095] q1 is 0, 1 or 2; and

[0096] q2 is 1 or 2.

[0097] 2. The compound of clause 1, having the formula II

[0098] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0099] 3. The compound of clause 1 or 2, having the formula III

[0100] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0101] 4. The compound of clause 1 or 2, having the formula IVIV,

[0102] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[0103] each R5ais independently H or R5; and

[0104] each of Z1and Z2is independently N, CH, or CR5.

[0105] 5. The compound of any one of the preceding clauses, having the formula V

[0106] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[0107] each R5ais independently H or R5; and

[0108] each of Z1and Z2is independently N, CH, or CR5.

[0109] 6. The compound of any one of clauses 1, 2, or 4, having the formula VI

[0110] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[0111] each R5ais independently H or R5,

[0112] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S, and

[0113] each of Z1and Z2, is independently N, CH, or CR5¸

[0114] wherein thepresent in ring A represents the aromaticity of ring A.

[0115] 7. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula VII

[0116] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[0117] each R5ais independently H or R5;

[0118] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S; and

[0119] each of Z1and Z2is independently N, CH, or CR5;

[0120] wherein thepresent in ring A represents the aromaticity of ring A.

[0121] 8. The compound of any one of clauses 1, 2, 4, or 6, having the formula VIII

[0122] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[0123] each R5ais independently H or R5;

[0124] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S;

[0125] each of Z1and Z2is independently N, CH, or CR5; and

[0126] each of Z3, Z4, and Z5is independently N, CH, CR1, or CR2;

[0127] wherein thepresent in ring A and ring C represents the aromaticity of ring A and ring C.

[0128] 9. The compound of any one of the preceding clauses, having the formula IX

[0129] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[0130] each R5ais independently H or R5;

[0131] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S;

[0132] each of Z1and Z2is independently N, CH, or CR5; and

[0133] each of Z3, Z4, and Z5is independently N, CH, CR1, or CR2;

[0134] wherein thepresent in ring A and ring C represents the aromaticity of ring A and ring C.

[0135] 10. The compound of any one of clauses 1, 2, or 4, having the formula X

[0136] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each of Z1and Z2is independently N, CH, or CR5.

[0137] 11. The compound of any one of clauses 1 to 5, or 10, having the formula XIXI

[0138] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each of Z1and Z2, is independently N, CH, or CR5.

[0139] 12. The compound of any one of clauses 1, 2, 4, 6, or 10, having the formula XII

[0140] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[0141] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S; and

[0142] each of Z1and Z2is independently N, CH, or CR5;

[0143] wherein thepresent in ring A represents the aromaticity of ring A.

[0144] 13. The compound of any one of clauses 1 to 7, or 10 to 12, having the formula XIII

[0145] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[0146] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S; and

[0147] each of Z1and Z2is independently N, CH, or CR5

[0148] wherein thepresent in ring A represents the aromaticity of ring A.

[0149] 14. The compound of any one of clauses 1, 2, 4, 6, 8, 10, or 12, having the formula XIV

[0150] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[0151] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S;

[0152] each of Z1and Z2is independently N, CH, or CR5; and

[0153] each of Z3, Z4, and Z5is independently N, CH, CR1, or CR2;

[0154] wherein thepresent in ring A and ring C represents the aromaticity of ring A and ring C.

[0155] 15. The compound of any one of the preceding clauses, having the formula XVXV

[0156] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[0157] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S;

[0158] each of Z1and Z2is independently N, CH, or CR5; and

[0159] each of Z3, Z4, and Z5is independently N, CH, CR1, or CR2;

[0160] wherein the present in ring A and ring C represents the aromaticity of ring A and ring C.

[0161] 16. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring C is of the formula

[0163] “ ” is a point of covalent attachment to ring A;

[0164] R1ais H or R1;

[0165] R1bis H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-ORe, C1-C6 alkyl-SRe, C1-C6 alkyl-NReRf, C1-C6 alkyl-C(O)Re, C1-C6 alkyl-C(O)ORe, C1-C6 alkyl- C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf,-NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; and

[0166] R2ais H or R2.

[0167] 17. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formula

[0168] wherein “” is a point of covalent attachment to ring A.

[0169] 18. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formula ,,

[0170] wherein “ ” is a point of covalent attachment to ring A.

[0171] 19. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein p is 1.

[0172] 20. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein X is NR8.

[0173] 21. The compound of any one of clauses 1 to 16, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formula

[0174] wherein “ ” is a point of covalent attachment to ring A.

[0175] 22. The compound of any one of clauses 1 to 16, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formula,

[0176] wherein “ ” is a point of covalent attachment to ring A.

[0177] 23. The compound of any one of clauses 1 to 16 or 22, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formula

[0178] wherein “ ” is a point of covalent attachment to ring A.

[0179] 24. The compound of any one of clauses 1 to 7 or 10 to 13, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formula

[0180] wherein “ ” is a point of covalent attachment to ring A.

[0181] 25. The compound of any one of the clauses 1 to 7, 10 to 13, or 24, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formula,

[0182] wherein “ ” is a point of covalent attachment to ring A.

[0183] 26. The compound of any one of the clauses 1 to 19, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein X is O.

[0184] 27. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is 4- to 10-membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, or -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), wherein each hydrogen atom in 4- to 10-membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, and -C1-C6 alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6 alkyl), -OC1-C6 alkylene-(O-C1-C6 alkyl), -C1-C6 alkylene-(O-Re), C6-C10 aryl, -C1-C6alkylene-(C6-C10aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl,-C1-C6 alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0185] 28. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is -C1-C6 alkylene-(4- to 10- membered heterocycloalkyl), wherein each hydrogen atom in -C1-C6alkylene-(4- to 10- membered heterocycloalkyl) is independently optionally substituted by deuterium, halogen, - Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1- C6 alkylene-(O-Re), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), haloalkyl, C3-C6 cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, - P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0186] 29. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is of the formula

[0188] wherein “ ” is a point of covalent attachment to X.

[0189] 30. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is of the formula

[0190] wherein “ ” is a point of covalent attachment to X.

[0191] 31. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein two R3, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6cycloalkyl.

[0192] 32. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5, when present, is independently deuterium, halogen, C1-C6 alkyl, -ORa, -SRa, -NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -CN, or -NO2, wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6 haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0193] 33. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5, when present, is independently deuterium, halogen, -NRaRb, or -CN.

[0194] 34. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5, when present, is independently deuterium, halogen, -NH2, or -CN.

[0195] 35. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R4, when present, is independently deuterium, halogen, or C1-C6 alkyl.

[0196] 36. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R4, when present, is independently deuterium, fluoro, or methyl.

[0197] 37. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y1, when present, is O.

[0198] 38. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y2, when present, is N.

[0199] 39. The compound of any one of clauses 1 to 32, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y1, when present, is N.

[0200] 40. The compound of any one of clauses 1 to 32, or 39, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein Y2, when present, is O.

[0201] 41. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein n1 is 0 or 2.

[0202] 42. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein n2 is 0.

[0203] 43. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein m3 is 2 or 3.

[0204] 44. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein m4 is 0.

[0205] 45. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein q1 is 1.

[0206] 46. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein q2 is 1.

[0207] 47. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein q2 is 2.

[0208] 48. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein p is 1.

[0209] 49. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Z1, when present, is N.

[0210] 50. The compound of any one of the preceding clauses, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Z2, when present, is N.

[0211] 51. The compound of clause 1, selected from the group consisting of (1'S)-6'-amino-3- (4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0212] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-methyl-1H- pyrazole-3-carboxamide;

[0213] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(oxetan-3- yl)-1H-pyrazole-3-carboxamide;

[0214] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(3- methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0215] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(1S)-1-(pyridin-2-yl)ethyl]-1H-pyrazole-3-carboxamide;

[0216] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)- oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0217] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3R)- oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0218] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{3-[1-(oxan-4- yl)-1H-1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0219] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(2- methoxyethyl)-1H-pyrazole-3-carboxamide;

[0220] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3R)- oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0221] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3S)- oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0222] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-methyl-1H-pyrazole-3-carboxamide;

[0223] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0224] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-(3-methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0225] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-[(1S)-1-(pyridin-2-yl)ethyl]-1H-pyrazole-3-carboxamide;

[0226] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-[(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0227] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-[(3R)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0228] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {3-[1-(oxan-4-yl)-1H-1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0229] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-(2-methoxyethyl)-1H-pyrazole-3-carboxamide;

[0230] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (3-{1-[(3R)-oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0231] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (3-{1-[(3S)-oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0232] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3S)- oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0233] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3R)- oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0234] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {7-oxo-6-[(3S)-oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2- yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0235] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {7-oxo-6-[(3R)-oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2- yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0236] 2-[1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-1H-pyrazol-3- yl]-N-(propan-2-yl)acetamide;

[0237] 2-[1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- 1H-pyrazol-3-yl]-N-(propan-2-yl)acetamide;

[0238] (1'S)-6'-amino-3-[4-(3-{1-[(3-methyloxetan-3-yl)methyl]-1H-1,2,3-triazol-4-yl}-1H- pyrazol-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0239] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxo-1,3- oxazolidin-3-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]- 7'-carbonitrile;

[0240] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (2-oxo-1,3-oxazolidin-3-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile;

[0241] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-[3-(pyrrolidine- 1-carbonyl)-1H-pyrazol-1-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile;

[0242] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- [3-(pyrrolidine-1-carbonyl)-1H-pyrazol-1-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0243] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-methyl-N- (oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0244] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-methyl-N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0245] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-[(3S)-oxolan-3- yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0246] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- [(3S)-oxolan-3-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- indene]-7'-carbonitrile;

[0247] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile;

[0248] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0249] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(2- oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0250] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0251] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2R,3S)-3-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0252] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S,4R)-4-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0253] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S,4R)-4-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0254] (1'S)-6'-amino-3-(4-[(5S)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0255] (1'S)-6'-amino-3-(4-[(5R)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0256] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- [(5S)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0257] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- [(5R)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0258] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (4-methyl-4,7-diazaspiro[2.5]octan-7-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0259] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(5- methyl-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0260] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (5-methyl-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0261] (1'S)-6'-amino-3-[4-(5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)-6-{(1S)-1-[(2S,4R)- 4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0262] (1'S)-6'-amino-3-[4-(5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0263] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(5- methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0264] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (5-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0265] (1'S)-6'-amino-3-[4-(5-methyl-2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0266] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (5-methyl-2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0267] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(5- methyl-2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0268] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0269] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0270] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0271] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0272] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0273] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0274] (1'S)-6'-amino-3-(4-[(3S)-1-methylpyrrolidin-3-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0275] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- [(3S)-1-methylpyrrolidin-3-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0276] (1R)-6-amino-3'-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 2,3-dihydrospiro[indene-1,7'-[5]oxa[4]azatricyclo[6.1.1.02,6]deca[2(6),3]diene]-7- carbonitrile;

[0277] (1'S)-6'-amino-3-(9-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-9H- purin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0278] (1'S)-6'-amino-3-(9-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-9H- purin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0279] (1'S)-6'-amino-3-(8-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-7,8- dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0280] (1'S)-6'-amino-3-(3-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-3H- imidazo[4,5-c]pyridin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0281] (1'S)-6'-amino-3-(1-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-1H- imidazo[4,5-c]pyridin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0282] (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0283] (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0284] (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0285] (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0286] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0287] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0288] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0289] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0290] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0291] (1'S)-6'-amino-3-(6-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-9H-purin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0292] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0293] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-imidazo[4,5-c]pyridin-6-yl)-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0294] (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0295] (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0296] (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0297] (1'S)-6'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0298] (1'S)-6'-amino-3-(9-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-6-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9H-purin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0299] (1'S)-6'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[4,3-c]pyridin-6-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0300] (1'S)-6'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-imidazo[4,5-c]pyridin-6-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0301] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(1H-pyrazol-1- yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0302] (1'S)-6'-amino-3-(4-[(3S)-3-methylpyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0303] (1'S)-6'-amino-3-(4-[cyclopropyl(methyl)amino]-6-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0304] (1'S)-6'-amino-3-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0305] (1'S)-6'-amino-3-(4-[(cyclopropylmethyl)(methyl)amino]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0306] (1'S)-6'-amino-3-(4-[(3R)-3-hydroxypyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0307] (1'S)-6'-amino-3-[4-(3,3-difluoropyrrolidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0308] (1'S)-6'-amino-3-[4-(6-azaspiro[2.5]octan-6-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0309] (1'S)-6'-amino-3-[4-(1,3-dihydro-2H-isoindol-2-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0310] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)- oxolan-3-yl]-1H-1,2,4-triazole-3-carboxamide;

[0311] (1'S)-6'-amino-3-(4-[3-(dimethylamino)piperidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0312] (1'S)-6'-amino-3-[4-(azepan-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0313] (1'S)-6'-amino-3-[4-(4-hydroxypiperidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0314] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(1,4-oxazepan- 4-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0315] (1'S)-6'-amino-3-[4-(3-hydroxy-3-methylazepan-1-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0316] (1'S)-6'-amino-3-[4-(4-hydroxy-4-methylazepan-1-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0317] (1'S)-6'-amino-3-[4-(4,4-difluoropiperidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0318] (1'S)-6'-amino-3-(4-[(3R)-3-methoxypyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0319] (1'S)-6'-amino-3-(4-{[(2R)-2-hydroxypropyl](methyl)amino}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0320] (1'S)-6'-amino-3-(4-{[(4-methoxyphenyl)methyl](methyl)amino}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0321] (1'S)-6'-amino-3-[4-(4-methylidenepiperidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0322] (1'S)-6'-amino-3-(4-[(3R)-3-fluoropyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0323] (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0324] (1'S)-6'-amino-3-(4-[(1R,5R)-2,6-diazabicyclo[3.2.0]heptan-6-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0325] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)- oxolan-3-yl]-1H-imidazole-4-carboxamide;

[0326] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3R)- oxolan-3-yl]-1H-imidazole-4-carboxamide;

[0327] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(1H-1,2,4- triazol-1-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0328] (1'S)-6'-amino-3-(4-[(3R)-3-hydroxy-2,2-dimethylazetidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0329] (1'S)-6'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0330] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3R)- oxolan-3-yl]-1H-1,2,4-triazole-3-carboxamide;

[0331] (1'S)-6'-amino-3-[4-(6-azabicyclo[3.1.1]heptan-6-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0332] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{6-oxo-5-[(3S)- oxolan-3-yl]-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0333] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(1H-1,2,3- triazol-1-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0334] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2H-1,2,3- triazol-2-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0335] 6'-amino-3-(4-[8a-(hydroxymethyl)-3-oxotetrahydro-3H-[1,3]oxazolo[3,4-a]pyrazin- 7(1H)-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0336] 6'-amino-3-(4-{[2,2-bis(hydroxymethyl)azetidin-3-yl]oxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0337] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(pyrrolidin-1- yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0338] (1'S)-6'-amino-3-(4-[(3R)-3-methylpyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0339] (1'S)-6'-amino-3-(4-[(3S)-3-hydroxypyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0340] (1'S)-6'-amino-3-[4-(3,3-difluoropiperidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0341] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3S)- oxolan-3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0342] (1'S)-6'-amino-3-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0343] 6'-amino-3-{4-[1-(1-methylpyrrolidin-2-yl)ethoxy]-6,6a,7,8,9,10- hexahydropyrido[1,2-d]pyrimido[5,4-b][1,4]oxazin-2-yl}-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0344] (1'S)-6'-amino-3-[(7S)-7-(difluoromethyl)-8-ethyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0345] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{4-oxo-5-[(3S)- oxolan-3-yl]-1,3,4,5-tetrahydro-2H-pyrrolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0346] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{4-oxo-5-[(3R)- oxolan-3-yl]-1,3,4,5-tetrahydro-2H-pyrrolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0347] 1-(2-[(1'S)-6'-amino-7'-cyano-3',3'-difluoro-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-4-yl)-N-[(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0348] (1'S,3'S)-6'-amino-3'-methyl-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6- (2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0349] (1'S)-6'-amino-5'-fluoro-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2- oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0350] 6'-amino-5'-fluoro-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile;

[0351] (1'S)-6'-amino-3-(4-[(3-hydroxyazetidin-3-yl)methoxy]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0352] (1'S)-6'-amino-3-(4-{[(3-hydroxyazetidin-3-yl)methyl](methyl)amino}-6-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; and

[0353] (1'S)-6'-amino-3-(4-[(3S)-3-cyanopyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0354] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0355] 52 The compound of clause 1, selected from the group consisting of (1'S)-6'-amino-3- (4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[2,1]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0356] (1R)-6-amino-3'-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 2,3-dihydrospiro[indene-1,7'-[4]oxa[5]azatricyclo[6.1.1.02,6]deca[2,5]diene]-7-carbonitrile;

[0357] (5'S)-3'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-5,6,6',7'-tetrahydro-4H-spiro[[2,1]benzoxazole-7,5'-cyclopenta[b]pyridine]-4'-carbonitrile;

[0358] (1'S)-6'-amino-4'-fluoro-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[2,1]benzoxazole-7,1'-indene]-7'- carbonitrile; and

[0359] (1'S)-6'-amino-3-(2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- 2',3',5,6-tetrahydro-4H-spiro[[2,1]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0360] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0361] 53. The compound of clause 1, selected from the group consisting of (1'R)-7'-amino-3- (4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0362] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- methyl-1H-pyrazole-3-carboxamide;

[0363] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- (oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0364] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- methyl-N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0365] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(3- methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0366] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- [(1S)-1-(pyridin-2-yl)ethyl]-1H-pyrazole-3-carboxamide;

[0367] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- [(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0368] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- [(3R)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0369] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{3-[1-(oxan-4- yl)-1H-1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0370] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(2- methoxyethyl)-1H-pyrazole-3-carboxamide;

[0371] (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3R)- oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0372] (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3S)- oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0373] (5'S)-3'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 5,6,7',8'-tetrahydro-4H,6'H-spiro[[1,2]benzoxazole-7,5'-quinoline]-4'-carbonitrile;

[0374] (5'R)-3'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 5,6,7',8'-tetrahydro-4H,6'H-spiro[[1,2]benzoxazole-7,5'-isoquinoline]-4'-carbonitrile;

[0375] (1'S)-7'-amino-5'-fluoro-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalene]-8'-carbonitrile;

[0376] (1'R)-7'-amino-3-(2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0377] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0378] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0379] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0380] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0381] (1'R)-7'-amino-3-(4-{[3-(dimethylamino)oxetan-3-yl]methoxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0382] (1'R)-7'-amino-3-(4-{[3-(dimethylamino)oxetan-3-yl]methoxy}-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0383] (1'R)-7'-amino-3-(4-{[3-(dimethylamino)oxetan-3-yl]methoxy}-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0384] (1'R)-7'-amino-3-(4-{[1-(dimethylamino)cyclopropyl]methoxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0385] (1'R)-7'-amino-3-(4-{[1-(dimethylamino)cyclopropyl]methoxy}-6-{(1S)-1-[(2S,4R)- 4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0386] (1'R)-7'-amino-3-(4-{[1-(dimethylamino)cyclopropyl]methoxy}-6-{(1S)-1-[(2S,4R)- 4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0387] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R,4S)-4-fluoropyrrolidin-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0388] (1'R)-7'-amino-3-(4-{[(3R,4S)-4-fluoropyrrolidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0389] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)-6-oxa-1- azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0390] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0391] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0392] (1'R)-7'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0393] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0394] (1'R)-7'-amino-3-(6-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9-[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-9H-purin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0395] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0396] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-imidazo[4,5-c]pyridin-6-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0397] (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0398] (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0399] (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0400] (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0401] (1'R)-7'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0402] (1'R)-7'-amino-3-(9-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-6-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9H-purin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0403] (1'R)-7'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[4,3-c]pyridin-6-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; and

[0404] (1'R)-7'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-imidazo[4,5-c]pyridin-6-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0405] (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0406] (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2R,3S)-3-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0407] (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2R,3S)-3-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0408] (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S,4R)-4-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0409] (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0410] (1'R)-7'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0411] (1'R)-7'-amino-3-[4-{(1S)-1-[(2R,3S)-3-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(2- oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0412] (1'R)-7'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(2- oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0413] (1'R)-7'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0414] (1'R)-7'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2R,3S)- 3-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0415] (1'R)-7'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2S,4R)- 4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0416] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2R,3S)-3- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0417] 1-(6-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-methyl-1H-pyrazole-3-carboxamide;

[0418] 1-(6-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-[(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0419] 1-(6-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-[(3R)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0420] 1-(6-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-(3-methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0421] (1'R)-7'-amino-3-[4-(6-methyl-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl)-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0422] (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3S)- oxolan-3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0423] (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3R)- oxolan-3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0424] (1'R)-7'-amino-3-[4-(6-methyl-7-oxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2- yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0425] (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3S)- oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'- carbonitrile;

[0426] (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3R)- oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'- carbonitrile;

[0427] (1'R)-7'-amino-3-[4-(5-methyl-6-oxo-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0428] (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{6-oxo-5-[(3S)- oxolan-3-yl]-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0429] (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{6-oxo-5-[(3R)- oxolan-3-yl]-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl}-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0430] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(piperidin-1- yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0431] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{4-oxo-5-[(3S)- oxolan-3-yl]-1,3,4,5-tetrahydro-2H-pyrrolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0432] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{4-oxo-5-[(3R)- oxolan-3-yl]-1,3,4,5-tetrahydro-2H-pyrrolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0433] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3S)- oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0434] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{6-oxo-5-[(3S)- oxolan-3-yl]-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0435] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3S)- oxolan-3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0436] (1'R)-7'-amino-3-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0437] (1'R)-7'-amino-3-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0438] (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-6- azaspiro[3.5]nonan-6-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalene]-8'-carbonitrile;

[0439] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-[(4S)-1-oxa-6- azaspiro[3.5]nonan-6-yl]pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalene]-8'-carbonitrile;

[0440] (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0441] (1'R)-7'-amino-3-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0442] (1'R)-7'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0443] (1'R)-7'-amino-3-(4-[(3R)-3-hydroxy-2,2-dimethylazetidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0444] (1'R)-7'-amino-3-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0445] 1-(2-[(1'S)-7'-amino-8'-cyano-4',4'-difluoro-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-4-yl)-N-[(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0446] (1'R)-7'-amino-3-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0447] (1'R)-7'-amino-3-(4-chloro-6-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalene]-8'-carbonitrile;

[0448] (1'R)-7'-amino-3-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalene]-8'-carbonitrile; and

[0449] (1'R)-7'-amino-3-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-6-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0450] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0451] 54. A pharmaceutical composition comprising at least one compound of any one of clauses 1 to 53, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable excipients.

[0452] 55. A method of treating disease, such as cancer, comprising administering to a subject in need of such treatment an effective amount of a compound of any one of clauses 1 to 53, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to clause 54.

[0453] 56. A compound of any one of clauses 1 to 53, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, for use in a method of treating cancer in a subject.

[0454] 57. A compound of any one of clauses 1 to 53, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, for treating cancer in a subject.

[0455] 58. Use of a compound of any one of clauses 1 to 53, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating cancer in a subject. DETAILED DESCRIPTION

[0456] Before the present disclosure is further described, it is to be understood that this disclosure is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended clauses.

[0457] For the sake of brevity, the disclosures of the publications cited in this specification, including patents, are herein incorporated by reference. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents, applications, published applications and other publications referred to herein are incorporated by reference in their entireties. If a definition set forth in this section is contrary to or otherwise inconsistent with a definition set forth in a patent, application, or other publication that is herein incorporated by reference, the definition set forth in this section prevails over the definition incorporated herein by reference.

[0458] As used herein and in the appended clauses, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the clauses may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of clause elements, or use of a “negative” limitation.

[0459] As used herein, the terms “including,” “containing,” and “comprising” are used in their open, non-limiting sense.

[0460] To provide a more concise description, some of the quantitative expressions given herein are not qualified with the term “about.” It is understood that, whether the term “about” is used explicitly or not, every quantity given herein is meant to refer to the actual given value, and it is also meant to refer to the approximation to such given value that would reasonably be inferred based on the ordinary skill in the art, including equivalents and approximations due to the experimental and / or measurement conditions for such given value. Whenever a yield is given as a percentage, such yield refers to a mass of the entity for which the yield is given with respect to the maximum amount of the same entity that could be obtained under the particular stoichiometric conditions. Concentrations that are given as percentages refer to mass ratios, unless indicated differently.

[0461] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure, the preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and / or materials in connection with which the publications are cited.

[0462] Except as otherwise noted, the methods and techniques of the present embodiments are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification. See, e.g., Loudon, Organic Chemistry, Fourth Edition, New York: Oxford University Press, 2002, pp.360-361, 1084-1085; Smith and March, March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Fifth Edition, Wiley-Interscience, 2001.

[0463] Chemical nomenclature for compounds described herein has generally been derived using the commercially-available ACD / Labs 2022.2.3 (Advanced Chemistry Development, Inc.) or ChemDraw Professional 22.2.0.3300 (PerkinElmer Informatics, Inc.).

[0464] As used herein and in connection with chemical structures depicting the variousembodiments described herein, “*”, “**”, and “ ”, each represent a point of covalentattachment of the chemical group or chemical structure in which the identifier is shown to an adjacent chemical group or chemical structure. For example, in a hypothetical chemical structure A-B, where A and B are joined by a covalent bond, in some embodiments, the portion of A-B defined by the group or chemical structure A can be represented by ,” represents a bond to A andthe point of covalent bond attachment to B. Alternatively, in some embodiments, the portion of A-B defined by the group or chemical structure B can be represented by,” represents a bond to B andthe point of covalent bond attachment to A.

[0465] It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination. All combinations of the embodiments pertaining to the chemical groups represented by the variables are specifically embraced by the present disclosure and are disclosed herein just as if each and every combination was individually and explicitly disclosed, to the extent that such combinations embrace compounds that are stable compounds (i.e., compounds that can be isolated, characterized, and tested for biological activity). In addition, all subcombinations of the chemical groups listed in the embodiments describing such variables are also specifically embraced by the present disclosure and are disclosed herein just as if each and every such sub-combination of chemical groups was individually and explicitly disclosed herein. CHEMICAL DEFINITIONS

[0466] The term “alkyl” refers to a straight- or branched-chain monovalent hydrocarbon group. The term “alkylene” refers to a straight- or branched-chain divalent hydrocarbon group. In some embodiments, it can be advantageous to limit the number of atoms in an “alkyl” or “alkylene” to a specific range of atoms, such as C1-C20 alkyl or C1-C20 alkylene, C1-C12 alkyl or C1-C12 alkylene, or C1-C6 alkyl or C1-C6 alkylene. Examples of alkyl groups include methyl (Me), ethyl (Et), n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl (tBu), pentyl, isopentyl, tert-pentyl, hexyl, isohexyl, and groups that in light of the ordinary skill in the art and the teachings provided herein would be considered equivalent to any one of the foregoing examples. Examples of alkylene groups include methylene (-CH2-), ethylene ((-CH2-)2), n- propylene ((-CH2-)3), iso-propylene ((-C(H)(CH3)CH2-)), n-butylene ((-CH2-)4), and the like. It will be appreciated that an alkyl or alkylene group can be unsubstituted or substituted as described herein. An alkyl or alkylene group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0467] The term “alkenyl” refers to a straight- or branched-chain mono-valent hydrocarbon group having one or more double bonds. In some embodiments, it can be advantageous to limitthe number of atoms in an “alkenyl” to a specific range of atoms, such as C2-C20 alkenyl, C2- C12 alkenyl, or C2-C6 alkenyl. Examples of alkenyl groups include ethenyl (or vinyl), allyl, and but-3-en-1-yl. Included within this term are cis and trans isomers and mixtures thereof. It will be appreciated that an alkenyl can be unsubstituted or substituted as described herein. An alkenyl group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0468] The term “alkynyl” refers to a straight- or branched-chain monovalent hydrocarbon group having one or more triple bonds. In some embodiments, it can be advantageous to limit the number of atoms in an “alkynyl” to a specific range of atoms, such as C2-C20alkynyl, C2- C12 alkynyl, or C2-C6 alkynyl. Examples of alkynyl groups include acetylenyl (-C≡CH) and propargyl (-CH2C≡CH), but-3-yn-1,4-diyl (-C≡C-CH2CH2-), and the like. It will be appreciated that an alkynyl group can be unsubstituted or substituted as described herein. An alkynyl group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0469] The term “cycloalkyl” refers to a saturated or partially saturated, monocyclic or polycyclic mono-valent carbocycle. In some embodiments, it can be advantageous to limit the number of atoms in a “cycloalkyl” to a specific range of atoms, such as having 3 to 12 ring atoms. Polycyclic carbocycles include fused, bridged, and spiro polycyclic systems. Illustrative examples of cycloalkyl groups include monovalent radicals of the following entities:In particular, a cyclopropyl moiety can be depicted by the structural formula. It will be appreciated that a cycloalkyl group can be unsubstituted or substituted as described herein. A cycloalkyl group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0470] The term “halogen” or “halo” represents chlorine, fluorine, bromine, or iodine.

[0471] The term “haloalkyl” refers to an alkyl group with one or more halo substituents. Examples of haloalkyl groups include –CF3, -(CH2)F, -CHF2, -CH2Br, -CH2CF3, and -CH2CH2F.

[0472] In certain embodiments, alkenyl may be substituted. For example, the alkenyl may be substituted with halo (e.g., fluoro). Illustratively, the alkenyl substituted with halo may be a =CHF. Illustratively, a hexahydro-1H-pyrrolizinyl moiety may be substituted by halo- substituted alkenyl, for example, a substituted hexahydro-1H-pyrrolizinyl moiety can be depicted by the structural formula.

[0473] The term “aryl” refers to a monovalent all-carbon monocyclic or fused-ring polycyclic group having a completely conjugated pi-electron system. In some embodiments, it can be advantageous to limit the number of atoms in an “aryl” to a specific range of atoms, such as mono-valent all-carbon monocyclic or fused-ring polycyclic groups of 6 to 14 carbon atoms (C6-C14 aryl), or monovalent all-carbon monocyclic or fused-ring polycyclic groups of 6 to 10 carbon atoms (C6-C10aryl).Examples, without limitation, of aryl groups are phenyl, naphthalenyl and anthracenyl. It will be appreciated that an aryl group can be unsubstituted or substituted as described herein. An aryl group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0474] The term “heterocycloalkyl” refers to a mono-valent monocyclic or polycyclic ring structure (e.g., heterobicyclyl or bicyclic heterocyclyl) that is saturated or partially saturated having one or more non-carbon ring atoms. In some embodiments, it can be advantageous to limit the number of atoms in a “heterocycloalkyl” to a specific range of ring atoms, such as from 3 to 12 ring atoms (3- to 12-membered), or 3 to 7 ring atoms (3- to 7-membered), or 3 to 6 ring atoms (3- to 6-membered), or 4 to 6 ring atoms (4- to 6-membered), 5 to 7 ring atoms (5- to 7-membered), or 4 to 10 ring atoms (4- to 10-membered). In some embodiments, it can be advantageous to limit the number and type of ring heteroatoms in “heterocycloalkyl” or to a specific range or type of heteroatoms, such as 1 to 5 ring heteroatoms selected from nitrogen, oxygen, and sulfur. Examples, without limitations, of mono-cyclic heterocycloalkyl groups include tetrahydrofuran, pyrrolidinyl, and morpholinyl. Polycyclic ring systems include fused, bridged, and spiro systems. In some embodiments, it can be advantageous to limit the number of atoms in a bicyclic “heterocycloalkyl” to a specific range of ring atoms, such as from 5 to 10 ring atoms (5- to 10-membered), or 6 to 10 ring atoms (6- to 10-membered). The ringstructure may optionally contain an oxo group or an imino group on a carbon ring member or up to two oxo groups on sulfur ring members. Examples, without limitations, of fused bicyclic, bridged bicyclic, and spiro bicyclic heterocycloalkyl groups include pyrrolizinyl, 2,5- diazabicyclo[2.2.2]octanyl, and 1-oxaspiro[4.5]decanyl. Illustrative examples of heterocycloalkyl groups include monovalent radicals of the following entities:

[0475] A three-membered heterocycle may contain at least one heteroatom ring atom, where the heteroatom ring atom is a sulfur, oxygen, or nitrogen. Non-limiting examples of three- membered heterocycle groups include monovalent and divalent radicals of oxirane, azetidine, and thiirane. A four-membered heterocycle may contain at least one heteroatom ring atom, where the heteroatom ring atom is a sulfur, oxygen, or nitrogen. Non-limiting examples of four-membered heterocycle groups include monovalent and divalent radicals of azitidine, oxtenane, and thietane. A five-membered heterocycle can contain up to four heteroatom ring atoms, where (a) at least one ring atom is oxygen and sulfur and zero, one, two, or three ring atoms are nitrogen, or (b) zero ring atoms are oxygen or sulfur and up to four ring atoms are nitrogen. Non-limiting examples of five-membered heterocyle groups include mono-valent and divalent radicals of pyrrolidine, tetrahydrofuran, 2, 5-dihydro-1H- pyrrole, pyrazolidine, thiazolidine, 4,5-dihydro-1H-imidazole, dihydrothiophen-2(3H)-one, tetrahydrothiophene 1,1-dioxide, imidazolidin-2-one, pyrrolidin-2-one, dihydrofuran-2(3H)-one, 1,3-dioxolan-2- one, and oxazolidin-2-one. A six-membered heterocycle can contain up to four heteroatomring atoms, where (a) at least one ring atom is oxygen and sulfur and zero, one, two, or three ring atoms are nitrogen, or (b) zero ring atoms are oxygen or sulfur and up to four ring atoms are nitrogen. Non-limiting examples of six-membered heterocycle groups include mono- valent or divalent radicals of piperidine, morpholine, 4H-1,4-thiazine, 1,2,3,4- tetrahydropyridine, piperazine, 1,3-oxazinan-2-one, piperazin-2-one, thiomorpholine, and thiomorpholine 1,1-dioxide.

[0476] A “heterobicyclyl” or “bicyclic heterocyclyl” refers to a heterocycle comprising a fused, bridged, or spiro bicyclic ring system that is saturated or partially saturated having one or more non-carbon ring atoms. As used herein, “heterobicyclyl” and “bicyclic heterocyclyl” can include one heterocycle ring fused to a cycloalkyl, heterocyclyl, aryl, or heteroaryl, where the ring stem overall is saturated or partially saturated. Non-limiting examples of “heterobicyclyl” and “bicyclic heterocyclyl” include, but are not limited to, radicals of the

[0477] It will be appreciated that a heterocycloalkyl group (e.g., a heteromonocyclyl or a heterobicyclyl or a bicyclic heterocyclyl) can be unsubstituted or substituted as described herein. A heterocycloalkyl group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0478] The term “heteroaryl” refers to a mono-valent monocyclic, fused bicyclic, or fused polycyclic aromatic heterocycle (ring structure having ring atoms or members selected from carbon atoms and up to four heteroatoms selected from nitrogen, oxygen, and sulfur) that is fully unsaturated and having from 3 to 12 ring atoms per heterocycle. The term “heteroarylene” refers to a divalent monocyclic, fused bicyclic, or fused polycyclic aromatic heterocycle (ring structure having ring atoms or members selected from carbon atoms and up to four heteroatoms selected from nitrogen, oxygen, and sulfur) having from 3 to 12 ring atoms per heterocycle. In some embodiments, it can be advantageous to limit the number of ring atoms in a “heteroaryl” or “heteroarylene” to a specific range of atom members, such as 5- to 10-membered heteroaryl. In some instances, a 5- to 10-membered heteroaryl can be a monocyclic ring or fused bicyclic rings having 5- to 10-ring atoms wherein at least one ring atom is a heteroatom, such as N, O, or S. The ring structure may optionally contain an oxogroup or an imino group on a carbon ring member or up to two oxo groups on sulfur ring members. Illustrative examples of 5- to 10-membered heteroaryl groups include monovalent radicals of the following entities, while examples of 5- to 10-membered heteroarylene groups include divalent radicals of the following entities, in the form of properly bonded moieties:

[0479] In some embodiments, a “monocyclic” heteroaryl can be an aromatic five- or six- membered heterocycle. A five-membered heteroaryl can contain up to four heteroatom ring atoms, where (a) at least one ring atom is oxygen and sulfur and zero, one, two, or three ring atoms are nitrogen, or (b) zero ring atoms are oxygen or sulfur and up to four ring atoms are nitrogen. Non-limiting examples of five-membered heteroaryl groups include mono-valent radicals of furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, isothiazole, pyrazole, imidazole, oxadiazole, thiadiazole, triazole, or tetrazole. A six-membered heteroaryl can contain up to four heteroatom ring atoms, where (a) at least one ring atom is oxygen and sulfur and zero, one, two, or three ring atoms are nitrogen, or (b) zero ring atoms are oxygen or sulfur and up to four ring atoms are nitrogen. Non-limiting examples of six-membered heteroaryl groups include monovalent radicals of pyridine, pyrazine, pyrimidine, pyridazine, or triazine. A “bicyclic heteroaryl” is a fused bicyclic system comprising one heteroaryl ring fused to a phenyl or another heteroaryl ring. Non-limiting examples of bicyclic heteroaryl groups include monovalent radicals of quinoline, isoquinoline, quinazoline, quinoxaline, 1,5-naphthyridine, 1,8-naphthyridine, isoquinolin-3(2H)-one, thieno[3,2-b]thiophene, 1H-pyrrolo[2,3-b]pyridine, indazole, 1H-benzo[d]imidazole, benzo[d]oxazole, and benzo[d]thiazole.

[0480] In particular, an isoquinolin-3(2H)-onyl moiety can be depicted by the structural formula.

[0481] In particular, a divalent pyridopyrimidine moiety can be depicted by the structural formula.

[0482] It will be appreciated that a heteroaryl group can be unsubstituted or substituted as described herein. A heteroaryl group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0483] It will be appreciated that a heteroaryl or heteroarylene group can be unsubstituted or substituted as described herein. A heteroaryl or heteroarylene group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0484] The term “oxo” represents a carbonyl oxygen. For example, a cyclopentyl substituted with oxo is cyclopentanone.

[0485] The term “substituted” means that the specified group or moiety bears one or more substituents. The term “unsubstituted” means that the specified group bears no substituents. Where the term “substituted” is used to describe a structural system, the substitution is meant to occur at any valency-allowed position on the system. In some embodiments, “substituted” means that the specified group or moiety bears one, two, or three substituents. In other embodiments, “substituted” means that the specified group or moiety bears one or two substituents. In still other embodiments, “substituted” means the specified group or moiety bears one substituent.

[0486] As used herein, the term “optionally substituted” refers to the replacement of one to six hydrogen radicals in a given structure with the radical of a specified substituent including, but not limited to: deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, 4- to 10- membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, OH, -OC1-C6alkyl, OC(O)C1-C6 alkyl, -OC(O)N(H or C1-C6 alkyl)2, OS(O)C1-C6 alkyl, OS(O)2C1-C6 alkyl, - OS(O)N(H or C1-C6alkyl)2, OS(O)2N(H or C1-C6alkyl)2, -SC1-C6alkyl, S(O)C1-C6alkyl, - S(O)2C1-C6 alkyl, S(O)N(H or C1-C6 alkyl)2, S(O)2N(H or C1-C6 alkyl)2, N(H or C1-C6 alkyl)2, -N(C1-C6alkyl)C(O)-C1-C6alkyl, N(C1-C6alkyl)C(O)OC1-C6alkyl, N(C1-C6alkyl)C(O)N(H or C1-C6 alkyl)2, N(C1-C6 alkyl)S(O)C1-C6 alkyl, -N(C1-C6 alkyl)S(O)2C1-C6 alkyl, -N(C1-C6alkyl)S(O)N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)S(O)2N(H or C1-C6 alkyl)2, C(O)C1-C6 alkyl, C(O)OC1-C6 alkyl, C(O)N(H or C1-C6 alkyl)2, -P(H or C1-C6 alkyl)2, P(O)(H or C1-C6 alkyl)2, -P(O)2(H or C1-C6 alkyl)2, -P(O)N(H or C1-C6 alkyl)2, P(O)2N(H or C1-C6 alkyl)2, P(O)OC1C6 alkyl, P(O)2OC1-C6 alkyl, CN, or -NO2. “Optionally substituted” refers to the replacement of one to four hydrogen radicals in a given structure with the substituents mentioned above. For example, one to three hydrogen radicals can be replaced by the optional substituent.

[0487] Any formula depicted herein is intended to represent a compound of that structural formula as well as certain variations or forms. For example, a formula given herein is intended to include a racemic form, or one or more enantiomeric, diastereomeric, or geometric isomers, or a mixture thereof. Additionally, any formula given herein is intended to refer also to a hydrate, solvate, or polymorph of such a compound, or a mixture thereof.

[0488] Any formula given herein is also intended to represent unlabeled forms as well as isotopically labeled forms of the compounds. Isotopically labeled compounds have structures depicted by the formulas given herein except that one or more atoms are replaced by an atom having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into compounds of the disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, chlorine, and iodine, such as2H,3H,11C,13C,14C,15N,18O,17O,31P,32P,35S,18F,36Cl, and125I, respectively. Such isotopically labelled compounds are useful in metabolic studies (preferably with14C), reaction kinetic studies (with, for example2H or3H), detection or imaging techniques [such as positron emission tomography (PET) or single- photon emission computed tomography (SPECT)] including drug or substrate tissue distribution assays, or in radioactive treatment of patients. Further, substitution with heavier isotopes such as deuterium (i.e.,2H) may afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements. Isotopically labeled compounds of this disclosure and prodrugs thereof can generally be prepared by carrying out the procedures disclosed in the schemes or in the examples and preparations described below by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent.

[0489] As described herein, a compound may be of a particular formula (e.g., of Formula (I)- (XV)), an isotopically labeled form thereof (e.g., an isotopically labeled form of the compound of Formula (I)-(XV)), or a pharmaceutically acceptable salt thereof (e.g., a pharmaceutically acceptable salt of the compound of Formula (I)-(XV) or a pharmaceutically acceptable salt of the isotopically labeled form of the compound of Formula (I)-(XV)).

[0490] Certain chemical entities of Formula (I)-(XV) may be depicted in two or more tautomeric forms. Any and all alternative tautomers are included within the scope of theseformulas, and no inference should be made as to whether the chemical entity exists as the tautomeric form in which it is drawn. It will be understood that the chemical entities described herein, and their constituent rings A, B, etc. can exist in different tautomeric forms. It will be readily appreciated by one of skill in the art that because of rapid interconversion, tautomers can generally be considered to be the same chemical compound. Examples of tautomers include but are not limited to enol-keto tautomers, amine-imine tautomers, and the like.

[0491] In particular, a ring option of isoquinolin-3(2H)-oneylene can exist as the following.

[0492] The nomenclature “(ATOM)i-(ATOM)j” with j > i, when applied herein to a class of substituents, is meant to refer to embodiments of this disclosure for which each and every one of the number of atom members, from i to j including i and j, is independently realized. By way of example, the term C1-C3 refers independently to embodiments that have one carbon member (C1), embodiments that have two carbon members (C2), and embodiments that have three carbon members (C3).

[0493] The disclosure also includes pharmaceutically acceptable salts of the compounds represented by Formula (I)-(XV), preferably of those described above and of the specific compounds exemplified herein, and pharmaceutical compositions comprising such salts, and methods of using such salts.

[0494] A “pharmaceutically acceptable salt” is intended to mean a salt of a free acid or base of a compound represented herein that is non-toxic, biologically tolerable, or otherwise biologically suitable for administration to the subject. See, generally, S.M. Berge, et al., “Pharmaceutical Salts,” J. Pharm. Sci., 1977, 66, 1-19. Preferred pharmaceutically acceptable salts are those that are pharmacologically effective and suitable for contact with the tissues ofsubjects without undue toxicity, irritation, or allergic response. A compound described herein may possess a sufficiently acidic group, a sufficiently basic group, both types of functional groups, or more than one of each type, and accordingly react with a number of inorganic or organic bases, and inorganic and organic acids, to form a pharmaceutically acceptable salt.,” wherein “W ” is an inorganic counter ion (e.g., an inorganic anion) or an organic counterion (e.g., an organic anion). In certain embodiments, W is an anion that is complexed witha cation of a compound of the disclosure to form a pharmaceutically acceptable salt.

[0495] It will be understood that the chemical entities described herein, can exist as a salt of a free acid or base of a compound represented herein and an inorganic or organic counter ion. Illustratively, the salt can be formed during the manufacture of the compound (e.g., a salt or a pharmaceutically acceptable salt) or can be substituted to a salt for further manufacture, formulation, or administration reasons. As illustrated herein, certain compounds include a “W ,” wherein “W ” is an inorganic counter ion (e.g., an inorganic anion) or an organiccounter ion (e.g., an organic anion). In certain embodiments, W is an anion that iscomplexed with a cation of a compound of the disclosure to form a pharmaceutically acceptable salt.

[0496] The term “inorganic counter ion” represents an inorganic ion that accompanies an ionic species in order to maintain electric neutrality. An inorganic counter ion may represent an anion or cation. An inorganic counterion may accompany a free acid or base of a compound represented herein. An inorganic ion may form by a reaction of an inorganic base or inorganic acid and a compound described herein that possesses a sufficiently acidic group, a sufficiently basic group, both types of functional groups, or more than one of each type.

[0497] The term “organic counter ion” represents an organic counter ion that accompanies an ionic species in order to maintain electric neutrality. The organic ion may represent an anion or cation. An organic counter ion may accompany a free acid or base of a compound represented herein. An organic ion may form by a reaction of an organic base or organic acid and a compound described herein that possesses a sufficiently acidic group, a sufficiently basic group, both types of functional groups, or more than one of each type.

[0498] Examples of pharmaceutically acceptable salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrogen-phosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caproates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyne-1,4-dioates, hexyne-1,6-dioates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates,hydroxybenzoates, methoxybenzoates, phthalates, sulfonates, methylsulfonates, propylsulfonates, besylates, xylenesulfonates, naphthalene-1-sulfonates, naphthalene-2- sulfonates, phenylacetates, phenylpropionates, phenylbutyrates, citrates, lactates, γ- hydroxybutyrates, glycolates, tartrates, and mandelates. Lists of other suitable pharmaceutically acceptable salts are found in Remington's Pharmaceutical Sciences, 17th Edition, Mack Publishing Company, Easton, Pa., 1985.

[0499] For a compound of Formula (I)-(XV) that contains a basic nitrogen, a pharmaceutically acceptable salt may be prepared by any suitable method available in the art, for example, treatment of the free base with an inorganic acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, nitric acid, boric acid, phosphoric acid, and the like, or with an organic acid, such as acetic acid, phenylacetic acid, propionic acid, stearic acid, lactic acid, ascorbic acid, maleic acid, hydroxymaleic acid, isethionic acid, succinic acid, valeric acid, fumaric acid, malonic acid, pyruvic acid, oxalic acid, glycolic acid, salicylic acid, oleic acid, palmitic acid, lauric acid, a pyranosidyl acid, such as glucuronic acid or galacturonic acid, an alpha-hydroxy acid, such as mandelic acid, citric acid, or tartaric acid, an amino acid, such as aspartic acid or glutamic acid, an aromatic acid, such as benzoic acid, 2-acetoxybenzoic acid, naphthoic acid, or cinnamic acid, a sulfonic acid, such as laurylsulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, or ethanesulfonic acid, or any compatible mixture of acids such as those given as examples herein, and any other acid and mixture thereof that are regarded as equivalents or acceptable substitutes in light of the ordinary level of skill in this technology.

[0500] The disclosure also relates to pharmaceutically acceptable prodrugs of the compounds of Formula (I)-(XV), and treatment methods employing such pharmaceutically acceptable prodrugs. The term “prodrug” means a precursor of a designated compound that, following administration to a subject, yields the compound in vivo via a chemical or physiological process such as solvolysis or enzymatic cleavage, or under physiological conditions (e.g., a prodrug on being brought to physiological pH is converted to the compound of Formula (I)-(XV)).

[0501] A “pharmaceutically acceptable prodrug” is a prodrug that is non-toxic, biologically tolerable, and otherwise biologically suitable for administration to the subject. Illustrative procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in “Design of Prodrugs,” ed. H. Bundgaard, Elsevier, 1985.

[0502] The present disclosure also relates to pharmaceutically active metabolites of compounds of Formula (I)-(XV), and uses of such metabolites in the methods of the disclosure. A “pharmaceutically active metabolite” means a pharmacologically active product of metabolism in the body of a compound of Formula (I)-(XV) or salt thereof. Prodrugs and active metabolites of a compound may be determined using routine techniques known oravailable in the art. See, e.g., Bertolini et al., J. Med. Chem.1997, 40, 2011-2016; Shan et al., J. Pharm. Sci. 1997, 86 (7), 765-767; Bagshawe, Drug Dev. Res. 1995, 34, 220-230; Bodor, Adv. Drug Res.1984, 13, 255-331; Bundgaard, Design of Prodrugs (Elsevier Press, 1985); and Larsen, Design and Application of Prodrugs, Drug Design and Development (Krogsgaard- Larsen et al., eds., Harwood Academic Publishers, 1991).

[0503] As used herein, the term “KRAS inhibitor” includes, but is not limited to, a compound that is capable of inhibiting the protein encoded by the KRAS gene, called K-Ras, that is involved in the RAS / MAPK signaling pathway. The terms KRAS gene, K-Ras, and RAS / MAPK signaling pathway will be known and understood by one of skill in the art. It will be appreciated that KRAS mutations occur in approximately one in seven of all human metastatic cancers, and that those mutations can occur in a variety of locations in the KRAS gene coding sequence. KRAS mutations primarily occur in KRAS codons 12 and 13, and also occur in codons 18, 61, 117, and 146 at low frequencies and have distinct effects on tumor cell signaling based on the codon and missense mutation. Examples of KRAS mutations include, but are not limited to KRAS G12C, KRAS G12D, KRAS G12V, KRAS G12R, KRAS G12S, KRAS G13C, KRAS G13D, KRAS A18D, KRAS Q61H, KRAS K117N, and the like. It will be understood by a person having ordinary skill in the art that reference to a inhibiting of KRAS mutations, such as KRAS G12D refers to inhibiting the protein encoded by the KRAS G12D gene, having a coding sequence (e.g. a guanine to adenine substitution, at position 35 on codon 12 of the KRAS coding sequence) that produces a K-Ras G12D protein, where a glycine at position 12 of the protein sequence is replaced by am aspartic acid. REPRESENTATIVE EMBODIMENTS

[0504] In some embodiments, the disclosure relates to a compound of the formula I,

[0505] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, ring C, R1, R2, R3, R4, R5, R6, R7, X, X1, X2, X3, m1, m2, m3, m4, n1, n2, p, q1, and q2 are as described herein.

[0506] In some embodiments, the disclosure provides a compound of the formula II,

[0507] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, ring C, R1, R2, R3, R4, R5, R6, R7, X, m1, m2, m3, m4, n1, n2, p, q1, and q2 are as described herein.

[0508] In some embodiments, the disclosure provides a compound of the formula III,

[0509] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, ring C, R1, R2, R3, R4, R5, R6, R7, X, m1, m2, m3, m4, n1, n2, p, q1, and q2 are as described herein.

[0510] In some embodiments, the disclosure provides a compound of the formula IV,

[0511] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5a, R6, R7, X, Z1, Z2, m1, m2, m4, n1, n2, p, q1, and q2 are as described herein.

[0512] In some embodiments, the disclosure provides a compound of the formula V,

[0513] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5a, R6, R7, X, Z1, Z2, m1, m2, m4, n1, n2, p, q1, and q2 are as described herein.

[0514] In some embodiments, the disclosure provides a compound of the formula VI,

[0515] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5a, R6, X, Z1, Z2, Y1, Y2, m1, m2, n1, n2, p, q1, and q2 are as described herein.

[0516] In some embodiments, the disclosure provides a compound of the formula VII,

[0517] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5a, R6, X, Z1, Z2, Y1, Y2, m1, m2, n1, n2, p, q1, and q2 are as described herein.

[0518] In some embodiments, the disclosure provides a compound of the formula VIII,

[0519] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R3, R4, R5a, R6, X, Z1, Z2, Z3, Z4, Z5, Y1, Y2, n1, n2, p, q1, and q2 are as described herein.

[0520] In some embodiments, the disclosure provides a compound of the formula IX,

[0521] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R3, R4, R5a, R6, X, Z1, Z2, Z3, Z4, Z5, Y1, Y2, n1, n2, p, q1, and q2 are as described herein.

[0522] In some embodiments, the disclosure provides a compound of the formula X,

[0523] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5, R6, R7, X, Z1, Z2, m1, m2, m4, n1, n2, p, q1, and q2 are as described herein.

[0524] In some embodiments, the disclosure provides a compound of the formula XI,

[0525] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5, R6, R7, X, Z1, Z2, m1, m2, m4, n1, n2, p, q1, and q2 are as described herein.

[0526] In some embodiments, the disclosure provides a compound of the formula XII,

[0527] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5, R6, X, Y1, Y2, Z1, Z2, m1, m2, n1, n2, p, q1, and q2 are as described herein.

[0528] In some embodiments, the disclosure provides a compound of the formula XIII,

[0529] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R1, R2, R3, R4, R5, R6, X, Y1, Y2, Z1, Z2, m1, m2, n1, n2, p, q1, and q2 are as described herein.

[0530] In some embodiments, the disclosure provides a compound of the formula XIV,

[0531] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R3, R4, R5, R6, X, Y1, Y2, Z1, Z2, Z3, Z4, Z5, n1, n2, p, q1, and q2 are as described herein.

[0532] In some embodiments, the disclosure provides a compound of the formula XV,XV

[0533] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A, ring C, R3, R4, R5, R6, X, Y1, Y2, Z1, Z2, Z3, Z4, Z5, n1, n2, p, q1, and q2 are as described herein.

[0534] In some embodiments, at least one hydrogen atom in the compound of the Formula (I)- (XV) is substituted by a deuterium. In some embodiments, at least one hydrogen atom in ring A, ring B, ring C, R1, R2, R3, R4, R5, R6, or R7in the compound of the formula (I)-(XV) is substituted by a deuterium.

[0535] In some embodiments, each of X1, X2, and X3is independently an -O-, -S-, -S(O)2-, - CHR3-, -C(R3)2-, or -CH2-, provided that no more than one of X1, X2, and X3is a -O-, -S-, or - S(O)2-. In some embodiments, each of X1, X2, and X3is independently -CHR3-, -C(R3)2-, or -CH2-. In some embodiments, each of X1, X2, and X3is independently -CH2-.

[0536] In some embodiments, q1 is 0, 1 or 2. In some embodiments, q1 is 1 or 2. In some embodiments, q1 is 0 or 1. In some embodiments, q1 is 1, such that the compound comprises the portionwherein denote points of connection to the rest of the compound.

[0537] In some embodiments, q2 is 1 or 2. In some embodiments, q2 is 1 such that the compound comprises the portion, wherein denote points of connection to the rest of the compound. In some embodiments, q2 is 2 such that the compoundcomprises the portionwherein denote points of connection tothe rest of the compound.

[0538] In some embodiments, each R3and R4, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -ORc, -OC(O)Rc, -OC(O)NRcRd, -OC(=NRc)NRcRd, -OS(O)Rc, -OS(O)2Rc, -OS(O)NRcRd, -OS(O)2NRcRd, -SRc, -S(O)Rc, -S(O)2Rc, -S(O)NRcRd, -S(O)2NRcRd, -NRcRd, -NRcC(O)Rd, - NRcC(O)ORd, -NRcC(O)NRcRd, -NRcC(=NRd)NRcRd, -NRcS(O)Rd, -NRcS(O)2Rd, -NRcS(O)NRcRd, -NRcS(O)2NRcRd, -C(O)Rc, -C(O)ORc, -C(O)NRcRd, -C(=NRc)NRcRd, - PRcRd, -P(O)RcRd, -P(O)2RcRd, -P(O)NRcRd, -P(O)2NRcRd, -P(O)ORc, -P(O)2ORc, -CN, or -NO2; or two R3or two R4, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6cycloalkyl or a 4- to 10-membered heterocycloalkyl; or two R3or two R4, when present, taken together with the carbon atom to which they are attached combine to form an oxo group or a C2-C6 alkenyl group; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, C1-C6haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2. In some embodiments, two R3, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6 cycloalkyl.

[0539] In some embodiments, each R4, when present, is independently deuterium, halogen, or C1-C6 alkyl. In some embodiments, each R4, when present, is independently deuterium, fluoro, or methyl

[0540] In some embodiments, n1 is 0, 1, 2, 3, or 4. In some embodiments, n1 is 0, 1, 2, or 3. In some embodiments, n1 is 0, 1, or 2. In some embodiments, n1 is 1, 2, or 3. In some embodiments, n1 is 1 or 2. In some embodiments, n1 is 0 or 1. In some embodiments, n1 is 0 or 2. In some embodiments, n1 is 0.

[0541] In some embodiments, n2 is 0, 1, 2, 3, or 4. In some embodiments, n1 is 0, 1, 2, or 3. In some embodiments, n2 is 0, 1, or 2. In some embodiments, n2 is 1, 2, or 3. In some embodiments, n2 is 1 or 2. In some embodiments, n2 is 0 or 1. In some embodiments, n2 is 0.

[0542] In some embodiments, ring A is a 5- or 6-membered heteroaryl. In some embodiments, ring A is 5-membered heteroaryl. In some embodiments, ring A is an oxazole.

[0543] In some embodiments, the compound comprises a portion of the formula

[0544] wherein,

[0545] “ ” is a point of covalent attachment to ring C.

[0546] In some embodiments, each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S. In some embodiments, Y1is O. In some embodiments, Y2is N. In some embodiments, Y1is N. In some embodiments, Y2is O. In some embodiments, Y1is O and Y2is N, or Y1is N and Y2is O.

[0547] In some embodiments, ring A is an unsubstituted 5- or 6-membered heteroaryl (m4 of R7is 0), or a 5- or 6-membered heteroaryl substituted with 1 of R7(m4 of R7). In some embodiments, ring A is an unsubstituted 5-membered heteroaryl (m4 of R7is 0). In some embodiments, ring A is an unsubstituted oxazole (m4 of R7is 0).

[0548] In some embodiments, R7, when present, is H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10- membered heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, and 5- to 10-membered heteroaryl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, C1-C6haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re,-OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0549] In some embodiments, m4 is 0 or 1. In some embodiments, m4 is 0. In some embodiments, m4 is 1.

[0550] In some embodiments, the compound comprises a portion of the formula,

[0551] wherein,

[0552] “ ” is a point of covalent attachment to ring C.

[0553] In some embodiments, ring B is phenyl or 5- or 6-membered heteroaryl having at least one nitrogen atom. In some embodiments, ring B is phenyl or pyridyl. In some embodiments, ring B is phenyl. In some embodiments, ring B is pyridyl.

[0554] In some embodiments, the compound comprises a portion of the formula

[0555] wherein,

[0556] “ ” is a point of covalent attachment to ring C.

[0557] In some embodiments, each of Z1and Z2is independently N, CH, or CR5. In some embodiments, Z1is N. In some embodiments, Z2is N. In some embodiments, Z1is N and Z2is CH or CR5. In some embodiments, Z2is N and Z1is CH or CR5.

[0558] In some embodiments, ring B is an unsubstituted phenyl or unsubstituted 5- or 6- membered heteroaryl (m3 of R5is 0), or a phenyl or 5- or 6-membered heteroaryl substituted with 1, 2, or 3 of R5(m3 of R5). In some embodiments, ring B is an unsubstituted phenyl (m3 of R5is 0), or a phenyl substituted with 1, 2, or 3 of R5(m3 of R5). In some embodiments, ringB is an unsubstituted 5- or 6-membered heteroaryl (m3 of R5is 0), or a 5- or 6-membered heteroaryl substituted with 1, 2, or 3 of R5(m3 of R5). In some embodiments, ring B is an unsubstituted pyridyl (m3 of R5is 0), or a pyridyl substituted with 1, 2, or 3 of R5(m3 of R5).

[0559] In some embodiments, each R5, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2; or two R5, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2. In some embodiments, each R5, when present, is independently deuterium, halogen, C1-C6alkyl, -ORa, -SRa, -NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -CN, or -NO2, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2. In some embodiments, each R5, when present, is independently deuterium, halogen, -NRaRb, or -CN. In some embodiments, each R5, when present, is independently deuterium, halogen, -NH2, or -CN.

[0560] In some embodiments, m3 is 0, 1, 2, or 3. In some embodiments, m3 is 1, 2, or 3. In some embodiments, m3 is 2 or 3. In some embodiments, m3 is 2. In some embodiments, m3 is 3.

[0561] In some embodiments, the compound comprises a portion of the formula,

[0562] wherein,

[0563] “ ” is a point of covalent attachment to ring C.

[0564] In some embodiments, X is -O-, -S-, or -NR8-. In some embodiments, X is -O-. In some embodiments, X is -NR8-. In some embodiments, R8is H, deuterium, C1-C6alkyl, C2- C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl; or an R1and R8, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6haloalkyl, C1-C6alkyl-ORe, C1-C6alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6 alkyl-C(O)ORe, C1-C6 alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2. In some embodiments, R8is H, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, or5- to 10-membered heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10- membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1- C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-ORe, C1-C6 alkyl-SRe, C1-C6 alkyl-NReRf, C1-C6 alkyl- C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2. In some embodiments, R8is optionally substituted C1-C6 alkyl, for example methyl, ethyl, propyl, or butyl. In some embodiments, R1and R8taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in 5- to 10-membered heteroaryl and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-ORe, C1-C6 alkyl-SRe, C1-C6 alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0565] In some embodiments, p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1.

[0566] In some embodiments, ring C is C6-C10 aryl or 5- to 10-membered heteroaryl. In some embodiments, ring C is C6-C10 aryl. In some embodiments, ring C is 5- to 10-membered heteroaryl and may contain at least one or at least two heteroatoms (e.g., nitrogen). In some embodiments, ring C is a 6-membered heteroaryl, for example pyrimidine and may be of the formulapyridine and may be of the formulawherein the represent connection points to the remaining portions of the compound.

[0567] In some embodiments, ring C is an unsubstituted C6-C10 aryl or unsubstituted 5- to 10- membered heteroaryl (m1 of R1and m2 of R2is 0), or a C6-C10aryl or 5- to 10-membered heteroaryl substituted with 1 or 2 of R1(m1 of R1) and / or 1 or 2 of R2(m2 of R2). In some embodiments, ring C is an unsubstituted 5- to 10-membered heteroaryl (m1 of R1and m2 of R2is 0), or 5- to 10-membered heteroaryl substituted with 1 or 2 of R1(m1 of R1) and / or 1 or 2 of R2(m2 of R2). In some embodiments, ring C is an unsubstituted C6-C10 aryl or unsubstituted 5- to 10-membered heteroaryl, or a C6-C10aryl or 5- to 10-membered heteroaryl substituted with one or more of R1and / or one or more of R2. In some embodiments, ring C is an unsubstituted 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryl substituted with one or more of R1and / or one or more of R2.

[0568] In some embodiments, ring C is an unsubstituted C6-C10aryl or unsubstituted 5- to 10- membered heteroaryl (m1 of R1is 0 and m2 of R2is 0), or a C6-C10 aryl or 5- to 10-membered heteroaryl substituted with 1 or 2 of R1(m1 of R1). In some embodiments, ring C is an unsubstituted 5- to 10-membered heteroaryl (m1 of R1is 0 and m2 of R2is 0), or 5- to 10- membered heteroaryl substituted with 1 or 2 of R1(m1 of R1). In some embodiments, ring C is an unsubstituted C6-C10aryl or unsubstituted 5- to 10-membered heteroaryl, or C6-C10aryl or 5- to 10-membered heteroaryl substituted with one or more of R1. In some embodiments, ring C is an unsubstituted 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryl substituted with one or more of R1.

[0569] In some embodiments, ring C is an unsubstituted C6-C10aryl or unsubstituted 5- to 10- membered heteroaryl (m1 of R1is 0 and m2 of R2is 0), or C6-C10 aryl or 5- to 10-membered heteroaryl substituted with 1 or 2 of R2(m2 of R2). In some embodiments, ring C is an unsubstituted 5- to 10-membered heteroaryl (m1 of R1is 0 and m2 of R2is 0), or 5- to 10- membered heteroaryl substituted with 1 or 2 of R2(m2 of R2). In some embodiments, ring C is an unsubstituted C6-C10 aryl or unsubstituted 5- to 10-membered heteroaryl, or a C6-C10 aryl or 5- to 10-membered heteroaryl substituted with one or more of R2. In some embodiments, ring C is an unsubstituted 5- to 10-membered heteroaryl, or 5- to 10-membered heteroaryl substituted with one or more of R2.

[0570] In some embodiments, ring C is of the formula

[0571] wherein,

[0572] “ ” is a point of covalent attachment to ring A.

[0573] In some embodiments, each of Z3, Z4, and Z5is independently N, CH, CR1, or CR2.

[0574] In some embodiments, ring C is of the formula

[0575] wherein,

[0576] “ ” is a point of covalent attachment to ring A.

[0577] In some embodiments, R1ais H or R1.

[0578] In some embodiments, R1bis H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-memberedheteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-ORe, C1-C6 alkyl-SRe, C1-C6 alkyl-NReRf, C1-C6 alkyl-C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0579] In some embodiments, R2ais H or R2.

[0580] In some embodiments, the compound comprises a portion of the formula

[0581] wherein “ ” is a point of covalent attachment to ring A.

[0582] In some embodiments, the compound comprises a portion of the formula

[0583] wherein “” is a point of covalent attachment to ring A.

[0584] In some embodiments, the compound comprises a portion of the formula

[0585] wherein “ ” is a point of covalent attachment to ring A.

[0586] In some embodiments, the compound comprises a portion of the formula a portion of the formula ,

[0587] wherein “ ” is a point of covalent attachment to ring A.

[0588] In some embodiments, the compound comprises a portion of the formula

[0589] wherein “” is a point of covalent attachment to ring A.

[0590] In some embodiments, the compound comprises a portion of the formula,

[0591] wherein “” is a point of covalent attachment to ring A.

[0592] In some embodiments, the compound comprises a portion of the formula

[0593] wherein “” is a point of covalent attachment to ring A.

[0594] In some embodiments, the compound comprises a portion of the formula

[0595] wherein “ ” is a point of covalent attachment to ring A.

[0596] In some embodiments, the compound comprises a portion of the formula

[0597] wherein “ ” is a point of covalent attachment to ring A.

[0598] In some embodiments, the compound comprises a portion of the formula

[0599] wherein “ ” is a point of covalent attachment to ring A.

[0600] In some embodiments, the compound comprises a portion of the formula

[0601] wherein “ ” is a point of covalent attachment to ring A.

[0602] In some embodiments, the compound comprises a portion of the formula

[0603] wherein “” is a point of covalent attachment to ring A.

[0604] In some embodiments, the compound comprises a portion of the formula,

[0605] wherein “” is a point of covalent attachment to ring A

[0606] In some embodiments, each R1, when present, is independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), -ORa, -OC(O)Ra,-OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2, or an R1and R8, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10- membered heteroaryl), and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkyl-ORe, C1-C6alkyl-SRe, C1-C6 alkyl-NReRf, C1-C6 alkyl-C(O)Re, C1-C6 alkyl-C(O)ORe, C1-C6 alkyl- C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0607] In some embodiments, R1is -ORa, wherein Rais 4- to 10-membered heterocycloalkyl (e.g., an 8-membered bicycle, such as 6-oxa-1-azaspiro[3.3]heptane), which is optionally substituted.

[0608] In some embodiments, R1is -ORa, wherein Rais 4- to 10-membered heterocycloalkyl (e.g., a 4-membered ring such as an azetidine or an oxetane), which is optionally substituted with one or two C1-C6 alkyl (e.g., methyl), each of which is optionally substituted with an Rg, for example hydroxy.

[0609] In some embodiments, R1is -ORa, wherein Rais C1-C6 alkylene-(4- to 10-membered heterocycloalkyl) (e.g., methyl substituted with a 4-membered ring such as an azetidine or an oxetane), which is optionally substituted with -N(C1-C6alkyl)2(e.g., -N(CH3)2), or one or two C1-C6 alkyl (e.g., methyl), each of which is optionally substituted with an Rg, for example hydroxy.

[0610] In some embodiments, R1is -ORa, wherein Rais 3- to 6-membered cycloalkyl) (e.g., methyl substituted with a cyclopropyl), which is optionally substituted with -N(C1-C6alkyl)2(e.g., -N(CH3)2).

[0611] In some embodiments, an R1and R8taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-ORe, C1-C6 alkyl-SRe, C1-C6 alkyl-NReRf, C1-C6 alkyl-C(O)Re, C1-C6 alkyl-C(O)ORe, C1-C6 alkyl- C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2. For example, in the portion of ring C, R1and R8taken together with the atoms to which they are attached, can combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl, which may be optionally substituted.

[0612] In some embodiments, each R2, when present, is independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2, or two R2, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0613] In some embodiments, R6is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, or -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), wherein each hydrogen atom in C1-C6 alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, and -C1-C6alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6 alkyl, -C1-C6 alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6 alkylene-(C6-C10 aryl), haloalkyl, C3-C6 cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0614] In some embodiments, R6is 4- to 10-membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10- membered heteroaryl, or -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), wherein each hydrogen atom in 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, and -C1-C6alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6 alkyl, -C1-C6 alkylene-(O-C1-C6 alkyl), -OC1-C6 alkylene-(O-C1-C6 alkyl), -C1-C6 alkylene-(O-Re), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), haloalkyl, C3-C6 cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6 alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2. In some embodiments, R6is -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), wherein each hydrogen atom in -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl) is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6 alkylene-(O-C1-C6 alkyl), -C1-C6 alkylene-(O-Re), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), haloalkyl, C3-C6 cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0615] In some embodiments, R6is of the formula

[0616] wherein “ ” is a point of covalent attachment to X.

[0617] In some embodiments, R6is of the formula

[0618] wherein “ ” is a point of covalent attachment to X. In some embodiments, R6 is ofthe formula

[0619] wherein “ ” is a point of covalent attachment to X.,

[0621] wherein “ ” is a point of covalent attachment to X.

[0622] In some embodiments, the compound is of the formula

[0623] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0624] In some embodiments, the compound is of the formula

[0625] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0626] In some embodiments, the compound is of the formula

[0627] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0628] In some embodiments, the compound is of the formula

[0629] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0630] In some embodiments, the compound is of the formula

[0631] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0632] In some embodiments, the compound is of the formula

[0633] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0634] In some embodiments, the compound is of the formula

[0635] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0636] In some embodiments, the compound is of the formula

[0637] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0638] In some embodiments, the compound is of the formula

[0639] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0640] In some embodiments, the compound is of the formula

[0641] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0642] In some embodiments, each Ra, Rb, Rc, Rd, Re, and Rfis independently selected from the group consisting of H, deuterium, C1-C6alkyl, C1-C6alkyl-(O-C1-C6alkyl), C2-C6alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkylene-(C3-C6 cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, and C1-C6 alkylene-(5- to 10-membered heteroaryl); or two of Raand Rb, or Rcand Rd, or Reand Rf, taken together with the atom or atoms to which they are attached, combine to form a C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl; or -Reand -Rftaken together with the carbon atom to which they are attached form an oxo groups or a C2-C6 alkenyl; wherein each hydrogen atom in C1-C6 alkyl, C1-C6 alkyl-(O-C1-C6 alkyl), C2-C6 alkenyl, C2- C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkylene-(C3-C6 cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, C1-C6alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, and C1-C6 alkylene-(5- to 10-membered heteroaryl) is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10- membered heteroaryl, -OH, -OC1-C6 alkyl, -OC(O)C1-C6 alkyl, -OC(O)N(H or C1-C6 alkyl)2, -OS(O)C1-C6alkyl, -OS(O)2C1-C6alkyl, -OS(O)N(H or C1-C6alkyl)2, -OS(O)2N(H or C1-C6alkyl)2, -SC1-C6 alkyl, -S(O)C1-C6 alkyl, -S(O)2C1-C6 alkyl, -S(O)N(H or C1-C6 alkyl)2, -S(O)2N(H or C1-C6alkyl)2, -N(H or C1-C6alkyl)2, -N(C1-C6alkyl)C(O)-C1-C6alkyl, -N(C1- C6 alkyl)C(O)OC1-C6 alkyl, -N(C1-C6 alkyl)C(O)N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)S(O)C1-C6alkyl, -N(C1-C6alkyl)S(O)2C1-C6alkyl, -N(C1-C6alkyl)S(O)N(H or C1-C6alkyl)2, -N(C1-C6 alkyl)S(O)2N(H or C1-C6 alkyl)2, -C(O)C1-C6 alkyl, -C(O)OC1-C6 alkyl, -C(O)N(H or C1-C6alkyl)2, -P(H or C1-C6alkyl)2, -P(O)(H or C1-C6alkyl)2, -P(O)2(H or C1- C6 alkyl)2, -P(O)N(H or C1-C6 alkyl)2, -P(O)2N(H or C1-C6 alkyl)2, -P(O)OC1-C6 alkyl, -P(O)2OC1-C6alkyl, -CN, or -NO2, wherein each hydrogen atom in C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, and 5- to 10-membered heteroaryl, is optionally substituted with one or more deuterium, halogen, or Rg.

[0643] In some embodiments, each Rgis independently C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -OH, -OC1-C6alkyl, -OC(O)C1-C6alkyl, -OC(O)N(H or C1-C6alkyl)2, -OS(O)C1-C6alkyl, -OS(O)2C1-C6 alkyl, -OS(O)N(H or C1-C6 alkyl)2, -OS(O)2N(H or C1-C6 alkyl)2, -SC1-C6 alkyl, -S(O)C1-C6alkyl, -S(O)2C1-C6alkyl, -S(O)N(H or C1-C6alkyl)2, -S(O)2N(H or C1-C6alkyl)2, -N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)C(O)-C1-C6 alkyl, -N(C1-C6 alkyl)C(O)OC1-C6 alkyl, -N(C1-C6alkyl)C(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)C1-C6alkyl, -N(C1-C6alkyl)S(O)2C1-C6 alkyl, -N(C1-C6 alkyl)S(O)N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)S(O)2N(H or C1-C6 alkyl)2, -C(O)C1-C6 alkyl, -C(O)OC1-C6 alkyl, -C(O)N(H or C1-C6 alkyl)2, -P(H or C1-C6 alkyl)2, -P(O)(H or C1-C6 alkyl)2, -P(O)2(H or C1-C6 alkyl)2, -P(O)N(H or C1-C6 alkyl)2, -P(O)2N(H or C1-C6 alkyl)2, -P(O)OC1-C6 alkyl, -P(O)2OC1-C6 alkyl, -CN, or -NO2.

[0644] In some embodiments, the compound is selected from Table 1. In some embodiments, the compound is selected from examples 1-191 of Table 1. In some embodiments, the compound is selected from examples 1-220 of Table 1.

[0645] The following represent illustrative embodiments of compounds of Formula (I) Table 1

[0646] and isotopically labeled form thereof, and pharmaceutically acceptable salts thereof.

[0647] In some embodiments, the disclosure provides a compound selected from the group consisting of

[0648] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0649] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-methyl-1H- pyrazole-3-carboxamide;

[0650] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(oxetan-3- yl)-1H-pyrazole-3-carboxamide;

[0651] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(3- methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0652] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(1S)-1- (pyridin-2-yl)ethyl]-1H-pyrazole-3-carboxamide;

[0653] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)- oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0654] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3R)- oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0655] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{3-[1-(oxan-4- yl)-1H-1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0656] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(2- methoxyethyl)-1H-pyrazole-3-carboxamide;

[0657] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3R)- oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0658] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3S)- oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0659] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-methyl-1H-pyrazole-3-carboxamide;

[0660] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0661] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-(3-methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0662] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-[(1S)-1-(pyridin-2-yl)ethyl]-1H-pyrazole-3-carboxamide;

[0663] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-[(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0664] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-[(3R)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0665] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {3-[1-(oxan-4-yl)-1H-1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0666] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-(2-methoxyethyl)-1H-pyrazole-3-carboxamide;

[0667] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (3-{1-[(3R)-oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0668] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (3-{1-[(3S)-oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0669] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3S)- oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0670] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3R)- oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0671] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {7-oxo-6-[(3S)-oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0672] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {7-oxo-6-[(3R)-oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2- yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0673] 2-[1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-1H-pyrazol-3- yl]-N-(propan-2-yl)acetamide;

[0674] 2-[1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- 1H-pyrazol-3-yl]-N-(propan-2-yl)acetamide;

[0675] (1'S)-6'-amino-3-[4-(3-{1-[(3-methyloxetan-3-yl)methyl]-1H-1,2,3-triazol-4-yl}-1H- pyrazol-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0676] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxo-1,3- oxazolidin-3-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]- 7'-carbonitrile;

[0677] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (2-oxo-1,3-oxazolidin-3-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile;

[0678] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-[3-(pyrrolidine- 1-carbonyl)-1H-pyrazol-1-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile;

[0679] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- [3-(pyrrolidine-1-carbonyl)-1H-pyrazol-1-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0680] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-methyl-N- (oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0681] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-methyl-N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0682] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-[(3S)-oxolan-3- yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0683] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-[(3S)-oxolan-3-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- indene]-7'-carbonitrile;

[0684] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile;

[0685] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0686] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(2- oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0687] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0688] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2R,3S)-3-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0689] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S,4R)-4-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0690] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S,4R)-4-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0691] (1'S)-6'-amino-3-(4-[(5S)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0692] (1'S)-6'-amino-3-(4-[(5R)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0693] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- [(5S)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0694] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- [(5R)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0695] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (4-methyl-4,7-diazaspiro[2.5]octan-7-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0696] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(5- methyl-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0697] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (5-methyl-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0698] (1'S)-6'-amino-3-[4-(5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)-6-{(1S)-1-[(2S,4R)- 4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0699] (1'S)-6'-amino-3-[4-(5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)-6-{(1S)-1-[(2R,3S)- 3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0700] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(5- methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0701] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (5-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0702] (1'S)-6'-amino-3-[4-(5-methyl-2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0703] (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0704] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (5-methyl-2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0705] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(5- methyl-2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0706] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0707] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0708] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0709] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0710] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0711] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0712] (1'S)-6'-amino-3-(4-[(3S)-1-methylpyrrolidin-3-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0713] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- [(3S)-1-methylpyrrolidin-3-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0714] (1R)-6-amino-3'-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 2,3-dihydrospiro[indene-1,7'-[5]oxa[4]azatricyclo[6.1.1.02,6]deca[2(6),3]diene]-7- carbonitrile;

[0715] (1'S)-6'-amino-3-(9-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-9H- purin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0716] (1'S)-6'-amino-3-(9-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-9H- purin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0717] (1'S)-6'-amino-3-(8-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-7,8- dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0718] (1'S)-6'-amino-3-(3-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-3H- imidazo[4,5-c]pyridin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0719] (1'S)-6'-amino-3-(1-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-1H- imidazo[4,5-c]pyridin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0720] (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0721] (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0722] (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0723] (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0724] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)-6-oxa-1- azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0725] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0726] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0727] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0728] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0729] (1'S)-6'-amino-3-(6-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-9H-purin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0730] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0731] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-imidazo[4,5-c]pyridin-6-yl)-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0732] (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0733] (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0734] (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0735] (1'S)-6'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0736] (1'S)-6'-amino-3-(9-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-6-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9H-purin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0737] (1'S)-6'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[4,3-c]pyridin-6-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0738] (1'S)-6'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-imidazo[4,5-c]pyridin-6-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0739] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(1H-pyrazol-1- yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0740] (1'S)-6'-amino-3-(4-[(3S)-3-methylpyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0741] (1'S)-6'-amino-3-(4-[cyclopropyl(methyl)amino]-6-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0742] (1'S)-6'-amino-3-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0743] (1'S)-6'-amino-3-(4-[(cyclopropylmethyl)(methyl)amino]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0744] (1'S)-6'-amino-3-(4-[(3R)-3-hydroxypyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0745] (1'S)-6'-amino-3-[4-(3,3-difluoropyrrolidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0746] (1'S)-6'-amino-3-[4-(6-azaspiro[2.5]octan-6-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0747] (1'S)-6'-amino-3-[4-(1,3-dihydro-2H-isoindol-2-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0748] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)- oxolan-3-yl]-1H-1,2,4-triazole-3-carboxamide;

[0749] (1'S)-6'-amino-3-(4-[3-(dimethylamino)piperidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0750] (1'S)-6'-amino-3-[4-(azepan-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0751] (1'S)-6'-amino-3-[4-(4-hydroxypiperidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0752] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(1,4-oxazepan- 4-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0753] (1'S)-6'-amino-3-[4-(3-hydroxy-3-methylazepan-1-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0754] (1'S)-6'-amino-3-[4-(4-hydroxy-4-methylazepan-1-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0755] (1'S)-6'-amino-3-[4-(4,4-difluoropiperidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0756] (1'S)-6'-amino-3-(4-[(3R)-3-methoxypyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0757] (1'S)-6'-amino-3-(4-{[(2R)-2-hydroxypropyl](methyl)amino}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0758] (1'S)-6'-amino-3-(4-{[(4-methoxyphenyl)methyl](methyl)amino}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0759] (1'S)-6'-amino-3-[4-(4-methylidenepiperidin-1-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0760] (1'S)-6'-amino-3-(4-[(3R)-3-fluoropyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0761] (1'S)-6'-amino-3-(4-[(1R,5R)-2,6-diazabicyclo[3.2.0]heptan-6-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0762] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)- oxolan-3-yl]-1H-imidazole-4-carboxamide;

[0763] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3R)- oxolan-3-yl]-1H-imidazole-4-carboxamide;

[0764] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(1H-1,2,4- triazol-1-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0765] (1'S)-6'-amino-3-(4-[(3R)-3-hydroxy-2,2-dimethylazetidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0766] (1'S)-6'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0767] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3R)- oxolan-3-yl]-1H-1,2,4-triazole-3-carboxamide;

[0768] (1'S)-6'-amino-3-[4-(6-azabicyclo[3.1.1]heptan-6-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0769] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{6-oxo-5-[(3S)- oxolan-3-yl]-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0770] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(1H-1,2,3- triazol-1-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0771] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-61,2,3- triazol-2-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0772] 6'-amino-3-(4-[8a-(hydroxymethyl)-3-oxotetrahydro-3H-[1,3]oxazolo[3,4-a]pyrazin- 7(1H)-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0773] 6'-amino-3-(4-{[2,2-bis(hydroxymethyl)azetidin-3-yl]oxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0774] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(pyrrolidin-1- yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0775] (1'S)-6'-amino-3-(4-[(3R)-3-methylpyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0776] (1'S)-6'-amino-3-(4-[(3S)-3-hydroxypyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0777] (1'S)-6'-amino-3-[4-(3,3-difluoropiperidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3S)-oxolan- 3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; 6'-amino-3-{4-[1-(1-methylpyrrolidin-2-yl)ethoxy]-6,6a,7,8,9,10-hexahydropyrido[1,2- d]pyrimido[5,4-b][1,4]oxazin-2-yl}-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- indene]-7'-carbonitrile; (1'S)-6'-amino-3-[(7S)-7-(difluoromethyl)-8-ethyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{4-oxo-5-[(3S)-oxolan- 3-yl]-1,3,4,5-tetrahydro-2H-pyrrolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{4-oxo-5-[(3R)-oxolan- 3-yl]-1,3,4,5-tetrahydro-2H-pyrrolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; 1-(2-[(1'S)-6'-amino-7'-cyano-3',3'-difluoro-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)- oxolan-3-yl]-1H-pyrazole-3-carboxamide; (1'S,3'S)-6'-amino-3'-methyl-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa- 5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-5'-fluoro-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile; 6'-amino-5'-fluoro-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(3-hydroxyazetidin-3-yl)methoxy]-6-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;(1'S)-6'-amino-3-(4-{[(3-hydroxyazetidin-3-yl)methyl](methyl)amino}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; and

[0778] (1'S)-6'-amino-3-(4-[(3S)-3-cyanopyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0779] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0780] In some embodiments, the disclosure provides a compound selected from the group consisting of

[0781] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0782] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-methyl-1H- pyrazole-3-carboxamide;

[0783] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(oxetan-3- yl)-1H-pyrazole-3-carboxamide;

[0784] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(3- methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0785] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(1S)-1- (pyridin-2-yl)ethyl]-1H-pyrazole-3-carboxamide;

[0786] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)- oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0787] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3R)- oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0788] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{3-[1-(oxan-4- yl)-1H-1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0789] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(2- methoxyethyl)-1H-pyrazole-3-carboxamide;

[0790] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3R)- oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0791] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3S)- oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0792] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-methyl-1H-pyrazole-3-carboxamide;

[0793] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0794] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-(3-methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0795] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-[(1S)-1-(pyridin-2-yl)ethyl]-1H-pyrazole-3-carboxamide;

[0796] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-[(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0797] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-[(3R)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0798] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {3-[1-(oxan-4-yl)-1H-1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0799] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-(2-methoxyethyl)-1H-pyrazole-3-carboxamide;

[0800] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (3-{1-[(3R)-oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0801] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (3-{1-[(3S)-oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0802] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3S)- oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0803] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3R)- oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0804] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {7-oxo-6-[(3S)-oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2- yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0805] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {7-oxo-6-[(3R)-oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2- yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0806] 2-[1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-1H-pyrazol-3- yl]-N-(propan-2-yl)acetamide;

[0807] 2-[1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- 1H-pyrazol-3-yl]-N-(propan-2-yl)acetamide;

[0808] (1'S)-6'-amino-3-[4-(3-{1-[(3-methyloxetan-3-yl)methyl]-1H-1,2,3-triazol-4-yl}-1H- pyrazol-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0809] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxo-1,3- oxazolidin-3-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]- 7'-carbonitrile;

[0810] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (2-oxo-1,3-oxazolidin-3-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile;

[0811] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-[3-(pyrrolidine- 1-carbonyl)-1H-pyrazol-1-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile;

[0812] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- [3-(pyrrolidine-1-carbonyl)-1H-pyrazol-1-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0813] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-methyl-N- (oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0814] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- N-methyl-N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0815] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-[(3S)-oxolan-3- yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0816] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- [(3S)-oxolan-3-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- indene]-7'-carbonitrile;

[0817] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile;

[0818] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0819] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(2- oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0820] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0821] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2R,3S)-3-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0822] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S,4R)-4-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0823] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S,4R)-4-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0824] (1'S)-6'-amino-3-(4-[(5S)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0825] (1'S)-6'-amino-3-(4-[(5R)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0826] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- [(5S)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0827] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- [(5R)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0828] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (4-methyl-4,7-diazaspiro[2.5]octan-7-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0829] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(5- methyl-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0830] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (5-methyl-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0831] (1'S)-6'-amino-3-[4-(5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)-6-{(1S)-1-[(2S,4R)- 4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0832] (1'S)-6'-amino-3-[4-(5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)-6-{(1S)-1-[(2R,3S)- 3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0833] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(5- methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0834] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (5-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0835] (1'S)-6'-amino-3-[4-(5-methyl-2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0836] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (5-methyl-2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0837] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(5- methyl-2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0838] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0839] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0840] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0841] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0842] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0843] (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0844] (1'S)-6'-amino-3-(4-[(3S)-1-methylpyrrolidin-3-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0845] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- [(3S)-1-methylpyrrolidin-3-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0846] (1R)-6-amino-3'-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 2,3-dihydrospiro[indene-1,7'-[5]oxa[4]azatricyclo[6.1.1.02,6]deca[2(6),3]diene]-7- carbonitrile;

[0847] (1'S)-6'-amino-3-(9-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-9H- purin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0848] (1'S)-6'-amino-3-(9-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-9H- purin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0849] (1'S)-6'-amino-3-(8-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-7,8- dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0850] (1'S)-6'-amino-3-(3-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-3H- imidazo[4,5-c]pyridin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0851] (1'S)-6'-amino-3-(1-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-1H- imidazo[4,5-c]pyridin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[0852] (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0853] (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0854] (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0855] (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0856] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)-6-oxa-1- azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0857] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0858] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0859] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0860] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0861] (1'S)-6'-amino-3-(6-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-9H-purin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0862] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0863] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-imidazo[4,5-c]pyridin-6-yl)-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0864] (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0865] (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0866] (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0867] (1'S)-6'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0868] (1'S)-6'-amino-3-(9-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-6-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9H-purin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0869] (1'S)-6'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[4,3-c]pyridin-6-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; and

[0870] (1'S)-6'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-imidazo[4,5-c]pyridin-6-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0871] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0872] In some embodiments, the disclosure provides a compound selected from the group consisting of (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2- yl)-2',3',5,6-tetrahydro-4H-spiro[[2,1]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0873] (1R)-6-amino-3'-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 2,3-dihydrospiro[indene-1,7'-[4]oxa[5]azatricyclo[6.1.1.02,6]deca[2,5]diene]-7-carbonitrile;

[0874] (5'S)-3'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 5,6,6',7'-tetrahydro-4H-spiro[[2,1]benzoxazole-7,5'-cyclopenta[b]pyridine]-4'-carbonitrile;

[0875] (1'S)-6'-amino-4'-fluoro-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[2,1]benzoxazole-7,1'-indene]-7'- carbonitrile; and

[0876] (1'S)-6'-amino-3-(2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- 2',3',5,6-tetrahydro-4H-spiro[[2,1]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0877] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0878] In some embodiments, the disclosure provides a compound selected (1'R)-7'-amino-3- (4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0879] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- methyl-1H-pyrazole-3-carboxamide;

[0880] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- (oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0881] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- methyl-N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0882] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(3- methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0883] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- [(1S)-1-(pyridin-2-yl)ethyl]-1H-pyrazole-3-carboxamide;

[0884] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- [(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0885] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- [(3R)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0886] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{3-[1-(oxan-4- yl)-1H-1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0887] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(2- methoxyethyl)-1H-pyrazole-3-carboxamide;

[0888] (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3R)- oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0889] (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3S)- oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0890] (5'S)-3'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 5,6,7',8'-tetrahydro-4H,6'H-spiro[[1,2]benzoxazole-7,5'-quinoline]-4'-carbonitrile;

[0891] (5'R)-3'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 5,6,7',8'-tetrahydro-4H,6'H-spiro[[1,2]benzoxazole-7,5'-isoquinoline]-4'-carbonitrile;

[0892] (1'S)-7'-amino-5'-fluoro-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalene]-8'-carbonitrile;

[0893] (1'R)-7'-amino-3-(2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0894] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0895] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0896] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0897] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0898] (1'R)-7'-amino-3-(4-{[3-(dimethylamino)oxetan-3-yl]methoxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0899] (1'R)-7'-amino-3-(4-{[3-(dimethylamino)oxetan-3-yl]methoxy}-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0900] (1'R)-7'-amino-3-(4-{[3-(dimethylamino)oxetan-3-yl]methoxy}-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0901] (1'R)-7'-amino-3-(4-{[1-(dimethylamino)cyclopropyl]methoxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0902] (1'R)-7'-amino-3-(4-{[1-(dimethylamino)cyclopropyl]methoxy}-6-{(1S)-1-[(2S,4R)- 4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0903] (1'R)-7'-amino-3-(4-{[1-(dimethylamino)cyclopropyl]methoxy}-6-{(1S)-1-[(2S,4R)- 4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0904] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R,4S)-4-fluoropyrrolidin-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0905] (1'R)-7'-amino-3-(4-{[(3R,4S)-4-fluoropyrrolidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0906] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)-6-oxa-1- azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0907] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0908] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0909] (1'R)-7'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0910] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0911] (1'R)-7'-amino-3-(6-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-9H-purin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0912] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0913] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-imidazo[4,5-c]pyridin-6-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0914] (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0915] (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0916] (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0917] (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0918] (1'R)-7'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0919] (1'R)-7'-amino-3-(9-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-6-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9H-purin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0920] (1'R)-7'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[4,3-c]pyridin-6-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; and

[0921] (1'R)-7'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-imidazo[4,5-c]pyridin-6-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0922] (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0923] (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2R,3S)-3-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0924] (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2R,3S)-3-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0925] (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S,4R)-4-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0926] (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0927] (1'R)-7'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- (2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0928] (1'R)-7'-amino-3-[4-{(1S)-1-[(2R,3S)-3-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(2- oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0929] (1'R)-7'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(2- oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0930] (1'R)-7'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0931] (1'R)-7'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2R,3S)- 3-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0932] (1'R)-7'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2S,4R)- 4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0933] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2R,3S)-3- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0934] 1-(6-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-methyl-1H-pyrazole-3-carboxamide;

[0935] 1-(6-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-[(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0936] 1-(6-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-[(3R)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0937] 1-(6-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-(3-methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0938] (1'R)-7'-amino-3-[4-(6-methyl-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl)-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0939] (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3S)- oxolan-3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0940] (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3R)- oxolan-3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0941] (1'R)-7'-amino-3-[4-(6-methyl-7-oxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2- yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0942] (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3S)- oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'- carbonitrile;

[0943] (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3R)- oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'- carbonitrile;

[0944] (1'R)-7'-amino-3-[4-(5-methyl-6-oxo-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0945] (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{6-oxo-5-[(3S)- oxolan-3-yl]-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl}-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0946] (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{6-oxo-5-[(3R)- oxolan-3-yl]-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl}-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0947] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(piperidin-1- yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{4-oxo-5-[(3S)-oxolan- 3-yl]-1,3,4,5-tetrahydro-2H-pyrrolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{4-oxo-5-[(3R)- oxolan-3-yl]-1,3,4,5-tetrahydro-2H-pyrrolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3S)-oxolan- 3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{6-oxo-5-[(3S)-oxolan- 3-yl]-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3S)-oxolan- 3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-6- azaspiro[3.5]nonan-6-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-[(4S)-1-oxa-6- azaspiro[3.5]nonan-6-yl]pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-[(3R)-3-hydroxy-2,2-dimethylazetidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; 1-(2-[(1'S)-7'-amino-8'-cyano-4',4'-difluoro-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-4-yl)-N-[(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide; (1'R)-7'-amino-3-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-chloro-6-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; and

[0948] (1'R)-7'-amino-3-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-6-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0949] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0950] In some embodiments, the disclosure provides a compound selected from the group consisting of (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2- yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0951] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- methyl-1H-pyrazole-3-carboxamide;

[0952] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- (oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0953] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- methyl-N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0954] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(3- methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0955] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- [(1S)-1-(pyridin-2-yl)ethyl]-1H-pyrazole-3-carboxamide;

[0956] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- [(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0957] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- [(3R)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0958] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{3-[1-(oxan-4- yl)-1H-1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0959] 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(2-methoxyethyl)-1H-pyrazole-3-carboxamide;

[0960] (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3R)- oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0961] (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3S)- oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0962] (5'S)-3'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 5,6,7',8'-tetrahydro-4H,6'H-spiro[[1,2]benzoxazole-7,5'-quinoline]-4'-carbonitrile;

[0963] (5'R)-3'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 5,6,7',8'-tetrahydro-4H,6'H-spiro[[1,2]benzoxazole-7,5'-isoquinoline]-4'-carbonitrile;

[0964] (1'S)-7'-amino-5'-fluoro-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalene]-8'-carbonitrile;

[0965] (1'R)-7'-amino-3-(2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0966] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0967] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0968] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0969] (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0970] (1'R)-7'-amino-3-(4-{[3-(dimethylamino)oxetan-3-yl]methoxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0971] (1'R)-7'-amino-3-(4-{[3-(dimethylamino)oxetan-3-yl]methoxy}-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0972] (1'R)-7'-amino-3-(4-{[3-(dimethylamino)oxetan-3-yl]methoxy}-6-{(1S)-1-[(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0973] (1'R)-7'-amino-3-(4-{[1-(dimethylamino)cyclopropyl]methoxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0974] (1'R)-7'-amino-3-(4-{[1-(dimethylamino)cyclopropyl]methoxy}-6-{(1S)-1-[(2S,4R)- 4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0975] (1'R)-7'-amino-3-(4-{[1-(dimethylamino)cyclopropyl]methoxy}-6-{(1S)-1-[(2S,4R)- 4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0976] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R,4S)-4-fluoropyrrolidin-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0977] (1'R)-7'-amino-3-(4-{[(3R,4S)-4-fluoropyrrolidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0978] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)-6-oxa-1- azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0979] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0980] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0981] (1'R)-7'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6- {[(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0982] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0983] (1'R)-7'-amino-3-(6-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-9H-purin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0984] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0985] (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1- [(3R)-6-oxa-1-azaspiro[3.3]heptan-3-yl]-1H-imidazo[4,5-c]pyridin-6-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0986] (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[0987] (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0988] (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0989] (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0990] (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1- [(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0991] (1'R)-7'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0992] (1'R)-7'-amino-3-(9-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-6-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9H-purin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0993] (1'R)-7'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[4,3-c]pyridin-6-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; and

[0994] (1'R)-7'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-imidazo[4,5-c]pyridin-6-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;

[0995] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0996] In some embodiments, the compound is selected from Table 2. In some embodiments,the compound is selected from examples 1a-191a of Table 2. In some embodiments, the compound is selected from examples 1a-220a of Table 2.

[0997] The following represent illustrative embodiments of compounds of Formula (I) Table 2

[0998] and isotopically labeled form thereof, and pharmaceutically acceptable salts thereof. ALTERNATIVE EMBODIMENTS

[0999] 1. A compound of the formula I, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof,

[1000] wherein

[1001] ring A is 5- or 6-membered heteroaryl;

[1002] ring B is phenyl or 5- or 6-membered heteroaryl having at least one nitrogen atom;

[1003] ring C is C6-C10aryl or 5- to 10-membered heteroaryl;

[1004] X is a -O-, -S-, or -NR8-;

[1005] each of X1, X2, and X3is independently an -O-, -S-, -S(O)2-, -CHR3-, -C(R3)2-, or -CH2-, provided that no more than one of X1, X2, and X3is a -O-, -S-, or -S(O)2-;

[1006] each R1, when present, is independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2, or an R1and R8, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10- membered heteroaryl), and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-ORe, C1-C6 alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl- C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[1007] each R2, when present, is independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2, or two R2, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[1008] each R3and R4, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -ORc, -OC(O)Rc, -OC(O)NRcRd, -OC(=NRc)NRcRd, -OS(O)Rc, -OS(O)2Rc, -OS(O)NRcRd, -OS(O)2NRcRd, -SRc, -S(O)Rc, -S(O)2Rc, -S(O)NRcRd, -S(O)2NRcRd, -NRcRd, -NRcC(O)Rd, -NRcC(O)ORd, -NRcC(O)NRcRd, -NRcC(=NRd)NRcRd, -NRcS(O)Rd, -NRcS(O)2Rd, -NRcS(O)NRcRd, -NRcS(O)2NRcRd, -C(O)Rc, -C(O)ORc, -C(O)NRcRd, -C(=NRc)NRcRd, -PRcRd, -P(O)RcRd, -P(O)2RcRd, -P(O)NRcRd, -P(O)2NRcRd, -P(O)ORc, -P(O)2ORc, -CN, or -NO2; or two R3or two R4, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6 cycloalkyl or a 4- to 10-membered heterocycloalkyl; or two R3or two R4, when present, taken together with the carbon atom to which they are attached combine to form an oxo group or a C2-C6alkenyl group; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1- C6 alkyl, C1-C6 haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf,-NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[1009] each R5, when present, is independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2; or two R5, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6 haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[1010] R6is C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10- membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, or -C1-C6alkylene-(4- to 10- membered heterocycloalkyl), wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10- membered heterocycloalkyl), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, and -C1-C6 alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), - OC1-C6 alkylene-(O-C1-C6 alkyl), -C1-C6 alkylene-(O-Re), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10- membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[1011] R7, when present, is H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, C1-C6 haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[1012] each Ra, Rb, Rc, Rd, Re, and Rfis independently selected from the group consisting of H, deuterium, C1-C6 alkyl, C1-C6 alkyl-(O-C1-C6 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, C3-C6cycloalkyl, C1-C6alkylene-(C3-C6cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, and C1-C6 alkylene-(5- to 10-membered heteroaryl); or two of Raand Rb, or Rcand Rd, or Reand Rf, taken together with the atom or atoms to which they are attached, combine to form a C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl; or -Reand -Rftaken together with the carbon atom to which they are attached form an oxo groups or a C2-C6 alkenyl; wherein each hydrogen atom in C1-C6alkyl, C1-C6alkyl-(O-C1-C6alkyl), C2-C6alkenyl, C2- C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkylene-(C3-C6 cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, and C1-C6 alkylene-(5- to 10-membered heteroaryl) is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10- membered heteroaryl, -OH, -OC1-C6 alkyl, -OC(O)C1-C6 alkyl, -OC(O)N(H or C1-C6 alkyl)2, -OS(O)C1-C6alkyl, -OS(O)2C1-C6alkyl, -OS(O)N(H or C1-C6alkyl)2, -OS(O)2N(H or C1-C6alkyl)2, -SC1-C6 alkyl, -S(O)C1-C6 alkyl, -S(O)2C1-C6 alkyl, -S(O)N(H or C1-C6 alkyl)2, -S(O)2N(H or C1-C6alkyl)2, -N(H or C1-C6alkyl)2, -N(C1-C6alkyl)C(O)-C1-C6alkyl, -N(C1- C6 alkyl)C(O)OC1-C6 alkyl, -N(C1-C6 alkyl)C(O)N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)S(O)C1-C6alkyl, -N(C1-C6alkyl)S(O)2C1-C6alkyl, -N(C1-C6alkyl)S(O)N(H or C1-C6alkyl)2, -N(C1-C6 alkyl)S(O)2N(H or C1-C6 alkyl)2, -C(O)C1-C6 alkyl, -C(O)OC1-C6 alkyl, -C(O)N(H or C1-C6alkyl)2, -P(H or C1-C6alkyl)2, -P(O)(H or C1-C6alkyl)2, -P(O)2(H or C1- C6 alkyl)2, -P(O)N(H or C1-C6 alkyl)2, -P(O)2N(H or C1-C6 alkyl)2, -P(O)OC1-C6 alkyl, -P(O)2OC1-C6 alkyl, -CN, or -NO2, wherein each hydrogen atom in C1-C6 alkyl, C1-C6haloalkyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, and 5- to 10- membered heteroaryl, is optionally substituted with one or more deuterium, halogen, or Rg;

[1013] each Rgis independently C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -OH, -OC1-C6 alkyl, -OC(O)C1-C6alkyl, -OC(O)N(H or C1-C6alkyl)2, -OS(O)C1-C6alkyl, -OS(O)2C1-C6alkyl, -OS(O)N(H or C1-C6 alkyl)2, -OS(O)2N(H or C1-C6 alkyl)2, -SC1-C6 alkyl, -S(O)C1-C6 alkyl, -S(O)2C1-C6alkyl, -S(O)N(H or C1-C6alkyl)2, -S(O)2N(H or C1-C6alkyl)2, -N(H or C1- C6 alkyl)2, -N(C1-C6 alkyl)C(O)-C1-C6 alkyl, -N(C1-C6 alkyl)C(O)OC1-C6 alkyl, -N(C1-C6 alkyl)C(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)C1-C6alkyl, -N(C1-C6alkyl)S(O)2C1-C6alkyl, -N(C1-C6 alkyl)S(O)N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)S(O)2N(H or C1-C6 alkyl)2, -C(O)C1-C6alkyl, -C(O)OC1-C6alkyl, -C(O)N(H or C1-C6alkyl)2, -P(H or C1-C6alkyl)2, -P(O)(H or C1-C6 alkyl)2, -P(O)2(H or C1-C6 alkyl)2, -P(O)N(H or C1-C6 alkyl)2, -P(O)2N(H or C1-C6alkyl)2, -P(O)OC1-C6alkyl, -P(O)2OC1-C6alkyl, -CN, or -NO2;

[1014] m1 is 0, 1, or 2;

[1015] m2 is 0, 1, or 2;

[1016] m3 is 0, 1, 2, or 3;

[1017] m4 is 0 or 1;

[1018] n1 is 0, 1, 2, 3, or 4;

[1019] n2 is 0, 1, 2, 3, or 4;

[1020] p is 0 or 1;

[1021] q1 is 0, 1 or 2; and

[1022] q2 is 1 or 2.

[1023] 2. The compound of embodiment 1, having the formula II

[1024] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[1025] 3. The compound of embodiment 1 or 2, having the formula III

[1026] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[1027] 4. The compound of embodiment 1 or 2, having the formula IV

[1028] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[1029] each R5ais independently H or R5; and

[1030] each of Z1and Z2is independently N, CH, or CR5.

[1031] 5. The compound of any one of the preceding embodiments, having the formula V

[1032] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[1033] each R5ais independently H or R5; and

[1034] each of Z1and Z2is independently N, CH, or CR5.

[1035] 6. The compound of any one of embodiments 1, 2, or 4, having the formula VI

[1036] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[1037] each R5ais independently H or R5,

[1038] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S, and

[1039] each of Z1and Z2, is independently N, CH, or CR5¸

[1040] wherein thepresent in ring A represents the aromaticity of ring A.

[1041] 7. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula VII

[1042] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[1043] each R5ais independently H or R5;

[1044] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S; and

[1045] each of Z1and Z2is independently N, CH, or CR5;

[1046] wherein thepresent in ring A represents the aromaticity of ring A.

[1047] 8. The compound of any one of embodiments 1, 2, 4, or 6, having the formula VIII

[1048] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[1049] each R5ais independently H or R5;

[1050] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S;

[1051] each of Z1and Z2is independently N, CH, or CR5; and

[1052] each of Z3, Z4, and Z5is independently N, CH, CR1, or CR2;

[1053] wherein thepresent in ring A and ring C represents the aromaticity of ring A and ring C.

[1054] 9. The compound of any one of the preceding embodiments, having the formula IX

[1055] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[1056] each R5ais independently H or R5;

[1057] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S;

[1058] each of Z1and Z2is independently N, CH, or CR5; and

[1059] each of Z3, Z4, and Z5is independently N, CH, CR1, or CR2;

[1060] wherein thepresent in ring A and ring C represents the aromaticity of ring A and ring C.

[1061] 10. The compound of any one of embodiments 1, 2, or 4, having the formula X

[1062] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each of Z1 and Z2is independently N, CH, or CR5.

[1063] 11. The compound of any one of embodiments 1 to 5, or 10, having the formula XI

[1064] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each of Z1and Z2, is independently N, CH, or CR5.

[1065] 12. The compound of any one of embodiments 1, 2, 4, 6, or 10, having the formula XII

[1066] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[1067] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S; and

[1068] each of Z1and Z2is independently N, CH, or CR5;

[1069] wherein the present in ring A represents the aromaticity of ring A.

[1070] 13. The compound of any one of embodiments 1 to 7, or 10 to 12, having the formula XIII

[1071] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[1072] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S; and

[1073] each of Z1and Z2is independently N, CH, or CR5

[1074] wherein thepresent in ring A represents the aromaticity of ring A.

[1075] 14. The compound of any one of embodiments 1, 2, 4, 6, 8, 10, or 12, having the formula XIV

[1076] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[1077] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S;

[1078] each of Z1and Z2is independently N, CH, or CR5; and

[1079] each of Z3, Z4, and Z5is independently N, CH, CR1, or CR2;

[1080] wherein thepresent in ring A and ring C represents the aromaticity of ring A and ring C.

[1081] 15. The compound of any one of the preceding embodiments, having the formula XV

[1082] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein

[1083] each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S;

[1084] each of Z1and Z2is independently N, CH, or CR5; and

[1085] each of Z3, Z4, and Z5is independently N, CH, CR1, or CR2;

[1086] wherein thepresent in ring A and ring C represents the aromaticity of ring A and ring C.

[1087] 16. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring C is of the formula

[1088] wherein,

[1089] “ ” is a point of covalent attachment to ring A;

[1090] R1ais H or R1;

[1091] R1bis H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1- C6 alkyl-ORe, C1-C6 alkyl-SRe, C1-C6 alkyl-NReRf, C1-C6 alkyl-C(O)Re, C1-C6 alkyl-C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; and

[1092] R2ais H or R2.

[1093] 17. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formula

[1094] wherein “” is a point of covalent attachment to ring A.

[1095] 18. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formula,

[1096] wherein “ ” is a point of covalent attachment to ring A.

[1097] 19. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein p is 1.

[1098] 20. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein X is NR8.

[1099] 21. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formula

[1100] wherein “ ” is a point of covalent attachment to ring A.

[1101] 22. The compound of any one of the embodiments 1 to 18, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein X is O.

[1102] 23. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is 4- to 10- membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6 alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, or -C1-C6 alkylene-(4- to 10- membered heterocycloalkyl), wherein each hydrogen atom in 4- to 10-membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, -C1-C6 alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and -C1-C6alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6 alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O- Re), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), haloalkyl, C3-C6 cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, - P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[1103] 24. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), wherein each hydrogen atom in -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl) is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6 alkyl, -C1-C6 alkylene-(O-C1-C6 alkyl), -OC1-C6 alkylene- (O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), haloalkyl, C3-C6 cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6 alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[1104] 25. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is of the formula

[1105] wherein “” is a point of covalent attachment to X.

[1106] 26. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is of the formula,

[1107] wherein “ ” is a point of covalent attachment to X.

[1108] 27. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein two R3, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6cycloalkyl.

[1109] 28. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5, when present, is independently deuterium, halogen, C1-C6 alkyl, -ORa, -SRa, -NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -CN, or -NO2, wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[1110] 29. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5, when present, is independently deuterium, halogen, -NRaRb, or -CN.

[1111] 30. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5, when present, is independently deuterium, halogen, -NH2, or -CN.

[1112] 31. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y1, when present, is O.

[1113] 32. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y2, when present, is N.

[1114] 33. The compound of any one of embodiments 1 to 30, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y1, when present, is N.

[1115] 34. The compound of any one of embodiments 1 to 30, or 33, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y2, when present, is O.

[1116] 35. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein n1 is 0 or 2.

[1117] 36. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein n2 is 0.

[1118] 37. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein m3 is 2 or 3.

[1119] 38. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein m4 is 0.

[1120] 39. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein q1 is 1.

[1121] 40. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein q2 is 1.

[1122] 41. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein q2 is 2.

[1123] 42. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein p is 1.

[1124] 43. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Z1, when present,is N.

[1125] 44. The compound of any one of the preceding embodiments, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Z2, when present, is N.

[1126] 45. The compound of embodiment 1, selected from the group consisting of (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1127] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-methyl- 1H-pyrazole-3-carboxamide;

[1128] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(oxetan- 3-yl)-1H-pyrazole-3-carboxamide;

[1129] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(3- methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[1130] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(1S)-1- (pyridin-2-yl)ethyl]-1H-pyrazole-3-carboxamide;

[1131] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)- oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[1132] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3R)- oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[1133] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{3-[1- (oxan-4-yl)-1H-1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1134] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(2- methoxyethyl)-1H-pyrazole-3-carboxamide;

[1135] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1- [(3R)-oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1136] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3S)-oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1137] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin- 4-yl)-N-methyl-1H-pyrazole-3-carboxamide;

[1138] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin- 4-yl)-N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[1139] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin- 4-yl)-N-(3-methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[1140] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin- 4-yl)-N-[(1S)-1-(pyridin-2-yl)ethyl]-1H-pyrazole-3-carboxamide;

[1141] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin- 4-yl)-N-[(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[1142] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin- 4-yl)-N-[(3R)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[1143] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2- yl]ethoxy}-6-{3-[1-(oxan-4-yl)-1H-1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1144] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin- 4-yl)-N-(2-methoxyethyl)-1H-pyrazole-3-carboxamide;

[1145] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2- yl]ethoxy}-6-(3-{1-[(3R)-oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2- yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1146] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2- yl]ethoxy}-6-(3-{1-[(3S)-oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2- yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1147] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo- 6-[(3S)-oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1148] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo- 6-[(3R)-oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1149] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2- yl]ethoxy}-6-{7-oxo-6-[(3S)-oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2- yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[1150] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2- yl]ethoxy}-6-{7-oxo-6-[(3R)-oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2- yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[1151] 2-[1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-4-yl)-1H-pyrazol-3-yl]-N-(propan-2-yl)acetamide;

[1152] 2-[1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin- 2-yl]ethoxy}pyrimidin-4-yl)-1H-pyrazol-3-yl]-N-(propan-2-yl)acetamide;

[1153] (1'S)-6'-amino-3-[4-(3-{1-[(3-methyloxetan-3-yl)methyl]-1H-1,2,3-triazol-4- yl}-1H-pyrazol-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1154] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxo- 1,3-oxazolidin-3-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- indene]-7'-carbonitrile;

[1155] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2- yl]ethoxy}-6-(2-oxo-1,3-oxazolidin-3-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1156] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-[3- (pyrrolidine-1-carbonyl)-1H-pyrazol-1-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1157] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2- yl]ethoxy}-6-[3-(pyrrolidine-1-carbonyl)-1H-pyrazol-1-yl]pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1158] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-methyl- N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[1159] 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin- 4-yl)-N-methyl-N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide;

[1160] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-[(3S)- oxolan-3-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;

[1161] (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2- yl]ethoxy}-6-[(3S)-oxolan-3-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1162] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa- 5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1163] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2- yl]ethoxy}-6-(2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1164] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2- yl]ethoxy}-6-(2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1165] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1166] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1167] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1168] (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1169] (1'S)-6'-amino-3-(4-[(5S)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]-6-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1170] (1'S)-6'-amino-3-(4-[(5R)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]-6-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1171] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2- yl]ethoxy}-6-[(5S)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1172] (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2- yl]ethoxy}-6-[(5R)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]pyrimidin-2-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1173] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2- yl]ethoxy}-6-(4-methyl-4,7-diazaspiro[2.5]octan-7-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1174] (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2- yl]ethoxy}-6-(5-methyl-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1175] (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2- yl]ethoxy}-6-(5-methyl-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1176] (1'S)-6'-amino-3-[4-(5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)-6-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;

[1177] (1'S)-6'-amino-3-[4-(5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)-6-{(1S)-1- [(2R,3S)-3-methoxy-1...

Claims

1. WHAT IS CLAIMED IS:

1. A compound of the formula I, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is 5- or 6-membered heteroaryl; ring B is phenyl or 5- or 6-membered heteroaryl having at least one nitrogen atom; ring C is C6-C10 aryl or 5- to 10-membered heteroaryl; X is a -O-, -S-, or -NR8-; each of X1, X2, and X3is independently an -O-, -S-, -S(O)2-, -CHR3-, -C(R3)2-, or -CH2-, provided that no more than one of X1, X2, and X3is a -O-, -S-, or -S(O)2-; each R1, when present, is independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2, or an R1and R8, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-ORe, C1-C6 alkyl-SRe, C1-C6 alkyl-NReRf, C1-C6 alkyl-C(O)Re, C1-C6 alkyl-C(O)ORe, C1-C6 alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; each R2, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2, or two R2, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6 haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; each R3and R4, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -ORc, -OC(O)Rc, -OC(O)NRcRd, -OC(=NRc)NRcRd, -OS(O)Rc, -OS(O)2Rc, -OS(O)NRcRd, -OS(O)2NRcRd, -SRc, -S(O)Rc, -S(O)2Rc, -S(O)NRcRd, -S(O)2NRcRd, -NRcRd, -NRcC(O)Rd, -NRcC(O)ORd, -NRcC(O)NRcRd, -NRcC(=NRd)NRcRd, -NRcS(O)Rd, -NRcS(O)2Rd, -NRcS(O)NRcRd, -NRcS(O)2NRcRd, -C(O)Rc, -C(O)ORc, -C(O)NRcRd, -C(=NRc)NRcRd, -PRcRd, -P(O)RcRd, -P(O)2RcRd, -P(O)NRcRd, -P(O)2NRcRd, -P(O)ORc, -P(O)2ORc, -CN, or -NO2; or two R3or two R4, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6 cycloalkyl or a 4- to 10-membered heterocycloalkyl; or two R3or two R4, when present, taken together with the carbon atom to which they are attached combine to form an oxo group or a C2-C6alkenyl group; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10- membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6 alkyl, C1-C6 haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; each R5, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2; or two R5, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6 haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; R6is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), 5- to 10-membered heteroaryl, or -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and -C1-C6 alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6 alkyl), -C1-C6 alkylene-(O-Re), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10- membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; R7, when present, is H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, and 5- to 10-membered heteroaryl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6 alkyl, C1-C6haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, - NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; R8, when present, is H, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl; or an R1and R8, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6 haloalkyl, C1-C6 alkyl-ORe, C1-C6 alkyl-SRe, C1-C6 alkyl-NReRf, C1-C6 alkyl-C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; each Ra, Rb, Rc, Rd, Re, and Rfis independently selected from the group consisting of H, deuterium, C1-C6alkyl, C1-C6alkyl-(O-C1-C6alkyl), C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6 alkylene-(C3-C6 cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and C1-C6 alkylene-(5- to 10-membered heteroaryl); or two of Raand Rb, or Rcand Rd, or Reand Rf, taken together with the atom or atoms to which they are attached, combine to form a C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl; or -Reand -Rftaken together with the carbon atom to which they are attached form an oxo groups or a C2-C6 alkenyl; wherein each hydrogen atom in C1-C6 alkyl, C1-C6 alkyl-(O-C1-C6 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkylene-(C3-C6 cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, C1-C6 alkylene-(C6-C10 aryl), 5- to 10- membered heteroaryl, and C1-C6alkylene-(5- to 10-membered heteroaryl) is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, -OH, -OC1-C6 alkyl, -OC(O)C1-C6 alkyl, -OC(O)N(H or C1-C6 alkyl)2, -OS(O)C1-C6 alkyl, -OS(O)2C1-C6alkyl, -OS(O)N(H or C1-C6alkyl)2, -OS(O)2N(H or C1-C6alkyl)2, -SC1-C6alkyl, -S(O)C1-C6 alkyl, -S(O)2C1-C6 alkyl, -S(O)N(H or C1-C6 alkyl)2, -S(O)2N(H or C1-C6 alkyl)2, -N(H or C1-C6alkyl)2, -N(C1-C6alkyl)C(O)-C1-C6alkyl, -N(C1-C6alkyl)C(O)OC1- C6 alkyl, -N(C1-C6 alkyl)C(O)N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)S(O)C1-C6 alkyl, -N(C1- C6alkyl)S(O)2C1-C6alkyl, -N(C1-C6alkyl)S(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)2N(H or C1-C6alkyl)2, -C(O)C1-C6alkyl, -C(O)OC1-C6alkyl, -C(O)N(H or C1-C6alkyl)2, -P(H or C1-C6 alkyl)2, -P(O)(H or C1-C6 alkyl)2, -P(O)2(H or C1-C6 alkyl)2, -P(O)N(H or C1-C6alkyl)2, -P(O)2N(H or C1-C6alkyl)2, -P(O)OC1-C6alkyl, -P(O)2OC1-C6alkyl, -CN, or -NO2, wherein each hydrogen atom in C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, and 5- to 10-membered heteroaryl, is optionally substituted with one or more deuterium, halogen, or Rg; each Rgis independently C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, 4- to 10- membered heterocycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, -OH, -OC1-C6 alkyl, -OC(O)C1-C6alkyl, -OC(O)N(H or C1-C6alkyl)2, -OS(O)C1-C6alkyl, -OS(O)2C1-C6alkyl, -OS(O)N(H or C1-C6 alkyl)2, -OS(O)2N(H or C1-C6 alkyl)2, -SC1-C6 alkyl, -S(O)C1-C6 alkyl, -S(O)2C1-C6 alkyl, -S(O)N(H or C1-C6 alkyl)2, -S(O)2N(H or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)C(O)-C1-C6 alkyl, -N(C1-C6 alkyl)C(O)OC1-C6 alkyl, -N(C1-C6 alkyl)C(O)N(H or C1-C6 alkyl)2, -N(C1-C6 alkyl)S(O)C1-C6 alkyl, -N(C1-C6 alkyl)S(O)2C1- C6alkyl, -N(C1-C6alkyl)S(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)2N(H or C1-C6alkyl)2, -C(O)C1-C6 alkyl, -C(O)OC1-C6 alkyl, -C(O)N(H or C1-C6 alkyl)2, -P(H or C1-C6 alkyl)2, -P(O)(H or C1-C6alkyl)2, -P(O)2(H or C1-C6alkyl)2, -P(O)N(H or C1-C6alkyl)2, -P(O)2N(H or C1-C6 alkyl)2, -P(O)OC1-C6 alkyl, -P(O)2OC1-C6 alkyl, -CN, or -NO2; m1 is 0, 1, or 2; m2 is 0, 1, or 2; m3 is 0, 1, 2, or 3; m4 is 0 or 1; n1 is 0, 1, 2, 3, or 4; n2 is 0, 1, 2, 3, or 4; p is 0 or 1; q1 is 0, 1 or 2; and q2 is 1 or 2.

2. The compound of claim 1, having the formula II an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 or 2, having the formula III an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 or 2, having the formula IV an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5ais independently H or R5; and each of Z1and Z2is independently N, CH, or CR5.

5. The compound of any one of the preceding claims, having the formula V an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5ais independently H or R5; and each of Z1and Z2is independently N, CH, or CR5.

6. The compound of any one of claims 1, 2, or 4, having the formula VI an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5ais independently H or R5, each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S, and each of Z1and Z2, is independently N, CH, or CR5¸ wherein the present in ring A represents the aromaticity of ring A.

7. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula VII an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5ais independently H or R5; each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S; and each of Z1and Z2is independently N, CH, or CR5; wherein the present in ring A represents the aromaticity of ring A.

8. The compound of any one of claims 1, 2, 4, or 6, having the formula VIII an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5ais independently H or R5; each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S; each of Z1and Z2is independently N, CH, or CR5; and each of Z3, Z4, and Z5is independently N, CH, CR1, or CR2; wherein the present in ring A and ring C represents the aromaticity of ring A and ring C.

9. The compound of any one of the preceding claims, having the formula IX an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5ais independently H or R5; each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S; each of Z1and Z2is independently N, CH, or CR5; and each of Z3, Z4, and Z5is independently N, CH, CR1, or CR2; wherein the present in ring A and ring C represents the aromaticity of ring A and ring C.

10. The compound of any one of claims 1, 2, or 4, having the formula X an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each of Z1and Z2is independently N, CH, or CR5.

11. The compound of any one of claims 1 to 5, or 10, having the formula XI X an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each of Z1and Z2, is independently N, CH, or CR5.

12. The compound of any one of claims 1, 2, 4, 6, or 10, having the formula XII an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S; and each of Z1and Z2is independently N, CH, or CR5; wherein the present in ring A represents the aromaticity of ring A.

13. The compound of any one of claims 1 to 7, or 10 to 12, having the formula XIII an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S; and each of Z1and Z2is independently N, CH, or CR5wherein the present in ring A represents the aromaticity of ring A.

14. The compound of any one of claims 1, 2, 4, 6, 8, 10, or 12, having the formula XIV an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S; each of Z1and Z2is independently N, CH, or CR5; and each of Z3, Z4, and Z5is independently N, CH, CR1, or CR2; wherein the present in ring A and ring C represents the aromaticity of ring A and ring C.

15. The compound of any one of the preceding claims, having the formula XV XV an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each of Y1and Y2is independently N, O, S, or CH, provided that one of Y1and Y2is N, O, or S; each of Z1and Z2is independently N, CH, or CR5; and each of Z3, Z4, and Z5is independently N, CH, CR1, or CR2; wherein the present in ring A and ring C represents the aromaticity of ring A and ring C.

16. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring C is of the formulawherein, “” is a point of covalent attachment to ring A;R1ais H or R1; R1bis H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-ORe, C1-C6alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl- C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf,-NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; and R2ais H or R2.

17. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formulawherein “ ” is a point of covalent attachment to ring A.

18. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formula, , ,,wherein “ ” is a point of covalent attachment to ring A.

19. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein p is 1.

20. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein X is NR8.

21. The compound of any one of claims 1 to 16, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formulawherein “ ” is a point of covalent attachment to ring A.

22. The compound of any one of claims 1 to 16, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formulawherein “ ” is a point of covalent attachment to ring A.

23. The compound of any one of claims 1 to 16 or 22, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formula, , , , ,wherein “ ” is a point of covalent attachment to ring A.

24. The compound of any one of the claims 1 to 7 or 10 to 13, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formulawherein “ ” is a point of covalent attachment to ring A.

25. The compound of any one of the claims 1 to 7, 10 to 13, or 24, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion of the formulawherein “ ” is a point of covalent attachment to ring A.

26. The compound of any one of the claims 1 to 19, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein X is O.

27. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is 4- to 10-membered heterocycloalkyl, -C1-C6 alkylene-(4- to 10-membered heterocycloalkyl), C6-C10 aryl, -C1-C6 alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, or -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), wherein each hydrogen atom in 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and -C1-C6 alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6 alkylene-(C6-C10 aryl), haloalkyl, C3-C6 cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, - P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

28. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is -C1-C6 alkylene-(4- to 10- membered heterocycloalkyl), wherein each hydrogen atom in -C1-C6 alkylene-(4- to 10- membered heterocycloalkyl) is independently optionally substituted by deuterium, halogen, - Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1- C6 alkylene-(O-Re), C6-C10 aryl, -C1-C6 alkylene-(C6-C10 aryl), haloalkyl, C3-C6 cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, - P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

29. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is of the formulawherein “ ” is a point of covalent attachment to X.

30. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is of the formulawherein “ ” is a point of covalent attachment to X.

31. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein two R3, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6 cycloalkyl.

32. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5, when present, is independently deuterium, halogen, C1-C6 alkyl, -ORa, -SRa, -NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -CN, or -NO2, wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 4- to 10- membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf,-P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

33. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5, when present, is independently deuterium, halogen, -NRaRb, or -CN.

34. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R5, when present, is independently deuterium, halogen, -NH2, or -CN.

35. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R4, when present, is independently deuterium, halogen, or C1-C6alkyl.

36. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein each R4, when present, is independently deuterium, fluoro, or methyl.

37. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y1, when present, is O.

38. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y2, when present, is N.

39. The compound of any one of claims 1 to 32, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y1, when present, is N.

40. The compound of any one of claims 1 to 32, or 39, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y2, when present, is O.

41. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein n1 is 0 or 2.

42. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein n2 is 0.

43. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein m3 is 2 or 3.

44. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein m4 is 0.

45. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein q1 is 1.

46. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein q2 is 1.

47. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein q2 is 2.

48. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein p is 1.

49. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Z1, when present, is N.

50. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Z2, when present, is N.

51. The compound of claim 1, selected from the group consisting of (1'S)-6'-amino-3-(4- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-methyl-1H-pyrazole- 3-carboxamide; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(oxetan-3-yl)-1H- pyrazole-3-carboxamide; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(3-methyloxetan-3- yl)-1H-pyrazole-3-carboxamide; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(1S)-1-(pyridin-2- yl)ethyl]-1H-pyrazole-3-carboxamide; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)-oxolan-3-yl]- 1H-pyrazole-3-carboxamide; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3R)-oxolan-3-yl]- 1H-pyrazole-3-carboxamide; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{3-[1-(oxan-4-yl)-1H- 1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(2-methoxyethyl)-1H- pyrazole-3-carboxamide; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3R)-oxolan-3- yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3S)-oxolan-3- yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- methyl-1H-pyrazole-3-carboxamide; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- (oxetan-3-yl)-1H-pyrazole-3-carboxamide; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(3- methyloxetan-3-yl)-1H-pyrazole-3-carboxamide; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(1S)- 1-(pyridin-2-yl)ethyl]-1H-pyrazole-3-carboxamide;1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)- oxolan-3-yl]-1H-pyrazole-3-carboxamide; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3R)- oxolan-3-yl]-1H-pyrazole-3-carboxamide; (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-{3-[1- (oxan-4-yl)-1H-1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(2- methoxyethyl)-1H-pyrazole-3-carboxamide; (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1- [(3R)-oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1- [(3S)-oxolan-3-yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3S)-oxolan- 3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3R)-oxolan- 3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo- 6-[(3S)-oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo- 6-[(3R)-oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; 2-[1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]- 3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-1H-pyrazol-3-yl]-N- (propan-2-yl)acetamide; 2-[1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]- 3-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-1H-pyrazol-3-yl]-N-(propan-2-yl)acetamide; (1'S)-6'-amino-3-[4-(3-{1-[(3-methyloxetan-3-yl)methyl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol- 1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxo-1,3-oxazolidin- 3-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxo- 1,3-oxazolidin-3-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-[3-(pyrrolidine-1- carbonyl)-1H-pyrazol-1-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-[3- (pyrrolidine-1-carbonyl)-1H-pyrazol-1-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-methyl-N-(oxetan-3- yl)-1H-pyrazole-3-carboxamide; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- methyl-N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-[(3S)-oxolan-3- yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-[(3S)- oxolan-3-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa- 5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2R,3S)-3-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S,4R)-4-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S,4R)-4-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(5S)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(5R)-5-methyl-4,7-diazaspiro[2.5]octan-7-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-[(5S)-5- methyl-4,7-diazaspiro[2.5]octan-7-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-[(5R)-5- methyl-4,7-diazaspiro[2.5]octan-7-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-(4- methyl-4,7-diazaspiro[2.5]octan-7-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(5-methyl- 5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-(5- methyl-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;(1'S)-6'-amino-3-[4-(5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-(5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)-6-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(5-methyl- 4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-(5- methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)pyrimidin-2-yl]-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-(5-methyl-2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-(5- methyl-2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(5-methyl- 2-oxa-5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy- 1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S,4R)-4-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2R,3S)-3-methoxy- 1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-{(1S)-1-[(2S,4R)-4-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(3S)-1-methylpyrrolidin-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-[(3S)-1- methylpyrrolidin-3-yl]pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- indene]-7'-carbonitrile; (1R)-6-amino-3'-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2,3- dihydrospiro[indene-1,7'-[5]oxa[4]azatricyclo[6.1.1.02,6]deca[2(6),3]diene]-7-carbonitrile; (1'S)-6'-amino-3-(9-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-9H-purin-6-yl)- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(9-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-9H-purin-6-yl)- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(8-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-7,8-dihydro- 6H-pyrimido[5,4-b][1,4]oxazin-4-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'- indene]-7'-carbonitrile; (1'S)-6'-amino-3-(3-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-3H- imidazo[4,5-c]pyridin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(1-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-1H- imidazo[4,5-c]pyridin-6-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)-6-oxa-1- azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)-6- oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)- 6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)- 6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1-[(3R)-6- oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(6-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9-[(3R)-6- oxa-1-azaspiro[3.3]heptan-3-yl]-9H-purin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1-[(3R)-6- oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1-[(3R)-6- oxa-1-azaspiro[3.3]heptan-3-yl]-1H-imidazo[4,5-c]pyridin-6-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1-[(2S,4R)- 4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1-[(2S,4R)- 4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1-[(2R,3S)- 3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile;(1'S)-6'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(9-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9H-purin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[4,3-c]pyridin-6-yl)-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-imidazo[4,5-c]pyridin-6-yl)-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(1H-pyrazol-1- yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-[(3S)-3-methylpyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-[cyclopropyl(methyl)amino]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(cyclopropylmethyl)(methyl)amino]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(3R)-3-hydroxypyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-[4-(3,3-difluoropyrrolidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-[4-(6-azaspiro[2.5]octan-6-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-(1,3-dihydro-2H-isoindol-2-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)-oxolan-3-yl]- 1H-1,2,4-triazole-3-carboxamide; (1'S)-6'-amino-3-(4-[3-(dimethylamino)piperidin-1-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-[4-(azepan-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-[4-(4-hydroxypiperidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(1,4-oxazepan-4- yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-[4-(3-hydroxy-3-methylazepan-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-[4-(4-hydroxy-4-methylazepan-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-[4-(4,4-difluoropiperidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-[(3R)-3-methoxypyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-{[(2R)-2-hydroxypropyl](methyl)amino}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{[(4-methoxyphenyl)methyl](methyl)amino}-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-(4-methylidenepiperidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-[(3R)-3-fluoropyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(1R,5R)-2,6-diazabicyclo[3.2.0]heptan-6-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)-oxolan-3-yl]- 1H-imidazole-4-carboxamide; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3R)-oxolan-3-yl]- 1H-imidazole-4-carboxamide; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(1H-1,2,4-triazol-1- yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-[(3R)-3-hydroxy-2,2-dimethylazetidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; 1-(2-[(1'S)-6'-amino-7'-cyano-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-inden]-3- yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3R)-oxolan-3-yl]- 1H-1,2,4-triazole-3-carboxamide; (1'S)-6'-amino-3-[4-(6-azabicyclo[3.1.1]heptan-6-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile;(1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{6-oxo-5-[(3S)-oxolan- 3-yl]-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(1H-1,2,3-triazol-1- yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2H-1,2,3-triazol-2- yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; 6'-amino-3-(4-[8a-(hydroxymethyl)-3-oxotetrahydro-3H-[1,3]oxazolo[3,4-a]pyrazin-7(1H)- yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; 6'-amino-3-(4-{[2,2-bis(hydroxymethyl)azetidin-3-yl]oxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(pyrrolidin-1- yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-[(3R)-3-methylpyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-[(3S)-3-hydroxypyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-[4-(3,3-difluoropiperidin-1-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3S)-oxolan- 3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; 6'-amino-3-{4-[1-(1-methylpyrrolidin-2-yl)ethoxy]-6,6a,7,8,9,10-hexahydropyrido[1,2- d]pyrimido[5,4-b][1,4]oxazin-2-yl}-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-[(7S)-7-(difluoromethyl)-8-ethyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{4-oxo-5-[(3S)-oxolan- 3-yl]-1,3,4,5-tetrahydro-2H-pyrrolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{4-oxo-5-[(3R)-oxolan- 3-yl]-1,3,4,5-tetrahydro-2H-pyrrolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-2',3',5,6-tetrahydro- 4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; 1-(2-[(1'S)-6'-amino-7'-cyano-3',3'-difluoro-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-inden]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)- oxolan-3-yl]-1H-pyrazole-3-carboxamide; (1'S,3'S)-6'-amino-3'-methyl-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa- 5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-5'-fluoro-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile; 6'-amino-5'-fluoro-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole- 7,1'-indene]-7'-carbonitrile; (1'S)-6'-amino-3-(4-[(3-hydroxyazetidin-3-yl)methoxy]-6-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'S)-6'-amino-3-(4-{[(3-hydroxyazetidin-3-yl)methyl](methyl)amino}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,1'-indene]-7'-carbonitrile; and (1'S)-6'-amino-3-(4-[(3S)-3-cyanopyrrolidin-1-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

52. The compound of claim 1, selected from the group consisting of (1'S)-6'-amino-3-(4- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2',3',5,6-tetrahydro-4H-spiro[[2,1]benzoxazole-7,1'-indene]-7'-carbonitrile; (1R)-6-amino-3'-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-2,3- dihydrospiro[indene-1,7'-[4]oxa[5]azatricyclo[6.1.1.02,6]deca[2,5]diene]-7-carbonitrile; (5'S)-3'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-5,6,6',7'- tetrahydro-4H-spiro[[2,1]benzoxazole-7,5'-cyclopenta[b]pyridine]-4'-carbonitrile; (1'S)-6'-amino-4'-fluoro-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 2',3',5,6-tetrahydro-4H-spiro[[2,1]benzoxazole-7,1'-indene]-7'-carbonitrile; and (1'S)-6'-amino-3-(2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-2',3',5,6- tetrahydro-4H-spiro[[2,1]benzoxazole-7,1'-indene]-7'-carbonitrile; an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

53. The compound of claim 1, selected from the group consisting of (1'R)-7'-amino-3-(4- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- methyl-1H-pyrazole-3-carboxamide; 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- (oxetan-3-yl)-1H-pyrazole-3-carboxamide; 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N- methyl-N-(oxetan-3-yl)-1H-pyrazole-3-carboxamide; 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(3- methyloxetan-3-yl)-1H-pyrazole-3-carboxamide; 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(1S)- 1-(pyridin-2-yl)ethyl]-1H-pyrazole-3-carboxamide; 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3S)- oxolan-3-yl]-1H-pyrazole-3-carboxamide; 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-[(3R)- oxolan-3-yl]-1H-pyrazole-3-carboxamide;(1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{3-[1-(oxan-4-yl)-1H- 1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; 1-(2-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-N-(2- methoxyethyl)-1H-pyrazole-3-carboxamide; (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3R)-oxolan-3- yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(3-{1-[(3S)-oxolan-3- yl]-1H-1,2,3-triazol-4-yl}-1H-pyrazol-1-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (5'S)-3'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-5,6,7',8'- tetrahydro-4H,6'H-spiro[[1,2]benzoxazole-7,5'-quinoline]-4'-carbonitrile; (5'R)-3'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-5,6,7',8'- tetrahydro-4H,6'H-spiro[[1,2]benzoxazole-7,5'-isoquinoline]-4'-carbonitrile; (1'S)-7'-amino-5'-fluoro-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2R,3S)-3-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[3-(dimethylamino)oxetan-3-yl]methoxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;(1'R)-7'-amino-3-(4-{[3-(dimethylamino)oxetan-3-yl]methoxy}-6-{(1S)-1-[(2S,4R)-4-fluoro- 1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[3-(dimethylamino)oxetan-3-yl]methoxy}-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[1-(dimethylamino)cyclopropyl]methoxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[1-(dimethylamino)cyclopropyl]methoxy}-6-{(1S)-1-[(2S,4R)-4-fluoro- 1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[1-(dimethylamino)cyclopropyl]methoxy}-6-{(1S)-1-[(2S,4R)-4- methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R,4S)- 4-fluoropyrrolidin-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[(3R,4S)-4-fluoropyrrolidin-3-yl]oxy}-6-{(1S)-1-[(2S,4R)-4-methoxy- 1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)-6-oxa-1- azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)-6- oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)- 6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-{[(3R)- 6-oxa-1-azaspiro[3.3]heptan-3-yl]oxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1-[(3R)-6- oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(6-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9-[(3R)-6- oxa-1-azaspiro[3.3]heptan-3-yl]-9H-purin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1-[(3R)-6- oxa-1-azaspiro[3.3]heptan-3-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1-[(3R)-6- oxa-1-azaspiro[3.3]heptan-3-yl]-1H-imidazo[4,5-c]pyridin-6-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1-[(2S,4R)- 4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1-[(2S,4R)- 4-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]oxy}-6-{(1S)-1-[(2R,3S)- 3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(9-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}-9H-purin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-pyrazolo[4,3-c]pyridin-6-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(1-[(3R)-6,6-difluoro-1-azaspiro[3.3]heptan-3-yl]-4-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}-1H-imidazo[4,5-c]pyridin-6-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2R,3S)-3-methoxy-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2R,3S)-3-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-6-{(1S)-1-[(2S,4R)-4-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa- 5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-{(1S)-1-[(2R,3S)-3-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa- 5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa- 5,8-diazaspiro[3.5]nonan-8-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2R,3S)-3- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-6-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{[(3R)-2,2-dimethylazetidin-3-yl]oxy}-6-{(1S)-1-[(2R,3S)-3-fluoro-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile;1-(6-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalen]-3-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-methyl-1H-pyrazole-3-carboxamide; 1-(6-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalen]-3-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-[(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide; 1-(6-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalen]-3-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-[(3R)-oxolan-3-yl]-1H-pyrazole-3-carboxamide; 1-(6-[(1'R)-7'-amino-8'-cyano-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalen]-3-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-(3-methyloxetan-3-yl)-1H-pyrazole-3-carboxamide; (1'R)-7'-amino-3-[4-(6-methyl-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl)-1-{(1S)- 1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3S)-oxolan- 3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3R)-oxolan- 3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-(6-methyl-7-oxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl)-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3S)-oxolan- 3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3R)-oxolan- 3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-(5-methyl-6-oxo-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{6-oxo-5-[(3S)-oxolan- 3-yl]-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{6-oxo-5-[(3R)-oxolan- 3-yl]-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'S)-6'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(piperidin-1- yl)pyrimidin-2-yl]-2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,1'-indene]-7'- carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{4-oxo-5-[(3S)-oxolan- 3-yl]-1,3,4,5-tetrahydro-2H-pyrrolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{4-oxo-5-[(3R)- oxolan-3-yl]-1,3,4,5-tetrahydro-2H-pyrrolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-3',4',5,6- tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3S)-oxolan- 3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{6-oxo-5-[(3S)-oxolan- 3-yl]-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-{7-oxo-6-[(3S)-oxolan- 3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}pyrimidin-2-yl)-3',4',5,6-tetrahydro- 2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-(2-oxa-6- azaspiro[3.5]nonan-6-yl)pyrimidin-2-yl]-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6-[(4S)-1-oxa-6- azaspiro[3.5]nonan-6-yl]pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole- 7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-(4,7-diazaspiro[2.5]octan-7-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-[(3R)-3-hydroxy-2,2-dimethylazetidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; 1-(2-[(1'S)-7'-amino-8'-cyano-4',4'-difluoro-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalen]-3-yl]-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-4-yl)-N-[(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide; (1'R)-7'-amino-3-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-(4-chloro-6-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2- yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'- naphthalene]-8'-carbonitrile; (1'R)-7'-amino-3-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 3',4',5,6-tetrahydro-2'H,4H-spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; and (1'R)-7'-amino-3-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-3',4',5,6-tetrahydro-2'H,4H- spiro[[1,2]benzoxazole-7,1'-naphthalene]-8'-carbonitrile; an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

54. A pharmaceutical composition comprising at least one compound of any one of claims 1 to 53, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable excipients.

55. A method of treating disease, such as cancer, comprising administering to a subject in need of such treatment an effective amount of a compound of any one of claims 1 to 53, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 54.

56. A compound of any one of claims 1 to 53, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, for use in a method of treating cancer in a subject.

57. A compound of any one of claims 1 to 53, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, for treating cancer in a subject.

58. Use of a compound of any one of claims 1 to 53, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating cancer in a subject.

Images