3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane derivatives as SMARCA2-degrading PROTACs for cancer treatment

Abstract

The present disclosure provides a compound represented by formula (A), or a pharmaceutically acceptable salt and / or stereoisomer thereof: formula (A), (where E is formula (I), formula (II), or formula (III), where R a , R b , R c , R 7 , R 8 , R 9 , R 10 , X 3 , W, L, and E are as defined herein. The compound represented by formula (A) is a SMARCA2 protein degrader and is thus useful for treating cancer and other diseases. 【Chemical 1】 JPEG2026522342001035.jpg51128

Description

[Technical Field]

[0001] This disclosure provides proteolytic chimeric (PROTAC) compounds and the use of such PROTAC compounds for the treatment of SMARCA2-dependent diseases or disorders in mammals. SMARCA2 degradation may, for example, provide antitumor effects. Therefore, this disclosure provides the use of SMARCA2 degraders and pharmaceutical compositions comprising SMARCA2 degraders for the treatment of cancer. The invention also provides intermediate compounds that may be useful in the preparation of such PROTACs. [Background technology]

[0002] Conventional "small molecule" drugs reversibly (or sometimes irreversibly) bind to target proteins as a means of modulating a given biological activity. In contrast, PROTACs reversibly bind to their target proteins but then lead to the degradation of those target proteins. Once this effect is achieved, PROTACs can theoretically repeat this process with another target protein. Thus, unlike "conventional small molecule" inhibitors, the PROTAC-driven degradation mechanism can theoretically act in a substoichiometric manner. This means that even with less exposure to PROTAC compounds, the desired level of efficacy can still be achieved in vivo. In practice, this is due to the degradation power of PROTACs (DC 50 and D max This could mean that it may have an improved effect than what would be reflected by its binding affinity.

[0003] The PROTAC molecule is described as having three parts: (1) a part that can bind to the protein to be degraded, (2) a second part that can bind to an E3 ubiquitin ligase, and (3) a linker that connects parts (1) and (2) together. When used, PROTAC simultaneously binds to both the target protein and the E3 ubiquitin ligase to form a ternary complex. The E3 ligase then recruits an E2-conjugating enzyme to the ternary complex, which ubiquitizes the target protein. This has the effect of labeling the target protein for degradation by the cellular proteasome mechanism. PROTAC can then dissociate from the target protein and initiate another cycle of this process in a catalytic manner. Meanwhile, the ubiquitinated target protein is recognized by the cellular proteasome mechanism and subsequently degraded by the cellular proteasome mechanism. This PROTAC-mediated approach may be valuable as a method for treating certain diseases, including cancer.

[0004] SMARCA4 is frequently mutated in several tumor types, including lung, liver, colon, skin, bladder, esophagus, stomach, brain, endometrial, cervical, and ovarian cancers. Furthermore, SMARCA2 has been established as essential for the growth of tumors with such SMARCA4 mutations. Therefore, selective suppression of SMARCA2 has been proposed as a therapeutic strategy for cancers that may contain SMARCA4 mutations. Thus, selective suppression of SMARCA2 may be useful for many cancer types, including lung, liver, colon, skin, bladder, esophageal, gastric, brain, endometrial, cervical, and ovarian cancers.

[0005] WO2019 / 207538 discloses certain PROTAC compounds described as “SMARCA2 / 4 degraders,” and WO2020251969 discloses PROTAC compounds that target one or more of SMARCA2, SMARCA4, and PB1. WO2019 / 195201 also discloses “bifunctional” compounds described as modulators of SMARCA2. WO2019 / 213005 relates to compounds said to degrade PBRM1. WO2018 / 144649 and WO2021 / 053495 also disclose certain PROTAC molecules. WO2021 / 053555 discloses glue-degrading compounds that bind to the E3 ubiquitin ligase, cereblon.

[0006] As part of the development of PROTACs for cancer, there is a need to develop further PROTAC compounds with beneficial / improved combinations of properties that make them more suitable for therapeutic use in humans. Properties of interest during drug discovery and development may relate to selectivity profile, absorption / bioavailability, distribution, metabolism, elimination, toxicity and side effect profile, stability, and manufacturability. [Overview of the project]

[0007] In one embodiment, the Disclosure provides PROTAC compounds represented by any one of the following formulas (A) and (I) to (V), and pharmaceutically acceptable salts thereof. In another embodiment, the Disclosure provides any one or more PROTAC compounds from the following Compound List 1, and pharmaceutically acceptable salts thereof. In another embodiment, the Disclosure provides any one or more PROTAC compounds from the following Compound List 2, and pharmaceutically acceptable salts thereof. In another embodiment, the Disclosure provides any one or more PROTAC compounds from the following Compound List 3, and pharmaceutically acceptable salts thereof. In another embodiment, the Disclosure provides any one or more PROTAC compounds from the following Compound List 4, and pharmaceutically acceptable salts thereof. Compounds having formula (A) and any one of (I) to (V), and pharmaceutically acceptable salts thereof, as well as compounds of Compound List 1, Compound List 2, Compound List 3, and / or Compound List 4, and pharmaceutically acceptable salts thereof, are collectively referred to as “Compounds of the Disclosure” or individually as “Compounds of the Disclosure.” The Compounds of the Disclosure exhibit proteolytic activity against SMARCA2. The Compounds of the Disclosure may also possess a degree of selectivity that is beneficial in minimizing certain undesirable off-target degradation activity. Therefore, the Compounds of the Disclosure may be useful in the treatment of cancer.

[0008] The Compounds of the Disclosure may also possess a remarkably beneficial combination of properties relevant in the context of drug discovery and development. The structural features observed in all three areas of PROTAC may act (collectively or possibly separately) toward such a beneficial combination and / or balance of additional beneficial properties. Avoiding off-target activity in drug development is often important to avoid or reduce undesirable toxicity, side effects, or other tolerable issues when used in patients.

[0009] In addition to being a degrading agent for SMARCA2, the compounds of the Disclosure possess a remarkable and beneficial combination of chemical and metabolic stability, as well as hydrolysis properties at pH 7.4, for example in human microsomes, and selectivity for SALL4 and / or Ikaros (IKZF1), which is expected to provide an improved safety profile for in vivo use. While we do not wish to be bound by any particular theory, the degradation of SALL4 and Ikaros (IKZF1) in particular is considered to pose a risk of serious undesirable effects in humans, such as developmental toxicity or myelotoxicity.

[0010] Furthermore, in this regard, molecules that degrade SMARCA2 have often been found to also degrade SMARCA4, which is considered undesirable off-target activity. The compounds of the Disclosure may exhibit a beneficial selectivity profile by achieving a potent degree of degradation of SMARCA2 while maintaining a margin of selectivity for SMARCA4, i.e., relatively lower degradation. Similar to the development of SMARCA2 PROTACs for use in cancer, it is also considered beneficial to have a potent degree of degradation of SMARCA2 while maintaining good selectivity for PBRM1, i.e., relatively lower degradation. The compounds of the Disclosure may exhibit a beneficial selectivity profile between SMARCA2 and PBRM1. Therefore, in combination, the compounds of the Disclosure may exhibit high efficacy against SMARCA2 while simultaneously achieving a beneficial selectivity profile with respect to SALL4 and / or Ikaros (IKZF1), and in some cases achieving remarkably beneficial selectivity against SMARCA4 and / or PBRM1.

[0011] In another embodiment, the Disclosure provides a pharmaceutical composition comprising a Compound of the Disclosure and one or more pharmaceutically acceptable excipients.

[0012] In another embodiment, the present disclosure provides a method for degrading the SMARCA2 protein in humans, comprising administering an effective amount of the compound of the present disclosure to a human being in need of such degradation.

[0013] In another embodiment, the present disclosure provides a method for reducing the SMARCA2 protein in humans, comprising administering an effective amount of the compound of the present disclosure to a person in need thereof.

[0014] In another aspect, the Disclosure provides a method for treating cancer in a human, comprising administering an effective amount of the Compound of the Disclosure to a human being in need of such treatment.

[0015] In another embodiment, the Disclosure provides a compound or a pharmaceutical composition thereof for use in degrading the SMARCA2 protein in humans.

[0016] In another embodiment, the Disclosure provides a compound or a pharmaceutical composition thereof for use in reducing the SMARCA2 protein in humans.

[0017] In another aspect, the Disclosure provides a compound or a pharmaceutical composition thereof for use in treating cancer in humans.

[0018] In another aspect, the Disclosure provides the use of the compounds of the Disclosure or a pharmaceutical composition thereof in the manufacture of a pharmaceutical for the degradation of the SMARCA2 protein in humans.

[0019] In another aspect, the Disclosure provides the use of the compounds of the Disclosure or a pharmaceutical composition thereof in the manufacture of a pharmacopoeia for reducing the SMARCA2 protein in humans.

[0020] In another aspect, the Disclosure provides the use of the compounds of the Disclosure or a pharmaceutical composition thereof in the manufacture of a pharmaceutical for the treatment of cancer in humans.

[0021] In another aspect, the Disclosure provides a method for preparing the Compounds of the Disclosure.

[0022] In another aspect, the Disclosure provides intermediates used to prepare the Compounds of the Disclosure.

[0023] Further embodiments and advantages of the present disclosure are partially described below, derived from the following description, or may become apparent through the implementation of the present disclosure. The embodiments and advantages of the present disclosure are realized and achieved by the elements and combinations particularly indicated in the appended claims. It should be understood that both the above summary and the following detailed description are illustrative and descriptive and do not limit the claimed invention. [Modes for carrying out the invention]

[0024] I. Compounds of the Disclosure Many embodiments of this disclosure are described in detail throughout this specification.

[0025] In one embodiment, the compounds of the present disclosure are compounds of formula (A), or pharmaceutically acceptable salts thereof:

[0026] [ka] (In the formula, E is

[0027] [ka] And, R 1 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0028] [ka] And, R 2 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0029] [ka] And, however, (i)R 1When R is hydrogen, halogen, (C1-C6) alkyl, or (C1-C6) alkoxy, 2 it is

[0030] [Chemical formula] and (ii) When R 2 is hydrogen, halogen, (C1-C6) alkyl, or (C1-C6) alkoxy, R 1 is

[0031] [Chemical formula] and R 11 is hydrogen or -(C1-C6) alkyl-O-P(=O)-(OH)2, X 1 is CR 3 or N, R 3 is hydrogen, halogen, or (C1-C6) alkyl, X 2 is CR 4 or N, R 4 is hydrogen, halogen, or (C1-C6) alkyl, R 5a is hydrogen, halogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, 4-6 member heterocycloalkyl, cyano, aryl, or 5- or 6-member heteroaryl, where (C1-C6) alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen or cyano, and 4-6 member heterocycloalkyl, aryl, or 5- or 6-member heteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, cyano, or (C1-C6) alkyl, R 5b is hydrogen, (C1-C6) alkyl, or (C3-C6) cycloalkyl, R 6is hydrogen, (C1-C6) alkyl, or cyano. X 3 This is -CH2CH2- or -CH2-O-CH2-, or X 3 It does not exist, L is -G 1 -G 2 -G 3 -G 4 -and here, G 1 It is bonded to W, G 1 This is a 4-6 member heterocycloalkylenyl optionally substituted with 1, 2, or 3 substituents independently selected from (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl, -O-CH2-CH2-, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, cyano, or hydroxyl, or a 7-11 member heterocycloalkylenyl optionally substituted with 1, 2, or 3 substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano. G 2 This is a (C1-C6) alkylenyl, a 4- to 6-membered heterocycloalkylenyl optionally substituted with -C(=O)-, 1, 2, or 3 fluorocarbons, or a direct bond. G 3 C(=O)-, C(=O)-CH2CH2-, (C1-C6)alkylenyl, tetrahydronaphthalenyl, halogen, (C1-C6)alkyl, (C 1- A 4-6 member heterocycloalkylenyl, optionally substituted with 1, 2, or 3 substituents independently selected from C6)alkoxy or cyano, a 7-11 member heterocycloalkyl-C(=O)- or 7-11 member heterocycloalkylenyl, optionally substituted with 1, 2, or 3 substituents independently selected from halogens, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano, G 4These are (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl, 4-6 member heterocycloalkylenyl, or direct bonds. W is

[0032] [ka] or direct bond, R 7 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 8 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 9 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 10 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R a is hydrogen or halogen, R b is hydrogen or halogen, R c (It is either hydrogen or methyl.) That is the case.

[0033] In another embodiment, the compounds of the present disclosure are compounds having formula (I), or pharmaceutically acceptable salts thereof:

[0034] [ka] (In the formula, E is

[0035] [ka] And, R 1 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0036] [ka] And, R 2 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0037] [ka] And, however, (i)R 1 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 2 teeth,

[0038] [ka] And, (ii)R 2 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 1 teeth,

[0039] [ka] And, R 11 is hydrogen or -(C1-C6)alkyl-OP(=O)-(OH)2, X 1 CR 3 or N, R 3 is hydrogen, halogen, or (C1-C6) alkyl, X 2 CR 4 or N, R 4is hydrogen, halogen, or (C1-C6) alkyl, R 5a This is hydrogen, halogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5 or 6-membered heteroaryl, where (C1-C6) alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen or cyano, and 4- to 6-membered heterocycloalkyl, aryl, or 5 or 6-membered heteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, cyano, or (C1-C6) alkyl. R 5b is hydrogen, (C1-C6) alkyl, or (C3-C6) cycloalkyl, R 6 is hydrogen, (C1-C6) alkyl, or cyano. X 3 is -CH2CH2- or -CH2-O-CH2-, or X 3 It does not exist, L is -G 1 -G 2 -G 3 -G 4 -and here, G 1 It is bonded to W, G 1 This is a 4-6 member heterocycloalkylenyl molecule optionally substituted with 1, 2, or 3 substituents independently selected from (C1-C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano, or a 7-11 member heterocycloalkylenyl molecule optionally substituted with 1, 2, or 3 substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano. G 2 is a (C1-C6) alkylenyl or direct bond, G 3This is a 4-6 member heterocycloalkylenyl, cyano, or 7-11 member heterocycloalkylenyl, which is optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6) alkyls, or (C1-C6) alkoxys. G 4 is a (C1-C6) alkylenyl or direct bond, W is

[0040] [ka] or direct bond, R 7 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 8 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 9 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 10 (These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogens, or one, two, or three halogens.) That is the case.

[0041] In another embodiment, the compounds of the present disclosure are compounds having formula (I), or pharmaceutically acceptable salts thereof:

[0042] [ka] (In the formula, E is

[0043] [ka] And, R 1 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0044] [ka] And, R 2 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0045] [ka] And, however, (i)R 1 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 2 teeth,

[0046] [ka] And, (ii)R 2 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 1 teeth,

[0047] [ka] And, R 11 is hydrogen or -(C1-C6)alkyl-OP(=O)-(OH)2, X 1 CR 3 or N, R 3 is hydrogen, halogen, or (C1-C6) alkyl, X 2 CR 4is N, R 4 is hydrogen, halogen, or (C1-C6) alkyl, R 5a is hydrogen, halogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, 4-6 member heterocycloalkyl, cyano, aryl, or 5- or 6-member heteroaryl, where (C1-C6) alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen or cyano, and 4-6 member heterocycloalkyl, aryl, or 5- or 6-member heteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, cyano, or (C1-C6) alkyl, R 5b is hydrogen, (C1-C6) alkyl, or (C3-C6) cycloalkyl, R 6 is hydrogen, (C1-C6) alkyl, or cyano, X 3 is -CH2CH2- or -CH2-O-CH2-, or X 3 is absent, L is -G 1 -G 2 -G 3 -G 4 -, where G 1 is bonded to W, G 1 is 4-6 member heterocycloalkenylenyl optionally substituted with 1, 2, or 3 substituents independently selected from (C1-C6) alkenyl, halogen, (C1-C6) alkyl, (C1-C6) alkoxy, or cyano, or 7-11 member heterocycloalkenylenyl optionally substituted with 1, 2, or 3 substituents independently selected from halogen, (C1-C6) alkyl, (C1-C6) alkoxy, or cyano, G 2 is (C1-C6) alkenylene or a direct bond, G 3is a 4- to 6-membered heterocycloalkylenyl optionally substituted with 1, 2, or 3 substituents independently selected from halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, cyano, halogen, (C 1 -C6)alkyl, (C1-C6)alkoxy, or a 7- to 11-membered heterocycloalkylenyl optionally substituted with 1, 2, or 3 substituents independently selected from cyano, or a 5- to 10-membered heteroarylenyl, and G 4 is (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl, or a direct bond, W is

[0048]

Chemical formula

[0049] In another embodiment, the compound of the present disclosure is a compound having the formula (II), or a pharmaceutically acceptable salt thereof:

[0050]

Chemical formula

[0051] In another embodiment, the compounds of the present disclosure are compounds having formula (III), or pharmaceutically acceptable salts thereof:

[0052] [ka] (In the formula, R 7 , R 8 , R 9 , R 10 W, L, and E are defined with respect to equation (I). That is the case.

[0053] In another embodiment, the compounds of the present disclosure are compounds having any one of formulas (A) or (I) to (III), where E is E-1, or pharmaceutically acceptable salts thereof.

[0054] In another embodiment, the compound of the present disclosure is R 5a A compound having one of formulas (A) or (I) to (III), wherein the element is hydrogen, or a pharmaceutically acceptable salt thereof.

[0055] In another embodiment, the compound of the present disclosure is R 5a The compound having any one of formulas (A) or (I) to (III), which is a (C1-C6) alkyl group optionally substituted with one, two, or three substituents independently selected from halogens or cyano compounds, or a pharmaceutically acceptable salt thereof.

[0056] In another embodiment, the compound of the present disclosure is R 5a A compound having one of formulas (A) or (I) to (III), wherein the compound is methyl, or a pharmaceutically acceptable salt thereof.

[0057] In another embodiment, the compound of the present disclosure is R 5a A compound having one of formulas (A) or (I) to (III), wherein (C3-C6) cycloalkyl, or a pharmaceutically acceptable salt thereof.

[0058] In another embodiment, the compound of the present disclosure is R 5a A compound having one of formulas (A) or (I) to (III), wherein the compound is cyclopropyl, or a pharmaceutically acceptable salt thereof.

[0059] In another embodiment, the compound of the present disclosure is R 5a The compound having any one of formulas (A) or (I) to (III), which is a 4- to 6-membered heterocycloalkyl, optionally substituted with one, two, or three substituents independently selected from halogens, cyanos, or (C1-C6) alkyls, or a pharmaceutically acceptable salt thereof.

[0060] In another embodiment, the compound of the present disclosure is R 5a A compound having one of formulas (A) or (I) to (III), in which the compound is cyano, or a pharmaceutically acceptable salt thereof.

[0061] In another embodiment, the compound of the present disclosure is R 5a The compound having formula (A) or any one of (I) to (III), wherein the aryl is optionally substituted with one, two, or three substituents independently selected from halogens, cyanos, or (C1-C6) alkyls, or a pharmaceutically acceptable salt thereof.

[0062] In another embodiment, the compound of the present disclosure is R 5a The compound having any one of formulas (A) or (I) to (III), which is a 5 or 6-membered heteroaryl, optionally substituted with 1, 2, or 3 substituents independently selected from halogens, cyanos, or (C1-C6) alkyls, or a pharmaceutically acceptable salt thereof.

[0063] In another embodiment, the compounds of the present disclosure are compounds having any one of formulas (A) or (I) to (III), where E is E-2, or pharmaceutically acceptable salts thereof.

[0064] In another embodiment, the compounds of the present disclosure are compounds having one of formulas (A) or (I) to (III), where E is E-3, or pharmaceutically acceptable salts thereof.

[0065] In another embodiment, the compounds of the present disclosure are R 1 but,

[0066] [ka] And, R 2 The compound is a compound having one of formulas (A) or (I) to (III), which is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, or a pharmaceutically acceptable salt thereof.

[0067] In another embodiment, the compound of the present disclosure is R 2 The compound is a hydrogen, halogen, or (C1-C6) alkyl compound having one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0068] In another embodiment, the compound of the present disclosure is R 2 The compound is a compound having one of formulas (A) or (I) to (III), which is hydrogen, fluoro, or methyl, or a pharmaceutically acceptable salt thereof.

[0069] In another embodiment, the compound of the present disclosure is R 11 A compound having one of formulas (A) or (I) to (III), wherein the element is hydrogen, or a pharmaceutically acceptable salt thereof.

[0070] In another embodiment, the compound of the present disclosure is X 1 CR 3It is a compound having one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0071] In another embodiment, the compound of the present disclosure is R 3 A compound having one of formulas (A) or (I) to (III), wherein the element is hydrogen, or a pharmaceutically acceptable salt thereof.

[0072] In another embodiment, the compound of the present disclosure is R 3 A compound having one of formulas (A) or (I) to (III), wherein the element is a halogen, or a pharmaceutically acceptable salt thereof.

[0073] In another embodiment, the compound of the present disclosure is R 3 A compound having one of formulas (A) or (I) to (III), wherein the element is (C1-C6) alkyl, or a pharmaceutically acceptable salt thereof.

[0074] In another embodiment, the compound of the present disclosure is X 1 A compound having one of formulas (A) or (I) to (III), where N is present, or a pharmaceutically acceptable salt thereof.

[0075] In another embodiment, the compound of the present disclosure is X 2 CR 4 It is a compound having one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0076] In another embodiment, the compound of the present disclosure is R 4 A compound having one of formulas (A) or (I) to (III), wherein the element is hydrogen, or a pharmaceutically acceptable salt thereof.

[0077] In another embodiment, the compound of the present disclosure is R 4 A compound having one of formulas (A) or (I) to (III), wherein the element is a halogen, or a pharmaceutically acceptable salt thereof.

[0078] In another embodiment, the compound of the present disclosure is R 4 A compound having one of formulas (A) or (I) to (III), wherein the element is (C1-C6) alkyl, or a pharmaceutically acceptable salt thereof.

[0079] In another embodiment, the compound of the present disclosure is X 2 A compound having one of formulas (A) or (I) to (III), where N is present, or a pharmaceutically acceptable salt thereof.

[0080] In another embodiment, the compound disclosed herein has E-1,

[0081] [ka] It is a compound having one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0082] In another embodiment, the compound disclosed herein has E-1,

[0083] [ka] It is a compound having one of the formulas (A) or (I) to (III).

[0084] In another embodiment, the compound of the present disclosure is such that E is

[0085] [ka] It is a compound having one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0086] In another embodiment, the compound disclosed herein has E-2,

[0087] [ka] It is a compound having one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0088] In another embodiment, the compound disclosed herein has E-3,

[0089] [ka] It is a compound having one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0090] In another embodiment, the compound of the present disclosure is such that E is

[0091] [ka] It is a compound having one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0092] In another embodiment, the compound of the present disclosure is G 1 The compound having any one of formulas (A) or (I) to (III), which is a 4- to 6-membered heterocycloalkylenyl that is optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos, or a pharmaceutically acceptable salt thereof.

[0093] In another embodiment, the compound of the present disclosure is G 1 A compound having any one of formulas (A) or (I) to (III), wherein is a (C3-C6)cycloalkylenyl, or a 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6)alkyl, (C1-C6)alkoxy, cyano, or hydroxyl, or a pharmaceutically acceptable salt thereof.

[0094] In another embodiment, the compounds of the present disclosure are G1 but,

[0095] [ka] And, Each R 12 These are independently halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos. n is 0, 1, 2, or 3. " * The bonds marked with " are G 2 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0096] In another embodiment, the compounds of the present disclosure are G 1 but,

[0097] [ka] And, Each R 12 These are independently halogen, (C1-C6)alkyl, (C1-C6)alkoxy, cyano, or hydroxyl. n is 0, 1, 2, or 3. " * The bonds marked with " are G 2 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0098] In another embodiment, the compounds of the present disclosure are each R 12 However, independently, the compound is fluoro, methyl, methoxy, cyano, or -CHF2, where n is 0, 1, or 2, having one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0099] In another embodiment, the compounds of the present disclosure are G 1 but,

[0100] [ka] And, " * The bonds marked with " are G 2 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0101] In another embodiment, the compounds of the present disclosure are G 1 but,

[0102] [ka] And, " * The bonds marked with " are G 2 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0103] In another embodiment, the compounds of the present disclosure are G 1 but,

[0104] [ka] And, X 4 It is -O-, Each R 12 These are independently halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos. " * The bonds marked with " are G 2 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0105] In another embodiment, the compounds of the present disclosure are G 1 but,

[0106] [ka] And, " * The bonds marked with " are G 2 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0107] In another embodiment, the compounds of the present disclosure are G 1 but,

[0108] [ka] And, " * The bonds marked with " are G 2 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0109] In another embodiment, the compound of the present disclosure is G 1 A compound having formula (A), wherein is cyclohexylenyl, or a pharmaceutically acceptable salt thereof.

[0110] In another embodiment, the compounds of the present disclosure are

[0111] [ka] " * The bonds marked with " are G 2 A compound having formula (A) that is bonded to, or a pharmaceutically acceptable salt thereof.

[0112] In another embodiment, the compound of the present disclosure is G 1The compound having any one of formulas (A) or (I) to (III), which is a 7- to 11-membered heterocycloalkylenyl that is optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos, or a pharmaceutically acceptable salt thereof.

[0113] In another embodiment, the compounds of the present disclosure are G 1 but,

[0114] [ka] And, Each R 13 These are independently selected from halogens, (C1-C6)alkyls, (C1-C6)alkoxys, or cyanos. o is 0, 1, 2, or 3. p, q, r, and s are independently 1, 2, or 3. " * The bonds marked with " are G 2 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0115] In another embodiment, the compounds of the present disclosure are G 1 but,

[0116] [ka] And, Each R 13 These are independently selected from halogens, (C1-C6)alkyls, (C1-C6)alkoxys, or cyanos. o is 0, 1, 2, or 3. p, q, r, and s are independently 1 or 2. " * The bonds marked with " are G 2A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0117] In another embodiment, the compounds of the present disclosure are p and q are 1, r is 1 or 2, s is 1 or 2, R 13 However, it is a halogen compound having one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0118] In another embodiment, the compound of the present disclosure is R 13 A compound having one of formulas (A) or (I) to (III), where is fluoro and o is 0, 1, or 2, or a pharmaceutically acceptable salt thereof.

[0119] In another embodiment, the compound of the present disclosure is G 1 but,

[0120] [ka] And, " * The bonds marked with " are G 2 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0121] In another embodiment, the compounds of the present disclosure are G 1 but,

[0122] [ka] And, a is either 0 or 1. b is either 0 or 1. " * The bonds marked with " are G 2A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0123] In another embodiment, the compound of the present disclosure is G 1 but,

[0124] [ka] And, " * The bonds marked with " are G 2 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0125] In another embodiment, the compound of the present disclosure is G 1 but,

[0126] [ka] And, " * The bonds marked with " are G 2 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0127] In another embodiment, the compound of the present disclosure is G 1 but,

[0128] [ka] And, " * The bonds marked with " are G 2 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0129] In another embodiment, the compound of the present disclosure is G 2A compound having one of formulas (A) or (I) to (III) in which the bond is a direct bond, or a pharmaceutically acceptable salt thereof.

[0130] In another embodiment, the compound of the present disclosure is G 2 A compound having any one of the formulas (A), where is -C(=O)-, or a pharmaceutically acceptable salt thereof.

[0131] In another embodiment, the compound of the present disclosure is G 2 A compound having one of formulas (A) or (I) to (III), wherein (C1-C6)alkylenyl is present, or a pharmaceutically acceptable salt thereof.

[0132] In another embodiment, the compound of the present disclosure is G 2 A compound having one of formulas (A) or (I) to (III), where -CH2-, or a pharmaceutically acceptable salt thereof.

[0133] In another embodiment, the compound of the present disclosure is G 3 The compound having any one of formulas (A) or (I) to (III), which is a 4- to 6-membered heterocycloalkylenyl that is optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos, or a pharmaceutically acceptable salt thereof.

[0134] In another embodiment, the compounds of the present disclosure are G 3 but,

[0135] [ka] And, Each R 14 These are independently halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos. t is 0, 1, 2, or 3. " * The bonds marked with " are G 4A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0136] In another embodiment, the compound of the present disclosure is R 14 The compound is a compound having one of formulas (A) or (I) to (III), where t is fluoro or methyl, and t is 0 or 1, or a pharmaceutically acceptable salt thereof.

[0137] In another embodiment, the compound of the present disclosure is G 3 but,

[0138] [ka] It is a compound having one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0139] In another embodiment, the compound of the present disclosure is G 3 The compound having any one of formulas (A) or (I) to (III), which is a 7- to 11-membered heterocycloalkylenyl that is optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos, or a pharmaceutically acceptable salt thereof.

[0140] In another embodiment, the compound of the present disclosure is G 3 but,

[0141] [ka] And, " * The bonds marked with " are G 4 A compound having formula (A) that is bonded to, or a pharmaceutically acceptable salt thereof.

[0142] In another embodiment, the compound of the present disclosure is G 3 but,

[0143] [ka] And, " * The bonds marked with " are G 4 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0144] In another embodiment, the compound of the present disclosure is G 3 but,

[0145] [ka] And, " * The bonds marked with " are G 4 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0146] In another embodiment, the compounds of the present disclosure are G 3 but,

[0147] [ka] And, Each R 15 These are independently selected from halogens, (C1-C6)alkyls, (C1-C6)alkoxys, or cyanos. u is 0, 1, 2, or 3, v, w, x, and y are independently 1, 2, or 3. " * The bonds marked with " are G 4 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0148] In another embodiment, the compounds of the present disclosure are compounds having any one of formulas (A) or (I) to (III), where v, w, x, and y are independently 1 or 2, or pharmaceutically acceptable salts thereof.

[0149] In another embodiment, the compound of the present disclosure is R 15 A compound having one of formulas (A) or (I) to (III), in which the compound is fluoro, or a pharmaceutically acceptable salt thereof.

[0150] In another embodiment, the compounds of the present disclosure are G 3 but,

[0151] [ka] And, x a and y a These are independently 1, 2, or 3, " * The bonds marked with " are G 4 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0152] In another embodiment, the compound of the present disclosure is G 3 but,

[0153] [ka] And, " * The bonds marked with " are G 4 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0154] In another embodiment, the compound of the present disclosure is G 3 but,

[0155] [ka] And, " * The bonds marked with " are G 4 A compound having one of formulas (A) or (I) to (III) bonded to it, or a pharmaceutically acceptable salt thereof.

[0156] In another embodiment, the compound of the present disclosure is G 3 but,

[0157] [ka] And, " * The bonds marked with " are G 4 A compound having formula (A) that is bonded to, or a pharmaceutically acceptable salt thereof.

[0158] In another embodiment, the compound of the present disclosure is G 4 A compound having one of formulas (A) or (I) to (III), wherein (C1-C6)alkylenyl is present, or a pharmaceutically acceptable salt thereof.

[0159] In another embodiment, the compound of the present disclosure is G 4 A compound having one of formulas (A) or (I) to (III), wherein the group is -CH2- or -CH2CH2-, or a pharmaceutically acceptable salt thereof.

[0160] In another embodiment, the compound of the present disclosure is G 4 A compound having one of formulas (A) or (I) to (III), wherein (C3-C6) cycloalkylenyl is present, or a pharmaceutically acceptable salt thereof.

[0161] In another embodiment, the compound of the present disclosure is G 4 but,

[0162] [ka] And, " * Bonds marked with '' are compounds having formula (A) or any one of (I) to (III) that are bonded to E, or pharmaceutically acceptable salts thereof.

[0163] In another embodiment, the compound of the present disclosure is G 4 but,

[0164] [ka] And, " * Bonds marked with '' are compounds having formula (A) or any one of (I) to (III) that are bonded to E, or pharmaceutically acceptable salts thereof.

[0165] In another embodiment, the compound of the present disclosure is G 4 A compound having one of formulas (A) or (I) to (III) in which the bond is a direct bond, or a pharmaceutically acceptable salt thereof.

[0166] In another embodiment, the compound of the present disclosure is such that L is

[0167] [ka]

[0168] [ka] and " * Bonds marked with '' are compounds having formula (A) or any one of (I) to (III) that are bonded to E, or pharmaceutically acceptable salts thereof.

[0169] In another embodiment, the compound of the present disclosure is such that L is

[0170] [ka]

[0171] [ka] And, " * Bonds marked with '' are compounds having formula (A) or any one of (I) to (III) that are bonded to E, or pharmaceutically acceptable salts thereof.

[0172] In another embodiment, the compound of the present disclosure is such that L is

[0173] [ka] And, " * Bonds marked with '' are compounds having formula (A) or any one of (I) to (III) that are bonded to E, or pharmaceutically acceptable salts thereof.

[0174] In another embodiment, the compound of the present disclosure is such that L is

[0175] [ka] and " * Bonds marked with '' are compounds having formula (A) or any one of (I) to (III) that are bonded to E, or pharmaceutically acceptable salts thereof.

[0176] In another embodiment, the compound of the present disclosure is W

[0177] [ka] It is a compound having one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0178] In another embodiment, the compounds of the present disclosure are compounds having any one of formulas (A) or (I) to (III), in which W is a direct bond, or pharmaceutically acceptable salts thereof.

[0179] In another embodiment, the compound of the present disclosure is R 7 The compound is a halogen, (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl, where the (C1-C6) alkyl is optionally substituted with one, two, or three halogens, and is a compound having any one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0180] In another embodiment, the compound of the present disclosure is R 7 However, it is a compound having one of formulas (A) or (I) to (III), which is a halogen or (C1-C6) alkyl, or a pharmaceutically acceptable salt thereof.

[0181] In another embodiment, the compound of the present disclosure is R 7 However, it is a compound having one of formulas (A) or (I) to (III) that is fluoro or methyl, or a pharmaceutically acceptable salt thereof.

[0182] In another embodiment, the compound of the present disclosure is R 8 , R 9 , and R 10 However, it is a compound having one of formulas (A) or (I) to (III), which is H, or a pharmaceutically acceptable salt thereof.

[0183] In another embodiment, the compound of the present disclosure is R 8 The compound is a halogen, (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl, where the (C1-C6) alkyl is optionally substituted with one, two, or three halogens, and is a compound having any one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0184] In another embodiment, the compound of the present disclosure is R 8However, it is a compound having one of formulas (A) or (I) to (III), which is a halogen or (C1-C6) alkyl, or a pharmaceutically acceptable salt thereof.

[0185] In another embodiment, the compound of the present disclosure is R 8 However, it is a compound having one of formulas (A) or (I) to (III) that is fluoro or methyl, or a pharmaceutically acceptable salt thereof.

[0186] In another embodiment, the compound of the present disclosure is R 7 , R 9 , and R 10 However, it is a compound having one of formulas (A) or (I) to (III), which is hydrogen, or a pharmaceutically acceptable salt thereof.

[0187] In another embodiment, the compound of the present disclosure is R 9 The compound is a halogen, (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl, where the (C1-C6) alkyl is optionally substituted with one, two, or three halogens, and is a compound having any one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0188] In another embodiment, the compound of the present disclosure is R 9 A compound having one of formulas (A) or (I) to (III), wherein the element is a halogen, or a pharmaceutically acceptable salt thereof.

[0189] In another embodiment, the compound of the present disclosure is R 9 A compound having one of formulas (A) or (I) to (III), in which the compound is fluoro, or a pharmaceutically acceptable salt thereof.

[0190] In another embodiment, the compound of the present disclosure is R 7 , R 8 , and R 10 However, it is a compound having one of formulas (A) or (I) to (III), which is hydrogen, or a pharmaceutically acceptable salt thereof.

[0191] In another embodiment, the compound of the present disclosure is R 10 The compound is a halogen, (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl, where the (C1-C6) alkyl is optionally substituted with one, two, or three halogens, and is a compound having any one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0192] In another embodiment, the compound of the present disclosure is R 10 A compound having one of formulas (A) or (I) to (III), wherein the element is a halogen, or a pharmaceutically acceptable salt thereof.

[0193] In another embodiment, the compound of the present disclosure is R 10 A compound having one of formulas (A) or (I) to (III), in which the compound is fluoro, or a pharmaceutically acceptable salt thereof.

[0194] In another embodiment, the compound of the present disclosure is R 7 , R 8 , and R 9 However, it is a compound having one of formulas (A) or (I) to (III), which is hydrogen, or a pharmaceutically acceptable salt thereof.

[0195] In another embodiment, the compound of the present disclosure is R 7 , R 8 , R 9 , and R 10 However, it is a compound having one of formulas (A) or (I) to (III), which is hydrogen, or a pharmaceutically acceptable salt thereof.

[0196] In another embodiment, the compounds of the present disclosure are compounds having formula (IV), or pharmaceutically acceptable salts thereof:

[0197] [ka] (In the formula, Each R12 It is independently fluoro, n is 0, 1, or 2. R 7 , R 8 , R 9 , and R 10 These are independently hydrogen, fluoro, or methyl. E is E-1, G 3 This is as defined with respect to equation (I). That is the case.

[0198] In another embodiment, the compounds of the present disclosure are G 3 but,

[0199] [ka] And, G 4 However, it is a compound having one of formulas (A) or (I) to (III) with a direct bond, -CH2- or -CH2CH2-, or a pharmaceutically acceptable salt thereof.

[0200] In another embodiment, the compound of the present disclosure is G 3 but,

[0201] [ka] It is a compound having one of formulas (A) or (I) to (III), or a pharmaceutically acceptable salt thereof.

[0202] In another embodiment, the compounds of the present disclosure are compounds having formula (V), or pharmaceutically acceptable salts thereof.

[0203] [ka] (In the formula, Each R 12 is fluoro or hydroxyl, n is 0, 1, 2, or 3. E is

[0204] [ka] And, R 1 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0205] [ka] And, R 2 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0206] [ka] And, however, (i)R 1 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 2 teeth,

[0207] [ka] And, (ii)R 2 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 1 teeth,

[0208] [ka] And, R 11 is hydrogen or -(C1-C6)alkyl-OP(=O)-(OH)2, X 1 CR 3 or N, R 3is hydrogen, halogen, or (C1-C6) alkyl, X 2 CR 4 or N, R 4 is hydrogen, halogen, or (C1-C6) alkyl, R 5a This is hydrogen, halogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5 or 6-membered heteroaryl, where (C1-C6) alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen or cyano, and 4- to 6-membered heterocycloalkyl, aryl, or 5 or 6-membered heteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, cyano, or (C1-C6) alkyl. R 5b is hydrogen, (C1-C6) alkyl, or (C3-C6) cycloalkyl, R 6 is hydrogen, (C1-C6) alkyl, or cyano. X 3 is either -CH2CH2- or does not exist. G 3 This refers to a 4-6 member heterocycloalkylenyl, halogen, (C1-C6) alkyl, (C1-C6) alkoxy, or cyano tetrahydronaphthalene, optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6) alkyl, (C1-C6) alkoxy, or cyano. 1 A 7-11 member heterocycloalkyl-C(=O)- or 7-11 member heterocycloalkylenyl, optionally substituted with one, two, or three substituents independently selected from -C6)alkyl, (C1-C6)alkoxy, or cyano. G 4 It does not exist, or it is cyclobutyrenyl. R 7 , R 8 , R 9 , and R 10 These are independently hydrogen, fluoro, methyl, or cyano, R aThese are hydrogen, chloro, methyl, or fluoro. R b These are hydrogen, chloro, methyl, or fluoro. R c (It is either hydrogen or methyl.) That is the case.

[0209] In another embodiment, the compounds of the present disclosure are G 3 but,

[0210] [ka] It is a compound having formula (V), or a pharmaceutically acceptable salt thereof.

[0211] In another embodiment, the compound of the present disclosure is G 3 but,

[0212] [ka] It is a compound having formula (V), or a pharmaceutically acceptable salt thereof.

[0213] In another embodiment, the compound of the present disclosure is G 3 but,

[0214] [ka] It is a compound having formula (V), or a pharmaceutically acceptable salt thereof.

[0215] In another embodiment, the compound of the present disclosure is any one or more of the compounds in Compound List 1, or a pharmaceutically acceptable salt thereof.

[0216] List of Compounds 1 1-[1-[1-[[7-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-7-azaspiro[3.5]nonane-2-yl]methyl]-4-piperidyl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[3-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]propa-2-inyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-4-piperidyl]indole-4-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-5-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-5-methylphenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-methylphenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-6-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2,6-difluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[2-[1-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-4-piperidyl]-1-methyl-indole-6-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-4-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-4-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]methyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-4-piperidyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[(2S)-4-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]morpholine-2-yl]methyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[2-[4-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]piperazin-1-yl]ethyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-(1-(3-((1-(3-(3-(3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-4-fluorophenyl)piperidine-4-yl)methyl)-3-azaspiro[5.5]undecane-9-yl)-3-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-5-yl)dihydropyrimidine-2,4(1H,3H)-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-(5-(7-((1-(5-(-3-(3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-fluorophenyl)piperidine-4-yl)methyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl)-2-methylphenyl)dihydropyrimidine-2,4(1H,3H)-dione, (3-(1-(7-((1-(5-(3-(3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-fluorophenyl)piperidine-4-yl)methyl)-7-azaspiro[3.5]nonane-2-yl)-3-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-dioxotetrahydropyrimidine-1(2H)-yl)methyl dihydrogen phosphate, or 1-(1-(2-((1-(5-(-3-(3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-fluorophenyl)piperidine-4-yl)methyl)-2-azaspiro[3.5]nonane-7-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)dihydropyrimidine-2,4(1H,3H)-dione.

[0217] In another embodiment, the compound of the present disclosure is any one or more of the compounds in Compound List 2, or a pharmaceutically acceptable salt thereof.

[0218] List of compounds 2 1-[1-[1-[[7-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-7-azaspiro[3.5]nonane-2-yl]methyl]-4-piperidyl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-5-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-5-methylphenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-methylphenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-6-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2,6-difluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-4-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-4-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-4-piperidyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-(1-(3-((1-(3-(3-(3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-4-fluorophenyl)piperidine-4-yl)methyl)-3-azaspiro[5.5]undecane-9-yl)-3-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-5-yl)dihydropyrimidine-2,4(1H,3H)-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, (3-(1-(7-((1-(5-(3-(3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-fluorophenyl)piperidine-4-yl)methyl)-7-azaspiro[3.5]nonane-2-yl)-3-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-dioxotetrahydropyrimidine-1(2H)-yl)methyl dihydrogen phosphate, or 1-(1-(2-((1-(5-(-3-(3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-fluorophenyl)piperidine-4-yl)methyl)-2-azaspiro[3.5]nonane-7-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)dihydropyrimidine-2,4(1H,3H)-dione.

[0219] In another embodiment, the compound of the present disclosure is any one or more of the compounds in Compound List 3, or a pharmaceutically acceptable salt thereof.

[0220] List of Compounds 3 1-[2-[1-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-4-piperidyl]-1-methyl-indole-6-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]methyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[(2S)-4-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]morpholine-2-yl]methyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, or 1-(5-(7-((1-(5-(-3-(3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-fluorophenyl)piperidine-4-yl)methyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl)-2-methylphenyl)dihydropyrimidine-2,4(1H,3H)-dione.

[0221] In another embodiment, the compound of the present disclosure is any one or more of the compounds in Compound List 4, or a pharmaceutically acceptable salt thereof.

[0222] List of compounds 4 1-[1-[(6r,9r)-4-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-1-oxa-4-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(1r,3r)-3-[8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octane-3-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[(2S)-4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]morpholine-2-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[7-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-7-azaspiro[3.5]nonane-2-yl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5r,8r)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-2-azaspiro[4.5]decane-8-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[(2R)-4-[[7-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-7-azaspiro[3.5]nonane-2-yl]methyl]morpholin-2-yl]methyl]3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,8-dihydro-5H-imidazo[1,2-a]pyrazine-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[(2S)-4-[[7-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-7-azaspiro[3.5]nonane-2-yl]methyl]morpholin-2-yl]methyl]3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[rel-(3aR,5r * ,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[rel-(3aR,5r * ,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[6-fluoro-1-[rel-(3R *)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[6-fluoro-1-[rel-(3R * )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-cyclopropyl-1-[rel-(3R * )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-cyclopropyl-1-[rel-(3R *)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-[[9-[5-(2,4-dioxohexahydropyrimidine-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridine-1-yl]-3-azaspiro[5.5]undecane-3-yl]methyl]-4-fluoro-1-piperidyl]benzonitrile, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-[[9-[5-(2,4-dioxohexahydropyrimidine-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridine-1-yl]-3-azaspiro[5.5]undecane-3-yl]methyl]-4-fluoro-1-piperidyl]benzonitrile, 1-[3-methyl-1-[3-[[rel-(4R * )-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-[[9-[5-(2,4-dioxohexahydropyrimidine-1-yl)-3-methyl-pyrrolo[2,3-b]pyridine-1-yl]-3-azaspiro[5.5]undecane-3-yl]methyl]-4-fluoro-1-piperidyl]benzonitrile, 1-[3-methyl-1-[3-[[rel-(4R * )-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-4-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-4-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-6-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[rel-(3S * )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[rel-(3R * )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 1), 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5r,8r)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[rel-(3S * )-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[rel-(3R * )-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5r,8r)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]piperazin-1-yl]methyl]spiro[5.5]undecane-3-yl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(3s,6s)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(3r,6r)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(1s,3s)-3-[4-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]piperazin-1-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-[[9-[5-(2,4-dioxohexahydropyrimidine-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridine-1-yl]-3-azaspiro[5.5]undecane-3-yl]methyl]-1-piperidyl]benzonitrile, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-[[2-[3-cyclopropyl-5-(2,4-dioxohexahydropyrimidine-1-yl)pyrrolo[2,3-b]pyridine-1-yl]-7-azaspiro[3.5]nonane-7-yl]methyl]-1-piperidyl]benzonitrile, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[(1R,5S,6s)-3-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3-azabicyclo[3.1.0]hexane-6-yl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[(1R,5S,6s)-3-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3-azabicyclo[3.1.0]hexane-6-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(1s,3s)-3-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octane-8-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[(2R)-4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]morpholine-2-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-6-fluoro-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-azabicyclo[3.2.1]octane-8-yl]-2-chlorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, or 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-6-fluoropyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione.

[0223] In another embodiment, the compound of the present disclosure is any one or more of the compounds in Compound List 5, or a pharmaceutically acceptable salt thereof.

[0224] List of Compounds 5 1-[1-[1-[[7-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-7-azaspiro[3.5]nonane-2-yl]methyl]-4-piperidyl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[3-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]propa-2-inyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-4-piperidyl]indole-4-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-5-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)43pyridine43e-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-5-methylphenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]43iridin-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)44-iridin-44e-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-5-methylphenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]44-iridin-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-methylphenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-6-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2,6-difluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[2-[1-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-4-piperidyl]-1-methyl-indole-6-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-4-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-4-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]methyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-4-piperidyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[(2S)-4-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]morpholine-2-yl]methyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[2-[4-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]piperazin-1-yl]ethyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-4-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[5-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]-2-methylphenyl]hexahydropyrimidine-2,4-dione, [3-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]-2,6-dioxo-hexahydropyrimidine-1-yl]methyl dihydrogen phosphate, 1-[1-[2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-2-azaspiro[3.5]nonane-7-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(6r,9r)-4-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-1-oxa-4-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(1r,3r)-3-[8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)46iridin46e-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octane-3-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]46iridin-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[(2S)-4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]morpholine-2-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[7-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-7-azaspiro[3.5]nonane-2-yl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5r,8r)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-2-azaspiro[4.5]decane-8-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[(2S)-4-[[7-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-7-azaspiro[3.5]nonane-2-yl]methyl]morpholin-2-yl]methyl]3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,8-dihydro-5H-imidazo[1,2-a]pyrazine-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[(2R)-4-[[7-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-7-azaspiro[3.5]nonane-2-yl]methyl]morpholin-2-yl]methyl]3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[rel-(3aR,5r * ,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 1)[ * [Absolute placement has not yet been confirmed] 1-[3-methyl-1-[7-[[(3aR,5s,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[(3aR,5r,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[rel-(3aR,5r * ,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]- 3,3a,4,5,6,6a-Hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3,5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 2)[ * [Absolute placement has not yet been confirmed] 1-[3-methyl-1-[7-[[(3aR,5s,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[(3aR,5r,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[6-fluoro-1-[rel-(3R * )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione (isomer 1)[ * [Absolute placement has not yet been confirmed] 1-[6-fluoro-1-[(3R)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[6-fluoro-1-[(3S)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[6-fluoro-1-[rel-(3R * )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione (isomer 2)[ * [Absolute placement has not yet been confirmed] 1-[6-fluoro-1-[(3R)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[6-fluoro-1-[(3S)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-cyclopropyl-1-[rel-(3R * )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 2)[ * [Absolute placement has not yet been confirmed] 1-[3-cyclopropyl-1-[(3R)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-cyclopropyl-1-[(3S)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-6-fluoropyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-cyclopropyl-1-[rel-(3R * )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 1)[ * [Absolute placement has not yet been confirmed] 1-[3-cyclopropyl-1-[(3R)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-cyclopropyl-1-[(3S)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-[[9-[5-(2,4-dioxohexahydropyrimidine-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridine-1-yl]-3-azaspiro[5.5]undecane-3-yl]methyl]-4-fluoro-1-piperidyl]benzonitrile, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[3-[[rel-(4R * )-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 2)[ * [Absolute placement has not yet been confirmed] 1-[3-methyl-1-[3-[[(4R)-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[3-[[(4S)-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-[[9-[5-(2,4-dioxohexahydropyrimidine-1-yl)-3-methyl-pyrrolo[2,3-b]pyridine-1-yl]-3-azaspiro[5.5]undecane-3-yl]methyl]-4-fluoro-1-piperidyl]benzonitrile, 1-[3-methyl-1-[3-[[rel-(4R * )-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 1)[ * [Absolute placement has not yet been confirmed] 1-[3-methyl-1-[3-[[(4R)-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[3-[[(4S)-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-4-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-4-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-6-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[rel-(3S * )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 2)[ * [Absolute placement has not yet been confirmed] 1-[3-methyl-1-[(3S)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[(3R)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[rel-(3R * )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 1)[ * [Absolute placement has not yet been confirmed] 1-[3-methyl-1-[(3S)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[(3R)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5r,8r)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[rel-(3S * )-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 1)[ * [Absolute placement has not yet been confirmed] 1-[3-methyl-1-[(3S)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[(3R)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[rel-(3R * )-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 2)[ * [Absolute placement has not yet been confirmed] 1-[3-methyl-1-[(3S)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[(3R)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5r,8r)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]piperazin-1-yl]methyl]spiro[5.5]undecane-3-yl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(3s,6s)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(3r,6r)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[4-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]piperazin-1-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-[[9-[5-(2,4-dioxohexahydropyrimidine-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridine-1-yl]-3-azaspiro[5.5]undecane-3-yl]methyl]-1-piperidyl]benzonitrile, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-[[2-[3-cyclopropyl-5-(2,4-dioxohexahydropyrimidine-1-yl)pyrrolo[2,3-b]pyridine-1-yl]-7-azaspiro[3.5]nonane-7-yl]methyl]-1-piperidyl]benzonitrile, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[(1R,5S,6s)-3-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3-azabicyclo[3.1.0]hexane-6-yl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[(1R,5S,6s)-3-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3-azabicyclo[3.1.0]hexane-6-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(1s,3s)-3-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octane-8-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[(2R)-4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]morpholine-2-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-6-fluoro-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-azabicyclo[3.2.1]octan-8-yl]-2-chlorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[8-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[1,2-a]pyrimidine-3-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(2S)-6-[[4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]piperazin-1-yl]methyl]tetralin-2-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(2R)-6-[[4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]piperazin-1-yl]methyl]tetralin-2-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(2S)-6-[[4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]piperazin-1-yl]methyl]tetralin-2-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(2R)-6-[[4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]piperazin-1-yl]methyl]tetralin-2-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[(1s,4s)-4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]cyclohexyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[(1r,4r)-4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]cyclohexyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(3r,6r)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(1r,4r)-4-[8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octane-3-yl]cyclohexyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(1s,4s)-4-[8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octane-3-yl]cyclohexyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(1r,3r)-3-[8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octane-3-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(3,5-difluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(3-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]piperidine-4-carbonyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-[[3-[3-cyclopropyl-5-(2,4-dioxohexahydropyrimidine-1-yl)pyrrolo[2,3-b]pyridine-1-yl]-1,5-dioxa-9-azaspiro[5.5]undecane-9-yl]methyl]-1-piperidyl]benzonitrile, 1-[1-[3-[[1-[5-[3-[3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-4-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(3-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(3-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(3,5-difluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(3,5-difluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(3-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(3,5-difluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenoxy]ethyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenoxy]ethyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[[1-[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenoxy]ethyl]-4-fluoro-4-piperidyl]methyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(3S)-1-[[1-[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenoxy]ethyl]-4-fluoro-4-piperidyl]methyl]pyrrolidine-3-yl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(3R)-1-[[1-[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenoxy]ethyl]-4-fluoro-4-piperidyl]methyl]pyrrolidine-3-yl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenoxy]ethyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-azabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-ethyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[rac-(2S,3aR,6aR)-5-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-2,3,3a,4,6,6a-hexahydrofluoro[2,3-c]pyrrole-2-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[rac-(2S,3aR,6aR)-5-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-2,3,3a,4,6,6a-hexahydrofluoro[2,3-c]pyrrole-2-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(3-chloro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxy-3-methylphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(3-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(3,5-difluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[(3S)-4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-methyl-piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[(3S)-4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-methyl-piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-hydroxy-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(3-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(3,5-difluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-6-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[2-[4-[2-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenoxy]ethyl]piperazin-1-yl]ethyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[2-[4-[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenoxy]ethyl]piperazin-1-yl]ethyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-4-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]indole-4-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-hydroxy-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[4-[[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]methyl]piperazine-1-carbonyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[4-[[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]methyl]piperazine-1-carbonyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[3-[4-[[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]methyl]piperazin-1-yl]-3-oxopropyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[3-[4-[[3-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]methyl]piperazin-1-yl]-3-oxopropyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, or a pharmaceutically acceptable salt thereof.

[0225] In another embodiment, the compounds of the present disclosure are any one or more compounds from Compound List 1, Compound List 2, Compound List 3, Compound List 4, and / or Compound List 5, or pharmaceutically acceptable salts thereof.

[0226] In another embodiment, the compounds of the present disclosure are

[0227] [ka] or a pharmaceutically acceptable salt thereof.

[0228] In another embodiment, the compounds of the present disclosure are

[0229] [ka] or a pharmaceutically acceptable salt thereof.

[0230] In another embodiment, the compounds of the present disclosure are

[0231] [ka] or a pharmaceutically acceptable salt thereof.

[0232] In another embodiment, the compounds of the present disclosure are

[0233] [ka] or a pharmaceutically acceptable salt thereof.

[0234] In another embodiment, the compounds of the present disclosure are

[0235] [ka] or a pharmaceutically acceptable salt thereof.

[0236] In another embodiment, the compounds of the present disclosure are

[0237] [ka] or a pharmaceutically acceptable salt thereof.

[0238] In another embodiment, the compounds of the present disclosure are

[0239] [ka] or a pharmaceutically acceptable salt thereof.

[0240] In another embodiment, the compounds of the present disclosure are

[0241] [ka] or a pharmaceutically acceptable salt thereof.

[0242] In another embodiment, the compounds of the present disclosure are

[0243] [ka] or a pharmaceutically acceptable salt thereof.

[0244] In another embodiment, the compounds of the present disclosure are

[0245] [ka] or a pharmaceutically acceptable salt thereof.

[0246] In another embodiment, the compounds of the present disclosure are

[0247] [ka] or a pharmaceutically acceptable salt thereof.

[0248] In another embodiment, the compounds of the present disclosure are

[0249] [ka] or a pharmaceutically acceptable salt thereof.

[0250] In another embodiment, the compounds of the present disclosure are

[0251] [ka] or a pharmaceutically acceptable salt thereof.

[0252] In another embodiment, the compounds of the present disclosure are

[0253] [ka] or a pharmaceutically acceptable salt thereof.

[0254] In another embodiment, the compounds of the present disclosure are

[0255] [ka] or a pharmaceutically acceptable salt thereof.

[0256] In another embodiment, the compounds of the present disclosure are

[0257] [ka] or a pharmaceutically acceptable salt thereof.

[0258] In another embodiment, the Disclosure provides a pharmaceutical composition comprising a compound of the Disclosure and one or more pharmaceutically acceptable excipients.

[0259] The compounds of this disclosure may have one or more chiral centers, and it is recognized that such compounds may be prepared, isolated, and / or supplied with or without the presence of one or more other possible enantiomers and / or diastereomer isomers of the compound, or that such isomers may be supplied in any relative proportion. The preparation of enantioenriched or enantiopurine and / or diastereoenriched or diastereopurine compounds may be carried out by standard techniques of organic chemistry well known in the art, for example, by synthesis from enantioenriched or enantiopurine starting materials and / or by using appropriately enantioenriched or enantiopurine catalysts during synthesis and / or by splitting racemic or partially enriched mixtures of stereoisomers, for example, via chiral chromatography. The scope of this disclosure includes mixtures of stereoisomers, as well as purified enantiomers or enantiomerically / diastereomerically enriched mixtures. It should be understood that this disclosure includes all combinations and subsets of the specific groups defined above.

[0260] In one embodiment, the Disclosure provides a composition comprising the compound of the Disclosure, optionally together with one or more other stereoisomers of the compound, if present, in the composition, wherein the compound of the Disclosure is present in the composition at a diastereomer excess of ≥55% (%de).

[0261] In another embodiment, %de in the above-described composition is ≥90%.

[0262] In another embodiment, %de in the above-described composition is ≥95%.

[0263] In another embodiment, %de in the above-described composition is ≥98%.

[0264] In another embodiment, %de in the above-described composition is ≥99%.

[0265] In another embodiment, the Disclosure provides a composition comprising the compound of the Disclosure, if present, optionally together with one or more other stereoisomers of the compound, the compound of the Disclosure present in the composition at an enantiomer excess of ≥55% (%ee).

[0266] In another embodiment, %ee in the above-described composition is ≥90%.

[0267] In another embodiment, %ee in the above-described composition is ≥95%.

[0268] In another embodiment, %ee in the above-described composition is ≥98%.

[0269] In another embodiment, %ee in the above-described composition is ≥99%.

[0270] In another embodiment, the Disclosure provides a composition comprising the compound of the Disclosure, if present, optionally together with one or more other stereoisomers of the compound, the compound of the Disclosure present in the composition with an enantiomer excess of ≥90% (%ee) and a diastereomer excess of ≥90% (%de).

[0271] In another embodiment, the Disclosure provides, optionally, a composition comprising the compound of the Disclosure together with one or more other stereoisomers of the compound, where %ee and %de of the compound of the Disclosure take any combination of values, for example, %ee is ≤5% and %de is ≥80%, %ee is ≤5% and %de is ≥90%, %ee is ≤5% and %de is ≥95%, %ee is ≤5% and %de is ≥98%, %ee is ≥95% and %de is ≥95%, %ee is ≥98% and %de is ≥98%, or %ee is ≥99% and %de is ≥99%.

[0272] The compounds of this disclosure may be prepared, used, or supplied in amorphous, crystalline, or semicrystalline form, and any given compound of this disclosure may be formed into more than one crystalline / polymorphic form, including hydrated forms, e.g., hemihydrate, monohydrate, dihydrate, trihydrate, or other stoichiometric forms of hydrate, and / or solvated forms. This disclosure encompasses all such solid forms of the compounds of this disclosure.

[0273] This disclosure encompasses the preparation and use of salts of the compounds herein. Pharmaceutically acceptable salts include, in particular, those described in Berge, J. Pharm. Sci., 66, 1-19, (1977), or those listed in PHStahl and CGWermuth, editors, Handbook of Pharmaceutical Salts; Properties, Selection and Use, Second Edition Stahl / Wermuth: Wiley-VCH / VHCA (2011) (see http: / / www.wiley.com / WileyCDA / WileyTitle / productCd-3906390519.html).

[0274] Suitable pharmaceutically acceptable salts may include acid or base addition salts.

[0275] Such base addition salts can be formed by the reaction of the compound of this disclosure with a suitable base in a suitable solvent, optionally such as an organic solvent, and the resulting salts can be isolated by various methods, including crystallization and filtration.

[0276] Such acid addition salts can be formed by the reaction of the compound of this disclosure with a suitable acid in a suitable solvent, optionally such as an organic solvent, and the resulting salts can be isolated by various methods, including crystallization and filtration.

[0277] Salts can be prepared in situ during the final isolation and purification of the compounds of the present disclosure. If a basic compound of the compounds of the present disclosure is isolated as a salt, the corresponding free base form of the compound can be prepared by any suitable method known in the art, including treatment of the salt with an inorganic or organic base. Similarly, if a compound of the present disclosure containing a carboxylic acid or other acidic functional group is isolated as a salt, the corresponding free acid form of the compound can be prepared by any suitable method known in the art, including treatment of the salt with an inorganic or organic acid.

[0278] If the compounds of this disclosure contain two or more basic moieties, it is understood that the stoichiometry of salt formation may include one, two, or more equivalent amounts of acid. Such salts may contain one, two, or more acid counterions, for example, dihydrochloride salts.

[0279] The stoichiometric and non-stoichiometric forms of pharmaceutically acceptable salts of the compounds of this disclosure are included within the scope of this specification, for example, including quasi-stoichiometric salts in which the counterion contains two or more acidic protons.

[0280] Representative pharmaceutically acceptable acid addition salts include 4-acetamidebenzoate, acetate, adipine, alginate, ascorbate, aspartate, benzenesulfonate (besilate), benzoate, bisulfate, tartrate, butyrate, calcium edetate, camphorate, camphor sulfonate (cansilate), caprine (decanoate), caproate (hexanoate), caprylate (octanoate), cinnamate, citrate, cyclamate, digluconate, 2,5-dihydroxybenzoate, disuccinate, dodecyl sulfate (estolate), edetate (ethylenediaminetetraacetate), estolate (lauryl sulfate), ethane-1,2-disulfonate (edisylate), and ethane. Sulfonate (esylate), formate, fumarate, galactarate (mucinate), gentisinate (2,5-dihydroxybenzoate), glucoheptonate (gluceptate), gluconate, glucuronate, glutamate, glutarate, glycerophosphate, glycolate, hexylresorcinate, hippurate, hydravamin (N,N'-di(dehydroabiethyl)ethylenediamine), hydrobromide, hydrochloride, hydroiodide, hydroxynaphthoate, isobutyrate, lactate, lactobionate, laurate, malate, maleate, malonate, mandelate, methanesulfonate (mesylate), methylsulfate, mucinate, naphthalene-1,Examples include, but are not limited to, 5-disulfonates (napadisylates), naphthalene-2-sulfonates (napsylates), nicotinates, nitrates, oleates, palmitates, p-aminobenzenesulfonates, p-aminosalicylates, pamoates (embonates), pantothenates, pectinates, persulfates, phenylacetates, phenylethylbarbiturates, phosphates, polygalacturonates, propionates, p-toluenesulfonates (tosylates), pyroglutamates, pyruvates, salicylates, sebacinates, stearates, basic acetates, succinates, sulfamates, sulfates, tannates, tartrates, theoclates (8-chlorotheophylline), thiocyansates, triethiodides, undecanoates, undecylenates, and valersates.

[0281] Typical pharmaceutically acceptable base addition salts include aluminum, 2-amino-2-(hydroxymethyl)-1,3-propanediol (TRIS), arginine, benetamine (N-benzylphenethylamine), benzathine (N,N'-dibenzylethylenediamine), bis-(2-hydroxyethyl)amine, bismuth, calcium, chloroprocaine, choline, cremisole (1-p-chlorobenzyl-2-pyrrolildine-1'-ylmethylbenzimidazole), cyclohexylamine, and di Examples include, but are not limited to, benzylethylenediamine, diethylamine, diethyltriamine, dimethylamine, dimethylethanolamine, dopamine, ethanolamine, ethylenediamine, L-histidine, iron, isoquinoline, lepidine, lithium, lysine, magnesium, meglumine (N-methylglucamine), piperazine, piperidine, potassium, procaine, kinin, quinoline, sodium, strontium, t-butylamine, tromethamine (tris(hydroxymethyl)aminomethane), and zinc.

[0282] The Disclosure also includes isotope-labeled compounds, which are identical to the compounds of the Disclosure except that one or more atoms are replaced by atoms having atomic masses or mass numbers different from those commonly found in nature. Examples of isotopes that may be incorporated into the compounds of the Disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, for example, 2 H, 3 H, 11 C, 13 C, 14 C, 15 N, 17 O, 18 O, 31 P, 32 P, 35 S, 18 F, 36 Cl, 123 I, and 125 I is one example.

[0283] Compounds of the Disclosure containing the aforementioned isotopes and / or other isotopes of other atoms are within the scope of the Disclosure. Examples of isotope-labeled compounds of the Disclosure include, 3 H, 14 Those incorporating radioactive isotopes such as 13C are useful in drug and / or substrate tissue distribution assays. Tritiated, i.e. 3 H, and carbon-14, i.e. 14 13C isotopes are particularly used due to their ease of preparation and detectability. 11 C and 18 The 15F isotope is particularly useful in PET (positron emission tomography). 125 I isotopes are particularly useful in SPECT (single-photon emission computerized tomography), and all are useful in brain imaging. Furthermore, deuterium, i.e. 2Substitution with heavier isotopes, such as 1H, can yield certain therapeutic benefits resulting from greater metabolic stability, e.g., increased in vivo half-life or reduced dose required, and may therefore be used in certain situations. The isotope-labeled compounds of this disclosure can generally be prepared by performing the procedures disclosed in the following schemes and / or examples, by using readily available isotope-labeling reagents in place of non-isotope-labeling reagents.

[0284] In another embodiment, the Disclosure provides a pharmaceutical composition comprising the compounds of the Disclosure and one or more excipients (also known in the pharmaceutical field as carriers and / or diluents). The excipients are compatible with the other components of the formulation and are acceptable in the sense that they are not harmful to its recipient, i.e., the patient.

[0285] II.How to use SMARCA4 mutations are known to be present in certain tumor / cancer types, including tumors / cancers of the lung, liver, colon, skin, bladder, cervix, and ovaries, and SMARCA2 is known to be essential for the growth of tumors containing such SMARCA4 mutations. Therefore, the compounds of this disclosure may be valuable as anticancer / antitemocyte agents, particularly against cancer / cancer types known to have SMARCA4 mutations, such as lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, and ovarian cancer.

[0286] The compounds of this disclosure may also be valuable against cancer types / tumors that are sensitive to SMARCA2 degradation, such as lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, and ovarian cancer.

[0287] The compounds of this disclosure may also have value as antitumor agents, particularly as selective inhibitors of the proliferation, survival, motility, dissemination, and invasiveness of mammalian cancer cells, resulting in inhibition of tumor growth and survival, as well as inhibition of metastatic tumor growth. In particular, the compounds of this disclosure may have value as antiproliferative and anti-invasive agents in the suppression and / or treatment of solid tumor diseases.

[0288] The compounds of this disclosure are also sensitive to the degradation of SMARCA2 and may be useful in the prevention or treatment of tumors involved in signaling steps that result in the proliferation and survival of tumor cells, as well as the migratory ability and invasiveness of metastatic tumor cells. Furthermore, the compounds of this disclosure may be useful in the prevention or treatment of tumors mediated alone or partially by the degradation of SMARCA2; that is, the compounds may be used to produce a SMARCA2 degradation effect in subjects requiring such treatment, such as warm-blooded animals, such as humans.

[0289] In one embodiment, the Disclosure provides a compound of the Disclosure or a pharmaceutical composition thereof for use in the treatment of cancer.

[0290] In another embodiment, the present disclosure provides a compound of the present disclosure or a pharmaceutical composition thereof for use in the treatment of solid tumors.

[0291] In another embodiment, the present disclosure provides a compound of the present disclosure or a pharmaceutical composition thereof for use in the treatment of SMARCA2-sensitive tumor types.

[0292] In another embodiment, the present disclosure provides a compound of the present disclosure or a pharmaceutical composition thereof for use in the treatment of tumor types having SMARCA4 mutations.

[0293] In another embodiment, the Disclosure provides compounds of the Disclosure or pharmaceutical compositions thereof for use in the treatment of lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer.

[0294] In another embodiment, the present disclosure provides a compound of the present disclosure or a pharmaceutical composition thereof for use in the treatment of SMARCA4 mutation cancer.

[0295] The amount of the compound of this disclosure, combined with one or more excipients to produce a single dosage form, will inevitably vary depending on the target being treated and the specific route of administration.

[0296] The size of the doses of the compounds disclosed herein for therapeutic or prophylactic purposes will naturally vary according to well-known medical principles, depending on the nature and severity of the disease condition, the age and sex of the animal or patient, and the route of administration.

[0297] In another embodiment, the present disclosure provides a compound of the present disclosure or a pharmaceutical composition thereof for use as a pharmaceutical.

[0298] In another embodiment, the Disclosure provides a compound of the Disclosure or a pharmaceutical composition thereof for use in therapeutic use.

[0299] In another embodiment, the present disclosure provides compounds of the present disclosure or pharmaceutical compositions thereof for use in methods of treating the body of a human or animal by therapeutic means.

[0300] In another embodiment, the Disclosure provides compounds of the Disclosure or pharmaceutical compositions thereof for use in generating antiproliferative effects in warm-blooded animals such as humans, for example.

[0301] In another embodiment, the Disclosure provides the use of the compounds of the Disclosure or a pharmaceutical composition thereof for the manufacture of a pharmaceutical for producing an antiproliferative effect in warm-blooded animals such as humans.

[0302] In another embodiment, the Disclosure provides a method for producing an antiproliferative effect in a warm-blooded animal such as a human requiring an antiproliferative effect, the method comprising administering an effective amount of the compound or pharmaceutical composition thereof to the animal.

[0303] In another embodiment, the Disclosure provides compounds of the Disclosure or pharmaceutical compositions thereof for use as anti-invasive agents in the containment and / or treatment of solid tumor diseases in warm-blooded animals such as humans.

[0304] In another embodiment, the Disclosure provides the use of the compounds of the Disclosure or a pharmaceutical composition thereof for the manufacture of a pharmaceutical for use as an anti-invasive agent in the containment and / or treatment of solid tumor diseases in warm-blooded animals such as humans.

[0305] In another embodiment, the Disclosure provides a method for producing an anti-invasive effect in a warm-blooded animal such as a human requiring an anti-invasive effect by containing and / or treating a solid tumor disease, the method comprising administering an effective amount of the compound of the Disclosure or a pharmaceutical composition thereof to the animal.

[0306] In another embodiment, the Disclosure provides compounds of the Disclosure or pharmaceutical compositions thereof for use, for example, in the prevention or treatment of cancer in warm-blooded animals such as humans.

[0307] In another embodiment, the Disclosure provides the use of the compounds of the Disclosure or a pharmaceutical composition thereof for, for example, the manufacture of a pharmaceutical for the prevention or treatment of cancer in warm-blooded animals such as humans.

[0308] In another embodiment, the Disclosure provides a method for the prevention or treatment of cancer in a warm-blooded animal, such as a human, that requires treatment for cancer, the method comprising administering an effective amount of the compound of the Disclosure or a pharmaceutical composition thereof to the animal.

[0309] In another embodiment, the Disclosure provides compounds of the Disclosure or pharmaceutical compositions thereof for use, for example, in the prevention or treatment of solid tumors in warm-blooded animals such as humans.

[0310] In another embodiment, the Disclosure provides the use of the compounds of the Disclosure or a pharmaceutical composition thereof for the manufacture of a pharmaceutical for the prevention or treatment of solid tumors in warm-blooded animals such as humans.

[0311] In another embodiment, the present disclosure provides a method for the prevention or treatment of solid tumors in warm-blooded animals such as humans that require treatment of solid tumors, the method comprising administering an effective amount of the compound of the present disclosure or a pharmaceutical composition thereof to the animal.

[0312] In another embodiment, the present disclosure provides compounds of the present disclosure or pharmaceutical compositions thereof for use in the prevention or treatment of tumor types sensitive to the degradation of SMARCA2.

[0313] In another embodiment, the Disclosure provides the use of the compounds of the Disclosure or a pharmaceutical composition thereof for the manufacture of a pharmacopoeia for the prevention or treatment of tumor types sensitive to the degradation of SMARCA2.

[0314] In another embodiment, the Disclosure provides a method for the prevention or treatment of SMARCA2-sensitive tumors in warm-blooded animals such as humans that require treatment of SMARCA2-sensitive tumors, comprising administering an effective amount of the compound of the Disclosure or a pharmaceutical composition thereof to the animal. Examples of SMARCA2-sensitive tumors include lung tumors, liver tumors, colon tumors, skin tumors, bladder tumors, cervical tumors, and ovarian tumors.

[0315] In another embodiment, the Disclosure provides compounds or pharmaceutical compositions thereof for use in providing a degrading effect on SMARCA2 in warm-blooded animals, such as humans.

[0316] In another embodiment, the Disclosure provides the use of the compounds of the Disclosure or a pharmaceutical composition thereof for the manufacture of a pharmaceutical to provide a degradative effect on SMARCA2 in a warm-blooded animal, such as a human.

[0317] In another embodiment, the Disclosure provides a method for providing a degrading effect on SMARCA2 in a warm-blooded animal such as a human that requires a degrading effect on SMARCA2, the method comprising administering an effective amount of the compound of the Disclosure or a pharmaceutical composition thereof to the animal.

[0318] In another embodiment, the Disclosure provides a compound or pharmaceutical composition thereof for use in providing a selective degradation effect on SMARCA2 in a warm-blooded animal, such as a human.

[0319] In another embodiment, the Disclosure provides the use of the compounds of the Disclosure or a pharmaceutical composition thereof for the manufacture of a pharmaceutical to provide a selective degrading effect on SMARCA2 in a warm-blooded animal, such as a human.

[0320] In another embodiment, the Disclosure provides a method for providing a selective degradation effect on SMARCA2 in a warm-blooded animal such as a human requiring a selective degradation effect on SMARCA2, the method comprising administering an effective amount of the compound or a pharmaceutical composition thereof of the Disclosure. SMARCA2 has been found to be essential for the growth of tumors containing SMARCA4 mutations, and certain tumor / cancer types are associated with such SMARCA4 mutations.

[0321] In another embodiment, the present disclosure provides a compound of the present disclosure or a pharmaceutical composition thereof for use in the treatment of tumor types having SMARCA4 mutations.

[0322] In another embodiment, the present disclosure provides the use of the compounds of the present disclosure or a pharmaceutical composition thereof for the manufacture of a pharmacopoeia for the prevention or treatment of tumor types having SMARCA4 mutations.

[0323] In another embodiment, the Disclosure provides a method for the prevention or treatment of a SMARCA4 mutation-containing tumor in a warm-blooded animal, such as a human, that requires the prevention or treatment of a SMARCA4 mutation-containing tumor, comprising administering an effective amount of the compound of the Disclosure or a pharmaceutical composition thereof to the animal. Tumor types known to have SMARCA4 mutations include lung tumors, liver tumors, colon tumors, skin tumors, bladder tumors, cervical tumors and ovarian tumors, for example, lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer and ovarian cancer.

[0324] In another embodiment, the Disclosure provides compounds of the Disclosure or pharmaceutical compositions thereof for use in the treatment of lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer.

[0325] In another embodiment, the Disclosure provides the use of the compounds of the Disclosure or a pharmaceutical composition thereof for the manufacture of a medicament for the treatment of lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer.

[0326] In another embodiment, the Disclosure provides a method for treating lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer in a warm-blooded animal such as a human requiring treatment for lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer, the method comprising administering an effective amount of the compound of the Disclosure or a pharmaceutical composition thereof to the animal.

[0327] In another embodiment in which cancer is referred to herein, cancer is lung cancer.

[0328] In another embodiment in which cancer is referred to herein, cancer is liver cancer.

[0329] In another embodiment in which cancer is referred to herein, cancer is colon cancer.

[0330] In another embodiment in which cancer is referred to herein, cancer is skin cancer.

[0331] In another embodiment in which cancer is referred to herein, cancer is bladder cancer.

[0332] In another embodiment in which cancer is referred to herein, cancer is cervical cancer.

[0333] In another embodiment in which cancer is referred to herein, cancer is ovarian cancer.

[0334] In another embodiment, the present disclosure provides a compound of the present disclosure or a pharmaceutical composition thereof for use in the treatment of SMARCA4 mutation cancer.

[0335] In another embodiment, the Disclosure provides the use of the compounds of the Disclosure or a pharmaceutical composition thereof for the manufacture of a pharmaceutical for the treatment of SMARCA4 mutation cancer.

[0336] In another embodiment, the Disclosure provides a method for treating SMARCA4-mutated cancer in a warm-blooded animal, such as a human, that requires treatment for SMARCA4-mutated cancer, the method comprising administering an effective amount of the compound or pharmaceutical composition thereof of the Disclosure.

[0337] III. Definition As used herein, the term “alkyl” refers to a saturated, linear, or branched hydrocarbon moiety having a specific number of carbon atoms. The term “(C1-C6)alkyl” refers to an alkyl moiety containing 1 to 6 carbon atoms. Exemplary alkyls include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, pentyl, and hexyl.

[0338] As used herein, the term "alkylenyl" refers to the divalent form of an alkyl group having a specified number of carbon atoms, either by itself or as part of another group. For example, the term "(C1-C6)alkylenyl" refers to an alkylenyl moiety containing 1 to 6 carbon atoms. Alkyrenyls can be optionally substituted with 1, 2, or 3 substituents independently selected from halogens, cyanos, and (C1-C6)alkoxys. Exemplary alkylenyl groups include, but are not limited to, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2(CH2)2CH2-, and -CH2(CH2)3CH2-.

[0339] "Alkoxy" refers to a group containing an alkyl radical as defined above, bonded via an oxygen-linked atom. The term "(C1-C6) alkoxy" refers to a linear or branched hydrocarbon radical having at least one and up to six carbon atoms bonded via an oxygen-linked atom. Useful examples of "(C1-C6) alkoxy" groups used herein include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, s-butoxy, isobutoxy, and t-butoxy.

[0340] As used herein, the term "cycloalkylenyl" refers to the divalent form of a cycloalkyl group having a specified number of carbon atoms in the ring, either by itself or as part of another group. For example, the term "(C3-C6)cycloalkylenyl" refers to the alkylenyl moiety containing 3 to 6 carbon atoms in the ring. Cycloalkylenyls may be optionally substituted with 1, 2, or 3 substituents independently selected from halogens, (C1-C6)alkyl, cyano, and (C1-C6)alkoxy groups. Exemplary cycloalkylenyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexy:

[0341] [ka] These include, but are not limited to, the following:

[0342] As used herein, the term "heterocycloalkyl" refers to a group or part comprising, either by itself or as part of another group, a saturated or partially unsaturated non-aromatic, monovalent, monocyclic, bicyclic, or spirocyclic radical having 4 to 11 ring atoms, each comprising carbon and one or two heteroatoms independently selected from oxygen, sulfur, and / or nitrogen.

[0343] As used herein, the term “4-6 membered heterocycloalkylenyl” refers to a divalent form of a monocyclic or bicyclic heterocycloalkyl having 4, 5, or 6 ring atoms, comprising carbon and one or two heteroatoms independently selected from oxygen, sulfur, and / or nitrogen, either by itself or as part of another group. A 4-6 membered heterocycloalkylenyl may be optionally substituted with 1, 2, or 3 substituents independently selected from halogens, (C1-C6)alkyl, cyano, or (C1-C6)alkoxy. In one embodiment, the 4-6 membered heterocycloalkylenyl is a divalent form of optionally substituted azetidine. In another embodiment, the 4-6 membered heterocycloalkyleny is a divalent form of optionally substituted piperidinyl. In yet another embodiment, the heterocycloalkyleny is a divalent form of optionally substituted piperazinyl. Exemplary heterocycloalkylenyl groups include:

[0344] [ka] These include, but are not limited to, the following:

[0345] As used herein, the term "7-11 membered heterocycloalkylenyl" refers to a divalent form of a bicyclic (including bridging bicyclic), fused, or spirocyclic heterocycloalkyl group having 7, 8, 9, 10, or 11 ring atoms, comprising carbon and 1, 2, or 3 heteroatoms independently selected from oxygen, sulfur, and / or nitrogen, either by itself or as part of another group. Examples of 7-11 membered heterocycloalkyl groups include:

[0346] [ka] These include, but are not limited to, the following:

[0347] The term "aryl" refers to an optionally substituted monocyclic, fused bicyclic, or fused tricyclic group having 6 to 14 carbon atoms and at least one aromatic ring that obeys Hückel's rule. Examples of "aryl" groups include phenyl, naphthyl, indenyl, dihydroindenyl, anthracenyl, and phenantrenyl.

[0348] "Heteroaryl" refers to a group or moiety containing an aromatic monovalent monocyclic or bicyclic radical containing 5 to 10 ring atoms, each containing 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. This term also includes bicyclic heterocyclic aryl compounds containing an aryl ring moiety fused to a heterocycloalkyl ring moiety, each containing 5 to 10 ring atoms, each containing 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or bicyclic heterocyclic heteroaryl compounds containing a heteroaryl ring moiety fused to a heterocycloalkyl ring moiety, each containing 5 to 10 ring atoms, each containing 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Examples of heteroaryls useful in this specification include, but are not limited to, furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridinyl, pyridadinyl, pyrazinyl, pyrimidinyl, triazinyl, benzofuranyl, isobenzofuryl, 2,3-dihydrobenzofuryl, 1,3-benzodioxolyl, dihydrobenzodioxynyl, benzothienyl, indolidine, indolyl, isoindolyl, dihydroindolyl, and benzoyl Examples include midazolyl, dihydrobenzimidazolyl, benzoxazolyl, dihydrobenzoxazolyl, benzothiazolyl, benzoisothiazolyl, dihydrobenziisothiazolyl, indazolyl, imidazopyridinyl, pyrazolopyridinyl, benzotriazolyl, triazolopyridinyl, purinyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, quinoxalinyl, sinnolinyl, phthalazinyl, quinazolinyl, 1,5-naphthilidinyl, 1,6-naphthilidinyl, 1,7-naphthilidinyl, 1,8-naphthilidinyl, and pteridinyl. Examples of five-membered heteroaryl groups include furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, and isothiazolyl. Examples of six-membered heteroaryl groups include oxopyridyl, pyridinyl, pyridadinyl, pyrazinyl, and pyrimidinyl.Examples of 6,6-condensed heteroaryl groups include quinolinyl, isoquinolinyl, quinoxalinyl, synnolinyl, phthalazinyl, quinazolinyl, 1,5-naphthilidinyl, 1,6-naphthilidinyl, 1,7-naphthilidinyl, 1,8-naphthilidinyl, and pteridinyl. Examples of 6,5-condensed heteroaryl groups include benzofuranyl, benzothienyl, benzimidazolyl, benzothiazolyl, indolidinyl, indolyl, isoindolyl, and indazolyl.

[0349] As used herein, the term “5-10 membered heteroarylenyl” refers to the divalent form of a “heteroaryl” group, either by itself or as part of another group. Examples of “5-10 membered heteroarylenyl” groups include:

[0350] [ka] These are some examples.

[0351] As used herein, “5-membered or 6-membered heteroaryl” refers to a group or part containing an aromatic monovalent monocyclic radical comprising five or six ring atoms, each comprising at least one carbon atom and one to four heteroatoms independently selected from nitrogen, oxygen, and sulfur. A selected 5-membered heteroaryl group contains one nitrogen, oxygen, or sulfur ring heteroatom and optionally contains one, two, or three additional nitrogen ring atoms. A selected 6-membered heteroaryl group contains one, two, or three nitrogen ring heteroatoms. Exemplary examples of 5-membered or 6-membered heteroaryl groups useful herein include, but are not limited to, furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyridadinyl, pyrazinyl, pyrimidinyl, and triazinyl.

[0352] The terms "halogen" and "halo" refer to fluoro, chloro, bromo, or iodo substituents.

[0353] As used herein, "hydroxy" refers to the radical -OH, either by itself or as part of a group.

[0354] As used herein, the term "cyano" refers to the radical-CN, either by itself or as part of a group.

[0355] As used herein, the term "optionally" means that the events described thereafter may or may not occur, and includes both events that occur and events that do not occur. Thus, the use of the term "optionally" includes cases where a feature is present and cases where a feature is not present. For example, "methyl optionally substituted with one or more Fs" includes -CH3, -CH2F, -CHF2, and -CF3.

[0356] In this disclosure, a group such as "ABC" where B is defined as a "direct bond" is equivalent to "AC," that is, A and C are directly linked to each other by a covalent bond.

[0357] The term "substituted" means that one or more hydrogen atoms on a given atom or group are replaced by the indicated substituent. However, any atom having such substituents retains its permissible valency, and it is assumed that those skilled in the art understand that the standard valencies of carbon, nitrogen, and oxygen are 4, 3, and 2, respectively.

[0358] "Pharmacologically acceptable" means a compound (including salts), material, composition, and / or dosage form that is suitable for use in contact with human and animal tissues without excessive toxicity, irritation, or other problems or complications, within reasonable limits of medical judgment, and that has a reasonable benefit-risk ratio.

[0359] As used herein, the term “treatment” means alleviating a particular condition, eliminating or reducing one or more symptoms of a condition, slowing or eliminating the progression of a condition, and delaying the recurrence of a condition in a patient or subject who has previously been affected or diagnosed with the condition.

[0360] The term "effective dose" refers to the amount of a drug or pharmaceutical product that elicits a biological or medical response in a tissue, system, animal, or human, as determined, for example, by a researcher or clinician.

[0361] The term “therapeutic dose” means any amount that results in improved treatment, cure, or remission of a disease, disorder, or side effect, or a reduction in the rate of progression of the disease or disorder, compared to a corresponding subject that has not received such an amount. The term also includes, within its scope, amounts effective in enhancing normal physiological function. For use in therapy, a therapeutic dose of the compounds of this disclosure may be administered as raw chemicals. Furthermore, the active ingredients may be provided as pharmaceutical compositions.

[0362] The compounds of this disclosure may have chiral centers and thus may result in enantiomers, diastereomers, and other stereoisomeric forms. This disclosure encompasses all such possible stereoisomeric forms, as well as their racemic and divided forms, and the preparation and use of mixtures thereof. Enantiomers and diastereomers may be separated according to methods known in the art in consideration of this disclosure. Where the compounds described herein contain olefinic double bonds or other geometrically asymmetric centers, they are intended to include both E and Z geometric isomers unless otherwise specified. All tautomers are also encompassed by this disclosure.

[0363] As used herein, the term “stereoisomer” is a general term for all isomers of individual molecules that differ only in the orientation of their atoms in space. The term “stereoisomer” includes enantiomers, atropisomers, and diastereomers (isomers of compounds having more than one chiral center that are not mirror images of each other).

[0364] The term "chiral center" or "chiral carbon atom" refers to a carbon atom to which four different groups are bonded.

[0365] The terms "enantiomer" and "of an enantiomer" refer to molecules that cannot be superimposed on their mirror image and are therefore optically active, where the enantiomer rotates the plane of polarization in one direction, and its mirror image compound rotates the plane of polarization in the opposite direction. Enantiomers can be separated by chiral chromatography using methods well known in the art.

[0366] The term "racemic" or "racemic mixture" refers to an equimolar mixture of enantiomers, which is optically inert.

[0367] The term "absolute configuration" refers to the spatial arrangement of atoms in a chiral molecular entity (or group) and its stereochemical description, such as R or S.

[0368] The stereochemical terms and conventions used herein are intended to be consistent with those found in Pure & Appl. Chem 68:2193 (1996), unless otherwise specified.

[0369] The term "enantiomer excess" or "ee" refers to a measure of how much more of one enantiomer is present compared to the other. For a mixture of R and S enantiomers, the percentage enantiomer excess is given by │RS│. * Defined as 100, where R and S are the respective mole or weight fractions of the enantiomer in a mixture such that R + S = 1. Using knowledge of the optical rotation of chiral substances, the percentage enantiomer excess is ([α] obs / [α] max ) * Defined as 100, where [α] obs is the optical rotation of the enantiomer mixture, and [α] maxis the optical rotation of the pure enantiomer. The enantiomer excess can be determined using various analytical techniques, including NMR spectroscopy, chiral column chromatography, or optical optical rotation analysis. The racemic compounds of the Disclosure can be separated by chiral HPLC, for example, using a CHIRALPAK IE column. In one embodiment, the compounds of the Disclosure have about 70% or more ee, for example, about 80% or more, about 90% or more, about 91% or more, about 92% or more, about 93% or more, about 94% or more, about 95% or more, about 96% or more, about 97% or more, about 98% or more, or about 99% or more.

[0370] The term "enantiomerically pure" or "enantiopure" refers to a sample of chiral substance in which all molecules (within the detection limit) have the same chiral orientation.

[0371] The terms "enantiomerically enriched" or "enantio-enriched" refer to a sample of chiral substance whose enantiomer ratio is greater than 50:50. Enantiomerically enriched compounds can be enantiomerically pure. Certain compounds in this disclosure are enantio-enriched.

[0372] The term "diastereomer excess" or "de" refers to a measure of how much more of one diastereomer is present compared to another, and is defined in the same way as enantiomer excess. Diastereomer excess can be determined using various analytical techniques, including NMR spectroscopy and column chromatography.

[0373] The term "diastereoenriched enriched" refers to a sample of chiral substance whose diastereomer ratio is greater than 50:50. Diastereoenriched compounds can be diastereomerically pure. Certain compounds in this disclosure are diastereoenriched.

[0374] As used herein, the term "about" includes a range of ±10% from the stated number. Therefore, "about 10" means 9 to 11.

[0375] IV. Specific Embodiments This disclosure also provides the following specific embodiments.

[0376] Embodiment 1. A compound having formula (I), or a pharmaceutically acceptable salt thereof:

[0377] [ka] (In the formula, E is

[0378] [ka] R 1 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0379] [ka] And, R 2 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0380] [ka] And, however, (i)R 1 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 2 teeth,

[0381] [ka] And, (ii)R 2If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 1 teeth,

[0382] [ka] And, R 11 is hydrogen or -(C1-C6)alkyl-OP(=O)-(OH)2, X 1 CR 3 or N, R 3 is hydrogen, halogen, or (C1-C6) alkyl, X 2 CR 4 or N, R 4 is hydrogen, halogen, or (C1-C6) alkyl, R 5a This is hydrogen, halogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5 or 6-membered heteroaryl, where (C1-C6) alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen or cyano, and 4- to 6-membered heterocycloalkyl, aryl, or 5 or 6-membered heteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, cyano, or (C1-C6) alkyl. R 5b is hydrogen, (C1-C6) alkyl, or (C3-C6) cycloalkyl, R 6 is hydrogen, (C1-C6) alkyl, or cyano. X 3 is -CH2CH2- or -CH2-O-CH2-, or X 3 It does not exist, L is -G 1 -G 2 -G 3 -G 4 -and here, G1 It is bonded to W, G 1 This is a 4-6 member heterocycloalkylenyl molecule optionally substituted with 1, 2, or 3 substituents independently selected from (C1-C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano, or a 7-11 member heterocycloalkylenyl molecule optionally substituted with 1, 2, or 3 substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano. G 2 is a (C1-C6) alkylenyl or direct bond, G 3 This is a 4-6 member heterocycloalkylenyl, cyano, or 7-11 member heterocycloalkylenyl, which is optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6) alkyls, or (C1-C6) alkoxys. G 4 is a (C1-C6) alkylenyl or direct bond, W is

[0383] [ka] It is a direct bond, R 7 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 8 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 9 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 10 (These are hydrogen, halogens, or (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with one, two, or three halogens.)

[0384] Embodiment 2. Compound of formula (I), or a pharmaceutically acceptable salt thereof:

[0385] [ka] (In the formula, E is

[0386] [ka] R 1 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0387] [ka] And, R 2 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0388] [ka] And, however, (i)R 1 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 2 teeth,

[0389] [ka] And, (ii)R 2 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 1 teeth,

[0390] [ka] And, R 11 is hydrogen or -(C1-C6)alkyl-OP(=O)-(OH)2, X 1 CR 3 or N, R 3 is hydrogen, halogen, or (C1-C6) alkyl, X 2 CR 4 or N, R 4 is hydrogen, halogen, or (C1-C6) alkyl, R 5a This is hydrogen, halogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5 or 6-membered heteroaryl, where (C1-C6) alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen or cyano, and 4- to 6-membered heterocycloalkyl, aryl, or 5 or 6-membered heteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, cyano, or (C1-C6) alkyl. R 5b is hydrogen, (C1-C6) alkyl, or (C3-C6) cycloalkyl, R 6 is hydrogen, (C1-C6) alkyl, or cyano. X 3 is -CH2CH2- or -CH2-O-CH2-, or X 3 It does not exist, L is -G 1 -G 2 -G 3 -G 4 -and here, G 1 It is bonded to W, G 1This is a 4-6 member heterocycloalkylenyl molecule optionally substituted with 1, 2, or 3 substituents independently selected from (C1-C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano, or a 7-11 member heterocycloalkylenyl molecule optionally substituted with 1, 2, or 3 substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano. G 2 is a (C1-C6) alkylenyl or direct bond, G 3 This refers to a 4-6 member heterocycloalkylenyl, cyano, halogen, (C1-C6) halogen, or (C1-C6) alkoxy compound optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6) alkyls, or (C1-C6) alkoxys. 1 A 7-11 member heterocycloalkylenyl or a 5-10 member heteroarylenyl, optionally substituted with one, two, or three substituents independently selected from -C6) alkyl, (C1-C6) alkoxy, or cyano. G 4 These are (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl, or direct bonds. W is

[0391] [ka] or direct bond, R 7 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 8 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 9 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 10 (These are hydrogen, halogens, or (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with one, two, or three halogens.)

[0392] Embodiment 3. Formula (II):

[0393] [ka] A compound according to Embodiment 1 or 2, or a pharmaceutically acceptable salt thereof, having the above.

[0394] Embodiment 4. Formula (III):

[0395] [ka] A compound according to Embodiment 1 or 2, or a pharmaceutically acceptable salt thereof, having the above.

[0396] Embodiment 5. The compound according to any one of Embodiments 1 to 4, or a pharmaceutically acceptable salt thereof, wherein E is E-1.

[0397] Embodiment 6. R 5a The compound according to Embodiment 5, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

[0398] Embodiment 7. R 5a The compound according to Embodiment 5, or a pharmaceutically acceptable salt thereof, wherein the (C1-C6) alkyl is optionally substituted with one, two, or three substituents independently selected from halogens or cyano compounds.

[0399] Embodiment 8. R 5a The compound according to Embodiment 7, or a pharmaceutically acceptable salt thereof, wherein the compound is methyl.

[0400] Embodiment 9. R 5aThe compound according to Embodiment 5, wherein (C3-C6) cycloalkyl, or a pharmaceutically acceptable salt thereof.

[0401] Embodiment 10. R 5a The compound according to Embodiment 9, or a pharmaceutically acceptable salt thereof, wherein is cyclopropyl.

[0402] Embodiment 11. R 5a The compound according to Embodiment 5, or a pharmaceutically acceptable salt thereof, wherein the compound is a 4- to 6-membered heterocycloalkyl group optionally substituted with one, two, or three substituents independently selected from halogens, cyanos, or (C1-C6)alkyl groups.

[0403] Embodiment 12. R 5a The compound according to Embodiment 5, or a pharmaceutically acceptable salt thereof, wherein the compound is cyano.

[0404] Embodiment 13. R 5a The compound according to Embodiment 5, or a pharmaceutically acceptable salt thereof, wherein the aryl is optionally substituted with one, two, or three substituents independently selected from halogens, cyanos, or (C1-C6)alkyls.

[0405] Embodiment 14. R 5a The compound according to Embodiment 5, or a pharmaceutically acceptable salt thereof, wherein the compound is a 5 or 6-membered heteroaryl, optionally substituted with one, two, or three substituents independently selected from halogens, cyanos, or (C1-C6)alkyls.

[0406] Embodiment 15. The compound according to any one of Embodiments 1 to 4, or a pharmaceutically acceptable salt thereof, wherein E is E-2.

[0407] Embodiment 16. The compound according to any one of Embodiments 1 to 4, or a pharmaceutically acceptable salt thereof, wherein E is E-3.

[0408] Embodiment 17. R 1 but,

[0409] [ka] And, R 2 The compound described in any one of Embodiments 1 to 16, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen, a halogen, a (C1-C6) alkyl, or a (C1-C6) alkoxy.

[0410] Embodiment 18. R 2 The compound described in Embodiment 17, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen, a halogen, or a (C1-C6) alkyl group.

[0411] Embodiment 19. R 2 The compound described in Embodiment 18, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen, fluoro, or methyl.

[0412] Embodiment 20. R 11 A compound according to any one of embodiments 17 to 19, wherein the compound is hydrogen, or a pharmaceutically acceptable salt thereof.

[0413] Embodiment 21. R 2 but,

[0414] [ka] And, R 1 The compound described in any one of Embodiments 1 to 16, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen, a halogen, a (C1-C6) alkyl, or a (C1-C6) alkoxy.

[0415] Embodiment 22. R 1 The compound described in Embodiment 21, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen, a halogen, or a (C1-C6) alkyl group.

[0416] Embodiment 23. R 1The compound described in Embodiment 22, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen, fluoro, or methyl.

[0417] Embodiment 24. R 11 A compound according to any one of embodiments 21 to 23, wherein the compound is hydrogen, or a pharmaceutically acceptable salt thereof.

[0418] Embodiment 25. X 1 CR 3 The compound described in any one of Embodiments 1 to 24, or a pharmaceutically acceptable salt thereof.

[0419] Embodiment 26. R 3 The compound according to Embodiment 25, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

[0420] Embodiment 27. R 3 A compound according to Embodiment 25, or a pharmaceutically acceptable salt thereof, wherein the halogen is present.

[0421] Embodiment 28. R 3 The compound according to Embodiment 25, wherein (C1-C6) alkyl, or a pharmaceutically acceptable salt thereof.

[0422] Embodiment 29. X 1 A compound according to any one of Embodiments 1 to 24, or a pharmaceutically acceptable salt thereof, wherein is N.

[0423] Embodiment 30. X 2 CR 4 The compound described in any one of Embodiments 1 to 29, or a pharmaceutically acceptable salt thereof.

[0424] Embodiment 31. R 4 A compound according to Embodiment 30 or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

[0425] Embodiment 32. R 4 A compound according to Embodiment 30, or a pharmaceutically acceptable salt thereof, wherein the halogen is present.

[0426] Embodiment 33. R 4 The compound according to Embodiment 30, or a pharmaceutically acceptable salt thereof, wherein (C1-C6) alkyl.

[0427] Embodiment 34. X 2 A compound according to any one of Embodiments 1 to 29, or a pharmaceutically acceptable salt thereof, wherein is N.

[0428] Embodiment 35. E-1 is,

[0429] [ka] The compound described in Embodiment 5, or a pharmaceutically acceptable salt thereof.

[0430] Embodiment 36. E-2 is,

[0431] [ka] The compound described in Embodiment 15, or a pharmaceutically acceptable salt thereof.

[0432] Embodiment 37. E-3 is,

[0433] [ka] The compound described in Embodiment 16, or a pharmaceutically acceptable salt thereof.

[0434] Embodiment 38. G 1 The compound according to any one of Embodiments 1 to 37, or a pharmaceutically acceptable salt thereof, is a 4- to 6-membered heterocycloalkylenyl, optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos.

[0435] Embodiment 39. G1 but,

[0436] [ka] And, Each R 12 These are independently halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos. n is 0, 1, 2, or 3. " * The bonds marked with " are G 2 A compound according to Embodiment 38, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0437] Embodiment 40. Each R 12 The compound according to Embodiment 39, or a pharmaceutically acceptable salt thereof, wherein n is independently fluoro, methyl, methoxy, cyano, or -CHF2, and n is 0, 1, or 2.

[0438] Embodiment 41. G 1 but,

[0439] [ka] " * The bonds marked with " are G 2 A compound according to Embodiment 38, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0440] Embodiment 42. G 1 but,

[0441] [ka] And, X 4 It is -O-, Each R 12 These are independently halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos. " *The bonds marked with " are G 2 A compound according to Embodiment 38, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0442] Embodiment 43. G 1 but,

[0443] [ka] " * The bonds marked with " are G 2 A compound according to Embodiment 42, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0444] Embodiment 44. G 1 but,

[0445] [ka] And, " * The bonds marked with " are G 2 A compound according to Embodiment 38, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0446] Embodiment 45. G 1 The compound according to any one of Embodiments 1 to 37, or a pharmaceutically acceptable salt thereof, is a 7- to 11-membered heterocycloalkylenyl, optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6)alkyls, (C1-C6)alkoxys, or cyanos.

[0447] Embodiment 46. G 1 but,

[0448] [ka] And, Each R 13These are independently selected from halogens, (C1-C6)alkyls, (C1-C6)alkoxys, or cyanos. o is 0, 1, 2, or 3. p, q, r, and s are independently 1, 2, or 3. " * The bonds marked with " are G 2 A compound according to Embodiment 45, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0449] Embodiment 47. p and q are 1, r is 1 or 2, s is 1 or 2, R 13 However, the compound described in Embodiment 46, or a pharmaceutically acceptable salt thereof, is a halogen.

[0450] Embodiment 48. R 13 The compound according to Embodiment 46, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro and the oxygen is 0, 1, or 2.

[0451] Embodiment 49. G 1 but,

[0452] [ka] And, " * The bonds marked with " are G 2 A compound according to Embodiment 46, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0453] Embodiment 50. G 1 but,

[0454] [ka] And, a is either 0 or 1. b is either 0 or 1. "* The bonds marked with " are G 2 A compound according to Embodiment 45, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0455] Embodiment 51. G 1 but,

[0456] [ka] " * The bonds marked with " are G 2 A compound according to Embodiment 50, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0457] Embodiment 52. G 2 However, the compound described in any one of Embodiments 1 to 49, or a pharmaceutically acceptable salt thereof, is directly bonded.

[0458] Embodiment 53. G 2 However, the compound described in any one of Embodiments 1 to 49, which is a (C1-C6) alkylenyl, or a pharmaceutically acceptable salt thereof.

[0459] Embodiment 54. G 2 The compound described in Embodiment 53, or a pharmaceutically acceptable salt thereof, wherein the compound is -CH2-.

[0460] Embodiment 55. G 3 The compound according to any one of Embodiments 1 to 54, or a pharmaceutically acceptable salt thereof, is a 4- to 6-membered heterocycloalkylenyl, which is optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos.

[0461] Embodiment 56. G 3 but,

[0462] [ka] Each R14 These are independently halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos. t is 0, 1, 2, or 3. " * The bonds marked with " are G 4 A compound according to Embodiment 55, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0463] Embodiment 57. R 14 The compound according to Embodiment 56, or a pharmaceutically acceptable salt thereof, wherein is fluoro or methyl and t is 0 or 1.

[0464] Embodiment 58. G 3 but,

[0465] [ka] The compound described in Embodiment 56, or a pharmaceutically acceptable salt thereof.

[0466] Embodiment 59. G 3 The compound according to any one of Embodiments 1 to 54, or a pharmaceutically acceptable salt thereof, is a 7- to 11-membered heterocycloalkylenyl, which is optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos.

[0467] Embodiment 60. G 3 but,

[0468] [ka] And, " * The bonds marked with " are G 4 A compound according to Embodiment 59, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0469] Embodiment 61. G 3 but,

[0470] [ka] And, Each R 15 These are independently selected from halogens, (C1-C6)alkyls, (C1-C6)alkoxys, or cyanos. u is 0, 1, 2, or 3. v, w, x, and y are independently 1, 2, or 3. " * The bonds marked with " are G 4 A compound according to Embodiment 59, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0471] Embodiment 62. The compound according to Embodiment 61, or a pharmaceutically acceptable salt thereof, wherein v, w, x, and y are independently 1 or 2.

[0472] Embodiment 63. G 3 but,

[0473] [ka] And, x a and y a These are independently 1, 2, or 3, " * The bonds marked with " are G 4 A compound according to Embodiment 59, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0474] Embodiment 64. G 3 but,

[0475] [ka] " * The bonds marked with " are G 4 A compound according to Embodiment 59, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0476] Embodiment 65. G 4 However, the compound described in any one of Embodiments 1 to 64, which is a (C1-C6) alkylenyl, or a pharmaceutically acceptable salt thereof.

[0477] Embodiment 66. G 4 The compound according to Embodiment 65, or a pharmaceutically acceptable salt thereof, wherein the compound is -CH2- or -CH2CH2-.

[0478] Embodiment 67. G 4 However, the compound described in any one of Embodiments 2 to 64, which is a (C3-C6) cycloalkylenyl, or a pharmaceutically acceptable salt thereof.

[0479] Embodiment 68.G 4 but,

[0480] [ka] The compound described in Embodiment 67, or a pharmaceutically acceptable salt thereof.

[0481] Embodiment 69. G 4 However, the compound described in any one of Embodiments 1 to 64, or a pharmaceutically acceptable salt thereof, is directly bonded.

[0482] Embodiment 70. L is

[0483] [ka]

[0484] [ka] " * The bond marked with " is bonded to E, and is a compound according to any one of Embodiments 1 to 37, or a pharmaceutically acceptable salt thereof.

[0485] Embodiment 71. L is

[0486] [ka] " * The bond marked with " is bonded to E, and is a compound according to any one of Embodiments 2 to 37, or a pharmaceutically acceptable salt thereof.

[0487] Embodiment 72. W is

[0488] [ka] The compound described in any one of Embodiments 1 to 71, or a pharmaceutically acceptable salt thereof.

[0489] Embodiment 73. A compound according to any one of Embodiments 1 to 71, or a pharmaceutically acceptable salt thereof, wherein W is a direct bond.

[0490] Embodiment 74. R 7 The compound described in any one of Embodiments 1 to 73, or a pharmaceutically acceptable salt thereof, is a halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, where the (C1-C6)alkyl is optionally substituted with one, two, or three halogens.

[0491] Embodiment 75. R 7 The compound described in Embodiment 74, or a pharmaceutically acceptable salt thereof, wherein the compound is a halogen or a (C1-C6) alkyl group.

[0492] Embodiment 76. R 7 The compound described in Embodiment 75, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro or methyl.

[0493] Embodiment 77. R 8 , R 9 , and R 10 A compound according to any one of embodiments 74 to 76, or a pharmaceutically acceptable salt thereof, wherein is H.

[0494] Embodiment 78. R 8 The compound described in any one of Embodiments 1 to 76, or a pharmaceutically acceptable salt thereof, is a halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, where the (C1-C6)alkyl is optionally substituted with one, two, or three halogens.

[0495] Embodiment 79. R 8 The compound described in Embodiment 78, or a pharmaceutically acceptable salt thereof, wherein the compound is a halogen or a (C1-C6) alkyl group.

[0496] Embodiment 80. R 8 The compound described in Embodiment 79, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro or methyl.

[0497] Embodiment 81. R 7 , R 9 , and R 10 A compound according to any one of embodiments 78 to 80, wherein the compound is hydrogen, or a pharmaceutically acceptable salt thereof.

[0498] Embodiment 82. R 9 The compound described in any one of Embodiments 1-76 or 67-69, or a pharmaceutically acceptable salt thereof, is a halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, where the (C1-C6)alkyl is optionally substituted with one, two, or three halogens.

[0499] Embodiment 83. R 9 A compound according to Embodiment 82, or a pharmaceutically acceptable salt thereof, wherein the halogen is present.

[0500] Embodiment 84. R 9 A compound according to Embodiment 83, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro.

[0501] Embodiment 85. R 7 , R 8 , and R10 A compound according to any one of embodiments 82 to 84, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

[0502] Embodiment 86. R 10 The compound described in any one of Embodiments 1-76, 78-80, or 82-84, or a pharmaceutically acceptable salt thereof, is a halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, where the (C1-C6)alkyl is optionally substituted with one, two, or three halogens.

[0503] Embodiment 87. R 10 A compound according to Embodiment 86, or a pharmaceutically acceptable salt thereof, wherein the halogen is present.

[0504] Embodiment 88. R 10 A compound according to Embodiment 87, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro.

[0505] Embodiment 89. R 7 , R 8 , and R 9 A compound according to any one of embodiments 86 to 88, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

[0506] Embodiment 90. R 7 , R 8 , R 9 , and R 10 A compound according to any one of Embodiments 1 to 73, or a pharmaceutically acceptable salt thereof, wherein is H.

[0507] Embodiment 91. Formula (IV):

[0508] [ka] (In the formula, Each R 12 It is independently fluoro, n is 0, 1, or 2. R 7 , R8 , R 9 , and R 10 (These are independently hydrogen, fluoro, or methyl.) A compound according to any one of embodiments 1 to 2, 5 to 9, or 35, or a pharmaceutically acceptable salt thereof, having the above.

[0509] Embodiment 92. G 3 but,

[0510] [ka] G 4 The compound described in Embodiment 91, or a pharmaceutically acceptable salt thereof, wherein the compound is directly bonded, -CH2- or -CH2CH2-.

[0511] Embodiment 93. G 3 but,

[0512] [ka] The compound described in Embodiment 91, or a pharmaceutically acceptable salt thereof.

[0513] Embodiment 94. A compound according to Embodiment 1, selected from any one or more compounds in Compound List 1, or a pharmaceutically acceptable salt thereof.

[0514] Embodiment 95. A compound according to Embodiment 1, selected from any one or more compounds from Compound List 2 and / or Compound List 3, or a pharmaceutically acceptable salt thereof.

[0515] Embodiment 96. A compound according to Embodiment 2, selected from any one or more of the compounds in Compound List 4, or a pharmaceutically acceptable salt thereof.

[0516] Embodiment 97. The compound is

[0517] [ka] The compound described in Embodiment 94, or a pharmaceutically acceptable salt thereof.

[0518] Embodiment 98. The compound is

[0519] [ka] The compound described in Embodiment 94, or a pharmaceutically acceptable salt thereof.

[0520] Embodiment 99. The compound is

[0521] [ka] The compound described in Embodiment 94, or a pharmaceutically acceptable salt thereof.

[0522] Embodiment 100. The compound is

[0523] [ka] The compound described in Embodiment 96, or a pharmaceutically acceptable salt thereof.

[0524] Embodiment 101. The compound is

[0525] [ka] The compound described in Embodiment 96, or a pharmaceutically acceptable salt thereof.

[0526] Embodiment 102. The compound is

[0527] [ka] The compound described in Embodiment 96, or a pharmaceutically acceptable salt thereof.

[0528] Embodiment 103. The compound is

[0529] [ka] The compound described in Embodiment 96, or a pharmaceutically acceptable salt thereof.

[0530] Embodiment 104. The compound is

[0531] [ka] The compound described in Embodiment 96, or a pharmaceutically acceptable salt thereof.

[0532] Embodiment 105. A pharmaceutical composition comprising a compound described in any one of Embodiments 1 to 104 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0533] Embodiment 106. A method for degrading the SMARCA2 protein in a human, comprising administering to a human in need of such degradation an effective amount of a compound described in any one of Embodiments 1 to 104 or a pharmaceutically acceptable salt thereof, or the composition described in Embodiment 105.

[0534] Embodiment 107. A method for reducing the level of SMARCA2 activity in a human, comprising administering to a human in need of such reduction an effective amount of a compound described in any one of Embodiments 1 to 104 or a pharmaceutically acceptable salt thereof, or a composition described in Embodiment 105.

[0535] Embodiment 108. A method for treating cancer in a human, comprising administering to a person in need of such treatment an effective amount of a compound described in any one of Embodiments 1 to 104, or a pharmaceutically acceptable salt thereof, or a composition described in Embodiment 105.

[0536] Embodiment 109. The method according to Embodiment 108, wherein the cancer is a SMARCA2-sensitive cancer.

[0537] Embodiment 110. The method according to Embodiment 108, wherein the cancer is a SMARCA2 mutation cancer.

[0538] Embodiment 111. The method according to any one of Embodiments 108 to 110, wherein the cancer is a solid tumor.

[0539] Embodiment 112. The method according to any one of Embodiments 108 to 110, wherein the cancer is lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer.

[0540] Embodiment 113. A compound according to any one of Embodiments 1 to 104, or a pharmaceutically acceptable salt thereof, or a composition according to Embodiment 105, for use in degrading the SMARCA2 protein in humans.

[0541] Embodiment 114. A compound according to any one of Embodiments 1 to 104, or a pharmaceutically acceptable salt thereof, or a composition according to Embodiment 105, for use in reducing the level of SMARCA2 activity in humans.

[0542] Embodiment 115. A compound according to any one of Embodiments 1 to 104, or a pharmaceutically acceptable salt thereof, or a composition according to Embodiment 105, for use in treating cancer in humans.

[0543] Embodiment 116. The compound for use according to Embodiment 115, wherein the cancer is a SMARCA2-sensitive cancer.

[0544] Embodiment 117. The compound for use according to Embodiment 115, wherein the cancer is a SMARCA2 mutation cancer.

[0545] Embodiment 118. The compound for use according to any one of Embodiments 115 to 117, wherein the cancer is a solid tumor.

[0546] Embodiment 119. The compound for use according to any one of Embodiments 115 to 117, wherein the cancer is lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer.

[0547] Embodiment 120. Use of a compound according to any one of Embodiments 1 to 104, or a pharmaceutically acceptable salt thereof, or the composition according to Embodiment 105, in the manufacture of a pharmaceutical for degrading the SMARCA2 protein in humans.

[0548] Embodiment 121. Use of a compound according to any one of Embodiments 1 to 104, or a pharmaceutically acceptable salt thereof, or the composition according to Embodiment 105, in the manufacture of a pharmaceutical product for reducing the level of SMARCA2 activity in humans.

[0549] Embodiment 122. Use of a compound according to any one of Embodiments 1 to 104, or a pharmaceutically acceptable salt thereof, or the composition according to Embodiment 105, in the manufacture of a pharmaceutical for the treatment of cancer in humans.

[0550] Embodiment 123. A compound, or a pharmaceutically acceptable salt thereof, for use as described in Embodiment 122, wherein the cancer is a SMARCA2-sensitive cancer.

[0551] Embodiment 124. A compound, or a pharmaceutically acceptable salt thereof, for use as described in Embodiment 122, wherein the cancer is a SMARCA2 mutation cancer.

[0552] Embodiment 125. A compound, or a pharmaceutically acceptable salt thereof, for use according to any one of Embodiments 122 to 124, wherein the cancer is a solid tumor.

[0553] Embodiment 126. A compound, or a pharmaceutically acceptable salt thereof, for use according to any one of Embodiments 122 to 124, wherein the cancer is lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer.

[0554] This disclosure also provides the following specific embodiments.

[0555] Embodiment A1. Compound of formula (A), or a pharmaceutically acceptable salt thereof:

[0556] [ka] (In the formula, E is

[0557] [ka] R 1 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0558] [ka] And, R 2 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0559] [ka] And, however, (i)R 1 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 2 teeth,

[0560] [ka] And, (ii)R 2If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 1 teeth,

[0561] [ka] And, R 11 is hydrogen or -(C1-C6)alkyl-OP(=O)-(OH)2, X 1 CR 3 or N, R 3 is hydrogen, halogen, or (C1-C6) alkyl, X 2 CR 4 or N, R 4 is hydrogen, halogen, or (C1-C6) alkyl, R 5a These are hydrogen, halogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, 4-6 member heterocycloalkyl, cyano, aryl, or 5 or 6 member heteroaryl. Here, the (C1-C6) alkyl group is optionally substituted with one, two, or three substituents independently selected from halogens or cyano compounds, and the 4-6 member heterocycloalkyl, aryl, or 5 or 6 member heteroaryl group is optionally substituted with one, two, or three substituents independently selected from halogens, cyano compounds, or (C1-C6) alkyl groups. R 5b is hydrogen, (C1-C6) alkyl, or (C3-C6) cycloalkyl, R 6 is hydrogen, (C1-C6) alkyl, or cyano. X 3 This is -CH2CH2- or -CH2-O-CH2-, or X 3 It does not exist, L is -G 1 -G 2 -G 3 -G 4-and here, G 1 It is bonded to W, G 1 This is a 4-6 member heterocycloalkylenyl optionally substituted with 1, 2, or 3 substituents independently selected from (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl, -O-CH2-CH2-, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, cyano, or hydroxyl, or a 7-11 member heterocycloalkylenyl optionally substituted with 1, 2, or 3 substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano. G 2 This is a (C1-C6) alkylenyl, a 4- to 6-membered heterocycloalkylenyl optionally substituted with -C(=O)-, 1, 2, or 3 fluorocarbons, or a direct bond. G 3 These are -C(=O)-, -C(=O)-CH2CH2-, (C1-C6)alkylenyl, tetrahydronaphthalenyl, halogen, (C 1- A 4-6 member heterocycloalkylenyl optionally substituted with 1, 2, or 3 substituents independently selected from C6)alkyl, (C1-C6)alkoxy, or cyano; a halogen, a 7-11 member heterocycloalkyl-C(=O)- or 7-11 member heterocycloalkylenyl optionally substituted with 1, 2, or 3 substituents independently selected from C1-C6)alkyl, (C1-C6)alkoxy, or cyano; G 4 These are (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl, 4-6 member heterocycloalkylenyl, or direct bonds. W is

[0562] [ka] or direct bond, R 7These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 8 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 9 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 10 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R a is hydrogen or halogen, R b is hydrogen or halogen, R c (It is hydrogen or methyl.)

[0563] Embodiment A2. Compound of formula (I), or a pharmaceutically acceptable salt thereof:

[0564] [ka] (In the formula, E is

[0565] [ka] R 1 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0566] [ka] And, R 2 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0567] [ka] And, however, (i)R 1 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 2 teeth,

[0568] [ka] And, (ii)R 2 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 1 teeth,

[0569] [ka] And, R 11 is hydrogen or -(C1-C6)alkyl-OP(=O)-(OH)2, X 1 CR 3 or N, R 3 is hydrogen, halogen, or (C1-C6) alkyl, X 2 CR 4 or N, R 4 is hydrogen, halogen, or (C1-C6) alkyl, R 5aThis is hydrogen, halogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5 or 6-membered heteroaryl, where (C1-C6) alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen or cyano, and 4- to 6-membered heterocycloalkyl, aryl, or 5 or 6-membered heteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, cyano, or (C1-C6) alkyl. R 5b is hydrogen, (C1-C6) alkyl, or (C3-C6) cycloalkyl, R 6 is hydrogen, (C1-C6) alkyl, or cyano. X 3 This is -CH2CH2- or -CH2-O-CH2-, or X 3 It does not exist, L is -G 1 -G 2 -G 3 -G 4 -and here, G 1 It is bonded to W, G 1 This is a 4-6 member heterocycloalkylenyl molecule optionally substituted with 1, 2, or 3 substituents independently selected from (C1-C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano, or a 7-11 member heterocycloalkylenyl molecule optionally substituted with 1, 2, or 3 substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano. G 2 is a (C1-C6) alkylenyl or direct bond, G 3 These are halogens, (C1-C6)alkyls, (C1-C 6)A 4-6 member heterocycloalkylenyl optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy or cyano, or a 7-11 member heterocycloalkylenyl optionally substituted with 1, 2, or 3 substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano. G 4 is a (C1-C6) alkylenyl or direct bond, W is

[0570] [ka] or direct bond, R 7 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 8 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 9 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 10 (These are hydrogen, halogens, or (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with one, two, or three halogens.)

[0571] Embodiment A3. Compound of formula (I), or a pharmaceutically acceptable salt thereof:

[0572] [ka] (In the formula, E is

[0573] [ka] R 1 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0574] [ka] And, R 2 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0575] [ka] And, however, (i)R 1 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 2 teeth,

[0576] [ka] And, (ii)R 2 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 1 teeth,

[0577] [ka] And, R 11 is hydrogen or -(C1-C6)alkyl-OP(=O)-(OH)2, X 1 CR 3 or N, R 3 is hydrogen, halogen, or (C1-C6) alkyl, X 2 CR 4 or N, R 4 is hydrogen, halogen, or (C1-C6) alkyl, R 5a This is hydrogen, halogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5 or 6-membered heteroaryl, where (C1-C6) alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen or cyano, and 4- to 6-membered heterocycloalkyl, aryl, or 5 or 6-membered heteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, cyano, or (C1-C6) alkyl. R 5b is hydrogen, (C1-C6) alkyl, or (C3-C6) cycloalkyl, R 6 is hydrogen, (C1-C6) alkyl, or cyano. X 3 is -CH2CH2- or -CH2-O-CH2-, or X 3 It does not exist, L is -G 1 -G 2 -G 3 -G 4 -and here, G 1 It is bonded to W, G 1 This is a 4-6 member heterocycloalkylenyl molecule optionally substituted with 1, 2, or 3 substituents independently selected from (C1-C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano, or a 7-11 member heterocycloalkylenyl molecule optionally substituted with 1, 2, or 3 substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano. G 2 is a (C1-C6) alkylenyl or direct bond, G 3 These are halogens, (C1-C6)alkyls, (C1-C 6)A 4-6 member heterocycloalkylenyl, a 7-11 member heterocycloalkylenyl, or a 5-10 member heteroarylenyl, optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano groups. G 4 These are (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl, or direct bonds. W is

[0578] [ka] or direct bond, R 7 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 8 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 9 These are (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with hydrogen, halogen, or one, two, or three halogens. R 10 (These are hydrogen, halogens, or (C1-C6) alkyl, cyano, or (C3-C6) cycloalkyl groups optionally substituted with one, two, or three halogens.)

[0579] Embodiment A4. Formula (II):

[0580] [ka] A compound according to Embodiment A2 or 3, or a pharmaceutically acceptable salt thereof, having the above characteristics.

[0581] Embodiment A5. Formula (III):

[0582] [ka] A compound according to Embodiment A2 or 3, or a pharmaceutically acceptable salt thereof, having the above characteristics.

[0583] Embodiment A6. R 5a A compound according to any one of Embodiments A1 to A5, wherein the compound is hydrogen, or a pharmaceutically acceptable salt thereof.

[0584] Embodiment A7. R 5a The compound according to any one of Embodiments A1 to 5, or a pharmaceutically acceptable salt thereof, wherein the (C1-C6) alkyl is optionally substituted with one, two, or three substituents independently selected from halogens or cyano compounds.

[0585] Embodiment A8. R 5a The compound described in Embodiment A7, or a pharmaceutically acceptable salt thereof, wherein the compound is methyl.

[0586] Embodiment A9. R 5a A compound according to any one of Embodiments A1 to A5, wherein (C3-C6) cycloalkyl is present, or a pharmaceutically acceptable salt thereof.

[0587] Embodiment A10. R 5a The compound according to Embodiment A9, or a pharmaceutically acceptable salt thereof, wherein is cyclopropyl.

[0588] Embodiment A11. R 5a The compound according to any one of Embodiments A1 to 5, or a pharmaceutically acceptable salt thereof, is a 4- to 6-membered heterocycloalkyl group, which is optionally substituted with one, two, or three substituents independently selected from halogens, cyanos, or (C1-C6)alkyl groups.

[0589] Embodiment A12. R 5aA compound according to any one of Embodiments A1 to A5, or a pharmaceutically acceptable salt thereof, wherein the compound is cyano.

[0590] Embodiment A13. R 1 but,

[0591] [ka] And, R 2 The compound described in any one of Embodiments A1 to 5, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen, a halogen, a (C1-C6) alkyl, or a (C1-C6) alkoxy.

[0592] Embodiment A14. R 2 The compound described in any one of Embodiments A1 to 5, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen, a halogen, or a (C1-C6) alkyl group.

[0593] Embodiment A15. R 2 The compound described in any one of Embodiments A1 to 5, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen, fluoro, or methyl.

[0594] Embodiment A16. R 11 A compound according to any one of Embodiments A1 to A5, wherein the compound is hydrogen, or a pharmaceutically acceptable salt thereof.

[0595] Embodiment A17. R 1 However, it is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, R 2 but,

[0596] [ka] The compound described in any one of Embodiments A1 to A5, or a pharmaceutically acceptable salt thereof.

[0597] Embodiment A18. R 1 The compound described in Embodiment A17, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen, a halogen, or a (C1-C6) alkyl group.

[0598] Embodiment A19. R 1 The compound described in Embodiment A18, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen, fluoro, or methyl.

[0599] Embodiment A20. R 11 A compound according to any one of embodiments A17 to A19, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

[0600] Embodiment A21. X 1 CR 3 The compound described in any one of Embodiments A1 to A5, or a pharmaceutically acceptable salt thereof.

[0601] Embodiment A22. R 3 A compound according to Embodiment A21, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

[0602] Embodiment A23. R 3 A compound according to Embodiment A21, or a pharmaceutically acceptable salt thereof, wherein the halogen is present.

[0603] Embodiment A24. R 3 The compound described in Embodiment A21, wherein (C1-C6) alkyl, or a pharmaceutically acceptable salt thereof.

[0604] Embodiment A25. X 1 A compound according to any one of Embodiments A1 to A5, or a pharmaceutically acceptable salt thereof, wherein is N.

[0605] Embodiment A26. X 2 CR 4 The compound described in any one of Embodiments A1 to A5, or a pharmaceutically acceptable salt thereof.

[0606] Embodiment A27. R 4 A compound according to Embodiment A26, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

[0607] Embodiment A28. R 4 A compound according to Embodiment A26, or a pharmaceutically acceptable salt thereof, wherein the halogen is present.

[0608] Embodiment A29. R 4 The compound described in Embodiment A26, wherein (C1-C6) alkyl, or a pharmaceutically acceptable salt thereof.

[0609] Embodiment A30. X 2 A compound according to any one of Embodiments A1 to A5, or a pharmaceutically acceptable salt thereof, wherein is N.

[0610] Embodiment A31. E is,

[0611] [ka] The compound described in any one of Embodiments A1 to A5, or a pharmaceutically acceptable salt thereof.

[0612] Embodiment A32. E is,

[0613] [ka] The compound described in any one of Embodiments A1 to A5, or a pharmaceutically acceptable salt thereof.

[0614] Embodiment A33. E is,

[0615] [ka] The compound described in any one of Embodiments A1 to A5, or a pharmaceutically acceptable salt thereof.

[0616] Embodiment A34. G 1However, (C3-C6) cycloalkylenyl, or halogen, (C1-C 6) A compound according to any one of Embodiments A1 to 33, or a pharmaceutically acceptable salt thereof, which is a 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from alkyl, (C1-C6) alkoxy, cyano, or hydroxyl.

[0617] Embodiment A35. G 1 but,

[0618] [ka] And, Each R 12 These are independently halogen, (C1-C6)alkyl, (C1-C6)alkoxy, cyano, or hydroxyl. n is 0, 1, 2, or 3. " * The bonds marked with " are G 2 A compound described in Embodiment A34, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0619] Embodiment A36. Each R 12 The compound according to Embodiment A35, or a pharmaceutically acceptable salt thereof, wherein n is independently fluoro, methyl, methoxy, cyano, or -CHF2, and n is 0, 1, or 2.

[0620] Embodiment A37. G 1 but,

[0621] [ka] " * The bonds marked with " are G 2 A compound described in Embodiment A35, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0622] Embodiment A38. G1 but,

[0623] [ka] And, X 4 It is -O-, Each R 12 These are independently halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos. " * The bonds marked with " are G 2 A compound described in Embodiment A34, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0624] Embodiment A39. G 1 but,

[0625] [ka] " * The bonds marked with " are G 2 A compound described in Embodiment A38, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0626] Embodiment A44. G 1 teeth,

[0627] [ka] And, " * The bonds marked with " are G 2 A compound described in Embodiment A34, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0628] Embodiment A41. G 1 The compound according to Embodiment A1, or a pharmaceutically acceptable salt thereof, wherein is cyclohexylenyl.

[0629] Embodiment A42. G1 but,

[0630] [ka] " * The bonds marked with " are G 2 A compound described in Embodiment A41, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0631] Embodiment A43. G 1 The compound according to any one of Embodiments A1 to 33, or a pharmaceutically acceptable salt thereof, is a 7- to 11-membered heterocycloalkylenyl, which is optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6)alkyls, (C1-C6)alkoxys, or cyanos.

[0632] Embodiment A44. G 1 but,

[0633] [ka] And, Each R 13 These are independently selected from halogens, (C1-C6)alkyls, (C1-C6)alkoxys, or cyanos. o is 0, 1, 2, or 3. p, q, r, and s are independently 1 or 2. " * The bonds marked with " are G 2 A compound described in Embodiment A43, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0634] Embodiment A45. p and q are 1, r is 1 or 2, s is 1 or 2, R 13 However, the compound described in Embodiment A44, or a pharmaceutically acceptable salt thereof, is a halogen.

[0635] Embodiment A46. R 13 The compound according to Embodiment A45, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro and the element o is 0, 1, or 2.

[0636] Embodiment A47. G 1 but,

[0637] [ka] And, " * The bonds marked with " are G 2 A compound described in Embodiment A44, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0638] Embodiment A48. G 1 but,

[0639] [ka] And, a is either 0 or 1. b is either 0 or 1. " * The bonds marked with " are G 2 A compound described in Embodiment A43, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0640] Embodiment A49. G 1 but,

[0641] [ka] " * The bonds marked with " are G 2 A compound described in Embodiment A48, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0642] Embodiment A50. G 1 but,

[0643] [ka] " * The bonds marked with " are G 2 A compound described in Embodiment A43, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0644] Embodiment A51. G 2 However, the compound described in any one of Embodiments A1 to 50, or a pharmaceutically acceptable salt thereof, is directly bonded.

[0645] Embodiment A52. G 2 However, the compound described in any one of Embodiments A1 or 6 to 50, or a pharmaceutically acceptable salt thereof, wherein C(=O).

[0646] Embodiment A53. G 2 However, the compound described in any one of Embodiments A1 to 50 is a (C1-C6)alkylenyl, or a pharmaceutically acceptable salt thereof.

[0647] Embodiment A54. G 2 The compound described in Embodiment A53, or a pharmaceutically acceptable salt thereof, wherein the compound is -CH2-.

[0648] Embodiment A55. G 3 The compound according to any one of Embodiments A1 to 54, or a pharmaceutically acceptable salt thereof, is a 4- to 6-membered heterocycloalkylenyl, optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos.

[0649] Embodiment A56. G 3 but,

[0650] [ka] Each R 14These are independently halogens, (C1-C6) alkyls, (C1-C6) alkoxys, or cyanos. t is 0, 1, 2, or 3. " * The bonds marked with " are G 4 A compound described in Embodiment A55, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0651] Embodiment A57. R 14 A compound according to Embodiment A56, or a pharmaceutically acceptable salt thereof, wherein is fluoro or methyl and t is 0 or 1.

[0652] Embodiment A58. G 3 but,

[0653] [ka] " * The bonds marked with " are G 4 A compound according to Embodiment A56, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0654] Embodiment A59. G 3 The compound according to any one of Embodiments A1 to 54, or a pharmaceutically acceptable salt thereof, is a 7- to 11-membered heterocycloalkylenyl, which is optionally substituted with one, two, or three substituents independently selected from halogens, (C1-C6)alkyls, (C1-C6)alkoxys, or cyanos.

[0655] Embodiment A60. G 3 but,

[0656] [ka] " * The bonds marked with " are G 4 A compound according to Embodiment A1, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0657] Embodiment A61. G3 but,

[0658] [ka] And, " * The bonds marked with " are G 4 A compound described in Embodiment A59, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0659] Embodiment A62. G 3 but,

[0660] [ka] " * The bonds marked with " are G 4 A compound described in Embodiment A59, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0661] Embodiment A63. G 3 but,

[0662] [ka] And, Each R 15 These are independently selected from halogens, (C1-C6)alkyls, (C1-C6)alkoxys, or cyanos. u is 0, 1, 2, or 3. v, w, x, and y are independently 1, 2, or 3. " * The bonds marked with " are G 4 A compound described in Embodiment A59, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0663] Embodiment A64. The compound according to Embodiment A63, or a pharmaceutically acceptable salt thereof, wherein v, w, x, and y are independently 1 or 2.

[0664] Embodiment A65. R15 A compound according to Embodiment A63, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro.

[0665] Embodiment A66. G 3 but,

[0666] [ka] And, x a and y a These are independently 1 or 2, " * The bonds marked with " are G 4 A compound described in Embodiment A59, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0667] Embodiment A67. G 3 but,

[0668] [ka] " * The bonds marked with " are G 4 A compound described in Embodiment A59, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0669] Embodiment A68. G 3 but,

[0670] [ka] And, " * The bonds marked with " are G 4 A compound according to Embodiment A1, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0671] Embodiment A69. G 4 However, the compound described in any one of Embodiments A1 to 68, which is a (C1-C6) alkylenyl, or a pharmaceutically acceptable salt thereof.

[0672] Embodiment A70. G 4 The compound described in Embodiment A69, or a pharmaceutically acceptable salt thereof, wherein the compound is -CH2- or -CH2CH2-.

[0673] Embodiment A71. G 4 However, the compound described in Embodiment A1, which is a (C3-C6) cycloalkylenyl, or a pharmaceutically acceptable salt thereof.

[0674] Embodiment A72.G 4 but,

[0675] [ka] " * The bond marked with " is bonded to E, the compound described in Embodiment A71, or a pharmaceutically acceptable salt thereof.

[0676] Embodiment A73. G 4 but,

[0677] [ka] " * The bonds marked with " are G 4 A compound described in Embodiment A71, or a pharmaceutically acceptable salt thereof, bonded to the compound.

[0678] Embodiment A74. G 4 However, the compound described in any one of Embodiments A1 to 68, or a pharmaceutically acceptable salt thereof, is directly bonded.

[0679] Embodiment A75. L is,

[0680] [ka]

[0681] [ka] " * The bond marked with " is bonded to E, and is a compound according to any one of embodiments A1 to 33, or a pharmaceutically acceptable salt thereof.

[0682] Embodiment A76. L is,

[0683] [ka] " * The bond marked with " is bonded to E, and is a compound according to any one of embodiments A1 to 33, or a pharmaceutically acceptable salt thereof.

[0684] Embodiment A77. W is

[0685] [ka] The compound described in any one of embodiments A1 to 76, or a pharmaceutically acceptable salt thereof.

[0686] Embodiment A78. A compound according to any one of Embodiments A1 to A76, or a pharmaceutically acceptable salt thereof, wherein W is a direct bond.

[0687] Embodiment AR 7 , R 8 , R 9 , and R 10 A compound according to any one of embodiments A1 to 78, or a pharmaceutically acceptable salt thereof, wherein is H.

[0688] Embodiment A80. R 7 The compound described in any one of Embodiments A1 to 78, or a pharmaceutically acceptable salt thereof, is a halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, where the (C1-C6)alkyl is optionally substituted with one, two, or three halogens.

[0689] Embodiment A81. R 7The compound described in Embodiment A80, or a pharmaceutically acceptable salt thereof, is a halogen or (C1-C6)alkyl.

[0690] Embodiment A82. R 7 The compound described in Embodiment A81, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro or methyl.

[0691] Embodiment A83. R 8 , R 9 , and R 10 A compound according to any one of embodiments A80 to A82, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

[0692] Embodiment A84. R 8 The compound described in any one of Embodiments A1 to 78, or a pharmaceutically acceptable salt thereof, is a halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, where the (C1-C6)alkyl is optionally substituted with one, two, or three halogens.

[0693] Embodiment A85. R 8 The compound described in Embodiment A84, or a pharmaceutically acceptable salt thereof, is a halogen or a (C1-C6) alkyl group.

[0694] Embodiment A86. R 8 The compound described in Embodiment A85, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro or methyl.

[0695] Embodiment A87. R 7 , R 9 , and R 10 A compound according to any one of embodiments A84 to A86, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

[0696] Embodiment A88. R 9The compound described in any one of Embodiments A1 to 78, or a pharmaceutically acceptable salt thereof, is a halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, where the (C1-C6)alkyl is optionally substituted with one, two, or three halogens.

[0697] Embodiment A89. R 9 A compound according to Embodiment A88, or a pharmaceutically acceptable salt thereof, wherein the halogen is present.

[0698] Embodiment A90. R 9 A compound according to Embodiment A89, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro.

[0699] Embodiment A91. R 7 , R 8 , and R 10 A compound according to any one of embodiments A88 to A90, wherein the compound is hydrogen, or a pharmaceutically acceptable salt thereof.

[0700] Embodiment A92. R 10 The compound described in any one of Embodiments A1 to 78, or a pharmaceutically acceptable salt thereof, is a halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, where the (C1-C6)alkyl is optionally substituted with one, two, or three halogens.

[0701] Embodiment A93. R 10 A compound according to Embodiment A92, or a pharmaceutically acceptable salt thereof, wherein the halogen is present.

[0702] Embodiment A94. R 10 A compound according to Embodiment A93, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro.

[0703] Embodiment A95. R 7 , R 9 , and R 9 A compound according to any one of embodiments A92 to A94, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

[0704] Embodiment A96. R 10 A compound according to any one of embodiments A1 to 78, or a pharmaceutically acceptable salt thereof, wherein the compound is cyano.

[0705] Embodiment A97. R 10 is cyano, R 7 , R 8 , and R 9 A compound according to Embodiment A96, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

[0706] Embodiment A98. A compound of formula (V), or a pharmaceutically acceptable salt thereof,

[0707] [ka] (In the formula, Each R 12 is fluoro or hydroxyl, n is 0, 1, 2, or 3. E is

[0708] [ka] R 1 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0709] [ka] And, R 2 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or

[0710] [ka] And, however, (i)R 1If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 2 teeth,

[0711] [ka] And, (ii)R 2 If R is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, 1 teeth,

[0712] [ka] And, R 11 is hydrogen or -(C1-C6)alkyl-OP(=O)-(OH)2, X 1 CR 3 or N, R 3 is hydrogen, halogen, or (C1-C6) alkyl, X 2 CR 4 or N, R 4 is hydrogen, halogen, or (C1-C6) alkyl, R 5a This is hydrogen, halogen, (C1-C6) alkyl, (C3-C6) cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5 or 6-membered heteroaryl, where (C1-C6) alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen or cyano, and 4- to 6-membered heterocycloalkyl, aryl, or 5 or 6-membered heteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, cyano, or (C1-C6) alkyl. R 5b is hydrogen, (C1-C6) alkyl, or (C3-C6) cycloalkyl, R 6 is hydrogen, (C1-C6) alkyl, or cyano. X 3 is either -CH2CH2- or does not exist. G 3 This is a 4-6 member heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from tetrahydronaphthalene, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano, or a 7-11 member heterocycloalkyl-C(=O)- or 7-11 member heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano. G 4 It does not exist, or it is cyclobutyrenyl. R 7 , R 8 , R 9 , and R 10 These are independently hydrogen, fluoro, methyl, or cyano, R a These are hydrogen, chloro, methyl, or fluoro. R b These are hydrogen, chloro, methyl, or fluoro. R c (It is either hydrogen or methyl.)

[0713] Embodiment A99. G 3 but,

[0714] [ka] The compound described in Embodiment A98, or a pharmaceutically acceptable salt thereof.

[0715] Embodiment A100. G 3 but,

[0716] [ka] The compound described in Embodiment A98, or a pharmaceutically acceptable salt thereof.

[0717] Embodiment A101. G 3 but,

[0718] [ka] The compound described in Embodiment A98, or a pharmaceutically acceptable salt thereof.

[0719] Embodiment A102. A compound according to Embodiment A1, or a pharmaceutically acceptable salt thereof, selected from any one or more compounds from Compound List 1, Compound List 2, Compound List 3, Compound List 4, and / or Compound List 5, or a pharmaceutically acceptable salt thereof.

[0720] Embodiment A103. The compound is

[0721] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0722] Embodiment A104. The compound is

[0723] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0724] Embodiment A105. The compound is

[0725] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0726] Embodiment A106. The compound is

[0727] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0728] Embodiment A107. The compound is

[0729] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0730] Embodiment A108. The compound is

[0731] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0732] Embodiment A109. The compound is

[0733] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0734] Embodiment A110. The compound is

[0735] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0736] Embodiment A111. The compound is

[0737] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0738] Embodiment A112. The compound is

[0739] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0740] Embodiment A113. The compound is

[0741] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0742] Embodiment A114. The compound is

[0743] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0744] Embodiment A115. The compound is

[0745] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0746] Embodiment A116. The compound is

[0747] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0748] Embodiment A117. The compound is

[0749] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0750] Embodiment A118. The compound is

[0751] [ka] The compound described in Embodiment A1 or 102, or a pharmaceutically acceptable salt thereof.

[0752] Embodiment A119. A pharmaceutical composition comprising a compound described in any one of Embodiments A1 to A18 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0753] Embodiment A120. A method for degrading the SMARCA2 protein in a human, comprising administering to a human in need of such degradation an effective amount of a compound described in any one of Embodiments A1 to A18 or a pharmaceutically acceptable salt thereof, or a composition described in Embodiment A119.

[0754] Embodiment A121. A method for reducing the level of SMARCA2 activity in a human, comprising administering to a human in need of such reduction an effective amount of a compound described in any one of Embodiments A1 to A18 or a pharmaceutically acceptable salt thereof, or a composition described in Embodiment A119.

[0755] Embodiment A122. A method for treating cancer in a human, comprising administering to a person in need of such treatment an effective amount of a compound described in any one of Embodiments A1 to A18, or a pharmaceutically acceptable salt thereof, or a composition described in Embodiment A119.

[0756] Embodiment A123. The method according to Embodiment A122, wherein the cancer is a SMARCA2-sensitive cancer.

[0757] Embodiment A124. The method according to Embodiment A122, wherein the cancer is a SMARCA2 mutation cancer.

[0758] Embodiment A125. The method according to any one of Embodiments A122 to A124, wherein the cancer is a solid tumor.

[0759] Embodiment A126. The method according to any one of Embodiments A122 to A124, wherein the cancer is lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer.

[0760] Embodiment A127. A compound according to any one of Embodiments A1 to A104, or a pharmaceutically acceptable salt thereof, or a composition according to Embodiment 105A, for use in degrading the SMARCA2 protein in humans.

[0761] Embodiment A128. A compound according to any one of Embodiments A1 to A118, or a pharmaceutically acceptable salt thereof, or a composition according to Embodiment A119, for use in reducing the level of SMARCA2 activity in humans.

[0762] Embodiment A129. A compound according to any one of Embodiments A1 to A18, or a pharmaceutically acceptable salt thereof, or a composition according to Embodiment A119, for use in treating cancer in humans.

[0763] Embodiment A130. The compound for use according to Embodiment A129, wherein the cancer is a SMARCA2-sensitive cancer.

[0764] Embodiment A131. The compound for use according to Embodiment A129, wherein the cancer is a SMARCA2 mutation cancer.

[0765] Embodiment A132. The compound for use according to any one of Embodiments A129 to A131, wherein the cancer is a solid tumor.

[0766] Embodiment A133. The compound for use according to any one of Embodiments A129 to A131, wherein the cancer is lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer.

[0767] Embodiment A134. Use of a compound according to any one of Embodiments A1 to A18, or a pharmaceutically acceptable salt thereof, or the composition according to Embodiment A119, in the manufacture of a pharmaceutical for degrading the SMARCA2 protein in humans.

[0768] Embodiment A135. Use of a compound according to any one of Embodiments A1 to A18, or a pharmaceutically acceptable salt thereof, or the composition according to Embodiment A119, in the manufacture of a pharmaceutical product for reducing the level of SMARCA2 activity in humans.

[0769] Embodiment A136. Use of a compound according to any one of Embodiments A1 to A18, or a pharmaceutically acceptable salt thereof, or a composition according to Embodiment A119, in the manufacture of a pharmaceutical for the treatment of cancer in humans.

[0770] Embodiment A137. A compound, or a pharmaceutically acceptable salt thereof, for use according to Embodiment A136, wherein the cancer is a SMARCA2-sensitive cancer.

[0771] Embodiment A138. A compound, or a pharmaceutically acceptable salt thereof, for use according to Embodiment A136, wherein the cancer is a SMARCA2 mutation cancer.

[0772] Embodiment A139. A compound, or a pharmaceutically acceptable salt thereof, for use according to any one of Embodiments A136 to A138, wherein the cancer is a solid tumor.

[0773] Embodiment A140. A compound, or a pharmaceutically acceptable salt thereof, for use according to any one of Embodiments A136 to A138, wherein the cancer is lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer. [Examples]

[0774] General experimental conditions and abbreviations Use the following abbreviations: AcOH = acetic acid, aq = aqueous solution, BINAP = (±)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene, Boc = tert-butyloxycarbonyl, Brettphos Pd G3 = [(2-di-cyclohexylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)] palladium(II) methanesulfonate, t-BuBrettPhos Pd G3 = [(2-di-tert-butylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate, (tBu)PhCphos = 2-[(tert-butyl)phenylphosphino]-2',6'-bis(N,N-dimethylamino)biphenyl, Cs2CO3 = cesium carbonate, CuI = copper(I) iodide, CPhos = 2-dicyclohexylphosphino-2',6'-bis(N,N-dimethylamino)biphenyl, DCE = 1,2-dichloroethane, DCM = dichloromethane, DIBAL-H = diisobutylaluminum hydride, DIPEA = N,N-diisopropylethylamine, DMA = N,N-dimethylacetamide, DMAP = 4-dimethylaminopyridine, DMF = N,N-dimethylformamide, DMSO = dimethyl sulfoxide, siRNA = ethyl acetate, EtOH = ethanol, Ephos = dicyclohexyl(3-isopropoxy-2',4',6'-triisopropyl-[1,1'-biphenyl]-2-yl)phosphane, EPhos Pd G4 = EPhos containing palladium catalyst - CAS number: 2132978-44-8, FA = formic acid, FSC = flash silica chromatography, g = grams, h = hours, HATU = (dimethylamino)-N,N-dimethyl(3-oxide-1H-[1,2,3]triazolo[4,5-b] Pyridinyl) Methaneiminium Hexafluorophosphate, HCl = hydrochloric acid, HPLC = high-performance liquid chromatography, KOtBu = potassium tert-butoxide, K3PO4 = tripotassium phosphate, LiHMDS = lithium hexamethyldisilazide, LiOH = lithium hydroxide, M = molar concentration, mg = milligram, min = minute, mL = milliliter, mmol = millimoles, MeCN = acetonitrile, MeOH = methanol, MTBE = methyl tert-butyl ether, N2 = nitrogen gas, Na2CO3 = sodium carbonate, Na2SO4 = sodium sulfate, NEt3 = triethylamine, NH4Cl = ammonium chloride, NH4HCO3 = ammonium bicarbonate, NH4OH = ammonium hydroxide, NMP = N-methylpyrrolidinone, NMR = nuclear magnetic resonance, Na(OAc)3BH = triacetoxide Sodium borohydride, Pd / C = palladium carbon, PdCl2(PPh3)2 = bis(triphenylphosphine)palladium(II) dichloride, Pd(dba)2 = palladium(O) bis(dibenzylideneacetone), Pd2(dba)3 = tris(dibenzylideneacetone)dipalladium(O), Pd(dppf)Cl2 = [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II), iPrOH = isopropyl alcohol, PyBOP = benzotriazole-1-yloxytripyrrolidino-phosphonium hexafluorophosphate, rt = room temperature (approx. 18~25℃), RPC = reversed phase chromatography, RP-HPLC = reversed phase high-performance liquid chromatography, RuPhos = 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl, RuPhos Pd G3 = (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl) [2-(2'-amino-1,1'-biphenyl)] palladium(II) methanesulfonate, SFC = supercritical fluid chromatography, SPhos Pd G2 = chloro(2-dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl) [2-(2'-amino-1,1'-Biphenyl) Palladium(II), TFA = Trifluoroacetic acid, THF = Tetrahydrofuran, TsOH = p-Toluene sulfonic acid monohydrate, wt% = Weight percent, Pd XPhos G3 = (2-Dicyclohexylphosphino-2',4',6'-Triisopropyl-1,1'-Biphenyl)[2-(2'-Amino-1,1'-Biphenyl)] Palladium(II) methanesulfonate.

[0775] NMR: Proton NMR ( 1 Unless otherwise specified, 1H NMR was performed in deuterated DMSO at temperatures ranging from 15 to 30°C and at 300 to 500 MHz. 19 1F NMR was performed in DMSO unless otherwise specified. Standard NMR abbreviations are used: s=singleline, d=doubleline, t=tripleline, q=quadrupline, dd=doubleline of doubleline, dt=doubleline of tripleline, m=multiline, br=broad.

[0776] Chromatography: The clean fractions containing the desired product were generally identified, combined, and then concentrated under reduced pressure. Flash chromatography was performed using normal-phase silica FLASH+ (40M, 25M, or 12M), Biotage Sfar Silica HC (5g, 10g, 25g, 100g), or SNAP (KP-Sil) cartridges (340, 100, 50, or 10), or Agela Flash Column silica-CS columns in conjunction with C18 flash columns, or standard flash chromatography. RP-HPLC was performed using XSelect or XBridge columns.

[0777] In general, all solvents used were commercially available analytical solvents. The anhydrous solvents used were those commonly used for reactions. The phase separator used in the examples was an ISOLUTE® Phase Separator column.

[0778] The concentration of a solution (to partially or completely remove the solvent) is generally carried out under reduced pressure at room temperature or slightly above.

[0779] The intermediates and examples described below were named using BIOVIA Draw 20.1 or Chem Draw. Starting materials were obtained from commercial sources or prepared through literature channels.

[0780] Example 1 Intermediate 1a: 7-tert-butyl 2-methyl 7-azaspiro[3.5]nonane-2,7-dicarboxylate

[0781] [ka]

[0782] Cs2CO3 (4.84 g, 14.85 mmol) was added to iodomethane (1.054 g, 7.43 mmol) and 7-(tert-butoxycarbonyl)-7-azaspiro[3.5]nonane-2-carboxylic acid (2 g, 7.43 mmol) in DMF (10 mL). The resulting mixture was stirred at room temperature for 6 hours. 40 mL of water was added, and the aqueous layer was extracted with ethyl acetate (2 × 75 mL). The combined organic extract was dried over Na2SO4, filtered, and concentrated to obtain the title compound (2.0 g, 95%) as a white solid. 1 H NMR(DMSO-d6)δ1.32-1.42(11H,m), 1.44-1.52(2H,m), 1.85-1.95(2H,m), 1 .95-2.05(2H,m), 3.05-3.20(3H,m), 3.21-3.28(2H,m), 3.58(3H,s), m / z(ES + )[M+H] + = 284.3.

[0783] Intermediate 1b: Benzyl 8-(3-bromophenyl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

[0784] [ka]

[0785] To a stirred solution of Cs2CO3 (5.29 g, 16.24 mmol), palladium(II) acetate (0.182 g, 0.81 mmol), and BINAP (0.506 g, 0.81 mmol) in 1,4-dioxane (20 mL), 1,3-dibromobenzene (1.916 g, 8.12 mmol) and benzyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate (2.0 g, 8.12 mmol) were added at room temperature. The resulting mixture was stirred at 100 °C for 16 hours. The reaction mixture was diluted with water (100 mL), extracted with phenylethylamine (3 × 100 mL), the organic layer was dried (Na2SO4), filtered, and evaporated. Purification by FSC (gradient: 0-70% phenylethylamine in petroleum ether) yielded the title compound (1.3 g, 39.9%) as a white solid. 1 H NMR(DMSO-d6)δ1.52(2H,d), 1.83-1.93(2H,m), 2.91-3.09(4H,m), 4.28(2H,d), 5.0 5(2H,d), 6.26(2H,d), 6.35(1H,s), 6.97(1H,t), 7.25-7.40(5H,m), m / z(ES+)[M+H] + =366.1.

[0786] Intermediate 1c: Methyl 7-[3-(3-benzyloxycarbonyl-3,8-diazabicyclo[3.2.1]octan-8-yl)phenyl]-7-azaspiro[3.5]nonane-2-carboxylate

[0787] [ka]

[0788] 4M HCl in MeOH (5 mL, 164.57 mmol) was added to intermediate 1a (318 mg, 1.12 mmol). The resulting mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure to obtain a white solid. To the crude product, RuPhos Pd G3 (94 mg, 0.11 mmol), RuPhos (50.0 mg, 0.11 mmol), Cs2CO3 (1096 mg, 3.36 mmol), and intermediate 1b (450 mg, 1.12 mmol) were added under nitrogen in dioxane (10 mL). The resulting mixture was stirred at 100°C for 2 hours. The reaction mixture was filtered and concentrated. Purification by FSC (gradient: 0-100% ethyl ether in petroleum ether) yielded the title compound (530 mg, 94%) as a yellow solid. 1 H NMR(DMSO-d6)δ1.51-1.71(6H,m), 1.83-2.07(6H,m), 2.95-3.23(7H,m), 3.52-3.56(2H,m), 3. 59(3H,s), 4.25(2H,d), 5.05(2H,d), 6.21-6.42(3H,m), 6.98(1H,t), 7.21-7.47(5H,m), m / z(ES + )[M+H] + = 504.4.

[0789] Intermediate 1d: Benzyl 8-[3-[2-(dimethoxymethyl)-7-azaspiro[3.5]nonane-7-yl]phenyl]-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

[0790] [ka]

[0791] DIBAL-H (169 mg, 1.19 mmol) was added to intermediate 1c (300 mg, 0.60 mmol) in DCM (5 mL) at -50°C under nitrogen. The resulting mixture was stirred at -50°C for 1 hour. A saturated NH4Cl solution was added to the mixture. The aqueous layer was back-extracted with DCM (2 × 30 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated to obtain a yellow solid. The product was used directly in the next step without further purification. TsOH (113 mg, 0.60 mmol) and trimethyl orthoformate (190 mg, 1.79 mmol) in DCM (5 mL) were added to the residue. The resulting mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated. Purification by FSC (gradient 0-100% ethyl ether in petroleum ether) yielded the title compound (130 mg, 42.0%) as a yellow solid. 1 H NMR(DMSO-d6)δ1.52-1.71(6H,m), 1.80-2.10(6H,m), 2.95-3.27(5H,m), 3.34(6H,s), 3.56(1H,s), 3. 61(4H,s), 4.27(2H,d), 5.07(2H,d), 6.28(2H,d), 6.38(1H,s), 6.99(1H,t), 7.18-7.46(5H,m), m / z(ES + )[M+H] + = 520.

[0792] Intermediate 1e: 7-[3-(3,8-diazabicyclo[3.2.1]octan-8-yl)phenyl]-2-(dimethoxymethyl)-7-azaspiro[3.5]nonane

[0793] [ka]

[0794] Pd / C (11.06 mg, 0.10 mmol) was added to intermediate 1d (270 mg, 0.52 mmol) in MeOH (4 mL) under hydrogen. The resulting mixture was stirred at room temperature for 6 hours. The reaction mixture was filtered through celite®, and the filtrate was concentrated to obtain the title compound (80 mg, 39.9%) as a white solid. m / z(ES) + )[M+H] + = 386.1.

[0795] Intermediate 1f: 2-[6-amino-5-[8-[3-[2-(dimethoxymethyl)-7-azaspiro[3.5]nonane-7-yl]phenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol

[0796] [ka]

[0797] DIPEA (0.095 mL, 0.54 mmol) was added to intermediate 1e (70 mg, 0.18 mmol) and 4-bromo-6-chloropyridazine-3-amine (37.8 mg, 0.18 mmol) in NMP (3 mL). The resulting mixture was stirred at 100°C for 3 hours. The reaction mixture was diluted with water (10 mL) and extracted with RINKAN (30 mL x 2). The combined extract was dried over Na2SO4, filtered, and concentrated. The crude material was used in the next step. Cs2CO3 (177 mg, 0.54 mmol), XPhos Pd G3 (15.36 mg, 0.02 mmol), (2-hydroxyphenyl)boronic acid (37.6 mg, 0.27 mmol), dioxane (1 mL), and water (1 mL) were added to the residue. The resulting mixture was stirred at 100°C for 2 hours. The solvent was removed. Purification by RPC (0-90% MeOH in water containing 0.5% NH4HCO3 gradient) yielded the title compound (40.0 mg, 38.6%) as a yellow solid. m / zES + )[M+H] + = 571.

[0798] Intermediate 1g: tert-butyl 4-(5-bromo-3-methylindole-1-yl)piperidine-1-carboxylate

[0799] [ka]

[0800] To a stirred solution of tert-butyl 4-methylsulfonyloxypiperidine-1-carboxylate (13.90 g, 49.74 mmol) and 5-bromo-3-methyl-1H-indole (5.50 g, 26.18 mmol) in DMF (30 mL), Cs2CO3 (16.20 g, 49.72 mmol) was added under N2 at room temperature. The resulting mixture was stirred at 95°C for 8.5 hours. The mixture was cooled to room temperature, and then additional tert-butyl 4-methylsulfonyloxypiperidine-1-carboxylate (14.00 g, 50.10 mmol) and Cs2CO3 (16.00 g, 49.11 mmol) were added under N2. The resulting mixture was stirred at 95°C for 14 hours, then cooled to room temperature, and diluted with ELISA (200 mL). The mixture was washed with water (2 × 50 mL) and brine (2 × 50 mL). The organic layer was dried and concentrated (Na₂SO₄). Purification by FSC (gradient: 0–40% DCM in hexane, followed by 0–30% siRNA in hexane) yielded the title compound (5.85 g, 57%) as a white foam. 1 H NMR(CDCl3): δ1.50(9H,s), 1.81-1.95(2H,m), 2.00-2.07(2H,m), 2.28(3H,d), 2.82-2.99(2H, m), 4.21-4.40(3H,m), 6.95(1H,s), 7.16-7.24(1H,m), 7.28-7.30(1H,m), 7.69(1H,d), m / z(ES + )[M-tBu+2H] + = 336.8.

[0801] Intermediate 1h: tert-butyl4-[5-(2,4-dioxohexahydropyrimidine-1-yl)-3-methyl-indole-1-yl]piperidine-1-carboxylate

[0802] [ka]

[0803] 1,4-Dioxane (100 mL) was added to 1 g (4.20 g, 10.68 mmol) of a degassed flask intermediate, Cs2CO3 (6.96 g, 21.36 mmol), Pd2(dba)3 (0.885 g, 0.97 mmol), EPhos (1.028 g, 1.92 mmol), and hexahydropyrimidine-2,4-dione (3.66 g, 32.03 mmol) at room temperature under argon. Argon was injected into the mixture for 5 minutes, and then the mixture was stirred at 100°C for 14 hours. The mixture was cooled to room temperature, diluted with SiO2 (100 mL), and filtered through celite®. The filtrate was then concentrated. Purification by FSC (gradient: 0-100% SiO2 in hexane) yielded the title compound (3.06 g, 67%) as a grayish-white solid. 1 H NMR (CDCl3): δ1.52(9H,s), 1.85-1.97(2H,m), 2.02-2.09(2H,m), 2.32(3H,d), 2.85-2.97(4H,m), 3.9 3(2H,t), 4.26-4.40(3H,m), 7.02(1H,s), 7.13(1H,dd), 7.37(1H,d), 7.40(1H,s), 7.48(1H,s), m / z(ES + )[M+Na] + = 449.2.

[0804] Intermediate 1i: 1-[3-methyl-1-(4-piperidyl)indole-5-yl]hexahydropyrimidine-2,4-dione

[0805] [ka]

[0806] At room temperature, TFA (0.289 mL, 3.75 mmol) was added to a solution of intermediate 1h (80 mg, 0.19 mmol) in DCM (1.0 mL). After 1 hour, the mixture was concentrated. Diethyl ether (2 mL) was added, and the resulting mixture was sonicated to obtain a solid precipitate. The supernatant was removed, and the solid was dried under reduced pressure to obtain the title compound in the form of trifluoroacetate (83 mg, 100%) as a pale pink solid. m / z(ES) + )[M+H] + = 326.9.

[0807] 1-[1-[1-[[7-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-7-azaspiro[3.5]nonane-2-yl]methyl]-4-piperidyl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione

[0808] [ka]

[0809] Formic acid (1 mL, 26.07 mmol) was added to intermediate 1f (35 mg, 0.06 mmol). The resulting mixture was stirred at room temperature for 1 hour, and the solvent was removed under reduced pressure. The crude material was dissolved in DMF (1.0 mL) and DCE (1.0 mL), and intermediate 1i (20.0 mg, 0.06 mmol) was added. The resulting mixture was stirred at room temperature for 1 hour. Sodium triacetoxyborohydride (39.0 mg, 0.18 mmol) was added, and the mixture was stirred at room temperature for 1 hour. The solvent was removed under reduced pressure. Purification by RPC (gradient: 0-60% MeCN in water containing 0.1% FA) yielded the title compound (5.60 mg, 10.01%) as a white solid. 1H NMR (DMSO-d6): δ1.45(2H,t), 1.53-1.59(2H,m), 1.65-1.71(2H,m), 1.83-2.07(8H,m), 2.08-2.21(4H,m), 2.2 3(3H,s), 2.46(2H,d), 2.73(2H,t), 2.91-3.04(4H,m), 3.06-3.13(2H,m), 3.25(2H,d), 3.77(3H,t), 4.25(1H,d ), 4.39(2H,d), 5.95(2H,s), 6.25(1H,d), 6.26(1H,d), 6.43(1H,s), 6.83-6.90(2H,m), 6.98-7.09(2H,m), 7.19-7.26(1H,m), 7.31(1H,s), 7.39(1H,d), 7.43-7.50(2H,m), 7.92(1H,d), 10.27(1H,s) (OH protons were not observed, m / z(ES) + )[M+H] + = 835.1.

[0810] Example 2 Intermediate 2a: tert-butyl2-(5-bromo-3-cyclopropyl-pyrrolo[2,3-b]pyridin-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate

[0811] [ka]

[0812] 5-bromo-3-cyclopropyl-1H-pyrrolo[2,3-b]pyridine (600 mg, 2.53 mmol), tert-butyl 2-hydroxy-7-azaspiro[3.5]nonane-7-carboxylate (611 mg, 2.53 mmol), 2-(tributyl-15-phosphaneylidene)acetonitrile (1222 mg, 5.06 mmol), and m-xylene (15 mL) were placed in a vial. The reaction was heated at 110°C for 16 hours, then cooled to room temperature and concentrated under vacuum. Purification by RPC (gradient: 5-100% MeCN in water containing 0.1% NH4HCO3) yielded the title compound (1000 mg, 86%) as a yellow solid. 1H NMR (DMSO-d6): δ0.63-0.73(2H,m), 0.82-0.90(2H,m), 1.40(9H,s), 1.57-1.67(4H,m), 1.91-2.02(1H,m), 2.16-2. 27(2H,m), 2.32-2.42(2H,td), 3.21-3.34(4H,m), 5.13-5.36(1H,m), 7.59(1H,s), 8.20(1H,d), 8.26(1H,d), m / z(ES + )[M+H] + = 460.2.

[0813] Intermediate 2b: tert-butyl2-[3-cyclopropyl-5-(2,4-dioxohexahydropyrimidine-1-yl)pyrrolo[2,3-b]pyridine-1-yl]-7-azaspiro[3.5]nonane-7-carboxylate

[0814] [ka]

[0815] Hexahydropyrimidine-2,4-dione (873 mg, 7.65 mmol), tBuBrettPhos Pd G3 (327 mg, 0.38 mmol), intermediate 2a (1762 mg, 3.83 mmol), and K3PO4 (1625 mg, 7.65 mmol) were placed in a 40 mL vial. The vial was then capped, evacuated, and filled with nitrogen. 1,4-dioxane (20 mL) was added, and then nitrogen was injected into the mixture for 15 minutes. The reaction was then heated at 100 °C for 16 hours. The reaction was cooled to room temperature and then diluted with siRNA (50 mL), and filtered through celite®. The filtrate was concentrated under reduced pressure. The resulting residue was purified by FSC (gradient: 0-100% siRNA in hexane, followed by 0-30% MeOH in siRNA) to obtain the title compound (1446 mg, 77%) as a brown, dry, thin film. 1H NMR (DMSO-d6): δ0.65-0.72(2H,m), 0.84-0.92(2H,m), 1.41(9H,s), 1.59 -1.69(4H,m), 1.91-1.98(1H,m), 2.22-2.29(2H,m), 2.32-2.43(2H,m), 2. 72-2.80(2H,m), 3.21-3.30(2H,m), 3.36(2H,d), 3.78-3.87(2H,m), 5.20- 5.36(1H,m), 7.57(1H,s), 7.96(1H,d), 8.17(1H,d), 10.40(1H,s), m / z(ES + )[M+H] + = 494.3.

[0816] Intermediate 2c: 1-[1-(7-azaspiro[3,5]nonanane-2-yl)-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione

[0817] [ka]

[0818] TFA (6.00 mL) was added to a stirred solution of intermediate 2b (1.974 g, 4 mmol) in DCM (24 mL). The resulting solution was stirred for 2 hours. The reaction mixture was concentrated. The title compound (1.457 g, 93%) was obtained as a white solid by purification using ion-exchange chromatography (Porpak Rxn CX 50 g cartridge) eluting with 2N NH3 in MeOH. 1 1H NMR (DMSO-d6): δ 0.67-0.74 (2H,m), 0.82-0.90 (2H,m), 1.60 (4H,dt), 1.88-2.00 (1H,m), 2.15-2.23 (2H,m), 2.30-2.38 (2H,m), 2.57-2.62 (2H,m), 2.67-2.72 (2H,m), 2.77 (2H,t), 3.82 (2H,t), 5.24 (1H,quin), 7.54 (1H,s), 7.95 (1H,d), 8.17 (1H,d), 10.37 (1H,br s) (NH protons not observed), m / z (ES +)[M+H] + = 394.4。

[0819] Intermediate 2d: 1-Bromo-3-(3,3-diethoxyprop-1-ynyl)benzene

[0820]

Chem.

[0821] Into a vial, 3,3-diethoxyprop-1-yne (0.860 mL, 6.00 mmol), 1-bromo-3-iodobenzene (0.765 mL, 6 mmol), PdCl2(PPh3)2 (0.632 g, 0.90 mmol), CuI (0.171 g, 0.90 mmol), DMF (20 mL) and NEt3 (10 mL) were charged. The reaction was degassed and stirred at room temperature for 1.5 h. The reaction was diluted with water, extracted with DCM (2 × 20 mL), washed with brine, dried over Na2SO4 and concentrated in vacuo. Purification by FCS (0 - 12% EtOAc in hexane) gave the title compound (1.272 g, 74.9%) as a colorless oil. 1 H NMR (CDCl3): δ 1.28 (6H, t), 3.64 - 3.70 (2H, m), 3.81 (2H, dq), 5.48 (1H, s), 7.18 (1H, t), 7.40 (1H, d), 7.47 (1H, d), 7.63 (1H, s), m / z (ES + )[M - OEt] + = 238.9。

[0822] Intermediate 2e: tert-Butyl 8-[3-(3,3-diethoxyprop-1-ynyl)phenyl]-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

[0823]

Chem.

[0824] Under nitrogen, intermediate 2d (1.272 g, 4.49 mmol) and RuPhos Pd in ​​1,4-dioxane (24 mL) To a stirred solution of G3 (0.376 g, 0.45 mmol), dicyclohexyl (2',6'-diisopropoxy-[1,1'-biphenyl]-2-yl)phosphane (0.210 g, 0.45 mmol), and cesium carbonate (2.93 g, 8.98 mmol), tert-butyl (-3,8-diazabicyclo[3.2.1]octane-3-carboxylate) (0.954 g, 4.49 mmol) was added. The vial was sealed, flushed with nitrogen for 5 minutes, and heated at 90°C for 4 hours. The reaction was filtered through a celite® plug and concentrated. Purification by FSC (gradient: 0-50% ELISA in hexane) yielded the title compound (0.943 g, 50.6%) as a brown viscous oil. 1 H NMR (CDCl3): δ1.30(6H,t), 1.47(9H,s), 1.77-1.94(2H,m), 1.98-2.07(2H,m), 3.20(1H,br d), 3.30(1H,br d), 3.59-3.78(4H,m), 3.84(2H,dq), 4.12-4.23(2H,m), 5.50(1H,s), 6.79(1H,d), 6.89(1H,d), 6.92(1H,s), 7.19(1H,t), m / z(ES + )[M+H] + = 415.6.

[0825] Intermediate 2f: 8-[3-(3,3-diethoxyprop-1-inyl)phenyl]-3,8-diazabicyclo[3.2.1]octane

[0826] [ka]

[0827] Intermediate 2e (0.803 g, 1.94 mmol) and HCl solution (1.25 M in EtOH, 15.50 mL, 19.37 mmol) were added to a vial. The reaction was heated at 40°C for 2 hours. Upon concentration in vacuum, the title compound (609 mg, 100%) was obtained as a brown thin film. m / z(ES)+ )[M+H] + = 315.5。

[0828] Intermediate 2g: 6-Chloro-4-[8-[3-(3,3-diethoxyprop-1-ynyl)phenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-amine

[0829]

Chemical Structure

[0830] Into a vial, intermediate 2f (610 mg, 1.94 mmol), 4-bromo-6-chloropyridazin-3-amine (809 mg, 3.88 mmol), n-butanol (8 mL), and DIPEA (1.694 mL, 9.70 mmol) were charged. The reaction was heated at 110 °C for 19 h. Purification by FCS (0 - 100% EtOAc in hexane, then 0 - 25% MeOH in EtOAc) gave a mixture of acetal products. This material was stirred in HCl solution (1.25 M in EtOH, 0.3 mL, 0.4 mmol) and EtOH (10 mL) at 50 °C for 18 h. Concentration in vacuo gave the title compound (351 mg, 40.9%) as a brown solid. 1 H NMR (DMSO-d6): δ 1.17 (6H, t), 1.9l - 1.97 (2H, m), 2.04 - 2.14 (2H, m), 3.12 (2H, br d), 3.24 (2H, br d), 3.37 - 3.47 (1H, m), 3.50 - 3.62 (2H, m), 3.66 - 3.72 ( 2H, m), 4.45 (2H, br s), 5.51 (1H, s), 6.79 (1H, d), 6.95 - 7.05 (3H, m), 7.14 (1H, s), 7.22 (1H, t), m / z (ES + )[M+H] + = 442.3。

[0831] Intermediate 2h: 2-[6-amino-5-[8-[3-(3,3-diethoxyprop-1-inyl)phenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol

[0832] [ka]

[0833] 1,4-Dioxane (7 mL) and water (0.700 mL) were mixed with (2-hydroxyphenyl)boronic acid (164 mg, 1.19 mmol), Cs2CO3 (518 mg, 1.59 mmol), and Xphos Pd G3 (67.2 mg, 0.08 mmol). 2 g of the intermediate (351 mg, 0.79 mmol) was added. The solution was aerated with N2 for 10 minutes, and the vial was degassed. The vial was sealed and stirred at 100°C for 30 minutes. The reaction was cooled to room temperature and concentrated under reduced pressure. The crude residue was partitioned between saturated NaHCO3 (50 mL) and DCM (50 mL). The aqueous layer was extracted with DCM (2 × 20 mL), and the combined organic extracts were washed with brine, dried, filtered, and concentrated. Purification by FSC (gradient: 0-100% butyl in hexane) yielded the title compound (239 mg, 60.2%) as a brown solid. 1 H NMR (DMSO-d6): δ1.14-1.21(6H,m), 1.94-1.99(2H,m), 2.09-2.25(2H,m), 3.08(2H,br d), 3.22-3.31(2H,m), 3.49-3.61(2H,m), 3.69(2H,dq), 4.47(2H,br s), 5.51(1H,s), 5.94(2H,s), 6.77(1H,d), 6.83-6.90(2H,m), 6.95-7.00(2H,m), 7.15-7.29(2H,m), 7.48(1H,s), 7.92(1H,d), 14.16(1H,br s), m / z (ES + )[M+H] + = 500.4.

[0834] Intermediate 2i: 3-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]propa-2-inal

[0835] [ka]

[0836] Intermediate 2h (153 mg, 0.31 mmol) and formic acid (0.5 mL) were added to a vial. The reaction was stirred at 40°C for 10 minutes. The reaction was concentrated under vacuum and dried by freeze-drying. The title compound was obtained as a brown solid (121 mg, 93%). m / z(ES) + )[M+H] + = 426.4.

[0837] 1-[1-[7-[3-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]propa-2-inyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione

[0838] [ka]

[0839] Intermediate 2c (59.0 mg, 0.15 mmol), intermediate 2i (63.8 mg, 0.15 mmol), and NMP (1.5 mL) were placed in vials. The solutions were stirred at room temperature for 30 minutes. Na(OAc)3BH (95 mg, 0.45 mmol) was added, and the reaction was stirred at room temperature for 15 minutes, followed by concentration under vacuum. Purification with RPC (0-50% MeCN in water containing 0.1% FA) yielded the title compound (12.12 mg, 9.84%). 1H NMR (DMSO-d6): δ0.66-0.70(2H,m), 0.83-0.89(2H,m), 1.70-1.80(4H,m), 1.89-1.98(3H,m), 2.14(2H,br d), 2.20-2.28(2H,m), 2.33-2.39(2H,m), 2.43-2.48(1H,m), 2.54-2.58(1H,m), 2.76(2H,t), 3.07(2H,br d), 3.19-3.24(2H,m), 3.45(2H,s), 3.76-3.85(4H,m), 4.44(2H,br s), 5.26(1H,quin), 5.92(2H,s), 6.72(1H,d), 6.83(1H,t), 6.87(1H,d), 6.89-6.96(2H,m), 7.15-7.24(2H,m) , 7.47(1H,s), 7.55(1H,s), 7.91(1H,dd), 7.94(1H,d), 8.16(1H,d), 10.37(1H,s), 13.17-15.05(1H,m), m / z(ES + )[M+H] + = 803.7.

[0840] Example 3 Intermediate 3a: 1-(3-bromophenyl)-4-(dibutoxymethyl)piperidine

[0841] [ka]

[0842] The solution was passed through with N2 for 10 minutes to degass the mixture of Pd2(dba)3 (0.229 g, 0.25 mmol), xanthophos (0.289 g, 0.50 mmol), potassium tert-butoxide (1.122 g, 10.00 mmol), 1-bromo-3-iodobenzene (0.956 mL, 7.50 mmol), 4-(dibutoxymethyl)piperidine (1.217 g, 5 mmol), and toluene (36 mL). The reaction was heated at 85°C for 1.75 hours, cooled to room temperature, and concentrated under reduced pressure. Purification by FSC (gradient: 0-20% siRNA in hexane) yielded the title compound (1.758 g, 88%) as a yellow oil. 1H NMR(CDCl3): δ0.94(6H,t), 1.35-1.49(6H,m), 1.53-1.63(4H,m), 1.71-1.84(1H,m), 1.87(2H,br d), 2.65-2.73(2H,m), 3.40-3.49(2H,m), 3.64(2H,dt), 3.69(2H,br d), 4.19(1H,d), 6.84(1H,dd), 6.89-6.95(1H,m), 7.03-7.06(1H,m), 7.06-7.11(1H,m), m / z(ES + )[M+Na] + =399.4.

[0843] Intermediate 3b: Benzyl 8-[3-[4-(dibutoxymethyl)-1-piperidyl]phenyl]-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

[0844] [ka]

[0845] The intermediate was prepared from benzyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate (0.927 g, 3.77 mmol) and intermediate 3a (1.50 g, 3.77 mmol) in the same manner as for intermediate 2e. Purification by FSC (gradient: 0-50% phenylethylamine in hexane) yielded the title compound (1.310 g, 61.7%) as a light brown oily substance. 1 H NMR(CDCl3): δ0.96(6H,t), 1.39-1.54(6H,m), 1.55-1.64(4H,m), 1.71-1.91(5H,m) , 2.00-2.06(2H,m), 2.67(2H,td), 3.32-3.53(4H,m), 3.62-3.74(6H,m), 3.79(1H,br d), 4.19-4.25(2H,m), 5.15(2H,s), 6.29-6.35(1H,m), 6.38-6.45(2H,m), 7.13(1H,t), 7.30-7.39(5H,m), m / z(ES + )[M+Na] + = 586.7.

[0846] Intermediate 3c: 8-[3-[4-(dibutoxymethyl)-1-piperidyl]phenyl]-3,8-diazabicyclo[3.2.1]octane

[0847] [ka]

[0848] Pd / C (100 mg, 0.09 mmol) was added, and intermediate 3b (1.3095 g, 2.32 mmol) and ammonium formate (1.465 g, 23.23 mmol) in MeOH (15 mL) were stirred at 50°C for 30 minutes. The reaction was cooled to room temperature, filtered through a celite® plug, eluted with MeOH and ethyl acetate, and concentrated. The resulting residue was partitioned between DCM (20 mL) and saturated NaHCO3 aqueous solution (20 mL). The layers were separated, and the aqueous layer was extracted with DCM (2 × 20 mL). The combined organic extracts were washed with water and brine, dried, and concentrated. The crude product had sufficient purity and was used in the next step without further purification to obtain the title compound (0.838 g, 84%) as a yellow solid. 1 H NMR (DMSO-d6): δ0.89(6H,t), 1.27-1.41(6H,m), 1.45-1.55(4H,m), 1.71(3H,br d), 1.78-1.93(4H,m), 2.39(2H,br d), 2.49-2.59(3H,m), 2.95(2H,br d), 3.39(2H,dt), 3.56(2H,dt), 3.63(2H,br d), 4.04(2H,br s), 4.19(1H,d), 6.18-6.25(2H,m), 6.29(1H,s), 6.96(1H,t), m / z(ES + )[M+Na] + = 452.2.

[0849] Intermediate 3D: 6-Chloro-4-[8-[3-[4-(dibutoxymethyl)-1-piperidyl]phenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazine-3-amine

[0850] [ka]

[0851] A mixture of intermediate 3c (838.2 mg, 1.95 mmol), 4-bromo-6-chloropyridazine-3-amine (813 mg, 3.90 mmol), DIPEA (9.75 mmol, 1.704 mL), and n-butanol (10 mL) was heated at 110°C for 8 hours. The reaction was cooled to room temperature and concentrated. Purification by FSC (gradient: 0-100% ethyl hexane) yielded the title compound (657 mg, 60.4%) as a brown solid. 1 H NMR (DMSO-d6): δ0.89(6H,t), 1.27-1.40(6H,m), 1.44-1.53(4H,m), 1.61-1.7 4(3H,m), 1.87-1.94(2H,m), 2.05-2.11(2H,m), 2.52-2.59(2H,m), 2.95(2H,br d), 3.17(2H,br d), 3.34-3.43(2H,m), 3.56(2H,dt), 3.66(2H,br d), 4.19(1H,d), 4.34(2H,br s), 5.79(2H,s), 6.27(1H,br d), 6.31(1H,br d), 6.39(1H,s), 6.85(1H,s), 7.00(1H,t), m / z(ES + )[M+H] + = 557.2.

[0852] Intermediate 3e: 2-[6-amino-5-[8-[3-[4-(dibutoxymethyl)-1-piperidyl]phenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol

[0853] [ka]

[0854] Starting with intermediate 3d (547 mg, 0.98 mmol), the compound was prepared in the same manner as intermediate 2h. Purification by FSC (gradient: 0-100% butyl in hexane) yielded the title compound (516 mg, 85%) as a brown solid. 1 H NMR (DMSO-d6): δ0.89(6H,t), 1.27-1.40(6H,m), 1.45-1.51(4H,m), 1.58-1.7 7(3H,m), 1.88-2.02(2H,m), 2.10-2.18(2H,m), 2.54-2.61(2H,m), 3.11(2H,br d), 3.27(2H,br d), 3.39(2H,dt), 3.56(2H,dt), 3.67(2H,br d), 4.19(1H,d), 4.39(2H,br s), 5.97(2H,br s), 6.28(1H,br d), 6.35(1H,br d), 6.43(1H,s), 6.84-6.90(2H,m), 7.02(1H,t), 7.23(1H,t), 7.45(1H,s), 7.89(1H,d), 14.05(1H,br s), m / z(ES + )[M+H] + = 615.4.

[0855] 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione

[0856] [ka]

[0857] Intermediate 3e (30.7 mg, 0.05 mmol), intermediate 2b (24.68 mg, 0.05 mmol), and formic acid (0.5 mL) were placed in a vial. The reaction was stirred at 40°C for 20 minutes, and then concentrated under vacuum. The resulting thin film was dissolved in DCM (0.5 mL) and iPrOH (0.100 mL) and stirred at room temperature for 30 minutes. Na(OAc)3BH (21.19 mg, 0.10 mmol) was added, and the reaction was stirred at room temperature for 30 minutes, and then concentrated under vacuum. Purification with RPC (0-100% MeCN in water containing 0.1% NH4OH) yielded the title compound (11.57 mg, 26.1%) as a white solid. 1 H NMR(DMSO-d6):δ0.69(2H,br d), 0.81-0.92(2H,m), 1.15-1.22(2H,m), 1.24-1.31(2H,m), 1.63-1.80(6 H,m), 1.90-1.98(3H,m), 2.09-2.26(6H,m), 2.28-2.45(5H,m), 2.62(2H,br t), 2.76(2H,br t), 3.10(2H,br d), 3.26(2H,br d), 3.65(2H,br d), 3.81(2H,br t), 4.39(2H,br s), 5.25(1H,quin), 5.93(2H,br s), 6.25-6.31(1H,m), 6.34(1H,br d), 6.42(1H,br s), 6.81-6.92(2H,m), 7.02(1H,br t), 7.23(1H,br t), 7.46(1H,s), 7.55(1H,s), 7.89-7.98(2H,m), 8.16-8.22(1H,m), 10.37(1H,s), 13.15-14.59(1H,m), m / z(ES + )[M+H] + = 862.6.

[0858] Example 4 Intermediate 4a: tert-butyl2-(5-bromo-3-methyl-indole-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate

[0859] [ka]

[0860] 5-Bromo-3-methyl-1H-indole (525 mg, 2.5 mmol), tert-butyl 2-hydroxy-7-azaspiro[3.5]nonane-7-carboxylate (1207 mg, 5.00 mmol), 2-(tributyl-15-phosphaneylidene)acetonitrile (1.310 mL, 5.00 mmol), and toluene (12 mL) were placed in a vial. The reaction was heated at 100°C for 6 hours, cooled to room temperature, and concentrated under vacuum. Purification by FCS (0-50% ethyl acetate in hexane) yielded the title compound (824 mg, 76%) as a yellow solid. 1 H NMR(CDCl3): δ1.48(9H,s), 1.59-1.64(2H,m), 1.70-1.77(2H,m), 2.16-2.22(2H,m), 2.30(3H,s), 2.51-2.58(2H,m), 3 .31-3.39(2H,m), 3.42-3.49(2H,m), 4.80(1H,quin), 7.02(1H,s), 7.14(1H,d), 7.23-7.26(1H,m), 7.68(1H,d), m / z(ES + )[M-tBu+2H] + = 377.1.

[0861] Intermediate 4b: tert-butyl2-[5-(2,4-dioxohexahydropyrimidine-1-yl)-3-methyl-indole-1-yl]-7-azaspiro[3.5]nonane-7-carboxylate

[0862] [ka]

[0863] Intermediate 4a (824 mg, 1.90 mmol), hexahydropyrimidine-2,4-dione (651 mg, 5.70 mmol), Cs2CO3 (1239 mg, 3.80 mmol), Ephos (102 mg, 0.19 mmol), and Ephos Pd G4 (175 mg, 0.19 mmol) were placed in a vial. The vial was evacuated and filled with nitrogen. 1,4-dioxane (12 mL) was added, and the reaction mixture was degassed by passing nitrogen through the solution for 10 minutes. The vial was sealed, and the resulting mixture was stirred at 100°C for 16 hours. The solvent was removed. Purification by FSC (gradient: 0-100% siRNA in hexane) yielded the title compound (727 mg, 82%) as a grayish-white solid. 1 H NMR (DMSO-d6): δ1.39(9H,s), 1.53-1.59(2H,m), 1.64-1.71(2H,m), 2.09-2.14(2H,m), 2.24(3H,s), 2.41-2.47(2H,m), 2.71(2H ,t), 3.19-3.27(2H,m), 3.32-3.36(2H,m), 3.75(2H,t), 4.98(1H,quin), 7.03(1H,dd), 7.36-7.43(3H,m), 10.23(1H,s), m / z(ES + )[M+Na] + = 489.2.

[0864] 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione

[0865] [ka]

[0866] Starting with intermediate 3e (30.7 mg, 0.05 mmol) and intermediate 4b (23.33 mg, 0.05 mmol), preparations were carried out in the same manner as in Example 3. Purification by RPC (gradient: 0-100% MeCN in water containing 0.1% NH4OH) yielded the title compound (11.30 mg, 25.5%) as a pale yellow solid. 1 H NMR (DMSO-d6): δ1.15-1.28(6H,m), 1.62-1.68(2H,m), 1.72-1.81(3H,m), 1.89-1.97(2H,m), 2.0 4-2.16(4H,m), 2.19-2.22(1H,m), 2.24(3H,s), 2.29-2.34(1H,m), 2.36-2.46(3H,m), 2.61(2H,br t), 2.71(3H,br t), 3.08(2H,br d), 3.25(2H,br d), 3.64(2H,br d), 3.75(2H,br t), 4.38(2H,br s), 4.88-5.01(1H,m), 5.92(2H,br s), 6.27(1H,br d), 6.33(1H,br d), 6.41(1H,br s), 6.81-6.89(2H,m), 6.94-7.09(2H,m), 7.21(1H,br t), 7.34-7.49(4H,m), 7.90(1H,br d), 10.23(1H,s), 12.39-14.59(1H,m), m / z(ES + )[M+H] + = 835.6.

[0867] Example 5 Intermediate 5a: tert-butyl 4-(4-bromoindole-1-yl)piperidine-1-carboxylate

[0868] [ka]

[0869] Under N2 conditions at room temperature, 2-tributyl-15-phosphaneylidene)acetonitrile (92.0 g, 382.56 mmol) was added to a stirred solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (77.0 g, 382.56 mmol) and 4-bromo-1H-indole (50.0 g, 255.04 mmol) in toluene (500 mL). The resulting mixture was stirred at 100 °C for 18 hours, then cooled to room temperature and concentrated under reduced pressure. Purification by RPC (gradient: 0-70% MeCN in water containing 0.4% NH4HCO3) yielded the title compound (20.0 g, 21%) as a yellow solid. 1 H NMR (DMSO-d6): δ1.44(9H,s), 1.76-2.00(4H,m), 2.98(2H,m), 4.13(2H,d), 4.60 (1H,m), 6.42(1H,d), 7.08(1H,t), 7.23-7.28(1H,m), 7.58-7.74(2H,m), m / z(ES + )[M+H] + =379.1.

[0870] Intermediate 5b: tert-butyl 4-[4-(2,4-dioxohexahydropyrimidine-1-yl)indole-1-yl]piperidine-1-carboxylate

[0871] [ka]

[0872] Starting with intermediate 5a (5 g, 13.18 mmol), the compound was prepared in the same manner as intermediate 4b. Purification by FSC (gradient: 0-60% butyl in petroleum ether) yielded the title compound (5.20 g, 96%) as a yellow solid. 1H NMR(CDCl3): δ1.52(9H,s), 1.86-2.01(2H,m), 2.06-2.14(2H,m), 2.86-3.00(4H,m), 3.95(2H,t), 4.23-4.50(3H,m), 6.42(1H,d), 7.06(1H,d), 7.22-7.27(2H,m), 7.38(1H,d), 7.55(1H,s), m / z(ES + )[M+Na] + = 435.2.

[0873] Intermediate 5c: 1-[1-(4-piperidyl)indole-4-yl]hexahydropyrimidine-2,4-dione

[0874] [ka]

[0875] Intermediate 5b (7.0 g, 16.97 mmol) was added to AcOH (20 mL). The resulting mixture was stirred at 100°C for 72 hours, then cooled to room temperature and concentrated under reduced pressure. Purification by RPC (gradient: 0-60% MeCN in water containing 0.4% HCl) yielded the title compound in the form of hydrochloride (4.50 g, 85%) as a red solid. 1 ¹H NMR (DMSO-d6): δ 1.89-2.30 (4H,m), 2.47-2.50 (2H,m), 2.75 (2H,t), 2.99-3.14 (2H,m), 3.76 (2H,t), 4.60-4.77 (1H,m), 6.44 (1H,d), 6.97 (1H,d), 7.16 (1H,t), 7.39 (1H,d), 7.57 (1H,d), 10.33 (1H,s) (NH protons not observed), m / z (ES + )[M+H] + = 313.2.

[0876] 1-[1-[1-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-4-piperidyl]indole-4-yl]hexahydropyrimidine-2,4-dione

[0877] [ka]

[0878] Starting with intermediate 3e (61.5 mg, 0.1 mmol) and intermediate 5c (97 mg, 0.20 mmol), preparations were carried out in the same manner as in Example 3. Purification with RPC (0-100% MeCN in water containing 0.1% NH4OH) yielded the title compound (22.30 mg, 26.3%) as a pale yellow solid. 1 H NMR (DMSO-d6): δ1.18-1.25(2H,m), 1.61-1.72(1H,m), 1.80(2H,br d), 1.88-2.05(6H,m), 2.09-2.15(2H,m), 2.19(2H,br t), 2.26(2H,br d), 2.62(2H,br t), 2.75(2H,t), 3.00(2H,br d), 3.09(2H,br d), 3.25(2H,br d), 3.66(2H,br d), 3.77(2H,t), 4.30-4.48(3H,m), 5.92(2H,s), 6.28(1H,br d), 6.33(1H,br d), 6.36-6.46(2H,m), 6.81-6.88(2H,m), 6.93-6.97(1H,m), 7.01(1H,t), 7.1 0-7.17(1H,m), 7.21(1H,t), 7.42-7.47(1H,m), 7.48-7.54(2H,m), 7.90(1H,br d), 10.31(1H,s), 12.34-14.69(1H,m), m / z(ES + )[M+H] + = 781.4.

[0879] Example 6 Intermediate 6a: tert-butyl9-(5-bromo-3-methyl-indole-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate

[0880] [ka]

[0881] At room temperature under nitrogen, 2.56 g, 9.52 mmol of tert-butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate and 1 g, 4.76 mmol of 5-bromo-3-methylindole were added to toluene (20 mL) with 3.74 mL, 14.28 mmol of 2-tributyl-15-phosphaneylidene)acetonitrile. The resulting mixture was stirred at 120 °C for 16 hours. The reaction mixture was poured into water (200 mL), extracted with ethyl acetate (3 × 200 mL), and the organic layer was dried over Na₂SO₄, filtered, and concentrated. Purification by FSC (gradient petroleum ether 0-20% ethyl acetate) yielded the title compound (1.900 g, 86%) as a white solid. 1 H NMR(DMSO-d6)δ1.24-1.38(4H,m), 1.41(9H,s), 1.58(2H,t), 1.65-1.97(7H,m), 2.22(3H,d), 3.31( 2H,d), 3.34(1H,s), 4.17-4.34(1H,m), 7.20(1H,dd), 7.38(1H,s), 7.44(1H,d), 7.64(1H,d), m / z(ES + )[M-tBu+2H] + = 405.2.

[0882] Intermediate 6b: tert-butyl9-[5-(2,4-dioxohexahydropyrimidine-1-yl)-3-methyl-indole-1-yl]-3-azaspiro[5.5]undecane-3-carboxylate

[0883] [ka]

[0884] Under nitrogen, di-μ-chlorobis[(1,2,3-4)-1-phenyl-2-propenyl]dipalladium(II) (0.057 g, 0.10 mmol) was added to intermediate 6a (1.9 g, 4.12 mmol), hexahydropyrimidine-2,4-dione (1.409 g, 12.35 mmol), Cs2CO3 (4.02 g, 12.35 mmol), and 2-(di-tert-butylphosphino)-2',4',6'-triisopropyl-3,6-dimethoxy-1,1'-biphenyl (0.100 g, 0.21 mmol) in dioxane (40 mL). The resulting mixture was stirred at 100 °C for 10 hours. The reaction mixture was filtered through celite®. The filtrate was poured into water (500 mL), extracted with ethyl acetate (3 × 500 mL), and the combined organic extract was dried (Na₂SO₄), filtered, and evaporated. The crude product was purified by FSC (gradient: 0-10% MeOH in DCM) to obtain the title compound (1.0 g, 49.1%) as a brown solid. 1 H NMR (DMSO-d6): δ1.41(13H,s), 1.60(2H,t), 1.69-2(6H,m), 2.24(3H,d), 2.51(2H,t), 2.73(2H,t), 3.7 7(2H,t), 4.28(1H,s), 5.76(2H,s), 7.04(1H,dd), 7.33-7.42(2H,m), 7.45(1H,d), 10.26(1H,s), m / z(ES + )[M+H] + = 495.2.

[0885] Intermediate 6c: 1-[1-(3-azaspiro[5,5]undecane-9-yl)-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione

[0886] [ka]

[0887] Intermediate 6b (1.5 g, 3.03 mmol) in MeCN (30 mL) was mixed with p-toluenesulfonic acid (0.627 g, 3.64 mmol) and stirred at 70°C for 3 hours. The product was filtered to obtain the title compound (1.0 g, 58.2%) as a white solid in the form of a tosylate. m / z(ES) + )[M+H] + =395.1.

[0888] Intermediate 6d: tert-butyl 8-(3-bromophenyl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

[0889] [ka]

[0890] Starting with 1,3-dibromobenzene (2.22 g, 9.42 mmol) and tert-butyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate (2 g, 9.42 mmol), the intermediate was prepared in the same manner as intermediate 1b. Purification by FSC (gradient: 0-30% SiO in petroleum ether) yielded the title compound (2.2 g, 63.6%) as a white solid, m / z (ES). + )[M+H] + =367.0.

[0891] Intermediate 6e: tert-butyl8-[3-[4-(dimethoxymethyl)-1-piperidyl]phenyl]-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

[0892] [ka]

[0893] A mixture of RuPhos (0.254 g, 0.54 mmol), RuPhos Pd G3 (0.455 g, 0.54 mmol), Cs2CO3 (5.32 g, 16.34 mmol), 4-(dimethoxymethyl)piperidine (0.867 g, 5.45 mmol), and intermediate 6d (2 g, 5.45 mmol) in 1,4-dioxane (40 mL) was stirred at 100 °C for 16 hours. The reaction mixture was diluted with water (100 mL), extracted with HCl (3 × 500 mL), the organic layer was dried (Na2SO4), filtered, and concentrated. Purification by FSC (gradient: 0-40% HCl in petroleum ether) yielded the title compound (2.0 g, 82%) as a yellow solid. m / z (ES) + )[M+H] + = 446.2.

[0894] Intermediate 6f: 6-Chloro-4-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]phenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazine-3-amine

[0895] [ka]

[0896] At room temperature, HCl (10 mL, 40.00 mmol) in MeOH was added to intermediate 6e (1.3 g, 2.92 mmol). The resulting mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure to obtain the amine. To the crude amine, 4-bromo-6-chloropyridazine-3-amine (0.608 g, 2.92 mmol), DIPEA (0.377 g, 2.92 mmol), and MeCN (15 mL) were added at room temperature. The resulting mixture was stirred at 80°C for 3 days. The reaction mixture was diluted with water (200 mL), extracted with siRNA (3 × 200 mL), the organic layer was dried (Na₂SO₄), filtered, and evaporated. Purification by RPC (gradient: 5-100% MeCN in water containing 0.1% NH₄HCO₃) yielded the title compound (0.900 g, 65.2%) as a yellow solid. 11H NMR (DMSO-d6): δ 1.92 (1H, s), 2.29 (3H, s), 3.06 - 3.21 (8H, m), 3.36 (6H, s), 3.52 - 3.69 (7H, m), 5.77 (4H, s), 7.13 (2H, d), 7.42 - 7.53 (2H, m), m / z (ES + ) [M + H] + = 473.0

[0897] Intermediate 6g: 1-[1-[3-[[1-[3-[3-(3-Amino-6-chloro-pyridazin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione

[0898]

Chemical Structure

[0899] Formic acid (1.0 mL) was added to Intermediate 6f (100 mg, 0.21 mmol). The resulting mixture was stirred at 40 °C for 30 minutes. The solvent was removed under reduced pressure to obtain the aldehyde. To the crude aldehyde, Intermediate 6c (120 mg, 0.21 mmol) and DCM (1 mL) were added at room temperature. Sodium triacetoxyborohydride (67.2 mg, 0.32 mmol) was added to the resulting solution, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with DCM (25 mL) and washed with saturated NH4HCO3 (3 × 25 mL). The organic layer was separated, dried (Na2SO4), filtered, and evaporated. Purification by FCS (gradient: 0 - 10% MeOH in DCM) gave the title compound (60.0 mg, 35.2%) as a yellow solid. 1H NMR (DMSO-d6): δ1.15-1.51(4H,m), 1.84(14H,d), 2.09(2H,d), 2.21-2.32(5H,m), 2.57-2.77(5H,m), 2.95(2H,d), 3.17(2H,d), 3.66(3 H,d), 3.77(3H,t), 4.32(4H,d), 5.82(2H,s), 6.26-6.46(3H,m), 6.87(1H,s), 6.97-7.1(2H,m), 7.3-7.49(4H,m), 10.26(1H,s), m / z(ES + )[M+H] + = 805.0.

[0900] 1-[1-[3-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione

[0901] [ka]

[0902] Starting with 6 g (45 mg, 0.06 mmol) of the intermediate, preparation was carried out in the same manner as for 2 h of the intermediate. Purification by RPC (gradient: 0-50% MeCN in water containing 0.1% FA) yielded the title compound (6.80 mg, 14.10%) as a white solid. 1H NMR (DMSO-d6): δ1.12-1.26(2H,m), 1.29-1.41(4H,m), 1.67(3H,s), 1.77(6H,q), 1.88(2H,d), 1.92-1.98(2H,m), 2.17(4H,dd), 2.23(3H,d), 2.37(4H,s), 2.62(2H,t), 2.73(2H,t), 3.10(2H,d), 3.25(1H,s), 3.27(1H,d), 3.65(2H ,d), 3.77(2H,t), 4.26(1H,t), 4.39(2H,d), 5.95(2H,s), 6.25-6.37(2H,m), 6.43(1H,t), 6.81-6.91(2H,m), 6.98- 7.08(2H,m), 7.19-7.27(1H,m), 7.38(2H,dd), 7.41-7.49(2H,m), 7.92(1H,dd), 8.19(1H,d), 10.27(1H,s), m / z(ES + )[M+H] + = 863.4.

[0903] Example 7 Intermediate 7a: 1-(5-chloro-2-fluorophenyl)-4-(dimethoxymethyl)piperidine

[0904] [ka]

[0905] Under nitrogen, copper(I) iodide (0.074 g, 0.39 mmol) was added to L-proline (0.045 g, 0.39 mmol), K3PO4 (2.483 g, 11.70 mmol), 4-(dimethoxymethyl)piperidine (0.621 g, 3.90 mmol), and 4-chloro-1-fluoro-2-iodobenzene (1 g, 3.90 mmol) in DMF (13 mL). The resulting mixture was stirred at 100 °C for 16 hours. Purification by RPC (gradient: 5-100% MeOH in water containing 0.5% NH4HCO3) yielded the title compound (0.470 g, 41.9%) as a gray solid. 1H NMR(DMSO-d6)δ1.21-1.46(3H,m), 1.64-1.78(3H,m), 2.57-2.68(2H,m), 3.28( 6H,s), 3.43(1H,s), 4.11(1H,d), 6.93-7.03(2H,m), 7.10-7.19(1H,m), m / z(ES + )[M+H] + = 288.3.

[0906] Intermediate 7b: tert-butyl8-[3-[4-(dimethoxymethyl)-1-piperidyl]-4-fluorophenyl]-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

[0907] [ka]

[0908] The intermediate was prepared from tert-butyl(3,8-diazabicyclo[3.2.1]octane-3-carboxylate) (332 mg, 1.56 mmol) and intermediate 7a (450 mg, 1.56 mmol) using the same method as for intermediate 2e. Purification by RPC (gradient: 5-100% MeOH in water containing 0.5% NH4HCO3) yielded the title compound (410 mg, 56.6%) as a yellow solid. 1 H NMR (DMSO-d6): δ1.33-1.36(1H,m), 1.33(10H,m), 1.42-1.51(1H,m), 1.60-1.76(6H,m), 1.82-1.91(2H,m), 2.52-2.68(2H,m), 2.96-3.08 (1H,m), 3.10-3.20(1H,m), 3.28(6H,s), 3.45-3.58(2H,m), 4.12(1H,d), 4.15-4.25(2H,m), 6.34-6.46(2H,m), 6.79-6.59(1H,m), m / z(ES + )[M+H] + = 464.4.

[0909] Intermediate 7c: 8-[3-[4-(dimethoxymethyl)-1-piperidyl]-4-fluorophenyl]-3,8-diazabicyclo[3.2.1]octane

[0910] [ka]

[0911] HCl (6 mL, 197.49 mmol, 4.0 M) in MeOH was added to intermediate 7b (400 mg, 0.86 mmol). The resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was adjusted to pH 9 with 7 M ammonia-methanol solution. The solvent was removed under reduced pressure. The reaction mixture was diluted with MeOH:DCM (1:3) (15 mL), and the solid was filtered off. The filtrate was concentrated under reduced pressure to obtain the title compound (300 mg, 87%) as a white solid. 1 H NMR (DMSO-d6): δ1.27-1.49(2H,m), 1.67-1.75(3H,m), 1.95-2.16(5H,m), 2.56-2.65(2H,m), 2.88-2.95(3H,m), 2.95 -3.10(2H,m), 3.26(6H,s), 3.32-3.40(1H,m), 4.12(1H,d), 4.33(2H,s), 6.36-6.49(2H,m), 6.91-7.03(1H,m), m / z(ES + )[M+H] + = 364.2.

[0912] Intermediate 7d: 6-Chloro-4-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-4-fluorophenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazine-3-amine

[0913] [ka]

[0914] Starting with intermediate 7c (300 mg, 0.83 mmol), the compound was prepared in the same manner as intermediate 3d. Purification by RPC (5-100% MeCN in water containing 0.5% NH4HCO3 gradient) yielded the title compound (200 mg, 45.3%) as a yellow solid. 1 H NMR(400MHz,CDCl3)δ1.50-1.60(2H,m), 1.65-1.76(1H,m), 1.77-1.84(2H ,m), 1.91-1.96(2H,m), 2.02-2.15(2H,m), 2.62-2.71(3H,m), 3.02-3.18( 4H,m), 3.31(6H,s), 3.39-3.46(2H,m), 4.05(1H,d), 4.16-4.27(2H,m), 4. 88-4.96(1H,m), 6.31(1H,s), 6.35-674(2H,m), 6.78-6.91(1H,m), m / z(ES + )[M+H] + = 492.5.

[0915] Intermediate 7e: 2-[6-amino-5-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-4-fluorophenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol

[0916] [ka]

[0917] Starting with intermediate 7d, the compound was prepared in the same manner as intermediate 2h. Purification by FSC (gradient: 0-10% MeOH in DCM) yielded the title compound (160 mg, 82%) as a yellow solid. 1H NMR(DMSO-d6)δ1.23-1.27(2H,m), 1.39-1.42(2H,m), 1.62-1.81(4H,m), 1 .91-1.97(3H,m), 2.10-2.20(2H,m), 2.53-2.63(3H,m), 3.05-3.13(2H,m), 3.27(6H,s), 4.25-4.31(2H,m), 5.95(2H,s), 6.44-6.49(2H,m), 6.79-6.92 (3H,m), 7.02-7.27(1H,m), 7.47(1H,s), 7.91(1H,d), 14.19(1H,s), m / z(ES + )[M+H] + =549.7

[0918] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione

[0919] [ka]

[0920] Starting with intermediate 7e (40 mg, 0.07 mmol) and intermediate 2b (28.7 mg, 0.07 mmol), preparations were made in the same manner as in Example 3. Purification by RPC (gradient: 10-50% MeCN in water containing 0.1% FA) yielded the title compound (11.0 mg, 16.46%) as a white solid. 1H NMR(DMSO-d6)δ0.66-0.73(2H,m), 0.84-0.91(2H,m), 1.21-1.29(2H,m), 1.66-1.83(7H,m), 1.90-1.98(3H,m), 2.10- 2.20(5H,m), 2.19-2.36(2H,m), 2.25-2.36(5H,m), 2.59-2.68(2H,m), 2.77(2H,t), 3.05-3.18(2H,m), 3.21-3.29(2H ,m), 3.34-3.40 (2H,m), 3.82 (2H,t), 4.25-4.41 (2H,m), 5.22-5.29 (1H,m), 5.96 (2H,s), 6.39-6.51 (2H,m), 6.84-6.97 (3H,m), 7.20-7.26 (1H,m), 7.47 (1H,s), 7.56 (1H,s), 7.89-7.97 (2H,m), 8.17 (1H,d), 10.40 (1H,s) (OH protons were not observed). 19 F NMR(DMSO-d6)δ-136.41, m / z(ES + )[M+H] + = 880.6.

[0921] Example 8 Intermediate 8a: tert-butyl8-(3-bromo-5-fluorophenyl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

[0922] [ka]

[0923] Starting with 1,3-dibromo-5-fluorobenzene (2 g, 7.88 mmol) and tert-butyl-3,8-diazabicyclo[3.2.1]octane-3-carboxylate (1.672 g, 7.88 mmol), the intermediate was prepared in the same manner as intermediate 1b. Purification by FSC (gradient 0-10% phenylethylamine in petroleum ether) yielded the title compound (1.280 g, 42.2%) as a white solid. 1H NMR(DMSO-d6)δ1.39(9H,s), 1.61-1.72(2H,m), 1.86-1.96(2H,m), 3.03(2H, dd), 3.55(2H,t), 4.33(2H,s), 6.65-6.78(2H,m), 6.86-6.91(1H,m), m / z(ES + )[M+H] + =385.

[0924] Intermediate 8b: tert-butyl8-[3-[4-(dimethoxymethyl)-1-piperidyl]-5-fluorophenyl]-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

[0925] [ka]

[0926] Starting with intermediate 8a (1.28 g, 3.32 mmol), the intermediate was prepared in the same manner as intermediate 6e. Purification by FSC (gradient: 0-40% phenylethylamine in petroleum ether) yielded the title compound (0.790 g, 51.3%) as a yellow solid. 1 H NMR(DMSO-d6)δ1.27(2H,d), 1.39(9H,s), 1.60-1.72(5H,m), 1.84-1.95(2H,m), 2.54-2.66(2H,m), 3.0 6(2H,dd), 3.27(6H,s), 3.52(2H,t), 3.70(2H,d), 4.08(1H,d), 4.26(2H,s), 5.94-6.17(3H,m), m / z(ES + )[M+H] + = 464.

[0927] Intermediate 8c: 6-Chloro-4-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-5-fluorophenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazine-3-amine

[0928] [ka]

[0929] Starting with intermediate 8b (490 mg, 1.06 mmol), the intermediate was prepared in the same manner as intermediate 6f. Purification by RPC (gradient: 3-80% MeCN in 0.1% NH4HCO3 water) yielded the title compound (260 mg, 50.1%) as a yellow solid. 1 H NMR(DMSO-d6)δ1.21-1.36(2H,m), 1.62-1.74(3H,m), 1.87-1.95(2H,m), 2.05-2.15(2H,m), 2.60(2H,t), 2.93(2H,d), 3. 16(2H,d), 3.27(5H,s), 3.60-3.76(3H,m), 4.08(1H,d), 4.36(2H,s), 5.82(2H,s), 6.01-6.18(3H,m), 6.89(1H,s), m / z(ES + )[M+H] + = 491.2.

[0930] Intermediate 8d: 2-[6-amino-5-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-5-fluorophenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol

[0931] [ka]

[0932] Starting with intermediate 8c (200 mg, 0.41 mmol), the intermediate 2h was prepared in the same manner as intermediate 2h. Purification by FSC (gradient: 0-100% DCM in petroleum ether and 0-10% EtOH in DCM) yielded the title compound (210 mg, 94%) as a yellow solid. 1H NMR(DMSO-d6)δ0.83-0.96(2H,m), 1.22-1.28(2H,m), 1.64-1.73(3H,m), 1.91-2.00( 2H,m), 2.15(2H,d), 2.61(2H,t), 3.08(2H,d), 3.25(6H,s), 3.71(2H,d), 4.08(1H,d) , 4.41(2H,s), 5.96(2H,s), 6.16-6.20(1H,m), 6.73-6.78(1H,m), 6.84-6.90(2H,m), 7.10-7.20(1H,m), 7.48(1H,s), 7.89-7.96(1H,m), 9.33(1H,s), 14.17(1H,s), m / z(ES + )[M+H] + = 549.

[0933] 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-5-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione

[0934] [ka]

[0935] Starting with intermediate 8d (60 mg, 0.11 mmol) and intermediate 2c (51.6 mg, 0.13 mmol), preparations were made in the same manner as in Example 1. Purification by RPC (gradient: 0-38% MeCN water containing 0.1% FA) yielded the title compound (14.88 mg, 14.72%) as a white solid. 1H NMR(DMSO-d6)δ0.66-0.71(2H,m), 0.84-0.90(2H,m), 1.17(2H,dtd), 1.60-1.80(6H,m), 1.93( 3H,dp), 2.05-2.25(8H,m), 2.34(5H,dd), 2.76(2H,t), 3.09(2H,d), 3.25(3H,d), 3.63(3H,d), 3.81(2H,t), 4.34-4.40(2H,m), 5.24(1H,p), 5.94(2H,s), 6.11(1H,s), 6.21(2H,d), 6.82-6.8 9(2H,m), 7.23(1H,t), 7.46(1H,s), 7.56(1H,s), 7.89-7.97(2H,m), 8.17(1H,d), 10.41(1H,s), 19 F NMR(DMSO-d6)δ-73.44,-112.18, m / z(ES + )[M+H] + = 880.6.

[0936] Example 9 Intermediate 9a: tert-butyl 8-(3-bromo-5-methylphenyl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

[0937] [ka]

[0938] Starting with 1,3-dibromo-5-methylbenzene (2 g, 8.00 mmol) and tert-butyl-3,8-diazabicyclo[3.2.1]octane-3-carboxylate (1.7 g, 8.00 mmol), the intermediate was prepared in the same manner as intermediate 1b. Purification by FSC (gradient: 0-7% phenylethylamine in petroleum ether) yielded the title compound (2.0 g, 65.5%) as a white solid. 1H NMR(DMSO-d6)δ1.39(9H,s), 1.59-1.73(2H,m), 1.82-1.96(2H,m), 2.22(3H,s), 2. 92-3.19(2H,m), 3.54(2H,t), 4.28(2H,s), 6.64-6.70(2H,m), 6.83(1H,d), m / z(ES + )[M+H] + =381.

[0939] Intermediate 9b: tert-butyl8-[3-[4-(dimethoxymethyl)-1-piperidyl]-5-methylphenyl]-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

[0940] [ka]

[0941] Starting with intermediate 9a (1 g, 2.62 mmol), the intermediate was prepared in the same manner as intermediate 6e. Purification by FSC (gradient 0-30% SiO in petroleum ether) yielded the title compound (0.900 g, 74.7%) as a yellow solid. 1 H NMR(DMSO-d6)δ1.22-1.33(2H,m), 1.39(9H,s), 1.58-1.73(5H,m), 1.82-1.93(2H,m), 2.16(3H,s), 2.56(2H,d), 3. 01(1H,d), 3.15(1H,d), 3.20(6H,s), 3.51(2H,t), 3.64(2H,d), 4.08(1H,d), 4.22(2H,s), 6.07-6.21(3H,m), m / z(ES + )[M+H] + =460.

[0942] Intermediate 9c: 6-Chloro-4-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-5-methylphenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazine-3-amine

[0943] [ka]

[0944] Starting with intermediate 9b (500 mg, 1.09 mmol), the compound was prepared in the same manner as intermediate 6f. Purification by RPC (gradient: 0-70% MeCN in water containing 0.1% FA) yielded the title compound (410 mg, 77%). 1 H NMR(DMSO-d6)δ0.81-0.89(2H,m), 1.22-1.36(3H,m), 1.66-1.70(2H,m) , 1.85-1.93(2H,m), 2.04-2.10(1H,m), 2.16(3H,s), 2.53-2.59(1H,m), 2.94(2H,d), 3.12-3.18(2H,m), 3.27(6H,s), 3.60-3.69(2H,m), 4.08(1 H,d), 4.33(2H,s), 5.81(2H,s), 6.09-6.23(3H,m), 6.87(1H,s), m / z(ES + )[M+H] + = 487.0.

[0945] Intermediate 9d: 2-[6-amino-5-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-5-methylphenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazine-3-yl]phenol

[0946] [ka]

[0947] Starting with intermediate 9c (200 mg, 0.41 mmol), the intermediate 2h was prepared in the same manner as intermediate 2h. Purification by FSC (gradient: 0-100% DCM in petroleum ether and 0-10% MeOH in DCM) yielded the title compound (200 mg, 89%) as a yellow solid. 1H NMR(DMSO-d6)δ1.17-1.41(4H,m), 1.60-1.73(3H,m), 1.85-1.97(2H,m), 2.11(1H,d ), 2.16(3H,s), 2.55(2H,d), 3.03-3.11(2H,m), 3.21(1H,s), 3.25(6H,s), 3.59-3.6 8(2H,m), 4.06(1H,d), 4.35(2H,s), 5.93(1H,s), 6.09(1H,s), 6.19(2H,d), 6.80-6. 89(2H,m), 7.16-7.24(1H,m), 7.44(1H,s), 7.86-7.94(1H,m), 14.15(1H,s), m / z(ES + )[M+H] + = 545.

[0948] 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)146iridin146e-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-5-methylphenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]146iridin-5-yl]hexahydropyrimidine-2,4-dione

[0949] [ka]

[0950] Starting with intermediate 9d (60 mg, 0.11 mmol) and intermediate 2c (52.0 mg, 0.13 mmol), preparations were made in the same manner as in Example 1. Purification with RPC (gradient: 0-38% MeCN water containing 0.1% FA) yielded the title compound (13.41 mg, 13.28%) as a white solid. 1H NMR(DMSO-d6)δ0.65-0.72(2H,m), 0.83-0.91(2H,m), 1.08-1.23(2H,m), 1.57-1.81(7H,m), 1.89-1.99(3H,m) ), 2.10-2.25(9H,m), 2.26-2.43(6H,m), 2.59-2.70(2H,m), 2.76(2H,t), 3.07(2H,d), 3.24(2H,d), 3.69(3H, d), 3.81(2H,t), 4.41(2H,d), 5.25(1H,m), 5.96(1H,s), 6.00-6.08(1H,m), 6.10-6.23(2H,m), 6.82-6.91(2H ,m), 7.19-7.26(1H,m), 7.48(1H,s), 7.56(1H,s), 7.90-7.97(2H,m), 8.14-8.18(1H,m), 10.41(1H,s), m / z(ES + )[M+H] + = 876.5.

[0951] Example 10 Intermediate 10a: tert-butyl 8-(3-bromo-4-methylphenyl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

[0952] [ka]

[0953] Under N2 conditions, tert-butyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate (1.430 g, 6.74 mmol), palladium(II) acetate (0.151 g, 0.67 mmol), Cs2CO3 (4.39 g, 13.47 mmol), and BINAP (0.419 g, 0.67 mmol) were added to 1,4-dioxane (20 mL) with 2-bromo-4-iodo-1-methylbenzene (2 g, 6.74 mmol). The resulting mixture was stirred at 100 °C for 16 hours. The reaction mixture was diluted with SiO2 (100 mL) and sequentially washed with saturated NH4Cl (100 mL x 2) and saturated brine (100 mL x 2). The organic layer was dried (Na2SO4), filtered, and removed by distillation to obtain the crude product. The crude product was purified by FSC (gradient: 0-7% RINKAN in petroleum ether) to obtain the title compound (2.280 g, 89%) as a purple solid. 1 H NMR(DMSO-d6)δ1.39(9H,s), 1.61-1.72(2H,m), 1.83-1.94(2H,m), 2.22(3H,s), 2.93-3.17( 2H,m), 3.53(2H,t), 4.25(2H,s), 6.76-6.83(1H,m), 7.07(1H,d), 7.11-7.17(1H,m), m / z(ES + )[M+H] + = 381.3.

[0954] Intermediate 10b: tert-butyl8-[3-[4-(dimethoxymethyl)-1-piperidyl]-4-methylphenyl]-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

[0955] [ka]

[0956] Starting with intermediate 10a (1 g, 2.62 mmol), the intermediate was prepared in the same manner as intermediate 6e. Purification by FSC (gradient: 0-30% MeCN in water containing 0.1% NH4HCO3) yielded the title compound (750 g, 62.2%) as a yellow solid. 1H NMR(DMSO-d6)δ1.36-1.46(11H,m), 1.59-1.75(5H,m), 1.81-1.92(2H,m), 2.09(3H,s), 2.52-2.67(2H,m), 2.95-3. 10(3H,m), 3.10-3.18(1H,m), 3.28(6H,s), 3.52(2H,t), 4.12(1H,d), 4.20(2H,s), 6.44(2H,d), 6.94(1H,d), m / z(ES + )[M+H] + =460.

[0957] Intermediate 10c: 6-Chloro-4-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-4-methylphenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazine-3-amine

[0958] [ka]

[0959] Starting with intermediate 10b (370 mg, 0.80 mmol), the intermediate was prepared in the same manner as intermediate 6f. Purification by RPC (3-80% MeCN in water containing a 0.1% gradient NH4HCO3) yielded the title compound (256 mg, 65.3%) as a yellow solid. 1 H NMR(DMSO-d6)δ1.26-1.45(2H,m), 1.61-1.77(3H,m), 1.85-1.96(2H,m), 2.00-2.12(2H,m), 2.09(3H,s), 2.53-2.64(2H,m), 2.95(2H, d), 3.06(2H,d), 3.16(2H,d), 3.28(6H,s), 4.12(1H,d), 4.30(2H,s), 5.81(2H,s), 6.42-6.48(2H,m), 6.86(1H,s), 6.94(1H,d), m / z(ES + )[M+H] + = 487.

[0960] Intermediate 10d: 2-[6-amino-5-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-4-methylphenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol

[0961] [ka]

[0962] Starting with intermediate 10c (200 mg, 0.41 mmol), the compound was prepared in the same manner as intermediate 2h. Purification by FSC (gradient: 0-40% DCM in petroleum ether) yielded the title compound (215 mg, 96%) as a yellow solid. 1 H NMR(DMSO-d6)δ1.32-1.46(2H,m), 1.59-1.76(4H,m), 1.87-2.05(3H,m), 2.10(3H,s), 2.11 -2.16(1H,m), 2.53-2.61(1H,m), 3.00-3.13(4H,m), 3.21-3.25(1H,m), 3.28(6H,s), 3.43-3 0.61(1H,m), 4.13(1H,d), 4.35(2H,s), 5.95(1H,s), 6.45-6.54(2H,m), 6.81-6.91(2H,m), 6.93-7.03(2H,m), 7.18-7.26(1H,m), 7.42-7.48(1H,m), 7.91(1H,d) (OH protons not observed), m / z(ES) + )[M+H] + = 545.3.

[0963] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-methylphenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione

[0964] [ka]

[0965] Starting with intermediate 10d (60 mg, 0.11 mmol) and intermediate 2c (52.0 mg, 0.13 mmol), preparations were made in the same manner as in Example 1. Purification by RPC (gradient: 0-50% MeCN in water containing 0.1% FA) yielded the title compound (14.05 mg, 14.23%) as a white solid. 1 H NMR(DMSO-d6)δ0.66-0.72(2H,m), 0.83-0.91(2H,m), 1.18-1.31(2H,m), 1.59-1.82(6H,m), 1.89-1.9 8(3H,m), 2.08-2.25(10H,m), 2.27-2.39(5H,m), 2.53-2.63(2H,m), 2.76(2H,t), 3.02-3.15(5H,m), 3 .25(3H,d), 3.81(2H,t), 4.34(2H,s), 5.23(1H,q), 5.93(2H,s), 6.44-6.54(2H,m), 6.86(2H,t), 6.95 (1H,d), 7.23(1H,t), 7.45(1H,s), 7.55(1H,s), 7.88-7.98(2H,m), 8.17(1H,d), 10.39(1H,s), m / z(ES + )[M+H] + = 877.2.

[0966] Example 11 Intermediate 11a: tert-butyl9-(5-bromo-3-cyclopropyl-pyrrolo[2,3-b]pyridin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate

[0967] [ka]

[0968] Starting with 5-bromo-3-cyclopropyl-1H-pyrrolo[2,3-b]pyridine (593 mg, 2.5 mmol) and tert-butyl-9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate (1010 mg, 3.75 mmol), the intermediate was prepared in the same manner as intermediate 2a. Purification by FSC (0-50% ethyl hexane) yielded the title compound (816 mg, 66.8%) as a colorless, dry thin film. 1 H NMR (DMSO-d6): δ0.58-0.67(2H,m), 0.76-0.91(2H,m), 1.23-1.34(4H,m), 1.39(9H,s), 1.57-1.66(4H,m), 1.78(2H,br d), 1.89-1.97(3H,m), 3.29-3.33(4H,m), 4.56(1H,tt), 7.52(1H,s), 8.17(1H,d), 8.24(1H,d), m / z(ES + )[M+H] + = 490.2.

[0969] Intermediate 11b: tert-butyl9-[3-cyclopropyl-5-(2,4-dioxohexahydropyrimidine-1-yl)pyrrolo[2,3-b]pyridin-1-yl]-3-azaspiro[5.5]undecane-3-carboxylate

[0970] [ka]

[0971] Starting with intermediate 11a (816 mg, 1.67 mmol), the compound was prepared in the same manner as intermediate 2b. Purification by FCS (0-100% butyl in hexane, followed by 0-30% MeOH in butyl) yielded the title compound (420 mg, 48.2%) as a brown solid. 1H NMR (DMSO-d6): δ0.60-0.69(2H,m), 0.79-0.90(2H,m), 1.25-1.35(4H,m), 1.39(9H,s), 1.59-1.69(4H,m), 1.80(2H,br d), 1.87-1.94(1H,m), 1.95-2.03(2H,m), 2.75(2H,t), 3.30-3.36(4H,m), 3.80(2 H,t), 4.60(1H,tt), 7.49(1H,s), 7.92(1H,d), 8....

Claims

1. Compounds of formula (A), or pharmaceutically acceptable salts thereof: 【Chemistry 1】 (In the formula, E is, 【Chemistry 2】 And, R １ is hydrogen, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) It is alkoxy, or 【Transformation 3】 And, R ２ is hydrogen, halogen, (C １ -C ６ -alkyl, (C １ -C ６ -alkoxy, or 【Chemistry 4】 And, however, (i) R １ Hydrogen, halogen, (C １ -C ６ ) alkyl, or (C １ -C ６ ) If it is an alkoxy, R ２ teeth, 【Transformation 5】 And, (ii) R ２ Hydrogen, halogen, (C １ -C ６ ) alkyl, or (C １ -C ６ ) If it is an alkoxy, R １ teeth, 【Transformation 6】 And, R １１ is hydrogen or -(C １ -C ６ ) alkyl-O-P(=O)-(OH) ２ And, X １ CR ３ or N, R ３ is hydrogen, halogen, or (C １ -C ６ ) is alkyl, X ２ CR ４ or N, R ４ is hydrogen, halogen, or (C １ -C ６ ) is alkyl, R ５ａ is hydrogen, halogen, (C １ -C ６ ) alkyl, (C ３ -C ６ ) Cycloalkyl, 4-6 member heterocycloalkyl, cyano, aryl, or 5 or 6 member heteroaryl, Here, (C １ -C ６ ) The alkyl is optionally substituted with one, two, or three substituents independently selected from halogens or cyanos, and the 4-6 member heterocycloalkyl, aryl, or 5 or 6 member heteroaryl is substituted with halogens, cyanos, or (C １ -C ６ ) optionally substituted with one, two, or three substituents independently selected from the alkyl group, R ５ｂ is hydrogen, (C １ -C ６ ) alkyl, or (C ３ -C ６ ) It is a cycloalkyl, R ６ is hydrogen, (C １ -C ６ ) Alkyl or cyano, X ３ is, -CH ２ CH ２ - or - CH ２ -O-CH ２ - and or X ３ It does not exist, L is -G １ -G ２ -G ３ -G ４ - and here, G １ It is bonded to W, G １ is, (C １ -C ６ ) Alkilenyl, (C ３ -C ６ ) Cycloalkylenyl, -O-CH ２ -CH ２ -, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) A 4- to 6-membered heterocycloalkylenyl or halogen optionally substituted with one, two, or three substituents independently selected from alkoxy, cyano, or hydroxyl, (C １ -C ６ ) alkyl, (C １ -C ６ ) A 7-11 member heterocycloalkylenyl, optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano, G ２ is, (C １ -C ６ ) an alkylenyl, a 4- to 6-membered heterocycloalkylenyl optionally substituted with -C(=O)-, 1, 2, or 3 fluorocarbons, or a direct bond, G ３ is a 4- to 6-membered heterocycloalkylene optionally substituted with 1, 2, or 3 substituents independently selected from -C(=O)-, -C(=O)-CH ２ CH ２ -, (C １ -C ６ ), alkylene, tetrahydronaphthalenenyl, halogen, (C １－ C ６ ), alkyl, (C １ -C ６ ), alkoxy, or cyano; a 7- to 11-membered heterocycloalkyl-C(=O)- or 7- to 11-membered heterocycloalkylene optionally substituted with 1, 2, or 3 substituents independently selected from halogen, (C １ -C ６ ), alkyl, (C １ -C ６ ), alkoxy, or cyano, G ４ is (C １ -C ６ ) alkenylenyl, (C ３ -C ６ ) cycloalkenylenyl, 4- to 6-membered hetero cycloalkenylenyl, or a direct bond, W is 【Transformation 7】 or direct bond, R ７ (C) is optionally substituted with hydrogen, halogen, or one, two, or three halogens. １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) It is a cycloalkyl, R ８ (C) is optionally substituted with hydrogen, halogen, or one, two, or three halogens. １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) It is a cycloalkyl, R ９ (C) is optionally substituted with hydrogen, halogen, or one, two, or three halogens. １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) It is a cycloalkyl, R １０ (C) is optionally substituted with hydrogen, halogen, or one, two, or three halogens. １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) It is a cycloalkyl, R ａ is hydrogen or halogen, R ｂ is hydrogen or halogen, R ｃ (It is hydrogen or methyl.)

2. Compounds of formula (I), or pharmaceutically acceptable salts thereof: 【Transformation 8】 (In the formula, E is, 【Chemistry 9】 And, R １ is hydrogen, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) It is alkoxy, or 【Chemistry 10】 And, R ２ is hydrogen, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) It is alkoxy, or 【Chemistry 11】 And, however, (i) R １ Hydrogen, halogen, (C １ -C ６ ) alkyl, or (C １ -C ６ ) If it is an alkoxy, R ２ teeth, 【Chemistry 12】 And, (ii) R ２ Hydrogen, halogen, (C １ -C ６ ) alkyl, or (C １ -C ６ ) If it is an alkoxy, R １ teeth, 【Chemistry 13】 And, R １１ is hydrogen or -(C １ -C ６ ) alkyl-O-P(=O)-(OH) ２ And, X １ CR ３ or N, R ３ is hydrogen, halogen, or (C １ -C ６ ) is alkyl, X ２ CR ４ or N, R ４ is hydrogen, halogen, or (C １ -C ６ ) is alkyl, R ５ａ is hydrogen, halogen, (C １ -C ６ ) alkyl, (C ３ -C ６ ) Cycloalkyl, 4-6 member heterocycloalkyl, cyano, aryl, or 5 or 6 member heteroaryl, where (C １ -C ６ ) The alkyl is optionally substituted with one, two, or three substituents independently selected from halogens or cyanos, and the 4-6 member heterocycloalkyl, aryl, or 5 or 6 member heteroaryl is substituted with halogens, cyanos, or (C １ -C ６ ) optionally substituted with one, two, or three substituents independently selected from the alkyl group, R ５ｂ is hydrogen, (C １ -C ６ ) alkyl, or (C ３ -C ６ ) It is a cycloalkyl, R ６ is hydrogen, (C １ -C ６ ) Alkyl or cyano, X ３ is, -CH ２ CH ２ - or - CH ２ -O-CH ２ - and or X ３ It does not exist, L is -G １ -G ２ -G ３ -G ４ - and here, G １ It is bonded to W, G １ is, (C １ -C ６ ) Alkyenyl, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) A 4- to 6-membered heterocycloalkylenyl or halogen optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano, (C １ -C ６ ) alkyl, (C １ -C ６ ) A 7-11 member heterocycloalkylenyl, optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano, G ２ is, (C １ -C ６ ) Alkyrenyl or direct bond, G ３ is halogen, (C １ -C ６ ) alkyl, (C １ -C ６） A 4-6 member heterocycloalkylenyl or halogen optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano compounds, (C １ -C ６ ) alkyl, (C １ -C ６ ) A 7-11 member heterocycloalkylenyl, optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano, G ４ is, (C １ -C ６ ) Alkyrenyl or direct bond, W is 【Chemistry 14】 or direct bond, R ７ (C) is optionally substituted with hydrogen, halogen, or one, two, or three halogens. １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) It is a cycloalkyl, R ８ (C) is optionally substituted with hydrogen, halogen, or one, two, or three halogens. １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) It is a cycloalkyl, R ９ (C) is optionally substituted with hydrogen, halogen, or one, two, or three halogens. １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) It is a cycloalkyl, R １０ (C) is optionally substituted with hydrogen, halogen, or one, two, or three halogens. １ -C ６ ) alkyl, cyano, or (C ３ -C ６ It is a cycloalkyl compound.

3. Compounds of formula (I), or pharmaceutically acceptable salts thereof: 【Chemistry 15】 (In the formula, E is, 【Chemistry 16】 And, R １ is hydrogen, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) It is alkoxy, or 【Chemistry 17】 And, R ２ is hydrogen, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) It is alkoxy, or [Chemistry 18] And, however, (i) R １ Hydrogen, halogen, (C １ -C ６ ) alkyl, or (C １ -C ６ ) If it is an alkoxy, R ２ teeth, 【Chemistry 19】 And, (ii) R ２ Hydrogen, halogen, (C １ -C ６ ) alkyl, or (C １ -C ６ ) If it is an alkoxy, R １ teeth, 【Chemistry 20】 And, R １１ is hydrogen or -(C １ -C ６ ) alkyl-O-P(=O)-(OH) ２ And, X １ CR ３ or N, R ３ is hydrogen, halogen, or (C １ -C ６ ) is alkyl, X ２ CR ４ or N, R ４ is hydrogen, halogen, or (C １ -C ６ ) is alkyl, R ５ａ is hydrogen, halogen, (C １ -C ６ ) alkyl, (C ３ -C ６ ) Cycloalkyl, 4-6 member heterocycloalkyl, cyano, aryl, or 5 or 6 member heteroaryl, where (C １ -C ６ ) The alkyl is optionally substituted with one, two, or three substituents independently selected from halogens or cyanos, and the 4-6 member heterocycloalkyl, aryl, or 5 or 6 member heteroaryl is substituted with halogens, cyanos, or (C １ -C ６ ) optionally substituted with one, two, or three substituents independently selected from the alkyl group, R ５ｂ is hydrogen, (C １ -C ６ ) alkyl, or (C ３ -C ６ ) It is a cycloalkyl, R ６ is hydrogen, (C １ -C ６ ) Alkyl or cyano, X ３ is, -CH ２ CH ２ - or - CH ２ -O-CH ２ - and or X ３ It does not exist, L is -G １ -G ２ -G ３ -G ４ - and here, G １ It is bonded to W, G １ is, (C １ -C ６ ) Alkyenyl, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) A 4- to 6-membered heterocycloalkylenyl or halogen optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano, (C １ -C ６ ) alkyl, (C １ -C ６ ) A 7-11 member heterocycloalkylenyl, optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano, G ２ is, (C １ -C ６ ) Alkyrenyl or direct bond, G ３ is halogen, (C １ -C ６ ) alkyl, (C １ -C ６） 4-6 member heterocycloalkylenyls, halogens, (C) optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano compounds. １ -C ６ ) alkyl, (C １ -C ６ ) A 7-11 member heterocycloalkylenyl or a 5-10 member heteroaryrenyl, optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano. G ４ is, (C １ -C ６ ) Alkilenyl, (C ３ -C ６ ) Cycloalkylenyl, or direct bond, W is 【Chemistry 21】 or direct bond, R ７ (C) is optionally substituted with hydrogen, halogen, or one, two, or three halogens. １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) It is a cycloalkyl, R ８ (C) is optionally substituted with hydrogen, halogen, or one, two, or three halogens. １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) It is a cycloalkyl, R ９ (C) is optionally substituted with hydrogen, halogen, or one, two, or three halogens. １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) It is a cycloalkyl, R １０ (C) is optionally substituted with hydrogen, halogen, or one, two, or three halogens. １ -C ６ ) alkyl, cyano, or (C ３ -C ６ It is a cycloalkyl compound.

4. Formula (II): 【Chemistry 22】 A compound according to claim 2 or 3, having the same, or a pharmaceutically acceptable salt thereof.

5. Formula (III): 【Chemistry 23】 A compound according to claim 2 or 3, having the same, or a pharmaceutically acceptable salt thereof.

6. R ５ａ A compound according to any one of claims 1 to 5, wherein the compound is hydrogen, or a pharmaceutically acceptable salt thereof.

7. R ５ａ However, it is optionally substituted with one, two, or three substituents independently selected from halogens or cyano compounds (C １ -C ６ A compound according to any one of claims 1 to 5, which is alkyl, or a pharmaceutically acceptable salt thereof.

8. R ５ａ The compound according to claim 7, wherein is methyl, or a pharmaceutically acceptable salt thereof.

9. R ５ａ But (C ３ -C ６ A compound according to any one of claims 1 to 5, which is a cycloalkyl compound, or a pharmaceutically acceptable salt thereof.

10. R ５ａ The compound according to claim 9, or a pharmaceutically acceptable salt thereof, wherein is cyclopropyl.

11. R ５ａ However, halogen, cyano, or (C １ -C ６ The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, which is a 4- to 6-membered heterocycloalkyl group optionally substituted with one, two, or three substituents independently selected from the alkyl group.

12. R ５ａ A compound according to any one of claims 1 to 5, wherein the compound is cyano, or a pharmaceutically acceptable salt thereof.

13. R １ but, 【Chemistry 24】 And, R ２ However, hydrogen, halogen, (C １ -C ６ ) alkyl, or (C １ -C ６ A compound according to any one of claims 1 to 5, which is an alkoxy, or a pharmaceutically acceptable salt thereof.

14. R ２ However, hydrogen, halogen, or (C １ -C ６ A compound according to any one of claims 1 to 5, which is alkyl, or a pharmaceutically acceptable salt thereof.

15. R ２ The compound according to any one of claims 1 to 5, wherein the compound is hydrogen, fluoro, or methyl, or a pharmaceutically acceptable salt thereof.

16. R １１ A compound according to any one of claims 1 to 5, wherein the compound is hydrogen, or a pharmaceutically acceptable salt thereof.

17. R １ However, hydrogen, halogen, (C １ -C ６ ) alkyl, or (C １ -C ６ ) is an alkoxy, R ２ but, 【Chemistry 25】 The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof.

18. R １ However, hydrogen, halogen, or (C １ -C ６ The compound according to claim 17, or a pharmaceutically acceptable salt thereof, wherein the compound is alkyl.

19. R １ The compound according to claim 18, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen, fluoro, or methyl.

20. R １１ A compound according to any one of claims 17 to 19, wherein the compound is hydrogen, or a pharmaceutically acceptable salt thereof.

21. X １ CR ３ The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof.

22. R ３ The compound according to claim 21, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

23. R ３ The compound according to claim 21, or a pharmaceutically acceptable salt thereof, wherein is a halogen.

24. R ３ But (C １ -C ６ The compound according to claim 21, or a pharmaceutically acceptable salt thereof, wherein the compound is alkyl.

25. X １ A compound according to any one of claims 1 to 5, wherein is N, or a pharmaceutically acceptable salt thereof.

26. X ２ CR ４ The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof.

27. R ４ The compound according to claim 26, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

28. R ４ The compound according to claim 26, or a pharmaceutically acceptable salt thereof, wherein is a halogen.

29. R ４ But (C １ -C ６ The compound according to claim 26, or a pharmaceutically acceptable salt thereof, wherein the compound is alkyl.

30. X ２ A compound according to any one of claims 1 to 5, wherein is N, or a pharmaceutically acceptable salt thereof.

31. E is, 【Chemistry 26】 The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof.

32. E is, 【Chemistry 27】 The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof.

33. E is, 【Chemistry 28】 The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof.

34. G １ However, (C ３ -C ６ ) Cycloalkylenyl, or halogen, (C １ -C ６） Alkyl, (C １ -C ６ A compound according to any one of claims 1 to 33, or a pharmaceutically acceptable salt thereof, which is a 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from alkoxy, cyano, or hydroxyl.

35. G １ but, 【Chemistry 29】 And, Each R １２ These are, independently, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) are alkoxy, cyano, or hydroxyl, n is 0, 1, 2, or 3. " ＊ The bonds marked with " are G ２ The compound according to claim 34, or a pharmaceutically acceptable salt thereof, which is bonded to.

36. Each R １２ However, independently, fluoro, methyl, methoxy, cyano, or -CHF ２ The compound according to claim 35, or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2.

37. G １ but, 【Transformation 30】 And, " ＊ The bonds marked with " are G ２ The compound according to claim 35, or a pharmaceutically acceptable salt thereof, which is bonded to.

38. G １ but, 【Chemistry 31】 And, X ４ It is -O-, Each R １２ These are, independently, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) Alkyl or cyano, " ＊ The bonds marked with " are G ２ The compound according to claim 34, or a pharmaceutically acceptable salt thereof, which is bonded to.

39. G １ but, 【Chemistry 32】 And, " ＊ The bonds marked with " are G ２ The compound according to claim 38, or a pharmaceutically acceptable salt thereof, which is bonded to.

40. G １ but, 【Transformation 33】 And, " ＊ The bonds marked with " are G ２ The compound according to claim 34, or a pharmaceutically acceptable salt thereof, which is bonded to.

41. G １ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein is cyclohexylenyl.

42. G １ but, 【Transformation 34】 And, " ＊ The bonds marked with " are G ２ The compound according to claim 41, or a pharmaceutically acceptable salt thereof, which is bonded to.

43. G １ However, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ A compound according to any one of claims 1 to 33, or a pharmaceutically acceptable salt thereof, which is a 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano.

44. G １ but, 【Chemistry 35】 And, Each R １３ These are, independently, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) Selected from alkoxy or cyano, o is 0, 1, 2, or 3. p, q, r, and s are independently 1 or 2. " ＊ The bonds marked with " are G ２ The compound according to claim 43, or a pharmaceutically acceptable salt thereof, which is bonded to.

45. p and q are 1, r is 1 or 2, s is 1 or 2, R １３ The compound according to claim 44, or a pharmaceutically acceptable salt thereof, which is a halogen.

46. R １３ The compound according to claim 45, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro and the element o is 0, 1, or 2.

47. G １ but, 【Transformation 36】 And, " ＊ The bonds marked with " are G ２ The compound according to claim 44, or a pharmaceutically acceptable salt thereof, which is bonded to.

48. G １ but, 【Chemistry 37】 And, a is either 0 or 1, b is either 0 or 1, " ＊ The bonds marked with " are G ２ The compound according to claim 43, or a pharmaceutically acceptable salt thereof, which is bonded to.

49. G １ but, 【Transformation 38】 And, " ＊ The bonds marked with " are G ２ The compound according to claim 48, or a pharmaceutically acceptable salt thereof, which is bonded to.

50. G １ but, 【Chemistry 39】 and " ＊ The bonds marked with " are G ２ The compound according to claim 43, or a pharmaceutically acceptable salt thereof, which is bonded to.

51. G ２ A compound according to any one of claims 1 to 50, wherein the bond is a direct bond, or a pharmaceutically acceptable salt thereof.

52. G ２ A compound according to any one of claims 1 or 6 to 50, wherein C (= O), or a pharmaceutically acceptable salt thereof.

53. G ２ However, (C １ -C ６ A compound according to any one of claims 1 to 50, which is an alkylenyl compound, or a pharmaceutically acceptable salt thereof.

54. G ２ However, -CH ２ - The compound according to claim 53, or a pharmaceutically acceptable salt thereof.

55. G ３ However, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ A compound according to any one of claims 1 to 54, or a pharmaceutically acceptable salt thereof, which is a 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano.

56. G ３ but, 【Chemistry 40】 And, Each R １４ These are, independently, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) Alkyl or cyano, t is 0, 1, 2, or 3. " ＊ The bonds marked with " are G ４ The compound according to claim 55, or a pharmaceutically acceptable salt thereof, which is bonded to.

57. R １４ The compound according to claim 56, or a pharmaceutically acceptable salt thereof, wherein is fluoro or methyl and t is 0 or 1.

58. G ３ but, 【Chemistry 41】 And, " ＊ The bonds marked with " are G ４ The compound according to claim 56, or a pharmaceutically acceptable salt thereof, which is bonded to.

59. G ３ However, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ A compound according to any one of claims 1 to 54, or a pharmaceutically acceptable salt thereof, which is a 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano.

60. G ３ but, 【Chemistry 42】 And, " ＊ The bonds marked with " are G ４ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, which is bonded to.

61. G ３ but, 【Chemistry 43】 And, " ＊ The bonds marked with " are G ４ The compound according to claim 59, or a pharmaceutically acceptable salt thereof, which is bonded to.

62. G ３ but, 【Chemistry 44】 and " ＊ The bonds marked with " are G ４ The compound according to claim 59, or a pharmaceutically acceptable salt thereof, which is bonded to.

63. G ３ but, 【Chemistry 45】 And, Each R １５ These are, independently, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) Selected from alkoxy or cyano, u is 0, 1, 2, or 3. v, w, x, and y are independently 1, 2, or 3. " ＊ The bonds marked with " are G ４ The compound according to claim 59, or a pharmaceutically acceptable salt thereof, which is bonded to.

64. The compound according to claim 63, or a pharmaceutically acceptable salt thereof, wherein v, w, x, and y are independently 1 or 2.

65. R １５ The compound according to claim 63, or a pharmaceutically acceptable salt thereof, wherein is fluoro.

66. G ３ but, 【Chemistry 46】 And, x ａ and y ａ These are independently 1 or 2, " ＊ The bonds marked with " are G ４ The compound according to claim 59, or a pharmaceutically acceptable salt thereof, which is bonded to.

67. G ３ but, 【Chemistry 47】 And, " ＊ The bonds marked with " are G ４ The compound according to claim 59, or a pharmaceutically acceptable salt thereof, which is bonded to.

68. G ３ but, 【Chemistry 48】 And, " ＊ The bonds marked with " are G ４ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, which is bonded to.

69. G ４ However, (C １ -C ６ A compound according to any one of claims 1 to 68, which is an alkylenyl compound, or a pharmaceutically acceptable salt thereof.

70. G ４ However, -CH ２ - or -CH ２ CH ２ - The compound according to claim 69, or a pharmaceutically acceptable salt thereof.

71. G ４ However, (C ３ -C ６ The compound according to claim 1, which is a cycloalkylenyl, or a pharmaceutically acceptable salt thereof.

72. G ４ but, 【Chemistry 49】 And, " ＊ The bond marked with " is bonded to E, the compound according to claim 71, or a pharmaceutically acceptable salt thereof.

73. G ４ but, [Transformation 50] And, " ＊ The bonds marked with " are G ４ The compound according to claim 71, or a pharmaceutically acceptable salt thereof, which is bonded to.

74. G ４ A compound according to any one of claims 1 to 68, wherein the bond is a direct bond, or a pharmaceutically acceptable salt thereof.

75. L, 【Chemistry 51】 【Chemistry 52】 And, " ＊ The bond marked with " is bonded to E, the compound according to any one of claims 1 to 33, or a pharmaceutically acceptable salt thereof.

76. L, 【Chemistry 53】 And, " ＊ The bond marked with " is bonded to E, the compound according to any one of claims 1 to 33, or a pharmaceutically acceptable salt thereof.

77. W 【Chemistry 54】 The compound according to any one of claims 1 to 76, or a pharmaceutically acceptable salt thereof.

78. A compound according to any one of claims 1 to 76, wherein W is a direct bond, or a pharmaceutically acceptable salt thereof.

79. R ７ , R ８ , R ９ , and R １０ A compound according to any one of claims 1 to 78, wherein is H, or a pharmaceutically acceptable salt thereof.

80. R ７ However, halogen, (C １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) is a cycloalkyl, where (C １ -C ６ The alkyl group is optionally substituted with one, two, or three halogens, the compound according to any one of claims 1 to 78, or a pharmaceutically acceptable salt thereof.

81. R ７ However, halogen or (C １ -C ６ The compound according to claim 80, or a pharmaceutically acceptable salt thereof, which is alkyl.

82. R ７ The compound according to claim 81, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro or methyl.

83. R ８ , R ９ , and R １０ The compound according to any one of claims 80 to 82, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

84. R ８ However, halogen, (C １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) is a cycloalkyl, where (C １ -C ６ The alkyl group is optionally substituted with one, two, or three halogens, the compound according to any one of claims 1 to 78, or a pharmaceutically acceptable salt thereof.

85. R ８ However, halogen or (C １ -C ６ The compound according to claim 84, or a pharmaceutically acceptable salt thereof, wherein the compound is alkyl.

86. R ８ The compound according to claim 85, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro or methyl.

87. R ７ , R ９ , and R １０ The compound according to any one of claims 84 to 86, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

88. R ９ However, halogen, (C １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) is a cycloalkyl, where (C １ -C ６ The alkyl group is optionally substituted with one, two, or three halogens, the compound according to any one of claims 1 to 78, or a pharmaceutically acceptable salt thereof.

89. R ９ The compound according to claim 88, or a pharmaceutically acceptable salt thereof, wherein is a halogen.

90. R ９ The compound according to claim 89, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro.

91. R ７ , R ８ , and R １０ The compound according to any one of claims 88 to 90, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

92. R １０ However, halogen, (C １ -C ６ ) alkyl, cyano, or (C ３ -C ６ ) is a cycloalkyl, where (C １ -C ６ The alkyl group is optionally substituted with one, two, or three halogens, the compound according to any one of claims 1 to 78, or a pharmaceutically acceptable salt thereof.

93. R １０ The compound according to claim 92, or a pharmaceutically acceptable salt thereof, wherein is a halogen.

94. R １０ The compound according to claim 93, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro.

95. R ７ , R ９ , and R ９ The compound according to any one of claims 92 to 94, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

96. R １０ A compound according to any one of claims 1 to 78, wherein the compound is cyano, or a pharmaceutically acceptable salt thereof.

97. R １０ is cyano, R ７ , R ８ , and R ９ The compound according to claim 96, or a pharmaceutically acceptable salt thereof, wherein the compound is hydrogen.

98. Compounds of formula (V), or pharmaceutically acceptable salts thereof, 【Transformation 55】 (In the formula, Each R １２ is fluoro or hydroxyl, n is 0, 1, 2, or 3. E is, 【Transformation 56】 And, R １ is hydrogen, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) It is alkoxy, or 【Chemistry 57】 And, R ２ is hydrogen, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) It is alkoxy, or 【Chemistry 58】 And, however, (i) R １ Hydrogen, halogen, (C １ -C ６ ) alkyl, or (C １ -C ６ ) If it is an alkoxy, R ２ teeth, 【Chemistry 59】 And, (ii) R ２ Hydrogen, halogen, (C １ -C ６ ) alkyl, or (C １ -C ６ ) If it is an alkoxy, R １ teeth, 【Transformation 60】 And, R １１ is hydrogen or -(C １ -C ６ ) alkyl-O-P(=O)-(OH) ２ And, X １ CR ３ or N, R ３ is hydrogen, halogen, or (C １ -C ６ ) is alkyl, X ２ CR ４ or N, R ４ is hydrogen, halogen, or (C １ -C ６ ) is alkyl, R ５ａ is hydrogen, halogen, (C １ -C ６ ) alkyl, (C ３ -C ６ ) Cycloalkyl, 4-6 member heterocycloalkyl, cyano, aryl, or 5 or 6 member heteroaryl, where (C １ -C ６ ) The alkyl is optionally substituted with one, two, or three substituents independently selected from halogens or cyanos, and the 4-6 member heterocycloalkyl, aryl, or 5 or 6 member heteroaryl is substituted with halogens, cyanos, or (C １ -C ６ ) optionally substituted with one, two, or three substituents independently selected from the alkyl group, R ５ｂ is hydrogen, (C １ -C ６ ) alkyl, or (C ３ -C ６ ) It is a cycloalkyl, R ６ is hydrogen, (C １ -C ６ ) Alkyl or cyano, X ３ is, -CH ２ CH ２ - is or does not exist, G ３ It is tetrahydronaphthalene, halogen, (C １ -C ６ ) alkyl, (C １ -C ６ ) 4-6 member heterocycloalkylenyls, halogens, (C) optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano compounds. １ -C ６ ) alkyl, (C １ -C ６ ) 7-11 member heterocycloalkyl-C(=O)- or 7-11 member heterocycloalkylenyl, optionally substituted with one, two, or three substituents independently selected from alkoxy or cyano, G ４ It does not exist, or it is cyclobutyrenyl. R ７ , R ８ , R ９ , and R １０ These are independently hydrogen, fluoro, methyl, or cyano, R ａ These are hydrogen, chloro, methyl, or fluoro. R ｂ These are hydrogen, chloro, methyl, or fluoro. R ｃ (It is hydrogen or methyl.)

99. G ３ but, 【Chemistry 61】 The compound according to claim 98, or a pharmaceutically acceptable salt thereof.

100. G ３ but, 【Transformation 62】 The compound according to claim 98, or a pharmaceutically acceptable salt thereof.

101. G ３ but, 【Transformation 63】 The compound according to claim 98, or a pharmaceutically acceptable salt thereof.

102. A compound according to claim 1, selected from any one or more of the following compounds, or a pharmaceutically acceptable salt thereof: 1-[1-[1-[[7-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-7-azaspiro[3.5]nonane-2-yl]methyl]-4-piperidyl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[3-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]propa-2-inyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-4-piperidyl]indole-4-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-5-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)490iridin490e-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-5-methylphenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]490iridin-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)490iridin490e-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-5-methylphenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]490iridin-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-methylphenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-6-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2,6-difluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[2-[1-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-4-piperidyl]-1-methyl-indole-6-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-4-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-4-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]methyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-4-piperidyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[(2S)-4-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]morpholine-2-yl]methyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[2-[4-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]piperazin-1-yl]ethyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-4-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[5-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]-2-methylphenyl]hexahydropyrimidine-2,4-dione, [3-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]-2,6-dioxo-hexahydropyrimidine-1-yl]methyl dihydrogen phosphat, 1-[1-[2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-2-azaspiro[3.5]nonane-7-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(6r,9r)-4-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-1-oxa-4-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(1r,3r)-3-[8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)493iridine493e-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octane-3-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]493iridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[(2S)-4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]morpholine-2-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[7-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-7-azaspiro[3.5]nonane-2-yl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5r,8r)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-2-azaspiro[4.5]decane-8-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[(2S)-4-[[7-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-7-azaspiro[3.5]nonane-2-yl]methyl]morpholine-2-yl]methyl]3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,8-dihydro-5H-imidazo[1,2-a]pyrazine-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[[(2R)-4-[[7-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-7-azaspiro[3.5]nonane-2-yl]methyl]morpholine-2-yl]methyl]3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[rel-3aR,5r ＊ ,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 1)[ ＊ [Absolute configuration has not yet been confirmed] 1-[3-methyl-1-[7-[[(3aR,5s,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[(3aR,5r,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[rel-3aR,5r ＊ ,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 2)[ ＊ [Absolute configuration has not yet been confirmed] 1-[3-methyl-1-[7-[[(3aR,5s,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[(3aR,5r,6aS)-2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-5-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[6-fluoro-1-[rel-(3R) ＊ )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione (isomer 1)[ ＊ [Absolute configuration has not yet been confirmed] 1-[6-fluoro-1-[(3R)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[6-fluoro-1-[(3S)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[6-fluoro-1-[rel-(3R) ＊ )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione (isomer 2)[ ＊ [Absolute configuration has not yet been confirmed] 1-[6-fluoro-1-[(3R)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- Diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[6-fluoro-1-[(3S)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-cyclopropyl-1-[rel-(3R ＊ )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 2)[ ＊ [Absolute configuration has not yet been confirmed] 1-[3-cyclopropyl-1-[(3R)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-cyclopropyl-1-[(3S)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-6-fluoropyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-cyclopropyl-1-[rel-(3R ＊ )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 1)[ ＊ [Absolute configuration has not yet been confirmed] 1-[3-cyclopropyl-1-[(3R)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-cyclopropyl-1-[(3S)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-[[9-[5-(2,4-dioxohexahydropyrimidine-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridine-1-yl]-3-azaspiro[5.5]undecane-3-yl]methyl]-4-fluoro-1-piperidyl]benzonitrile, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[3-[[rel-(4R ＊ )-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 2)[ ＊ [Absolute configuration has not yet been confirmed] 1-[3-methyl-1-[3-[[(4R)-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[3-[[4(S)-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-[[9-[5-(2,4-dioxohexahydropyrimidine-1-yl)-3-methylpyrrolo[2,3-b]pyridine-1-yl]-3-azaspiro[5.5]undecane-3-yl]methyl]-4-fluoro-1-piperidyl]benzonitrile, 1-[3-methyl-1-[3-[[rel-(4R ＊ )-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 1)[ ＊ [Absolute configuration has not yet been confirmed] 1-[3-methyl-1-[3-[[(4R)-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[3-[[(4S)-1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-4-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-4-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-6-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[rel-(3S ＊ )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 2)[ ＊ [Absolute configuration has not yet been confirmed] 1-[3-methyl-1-[(3S)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[(3R)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[rel-(3R ＊ )-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 1)[ ＊ [Absolute configuration has not yet been confirmed] 1-[3-methyl-1-[(3S)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[(3R)-8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5r,8r)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[rel-(3S ＊ )-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 1)[ ＊ [Absolute configuration has not yet been confirmed] 1-[3-methyl-1-[3S)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[(3R)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[rel-(3R ＊ )-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione (isomer 2)[ ＊ [Absolute configuration has not yet been confirmed] 1-[3-methyl-1-[(3S)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[(3R)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5r,8r)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]piperazin-1-yl]methyl]spiro[5.5]undecane-3-yl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(3s,6s)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(3r,6r)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[4-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]piperazin-1-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-[[9-[5-(2,4-dioxohexahydropyrimidine-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridine-1-yl]-3-azaspiro[5.5]undecane-3-yl]methyl]-1-piperidyl]benzonitrile, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-[4-[[2-[3-cyclopropyl-5-(2,4-dioxohexahydropyrimidine-1-yl)pyrrolo[2,3-b]pyridine-1-yl]-7-azaspiro[3.5]nonane-7-yl]methyl]-1-piperidyl]benzonitrile, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[(1R,5S,6s)-3-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3-azabicyclo[3.1.0]hexane-6-yl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[(1R,5S,6s)-3-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-3-azabicyclo[3.1.0]hexane-6-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(1s,3s)-3-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octane-8-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[(2R)-4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]morpholine-2-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-6-fluoro-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-azabicyclo[3.2.1]octane-8-yl]-2-chlorophenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[8-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]pyrrolo[1,2-a]pyrimidine-3-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(2S)-6-[[4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]piperazin-1-yl]methyl]tetralin-2-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(2R)-6-[[4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]piperazin-1-yl]methyl]tetralin-2-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(2S)-6-[[4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]piperazin-1-yl]methyl]tetralin-2-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(2R)-6-[[4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]piperazin-1-yl]methyl]tetralin-2-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[(1s,4s)-4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]cyclohexyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[(1r,4r)-4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]cyclohexyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(3r,6r)-9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(1r,4r)-4-[8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octane-3-yl]cyclohexyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(1s,4s)-4-[8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octane-3-yl]cyclohexyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(1r,3r)-3-[8-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-fluoro-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octane-3-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(3,5-difluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(3-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]piperidine-4-carbonyl]-7-azaspiro[3.5]nonane-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-[4-[[3-[3-cyclopropyl-5-(2,4-dioxohexahydropyrimidine-1-yl)pyrrolo[2,3-b]pyridine-1-yl]-1,5-dioxa-9-azaspiro[5.5]undecane-9-yl]methyl]-1-piperidyl]benzonitrile, 1-[1-[3-[[1-[5-[3-[3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-4-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(5-fluoro-2-hydroxy-phenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(3-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(3-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(3,5-difluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(3,5-difluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(3-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(3,5-difluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenoxy]ethyl]-3-azaspiro[5.5]undecane-9-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[7-[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenoxy]ethyl]-7-azaspiro[3.5]nonane-2-yl]-3-methylpyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[[1-[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenoxy]ethyl]-4-fluoro-4-piperidyl]methyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(3S)-1-[[1-[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenoxy]ethyl]-4-fluoro-4-piperidyl]methyl]pyrroridine-3-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(3R)-1-[[1-[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenoxy]ethyl]-4-fluoro-4-piperidyl]methyl]pyrroridine-3-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenoxy]ethyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-azabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-ethyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[rac-(2S,3aR,6aR)-5-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-2,3,3a,4,6,6a-hexahydrofl[2,3-c]pyrrole-2-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[3-methyl-1-[7-[[rac-(2S,3aR,6aR)-5-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-2,3,3a,4,6,6a-hexahydrofl[2,3-c]pyrrole-2-yl]methyl]-7-azaspiro[3.5]nonane-2-yl]pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(3-chloro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxy-3-methylphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(5-fluoro-2-hydroxy-phenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[5s,8s)-2-[[1-[5-[3-[3-amino-6-(3-fluoro-2-hydroxy-phenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methyl-indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[5s,8s)-2-[[1-[5-[3-[3-amino-6-(3,5-difluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]-3-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[(3S)-4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-methyl-piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[(3S)-4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-methyl-piperazin-1-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-yl]-2-fluorophenyl]-4-hydroxy-4-piperidyl]methyl]-3-azaspiro[5.5]undecane-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(3-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-amino-6-(3,5-difluoro-2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decane-8-yl]indole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-6-methylindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[2-[4-[2-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenoxy]ethyl]piperazine-1-yl]ethyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[2-[4-[2-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenoxy]ethyl]piperazin-1-yl]ethyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-4-fluoroindole-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]indole-4-yl]hexahydropyrimidine-2,4-dione, 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]-4-hydroxy-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecane-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, 1-[1-[1-[4-[[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]methyl]piperazine-1-carbonyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, -[1-[1-[4-[[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]methyl]piperazine-1-carbonyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, -[1-[1-[3-[4-[[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluorophenyl]methyl]piperazin-1-yl]-3-oxopropyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, or 1-[1-[1-[3-[4-[[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]methyl]piperazin-1-yl]-3-oxopropyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridine-5-yl]hexahydropyrimidine-2,4-dione, or a pharmaceutically acceptable salt thereof.

103. A pharmaceutical composition comprising a compound according to any one of claims 1 to 102 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

104. A method for degrading the SMARCA2 protein in a human, comprising administering to a human in need of such degradation an effective amount of a compound according to any one of claims 1 to 102, or a pharmaceutically acceptable salt thereof, or a composition according to claim 103.

105. A method for reducing the level of SMARCA2 activity in a human, comprising administering to a human in need of such reduction an effective amount of a compound according to any one of claims 1 to 102, or a pharmaceutically acceptable salt thereof, or a composition according to claim 103.

106. A method for treating cancer in a human being, comprising administering to a person in need of such treatment an effective amount of a compound according to any one of claims 1 to 102, or a pharmaceutically acceptable salt thereof, or a composition according to claim 103.

107. The method according to claim 106, wherein the cancer is a SMARCA2-sensitive cancer.

108. The method according to claim 106, wherein the cancer is a SMARCA2 mutation cancer.

109. The method according to any one of claims 106 to 108, wherein the cancer is a solid tumor.

110. The method according to any one of claims 106 to 108, wherein the cancer is lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer.

111. A compound according to any one of claims 1 to 102, or a pharmaceutically acceptable salt thereof, or a composition according to claim 103, for use in degrading the SMARCA2 protein in humans.

112. A compound according to any one of claims 1 to 102, or a pharmaceutically acceptable salt thereof, or a composition according to claim 103, for use in reducing the level of SMARCA2 activity in humans.

113. A compound according to any one of claims 1 to 102, or a pharmaceutically acceptable salt thereof, or a composition according to claim 103, for use in treating cancer in humans.

114. The compound for use according to claim 113, wherein the cancer is a SMARCA2-sensitive cancer.

115. The compound for use according to claim 113, wherein the cancer is a SMARCA2 mutation cancer.

116. The compound for use according to any one of claims 113 to 115, wherein the cancer is a solid tumor.

117. The compound for use according to any one of claims 113 to 115, wherein the cancer is lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer.

118. Use of a compound according to any one of claims 1 to 102, or a pharmaceutically acceptable salt thereof, or the composition according to claim 103, in the manufacture of a pharmaceutical for degrading the SMARCA2 protein in humans.

119. Use of a compound according to any one of claims 1 to 102, or a pharmaceutically acceptable salt thereof, or the composition according to claim 103, in the manufacture of a pharmaceutical product for reducing the level of SMARCA2 activity in humans.

120. Use of a compound according to any one of claims 1 to 102, or a pharmaceutically acceptable salt thereof, or the composition according to claim 103, in the manufacture of a pharmaceutical product for treating cancer in humans.

121. A compound or a pharmaceutically acceptable salt thereof for use according to claim 120, wherein the cancer is a SMARCA2-sensitive cancer.

122. A compound or a pharmaceutically acceptable salt thereof for use according to claim 120, wherein the cancer is a SMARCA2 mutation cancer.

123. A compound for use according to any one of claims 120 to 122, or a pharmaceutically acceptable salt thereof, wherein the cancer is a solid tumor.

124. A compound or a pharmaceutically acceptable salt thereof for use according to any one of claims 120 to 122, wherein the cancer is lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer, or ovarian cancer.

Images