3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octane derivatives as smarca2 degrading protacs for the treatment of cancer

Abstract

The present disclosure provides compounds represented by Formula (A), or a pharmaceutically acceptable salt and / or stereoisomer thereof: Formula (A), wherein E is: Formula (I), Formula (II), or Formula (III); wherein Ra, Rb, Rc, R7, R8, R9, R10, X3, W, L, and E are as defined in the specification. Compounds represented by Formula (A) are SMARCA2 protein degraders and are thus useful for treating cancer and other diseases.

Description

SMARCA2 DEGRADERS AND USES THEREOF BACKGROUND Field

[0001] The present disclosure provides Proteolysis Targeting Chimera (PROTAC) compounds and the use of such PROTAC compounds for the treatment of diseases or disorders dependent on SMARCA2 in mammals. Degradation of SMARCA2 may provide, for example, an anti-tumor effect. The present disclosure thus provides the use of SMARCA2 degraders and pharmaceutical compositions comprising SMARCA2 degraders for the treatment of cancer. It also provides intermediate compounds that may be useful in the preparation of such PROTACs. Background

[0002] Traditional "small molecule" drugs reversibly (or sometimes irreversibly) bind to a target protein as a means of modulating a given biological activity. In contrast, PROTACs bind to their target proteins reversibly, but then bring about the target protein's degradation. Having achieved this effect, the PROTAC is in theory able to repeat this process with another target protein. Accordingly, unlike traditional small molecule inhibitors, the PROTAC-driven degradation mechanism can in theory operate in a sub- stoichiometric manner - meaning that more modest exposures of a PROTAC compound could still achieve a desired level of efficacy in vivo. In practice, this means that the degradation power (DC50and Dmax) of a PROTAC may have an improved effect over that reflected by its binding affinity.

[0003] PROTAC molecules are described as having three parts - (1) a part that is capable of binding to the protein to be degraded, (2) a second part that is capable of binding to an E3 ubiquitin ligase, and (3) a linker that connects parts (1) and (2) together. In use, the PROTAC binds to both the target protein and E3 ubiquitin ligase simultaneously to form a ternary complex. The E3 ligase then recruits an E2 conjugating enzyme to the ternary complex, which ubiquitinates the target protein. This has the effect of labelling the target protein for degradation by the cell's proteasome machinery. A PROTAC can then dissociate from the target protein and initiate another cycle of this process in a catalytic manner. Meanwhile, the ubiquitinated target proteins are recognized by the cell's proteasome machinery and are then degraded by it. This PROTAC-mediated approach may be valuable as a method of treating certain diseases, including cancer.

[0004] SMARCA4 is a frequently mutated in several tumor types - including lung, liver, colon, skin, bladder, esophageal, gastric, brain, endometrial, cervical and ovarian cancers. Furthermore, it has been established that SMARCA2 is essential for growth of tumors harboring such SMARCA4 mutations. Accordingly, selective suppression of SMARCA2 has been proposed as a therapeutic strategy against cancers that may include SMARCA4 mutations. Accordingly, selective suppression of SMARCA2 may be useful against a number of 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 "SMARCA 2 / 4 degraders" and WO2020251969 discloses PROTAC compounds which 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 that are said to degrade PBRM1. WO2018 / 144649 and WO2021 / 053495 also disclose certain PROTAC molecules. WO2021 / 053555 discloses glue degrader compounds which bind to the E3 ubiquitin ligase, cereblon.

[0006] As part of developing a PROTAC against cancer, there is a need to develop further PROTAC compounds with a combination of beneficial / improved properties that make them more suitable for use as a therapeutic drug for human use. Properties of interest during pharmaceutical discovery and development may relate to selectivity profile, absorption / bioavailability, distribution, metabolism, elimination, toxicity and side-effect profile, stability, manufacturability, and so on. BRIEF SUMMARY

[0007] In one aspect, the present disclosure provides PROTAC compounds represented by any one of Formulae (A) and (I)-(V), below, and the pharmaceutically acceptable salts thereof. In another aspect, the present disclosure provides any one or more of the PROTAC compounds of Compound List 1, below, and the pharmaceutically acceptable salts thereof. In another aspect, the present disclosure provides any one or more of the PROTAC compounds of Compound List 2, below, and the pharmaceutically acceptable salts thereof. In another aspect, the present disclosure provides any one or more of the PROTAC compounds of Compound List 3, below, and the pharmaceutically acceptable salts thereof. In another aspect, the present disclosure provides any one or more of the PROTAC compounds of Compound List 4, below, and the pharmaceutically acceptable salts thereof. Compounds having any one of Formulae (A) and (I)-(V), and the pharmaceutically acceptable salts thereof, and the compounds of Compound List 1, Compound List 2, Compound List 3, and / or Compound List 4, and the pharmaceutically acceptable salts thereof, are collectively referred to as "Compounds of the Disclosure" or individually as a "Compound of the Disclosure." Compounds of the Disclosure exhibit protein degradation activity against SMARCA2. Compounds of the Disclosure also may have a beneficial degree of selectivity to minimize certain undesirable off-target degradation activities. As such, Compounds of the Disclosure may be useful in the treatment of cancer.

[0008] Compounds of the Disclosure also may have a surprisingly beneficial combination of properties of relevance in the context of pharmaceutical discovery and development. Structural features found in all three regions of a PROTAC have the potential to operate (collectively or in some cases separately) towards delivering a beneficial combination and / or balance of such additional beneficial properties. Avoidance of off-target activity in pharmaceutical development is often important to avoid or reduce unwanted toxicities, side-effects or other problems with tolerability when used in patients.

[0009] As well as being degraders of SMARCA2, Compounds of the Disclosure have a surprising and beneficial combination of properties relating, for example. to chemical and metabolic stability, e.g. in human microsomes and to hydrolysis at pH 7.4, and selectivity against SALL4 and / or Ikaros (IKZF1) – which is expected to provide an improved safety profile for use in vivo. Without wishing to be bound by any particular theory, it is believed that degradation of SALL4 and Ikaros (IKZF1) amongst others may risk serious unwanted effects in humans, for example, developmental toxicities or bone marrow toxicities.

[0010] Also, in this regard, it has been found that molecules that degrade SMARCA2 can often also degrade SMARCA4, which is regarded as an undesirable off-target activity. Compounds of the Disclosure may show a beneficial selectivity profile by achieving a potent degree of degradation against SMARCA2 while having a margin of selectivity, i.e., relatively lower degradation, against SMARCA4. In a similar manner in the development of a SMARCA2 PROTAC for use in cancer, it is also regarded as beneficial to have a potent degree of degradation against SMARCA2 while having a good margin of selectivity, i.e., relatively lower degradation, against PBRM1. Compounds of the Disclosure may show a beneficial selectivity profile between SMARCA2 and PBRM1. Thus, in combination, Compounds of the Disclosure may show high potency against SMARCA2 while simultaneously achieving a beneficial selectivity profile with respect to SALL4 and / or Ikaros (IKZF1), and in some cases a surprisingly beneficial margin of selectivity against SMARCA4 and / or PBRM1.

[0011] In another aspect, the present disclosure provides pharmaceutical compositions comprising a Compound of the Disclosure and one or more pharmaceutically acceptable excipients.

[0012] In another aspect, the present disclosure provides methods of degrading SMARCA2 protein in a human, comprising administering to a human in need thereof an effective amount of a Compound of the Disclosure.

[0013] In another aspect, the present disclosure provides methods of reducing SMARCA2 protein in a human, comprising administering to a human in need thereof an effective amount of a Compound of the Disclosure.

[0014] In another aspect, the present disclosure provides methods of treating cancer in a human, comprising administering to a human in need thereof an effective amount of a Compound of the Disclosure.

[0015] In another aspect, the present disclosure provides a Compound of the Disclosure, or pharmaceutical composition thereof, for use in degrading SMARCA2 protein in a human.

[0016] In another aspect, the present disclosure provides a Compound of the Disclosure, or pharmaceutical composition thereof, for use in reducing SMARCA2 protein in a human.

[0017] In another aspect, the present disclosure provides a Compound of the Disclosure, or pharmaceutical composition thereof, for use in treating cancer in a human.

[0018] In another aspect, the present disclosure provides use of a Compound of the Disclosure, or pharmaceutical composition thereof in the manufacture of a medicament for degrading SMARCA2 protein in a human.

[0019] In another aspect, the present disclosure provides use of a Compound of the Disclosure, or pharmaceutical composition thereof in the manufacture of a medicament for reducing SMARCA2 protein in a human.

[0020] In another aspect, the present disclosure provides use of a Compound of the Disclosure, or pharmaceutical composition thereof in the manufacture of a medicament for treating cancer in a human.

[0021] In another aspect, the present disclosure provides methods of preparing Compounds of the Disclosure.

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

[0023] Additional embodiments and advantages of the disclosure will be set forth, in part, in the description that follows, and will flow from the description, or can be learned by practice of the disclosure. The embodiments and advantages of the disclosure will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing summary and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed. DETAILED DESCRIPTION I. Compounds of the Disclosure

[0024] Many embodiments of this disclosure are detailed throughout the specification.

[0025] In one embodiment, Compounds of the Disclosure are compounds of Formula (A), or pharmaceutically acceptable salt thereof: , wherein:

[0026] E is: ;

[0027] R1is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or ;

[0028] R2is hydrogen, halogen, (C1-alkoxy, or ;

[0029] with the provisos:

[0030] (i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is:

[0031] (ii) when R2is hydrogen,or (C1-C6)alkoxy, then R1is ;

[0032] R11is hydrogen or -(C1-C6)2;

[0033] X1is CR3or N;

[0034] R3is hydrogen, halogen, or (C1-C6)alkyl;

[0035] X2is CR4or N;

[0036] R4is hydrogen, halogen, or (C1-C6)alkyl;

[0037] R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl,

[0038] wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6- membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl;

[0039] R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl;

[0040] R6is hydrogen, (C1-C6)alkyl, or cyano;

[0041] X3is -CH2CH2- or -CH2-O-CH2-;

[0042] or X3is absent;

[0043] L is G1-G2-G3-G4-, wherein G1is attached to W;

[0044] G1is (C1-C6)alkylenyl; (C3-C6)cycloalkylenyl; -O-CH2-CH2-; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, cyano, or hydroxyl; or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1- C6)alkyl, (C1-C6)alkoxy, or cyano;

[0045] G2is (C1-C6)alkylenyl, -C(=O)-, 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three fluoro, or a direct bond;

[0046] G3is -C(=O)-; -C(=O)-CH2CH2-; (C1-C6)alkylenyl; tetrahydronaphthalenenyl; 4- to 6- membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy or cyano; 7- to 11-membered heterocycloalkyl-C(=O)-, or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano;

[0047] G4is (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl; 4- to 6-membered heterocycloalkylenyl; or a direct bond;

[0048] W is -C≡C- or a direct bond;

[0049] R7is hydrogen; halogen; (C1-C6)alkyl optionally substituted with one, two, or three halogen; cyano; or (C3-C6)cycloalkyl;

[0050] R8is hydrogen; halogen; (C1-C6)alkyl optionally substituted with one, two, or three halogen; cyano; or (C3-C6)cycloalkyl;

[0051] R9is hydrogen; halogen; (C1-C6)alkyl optionally substituted with one, two, or three halogen; cyano; or (C3-C6)cycloalkyl;

[0052] R10is hydrogen; halogen; (C1-C6)alkyl optionally substituted with one, two, or three halogen; cyano; or (C3-C6)cycloalkyl;

[0053] Rais hydrogen or halogen;

[0054] Rbis hydrogen or halogen; and

[0055] Rcis hydrogen or methyl.

[0056] In another embodiment, Compounds of the Disclosure are compounds having Formula (I), or a pharmaceutically acceptable salt thereof: (I),wherein:

[0057] E is: ;

[0058] R1is;

[0059] R2is hydrogen, halogen, (C1-alkoxy, or ; with the provisos:

[0060] (i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is:

[0061] (ii) when R2is hydrogen,or (C1-C6)alkoxy, then R1is ;

[0062] R11is hydrogen or -(C -C1 6) 2;

[0063] X1is CR3or N;

[0064] R3is hydrogen, halogen, or (C1-C6)alkyl;

[0065] X2is CR4or N;

[0066] R4is hydrogen, halogen, or (C1-C6)alkyl;

[0067] R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl;

[0068] R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl;

[0069] R6is hydrogen, (C1-C6)alkyl, or cyano;

[0070] X3is -CH2CH2- or -CH2-O-CH2-; or

[0071] X3is absent;

[0072] L is -G1-G2-G3-G4-, wherein G1is attached to W;

[0073] G1is (C1-C6)alkyenyl; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano;

[0074] G2is (C1-C6)alkylenyl or a direct bond;

[0075] G3is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, or (C1-C6)alkoxy; cyano; or 7- to 11- membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano;

[0076] G4is (C1-C6)alkylenyl or a direct bond;

[0077] W is -C≡C- or a direct bond;

[0078] R7is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl;

[0079] R8is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl;

[0080] R9is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; and

[0081] R10is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl.

[0082] In another embodiment, Compounds of the Disclosure are compounds having Formula (I), or pharmaceutically acceptable salt thereof: (I),wherein:

[0083] E is:;

[0084] R1is hydrogen, a ogen, (C1-C6)a y , (C1-C6)a oxy, or ;

[0085] R2is hydrogen, halogen, (C1-alkoxy, or ; with the provisos:

[0086] (i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is:

[0087] (ii) when R2is hydrogen,or (C1-C6)alkoxy, then R1is: ;

[0088] R11is hydrogen or -(C1-C6)2;

[0089] X1is CR3or N;

[0090] R3is hydrogen, halogen, or (C1-C6)alkyl;

[0091] X2is CR4or N;

[0092] R4is hydrogen, halogen, or (C1-C6)alkyl;

[0093] R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl;

[0094] R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl;

[0095] R6is hydrogen, (C1-C6)alkyl, or cyano;

[0096] X3is -CH2CH2- or -CH2-O-CH2-; or

[0097] X3is absent;

[0098] L is -G1-G2-G3-G4-, wherein G1is attached to W;

[0099] G1is (C1-C6)alkyenyl; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano;

[0100] G2is (C1-C6)alkylenyl or a direct bond;

[0101] G3is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, or (C1-C6)alkoxy; cyano; 7- to 11- membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; or 5- to 10-membered heteroarylenyl;

[0102] G4is (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl, or a direct bond;

[0103] W is -C≡C- or a direct bond;

[0104] R7is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl;

[0105] R8is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl;

[0106] R9is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; and

[0107] R10is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl.

[0108] In another embodiment, Compounds of the Disclosure are compounds having Formula (II), or a pharmaceutically acceptable salt thereof: , wherein R7, R8, R9,with Formula (I).

[0109] In another embodiment, Compounds of the Disclosure are compounds having Formula (III), or a pharmaceutically acceptable salt thereof:I), wherein R7, R8, R9, R , W, L, and E are as de ned n connect on with Formula (I).

[0110] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein E is E-1.

[0111] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R5ais hydrogen.

[0112] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R5ais (C1-C6)alkyl optionally substituted with one, two, or three substituents independently selected from halogen or cyano.

[0113] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R5ais methyl.

[0114] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R5ais (C3-C6)cycloalkyl.

[0115] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R5ais cyclopropyl.

[0116] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R5ais 4- to 6-membered heterocycloalkyl optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl.

[0117] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R5ais cyano.

[0118] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R5ais aryl optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl.

[0119] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R5ais 5- or 6-membered heteroaryl optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl.

[0120] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein E is E-2.

[0121] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein E is E-3.

[0122] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0123] R1is:

[0124] R2is hydrogen, halogen,alkoxy.

[0125] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R2is hydrogen, halogen, or (C1-C6)alkyl.

[0126] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R2is hydrogen, fluoro, or methyl.

[0127] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R11is hydrogen.

[0128] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein X1is CR3.

[0129] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R3is hydrogen.

[0130] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R3is halogen.

[0131] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R3is (C1-C6)alkyl.

[0132] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein X1is N.

[0133] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein X2is CR4.

[0134] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R4is hydrogen.

[0135] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R4is halogen.

[0136] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R4is (C1-C6)alkyl.

[0137] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein X2is N.

[0138] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein E-1 is: , , orone of Formulae (A) or (I)-(III), wherein E-1 is: , ,, ,

[0140] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein E is: .

[0141] Inhaving any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein E-2 is: .

[0142] In another are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein E-3 is: .

[0143] In another Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein E is:.

[0144] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G1is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano.

[0145] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G1is (C3-C6)cycloalkylenyl; or 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, cyano, or hydroxyl.

[0146] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0147] G1is: ;

[0148] each R12is independently halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano;

[0149] n is 0, 1, 2, or 3; and

[0150] the bond marked with an "*" is attached to G2.

[0151] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0152] G1is: ;

[0153] each R12is independently(C1-C6)alkoxy, cyano, or hydroxyl;

[0154] n is 0, 1, 2, or 3; and

[0155] the bond marked with an "*" is attached to G2.

[0156] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein each R12is independently fluoro, methyl, methoxy, cyano, or -CHF2; and n is 0, 1, or 2.

[0157] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0158] G1is:nd

[0159] the bond marked with an is attached to G .

[0160] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0100] G1is:

[0162] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0163] G1is: ;

[0164] X4is -O-;

[0165] each R12is independently halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; and

[0166] the bond marked with an “*” is attached to G2.

[0167] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0168] G1is:

[0169] the bond marked with

[0170] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0171] G1is:

[0172] the bond marked with an "*"

[0173] In another embodiment, Compounds of the Disclosure are compounds having Formula (A), or a pharmaceutically acceptable salt thereof, wherein G1is cyclohexylenyl.

[0174] In another embodiment, Compounds of the Disclosure are compounds having Formula (A), or a pharmaceutically acceptable salt thereof, wherein:

[0175] the bond marked

[0176] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G1is 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano.

[0177] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0178] G1is: ;

[0179] each R13is independently(C1-C6)alkyl, (C1-C6)alkoxy, or cyano;

[0180] o is 0, 1, 2, or 3;

[0181] p, q, r, and s are independently is 1, 2, or 3; and

[0182] the bond marked with an "*" is attached to G2.

[0183] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0184] G1is: ;

[0185] each R13is independently(C1-C6)alkyl, (C1-C6)alkoxy, or cyano;

[0186] o is 0, 1, 2, or 3;

[0187] p, q, r, and s are independently 1 or 2;

[0188] the bond marked with an "*" is attached to G2.

[0189] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0190] p and q are 1;

[0191] r is 1 or 2;

[0192] s is 1 or 2; and

[0193] R13is halogen.

[0194] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R13is fluoro and o is 0, 1, or 2.

[0195] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G1is:

[0196] the bond marked with an

[0197] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0198] G1is: ;

[0199] a is 0 or 1;

[0200] b is 0 or 1; and

[0201] the bond marked with an "*" is attached to G2.

[0202] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G1is:

[0203]

[0204] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G1is:

[0205] the bond marked

[0206] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G1is:nd

[0207] the bond marked with an is attached to G

[0208] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G2is a direct bond.

[0209] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A), or a pharmaceutically acceptable salt thereof, wherein G2is a -C(=O)-.

[0210] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G2is (C1-C6)alkylenyl.

[0211] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G2is -CH2-.

[0212] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G3is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano.

[0213] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0214] G3is: ;

[0215]

[0216] t is 0, 1, 2, or 3; and

[0217] the bond marked with an "*" is attached to G4.

[0218] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R14is fluoro or methyl and t is 0 or 1.

[0219] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G3is: .

[0220] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G3is 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano.

[0221] In another embodiment, Compounds of the Disclosure are compounds having Formulae (A), or a pharmaceutically acceptable salt thereof, wherein G3is:

[0222] the bond

[0223] In anotherhaving any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G3is:

[0224] the bond marked with an "*"

[0225] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G3is:

[0226] the bond marked

[0227] In another compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0228] G3is: ;

[0229] each R15is independently(C1-C6)alkyl, (C1-C6)alkoxy, or cyano;

[0230] u is 0, 1, 2, or 3;

[0231] v, w, x, and y are independently is 1, 2, or 3; and

[0232] the bond marked with an "*" is attached to G4.

[0233] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein v, w, x, and y are independently 1 or 2.

[0234] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R15is fluoro.

[0235] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0236] G3is: ;

[0237] xaand yaare independently

[0238] the bond marked with an "*" is attached to G4.

[0239] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G3is: ,

[0241] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G3is: ,,

[0242] the bond marked with an is attached to G .

[0243] In another embodiment, Compounds of the Disclosure are compounds having Formulae (A), or a pharmaceutically acceptable salt thereof, wherein G3is: ; andthe bond marked with an “*” to

[0244] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G4is (C1-C6)alkylenyl.

[0245] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G4is -CH2- or -CH2CH2-.

[0246] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G4is (C3-C6)cycloalkylenyl.

[0247] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G4is :

[0248] the bond marked

[0249] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G4is:

[0250] the bond marked with

[0251] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G4is a direct bond.

[0252] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein L is:, , , ,, or

[0253] the bond marked with an is attached to E.

[0254] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein L is: ,, , , , ,

[0255] the bond marked with an is attached to E.

[0256] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein L is:

[0258] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein L is: ;

[0260] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein W is -C≡C- .

[0261] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein W is a direct bond.

[0262] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R7is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen.

[0263] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R7is halogen or (C1-C6)alkyl.

[0264] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R7is fluoro or methyl.

[0265] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R8, R9, and R10are H.

[0266] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R8is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen.

[0267] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R8is halogen or (C1- C6)alkyl.

[0268] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R8is fluoro or methyl.

[0269] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R7, R9, and R10are hydrogen.

[0270] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R9is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen.

[0271] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R9is halogen.

[0272] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R9is fluoro.

[0273] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R7, R8, and R10are hydrogen.

[0274] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R10is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen.

[0275] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R10is halogen.

[0276] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R10is fluoro.

[0277] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R7, R8, and R9are hydrogen.

[0278] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein R7, R8, R9, and R10are hydrogen.

[0279] In another embodiment, Compounds of the Disclosure are compounds having having Formula (IV), or a pharmaceutically acceptable salt thereof:V), wherein:

[0280] each R12is independently fluoro;

[0281] n is 0, 1, or 2; and

[0282] R7, R8, R9, and R10are independently hydrogen, fluoro, or methyl

[0283] E is E-1; and

[0284] G3is as defined in connection with Formula (I).

[0285] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein:

[0286] G3is: ,.

[0288] In another embodiment, Compounds of the Disclosure are compounds having any one of Formulae (A) or (I)-(III), or a pharmaceutically acceptable salt thereof, wherein G3is: .

[0289] In another having Formula (V), or pharmaceutically acceptable salt thereof,V), wherein:

[0290] each R12is fluoro or hydroxyl;

[0291] n is 0, 1, 2, or 3;

[0292] E is: ;

[0293] R1is;

[0294] R2is hydrogen, halogen, (C1-alkoxy, or ;

[0295] with the provisos:

[0296] (i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is:

[0297] (ii) when R2is hydrogen,or (C1-C6)alkoxy, then R1is: ;

[0298] R11is hydrogen or -(C1-C6) 2;

[0299] X1is CR3or N;

[0300] R3is hydrogen, halogen, or (C1-C6)alkyl;

[0301] X2is CR4or N;

[0302] R4is hydrogen, halogen, or (C1-C6)alkyl;

[0303] R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl;

[0304] R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl;

[0305] R6is hydrogen, (C1-C6)alkyl, or cyano;

[0306] X3is -CH2CH2- or absent;

[0307] G3is tetrahydronaphthalene; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; 7- to 11-membered heterocycloalkyl-C(=O)-, or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1- C6)alkoxy, or cyano;

[0308] G4is absent or cyclobutylenyl;

[0309] R7, R8, R9, and R10are independently hydrogen, fluoro, methyl, or cyano;

[0310] Rais hydrogen, chloro, methyl, or fluoro;

[0311] Rbis hydrogen, chloro, methyl, or fluoro; and

[0312] Rcis hydrogen or methyl.

[0313] In another embodiment, Compounds of the Disclosure are compounds having Formula (V), or pharmaceutically acceptable salt thereof, wherein:

[0314] G3is: ,, or pharmaceutically acceptable salt thereof, wherein G3is:.

[0316] In anot er embod ment, Compounds o t e D sc osure are compounds av ng Formula (V), or pharmaceutically acceptable salt thereof, wherein G3is: ,of Compound List 1, or a pharmaceutically acceptable salt thereof. Compound List 1

[0318] 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]nonan-2-yl]methyl]-4-piperidyl]-3-methyl-indol-5-yl]hexahydropyrimidine- 2,4-dione;

[0319] 1-[1-[7-[3-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]phenyl]prop-2-ynyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0320] 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]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0321] 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]nonan-2-yl]-3-methyl-indol-5-yl]hexahydropyrimidine- 2,4-dione;

[0322] 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]indol-4-yl]hexahydropyrimidine-2,4-dione;

[0323] 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]undecan-9-yl]-3-methyl-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0324] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0325] 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-5-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0326] 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-5-methyl-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0327] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-methyl-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0328] 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0329] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]indol-5-yl]hexahydropyrimidine- 2,4-dione;

[0330] 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-methyl-pyrrolo[2,3-b]pyridin- 5-yl]hexahydropyrimidine-2,4-dione;

[0331] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-6-fluoro-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0332] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0333] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0334] 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-difluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0335] 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0336] 1-[2-[1-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-4-piperidyl]-1-methyl-indol-6-yl]hexahydropyrimidine-2,4- dione;

[0337] 1-[1-[7-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluoro- phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0338] 1-[1-[7-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluoro- phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4- dione;

[0339] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-4-fluoro-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0340] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-4-methyl-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0341] 1-[1-[[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9- yl]methyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0342] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0343] 1-[1-[1-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-4-piperidyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0344] 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0345] 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0346] 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]nonan-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0347] 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-fluoro-phenyl]-4-piperidyl]methyl]morpholin-2-yl]methyl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0348] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0349] 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-fluoro-phenyl]-4-piperidyl]methyl]piperazin-1-yl]ethyl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0350] 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)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]undecan-3-yl]-3-methyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0351] 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)piperidin-4-yl)methyl)-3-azaspiro[5.5]undecan-9-yl)-3-cyclopropyl-1H-pyrrolo[2,3- b]pyridin-5-yl)dihydropyrimidine-2,4(1H,3H)-dione;

[0352] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0353] 1-[1-[3-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluoro- phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0354] 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)piperidin-4-yl)methyl)-2,7-diazaspiro[3.5]nonane-2- carbonyl)-2-methylphenyl)dihydropyrimidine-2,4(1H,3H)-dione;

[0355] (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)piperidin-4-yl)methyl)-7-azaspiro[3.5]nonan-2-yl)-3- cyclopropyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-dioxotetrahydropyrimidin-1(2H)-yl)methyl dihydrogen phosphate; or

[0356] 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)piperidin-4-yl)methyl)-2-azaspiro[3.5]nonan-7-yl)-3- methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)dihydropyrimidine-2,4(1H,3H)-dione.

[0357] In another embodiment, Compounds of the Disclosure are any one or more of the compounds of Compound List 2, or a pharmaceutically acceptable salt thereof. Compound List 2

[0358] 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]nonan-2-yl]methyl]-4-piperidyl]-3-methyl-indol-5-yl]hexahydropyrimidine- 2,4-dione;

[0359] 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]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0360] 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]nonan-2-yl]-3-methyl-indol-5-yl]hexahydropyrimidine- 2,4-dione;

[0361] 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]undecan-9-yl]-3-methyl-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0362] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0363] 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-5-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0364] 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-5-methyl-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0365] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-methyl-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0366] 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0367] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]indol-5-yl]hexahydropyrimidine- 2,4-dione;

[0368] 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-methyl-pyrrolo[2,3-b]pyridin- 5-yl]hexahydropyrimidine-2,4-dione;

[0369] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-6-fluoro-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0370] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0371] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0372] 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-difluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0373] 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0374] 1-[1-[7-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluoro- phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0375] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-4-fluoro-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0376] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-4-methyl-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0377] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0378] 1-[1-[1-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-4-piperidyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0379] 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0380] 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0381] 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]nonan-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0382] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0383] 1-[1-[9-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)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]undecan-3-yl]-3-methyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0384] 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)piperidin-4-yl)methyl)-3-azaspiro[5.5]undecan-9-yl)-3-cyclopropyl-1H-pyrrolo[2,3- b]pyridin-5-yl)dihydropyrimidine-2,4(1H,3H)-dione;

[0385] 1-[1-[7-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0386] 1-[1-[3-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluoro- phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0387] (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)piperidin-4-yl)methyl)-7-azaspiro[3.5]nonan-2-yl)-3- cyclopropyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-dioxotetrahydropyrimidin-1(2H)-yl)methyl dihydrogen phosphate; or

[0388] 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)piperidin-4-yl)methyl)-2-azaspiro[3.5]nonan-7-yl)-3- methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)dihydropyrimidine-2,4(1H,3H)-dione.

[0389] In another embodiment, Compounds of the Disclosure are any one or more of the compounds of Compound List 3, or a pharmaceutically acceptable salt thereof.Compound List 3

[0390] 1-[2-[1-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-4-piperidyl]-1-methyl-indol-6-yl]hexahydropyrimidine-2,4- dione;

[0391] 1-[1-[7-[[1-[5-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluoro- phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4- dione;

[0392] 1-[1-[[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9- yl]methyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0393] 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-fluoro-phenyl]-4-piperidyl]methyl]morpholin-2-yl]methyl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione; or

[0394] 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)piperidin-4-yl)methyl)-2,7-diazaspiro[3.5]nonane-2- carbonyl)-2-methylphenyl)dihydropyrimidine-2,4(1H,3H)-dione.

[0395] In another embodiment, Compounds of the Disclosure are any one or more of the compounds of Compound List 4, or a pharmaceutically acceptable salt thereof. Compound List 4

[0101] 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]undecan-9-yl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0396] 1-[1-[(1r,3r)-3-[8-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0397] 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-fluoro-phenyl]morpholin-2-yl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0398] 1-[1-[7-[7-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-7-azaspiro[3.5]nonan-2-yl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0399] 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-fluoro-phenyl]-4-piperidyl]methyl]-2-azaspiro[4.5]decan-8-yl]-3-ethyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0400] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-ethyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0401] 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-fluoro-phenyl]-7-azaspiro[3.5]nonan-2-yl]methyl]morpholin-2- yl]methyl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0402] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-6,8-dihydro-5H-imidazo[1,2- a]pyrazin-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0403] 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-fluoro-phenyl]-7-azaspiro[3.5]nonan-2-yl]methyl]morpholin-2- yl]methyl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0404] 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-fluoro-phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5- yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0405] 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-fluoro-phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5- yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0406] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]indol-5-yl]hexahydropyrimidine-2,4-dione;

[0407] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]indol-5-yl]hexahydropyrimidine-2,4-dione;

[0408] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0409] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0410] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0411] 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-dioxohexahydropyrimidin-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridin-1-yl]-3-azaspiro[5.5]undecan-3- yl]methyl]-4-fluoro-1-piperidyl]benzonitrile;

[0412] 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-dioxohexahydropyrimidin-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridin-1-yl]-3-azaspiro[5.5]undecan-3- yl]methyl]-4-fluoro-1-piperidyl]benzonitrile;

[0413] 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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0414] 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-dioxohexahydropyrimidin-1-yl)-3-methyl-pyrrolo[2,3-b]pyridin-1-yl]-3-azaspiro[5.5]undecan- 3-yl]methyl]-4-fluoro-1-piperidyl]benzonitrile;

[0415] 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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0416] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-4- methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0417] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-4- fluoro-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0418] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-6- fluoro-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0419] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)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]undecan-3- yl]-3-ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0420] 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-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-6,10-dioxa-2- azaspiro[4.5]decan-8-yl]-3-ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0421] 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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0422] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0423] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 1)

[0424] 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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0425] 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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0426] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0427] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0428] 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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0429] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]indol-5- yl]hexahydropyrimidine-2,4-dione;

[0430] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0431] 1-[1-[9-[[4-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]piperazin-1-yl]methyl]spiro[5.5]undecan-3-yl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0432] 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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0433] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0434] 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-fluoro-phenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9- azaspiro[5.5]undecan-3-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0435] 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-fluoro-phenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9- azaspiro[5.5]undecan-3-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0436] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9- yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0437] 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-fluoro-phenyl]-4-piperidyl]methyl]piperazin-1-yl]cyclobutyl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0438] 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-dioxohexahydropyrimidin-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridin-1-yl]-3-azaspiro[5.5]undecan-3- yl]methyl]-1-piperidyl]benzonitrile;

[0439] 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-dioxohexahydropyrimidin-1-yl)pyrrolo[2,3-b]pyridin-1-yl]-7- azaspiro[3.5]nonan-7-yl]methyl]-1-piperidyl]benzonitrile;

[0440] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0441] 1-[1-[3-[[(1R,5S,6s)-3-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-3-azabicyclo[3.1.0]hexan-6-yl]methyl]-3- azaspiro[5.5]undecan-9-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0442] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)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]undecan-3- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0443] 1-[1-[7-[[(1R,5S,6s)-3-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-3-azabicyclo[3.1.0]hexan-6-yl]methyl]-7- azaspiro[3.5]nonan-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0444] 1-[1-[(1s,3s)-3-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octan-8- yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0445] 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-fluoro-phenyl]morpholin-2-yl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0446] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-6-fluoro- 3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0447] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-azabicyclo[3.2.1]octan-8- yl]-2-chloro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione; or

[0448] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-6-fluoro- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione.

[0449] In another embodiment, Compounds of the Disclosure are any one or more of the compounds of Compound List 5, or a pharmaceutically acceptable salt thereof. Compound List 5

[0450] 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]nonan-2-yl]methyl]-4-piperidyl]-3-methyl-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0451] 1-[1-[7-[3-[3-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]phenyl]prop-2-ynyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0452] 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]nonan-2-yl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0453] 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]nonan-2-yl]-3-methyl-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0454] 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]indol-4-yl]hexahydropyrimidine- 2,4-dione;

[0455] 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]undecan-9-yl]-3-methyl-indol- 5-yl]hexahydropyrimidine-2,4-dione;

[0456] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0457] 1-[1-[7-[[1-[3-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-5-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0458] 1-[1-[7-[[1-[3-[3-[3-Amino-6-(2-hydroxyphenyl)43yridine43e-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-5-methyl-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- cyclopropyl-pyrrolo[2,3-b]43yridine-5-yl]hexahydropyrimidine-2,4-dione;

[0459] 1-[1-[7-[[1-[3-[3-[3-Amino-6-(2-hydroxyphenyl)44yridine44e-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-5-methyl-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- cyclopropyl-pyrrolo[2,3-b]44yridine-5-yl]hexahydropyrimidine-2,4-dione;

[0460] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-methyl-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0461] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0462] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]indol-5- yl]hexahydropyrimidine-2,4-dione;

[0463] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0464] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-6-fluoro- indol-5-yl]hexahydropyrimidine-2,4-dione

[0465] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0466] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0467] 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-difluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0468] 1-[1-[3-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0469] 1-[2-[1-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-4-piperidyl]-1-methyl-indol-6- yl]hexahydropyrimidine-2,4-dione;

[0470] 1-[1-[7-[[1-[5-[4-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluoro- phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0471] 1-[1-[7-[[1-[5-[4-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluoro- phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4- dione;

[0472] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-4-fluoro- indol-5-yl]hexahydropyrimidine-2,4-dione;

[0473] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-4- methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0474] 1-[1-[[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9- yl]methyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0475] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]- 3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0476] 1-[1-[1-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-4-piperidyl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0477] 1-[1-[7-[[1-[3-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0478] 1-[1-[7-[[1-[3-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0479] 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]nonan-2-yl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0480] 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-fluoro-phenyl]-4-piperidyl]methyl]morpholin-2-yl]methyl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0481] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0482] 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-fluoro-phenyl]-4-piperidyl]methyl]piperazin-1-yl]ethyl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0483] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)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]undecan-3- yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0484] 1-[1-[3-[[1-[3-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-4-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0485] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0486] 1-[1-[3-[[1-[5-[4-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluoro- phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0487] 1-[5-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-2,7-diazaspiro[3.5]nonane-2- carbonyl]-2-methyl-phenyl]hexahydropyrimidine-2,4-dione;

[0488] [3-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]-2,6-dioxo-hexahydropyrimidin-1-yl]methyl dihydrogen phosphate;

[0489] 1-[1-[2-[[1-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-2-azaspiro[3.5]nonan-7-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0490] 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]undecan-9-yl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0491] 1-[1-[(1r,3r)-3-[8-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)46yridine46e-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]46yridine-5-yl]hexahydropyrimidine-2,4-dione;

[0492] 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-fluoro-phenyl]morpholin-2-yl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0493] 1-[1-[7-[7-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]-7-azaspiro[3.5]nonan-2-yl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0494] 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-fluoro-phenyl]-4-piperidyl]methyl]-2-azaspiro[4.5]decan-8-yl]-3-ethyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0495] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-ethyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0496] 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-fluoro-phenyl]-7-azaspiro[3.5]nonan-2-yl]methyl]morpholin-2- yl]methyl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0497] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-6,8-dihydro-5H-imidazo[1,2- a]pyrazin-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0498] 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-fluoro-phenyl]-7-azaspiro[3.5]nonan-2-yl]methyl]morpholin-2- yl]methyl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0499] 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-fluoro-phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5- yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 1) [*absolute configuration not yet confirmed];

[0500] 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]octan-8-yl]-2-fluoro-phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5- yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0501] 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]octan-8-yl]-2-fluoro-phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5- yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0502] 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-fluoro-phenyl]-

[0503] 3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]methyl]-7-azaspiro[3.5]nonan-2- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 2) [*absolute configuration not yet confirmed];

[0504] 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]octan-8-yl]-2-fluoro-phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5- yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0505] 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]octan-8-yl]-2-fluoro-phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5- yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0506] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]indol-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 1) [*absolute configuration not yet confirmed];

[0507] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]indol-5-yl]hexahydropyrimidine-2,4-dione;

[0508] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]indol-5-yl]hexahydropyrimidine-2,4-dione;

[0509] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]indol-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 2) [*absolute configuration not yet confirmed];

[0510] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]indol-5-yl]hexahydropyrimidine-2,4-dione;

[0511] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]indol-5-yl]hexahydropyrimidine-2,4-dione;

[0512] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 2) [*absolute configuration not yet confirmed];

[0513] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0514] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-6-fluoro- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0515] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 1) [*absolute configuration not yet confirmed];

[0516] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0517] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0518] 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-dioxohexahydropyrimidin-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridin-1-yl]-3-azaspiro[5.5]undecan-3- yl]methyl]-4-fluoro-1-piperidyl]benzonitrile;

[0519] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9- yl]-3-ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0520] 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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 2) [*absolute configuration not yet confirmed];

[0521] 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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0522] 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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0523] 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-dioxohexahydropyrimidin-1-yl)-3-methyl-pyrrolo[2,3-b]pyridin-1-yl]-3-azaspiro[5.5]undecan- 3-yl]methyl]-4-fluoro-1-piperidyl]benzonitrile;

[0524] 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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 1) [*absolute configuration not yet confirmed];

[0525] 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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0526] 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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0527] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-4- methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0528] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-4- fluoro-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0529] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-6- fluoro-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0530] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)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]undecan-3- yl]-3-ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0531] 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-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-6,10-dioxa-2- azaspiro[4.5]decan-8-yl]-3-ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0532] 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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0533] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 2) [*absolute configuration not yet confirmed];

[0534] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0535] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0536] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 1) [*absolute configuration not yet confirmed];

[0537] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0538] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0539] 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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0540] 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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0541] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 1) [*absolute configuration not yet confirmed];

[0542] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0543] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0544] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 2) [*absolute configuration not yet confirmed];

[0545] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0546] 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0547] 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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0548] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]indol-5- yl]hexahydropyrimidine-2,4-dione;

[0549] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0550] 1-[1-[9-[[4-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]piperazin-1-yl]methyl]spiro[5.5]undecan-3-yl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0551] 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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0552] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0553] 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-fluoro-phenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9- azaspiro[5.5]undecan-3-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0554] 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-fluoro-phenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9- azaspiro[5.5]undecan-3-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0555] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9- yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0556] 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-fluoro-phenyl]-4-piperidyl]methyl]piperazin-1-yl]cyclobutyl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0557] 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-dioxohexahydropyrimidin-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridin-1-yl]-3-azaspiro[5.5]undecan-3- yl]methyl]-1-piperidyl]benzonitrile;

[0558] 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-dioxohexahydropyrimidin-1-yl)pyrrolo[2,3-b]pyridin-1-yl]-7- azaspiro[3.5]nonan-7-yl]methyl]-1-piperidyl]benzonitrile;

[0559] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0560] 1-[1-[3-[[(1R,5S,6s)-3-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-3-azabicyclo[3.1.0]hexan-6-yl]methyl]-3- azaspiro[5.5]undecan-9-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0561] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)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]undecan-3- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0562] 1-[1-[7-[[(1R,5S,6s)-3-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-3-azabicyclo[3.1.0]hexan-6-yl]methyl]-7- azaspiro[3.5]nonan-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0563] 1-[1-[(1s,3s)-3-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octan-8- yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0564] 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-fluoro-phenyl]morpholin-2-yl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0565] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-6-fluoro- 3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0566] 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-azabicyclo[3.2.1]octan-8- yl]-2-chloro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0567] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)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]undecan-3- yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0568] 1-[8-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9- yl]pyrrolo[1,2-a]pyrimidin-3-yl]hexahydropyrimidine-2,4-dione;

[0569] 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-fluoro-phenyl]piperazin-1-yl]methyl]tetralin-2-yl]indol-5- yl]hexahydropyrimidine-2,4-dione;

[0570] 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-fluoro-phenyl]piperazin-1-yl]methyl]tetralin-2-yl]indol-5- yl]hexahydropyrimidine-2,4-dione;

[0571] 1-[1-[(2S)-6-[[4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-

[0572] diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]piperazin-1-yl]methyl]tetralin-2-yl]indol-5- yl]hexahydropyrimidine-2,4-dione; 1-[1-[(2R)-6-[[4-[5-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-

[0573] diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]piperazin-1-yl]methyl]tetralin-2-yl]indol-5- yl]hexahydropyrimidine-2,4-dione;

[0574] 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-fluoro-phenyl]cyclohexyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0575] 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-fluoro-phenyl]cyclohexyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0576] 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-fluoro-phenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9- azaspiro[5.5]undecan-3-yl]indol-5-yl]hexahydropyrimidine-2,4-dione;

[0577] 1-[1-[(1r,4r)-4-[8-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]cyclohexyl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0578] 1-[1-[(1s,4s)-4-[8-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]cyclohexyl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0579] 1-[1-[(1r,3r)-3-[8-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-3,8- diazabicyclo[3.2.1]octan-3-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4- dione;

[0580] 1-[1-[3-[[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]-3-azaspiro[5.5]undecan-9-yl]-3- ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0581] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(3,5-difluoro-2-hydroxy-phenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0582] 1-[1-[3-[[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]-3-azaspiro[5.5]undecan-9-yl]-3- ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0583] 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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0584] 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]undecan-9-yl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0585] 1-[1-[7-[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenyl]piperidine-4-carbonyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0586] 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]undecan-9-yl]-3-ethyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0587] 1-[1-[9-[[1-[3-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0588] 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-dioxohexahydropyrimidin-1-yl)pyrrolo[2,3-b]pyridin-1-yl]-1,5-dioxa-9- azaspiro[5.5]undecan-9-yl]methyl]-1-piperidyl]benzonitrile;

[0589] 1-[1-[3-[[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]-3-azaspiro[5.5]undecan-9-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0590] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)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]undecan-3- yl]-4-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0591] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)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]undecan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0592] 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]undecan-3- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0593] 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]undecan-3- yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0594] 1-[1-[9-[[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]-1,5-dioxa-9-azaspiro[5.5]undecan-3- yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0595] 1-[1-[9-[[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]-1,5-dioxa-9-azaspiro[5.5]undecan-3- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0596] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(3,5-difluoro-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]undecan-3- yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0597] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(3,5-difluoro-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]undecan-3- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0598] 1-[1-[3-[[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]-3-azaspiro[5.5]undecan-9-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0599] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(3,5-difluoro-2-hydroxy-phenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0600] 1-[1-[3-[2-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenoxy]ethyl]-3-azaspiro[5.5]undecan-9-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0601] 1-[1-[7-[2-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenoxy]ethyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0602] 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-fluoro-phenoxy]ethyl]-4-fluoro-4-piperidyl]methyl]-4-piperidyl]-3- methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0603] 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-fluoro-phenoxy]ethyl]-4-fluoro-4-piperidyl]methyl]pyrrolidin-3-yl]-3- methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0604] 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-fluoro-phenoxy]ethyl]-4-fluoro-4-piperidyl]methyl]pyrrolidin-3-yl]-3- methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0605] 1-[1-[3-[2-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan- 8-yl]-2-fluoro-phenoxy]ethyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione;

[0606] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)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]undecan-3- yl]indol-5-yl]hexahydropyrimidine-2,4-dione;

[0607] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-azabicyclo[3.2.1]octan-8- yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-3-cyclopropyl-indol-5- yl]hexahydropyrimidine-2,4-dione;

[0608] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)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]undecan-3- yl]-3-ethyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0609] 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-fluoro-phenyl]-2,3,3a,4,6,6a-hexahydrofuro[2,3-c]pyrrol-2- yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0610] 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-fluoro-phenyl]-2,3,3a,4,6,6a-hexahydrofuro[2,3-c]pyrrol-2- yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0611] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(3-chloro-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]undecan-3- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0612] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxy-3-methyl-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]undecan-3- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0613] 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]decan-8- yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0614] 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]decan-8- yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0615] 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-Amino-6-(3,5-difluoro-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]decan-8- yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0616] 1-[1-[3-[[1-[5-[(3S)-4-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-methyl-piperazin-1- yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0617] 1-[1-[9-[[1-[5-[(3S)-4-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-methyl-piperazin-1- yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0618] 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-hydroxy-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0619] 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]decan-8- yl]indol-5-yl]hexahydropyrimidine-2,4-dione;

[0620] 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]decan-8- yl]indol-5-yl]hexahydropyrimidine-2,4-dione;

[0621] 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-Amino-6-(3,5-difluoro-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]decan-8- yl]indol-5-yl]hexahydropyrimidine-2,4-dione;

[0622] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)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]undecan-3- yl]-6-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0623] 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]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0624] 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-fluoro-phenoxy]ethyl]piperazin-1-yl]ethyl]-4-piperidyl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0625] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)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]undecan-3- yl]-4-fluoro-indol-5-yl]hexahydropyrimidine-2,4-dione;

[0626] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)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]undecan-3- yl]indol-4-yl]hexahydropyrimidine-2,4-dione;

[0627] 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-hydroxy-4-piperidyl]methyl]-1,5-dioxa-9- azaspiro[5.5]undecan-3-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0628] 1-[1-[1-[4-[[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]methyl]piperazine-1-carbonyl]-4-piperidyl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0629] 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]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0630] 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-fluoro-phenyl]methyl]piperazin-1-yl]-3-oxo-propyl]-4-piperidyl]-3- methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione;

[0631] 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-oxo-propyl]-4-piperidyl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione; or pharmaceutically acceptable salts thereof.

[0632] In another embodiment, Compounds of the Disclosure are any one or more of the compounds of Compound List 1, Compound List 2, Compound List 3, Compound List 4, and / or Compound List 5, or a pharmaceutically acceptable salt thereof

[0633] In another embodiment, a Compound of the Disclosure is: ,or a

[0634] In another embodiment, a Compound of the Disclosure is: ,or a

[0635] In another embodiment, a Compound of the Disclosure is: ,or a

[0636] In another embodiment, a Compound of the Disclosure is: ,or a

[0637] In another embodiment, a Compound of the Disclosure is: ,or a

[0638] In another embodiment, a Compound of the Disclosure is: ,or a

[0639] In another embodiment, a Compound of the Disclosure is: ,or a

[0640] In another embodiment, a Compound of the Disclosure is: ,or a

[0641] In another embodiment, a Compound of the Disclosure is:, or a pharmaceutically acceptable salt thereof.

[0642] In another embodiment, a Compound of the Disclosure is: ,or a

[0643] In another embodiment, a Compound of the Disclosure is: ,or a

[0644] In another embodiment, a Compound of the Disclosure is: ,or a

[0645] In another embodiment, a Compound of the Disclosure is:, or a pharmaceutically acceptable salt thereof.

[0646] In another embodiment, a Compound of the Disclosure is: ,or a

[0647] In another embodiment, a Compound of the Disclosure is: ,or a

[0648] In another embodiment, a Compound of the Disclosure is: ,or a

[0649] In another embodiment, the present disclosure provides pharmaceutical compositions comprising a Compound of the Disclosure and one or more pharmaceutically acceptable excipients.

[0650] Compounds of the Disclosure may have one or more chiral centres and it will be recognised that such compounds may be prepared, isolated and / or supplied with or without the presence of one or more of the other possible enantiomeric and / or diastereomeric isomers of the compounds, or that such isomers may be provided in any relative proportions. The preparation of enantioenriched or enantiopure and / or diastereoenriched or diastereopure compounds may be carried out by standard techniques of organic chemistry that are well known in the art, for example by synthesis from enantioenriched or enantiopure starting materials, and / or by use of an appropriately enantioenriched or enantiopure catalyst during synthesis, and / or by resolution of a racemic or partially enriched mixture of stereoisomers, for example via chiral chromatography. The scope of the present disclosure includes mixtures of stereoisomers as well as purified enantiomers or enantiomerically / diastereomerically enriched mixtures. It is to be understood that the present disclosure includes all combinations and subsets of the particular groups defined hereinabove.

[0651] In one embodiment, the present disclosure provides a composition comprising a Compound of the Disclosure optionally together with one or more of the other stereoisomeric forms of the compound, if any, wherein the Compound of the Disclosure is present within the composition with a diastereomeric excess (%de) of ^ 55%.

[0652] In another embodiment, the %de in the above-mentioned composition is ^ 90%.

[0653] In another embodiment, the %de in the above-mentioned composition is ^ 95%.

[0654] In another embodiment, the %de in the above-mentioned composition is ^ 98%.

[0655] In another embodiment, the %de in the above-mentioned composition is ^ 99%.

[0656] In another embodiment, the present disclosure provides a composition comprising a Compound of the Disclosure optionally together with one or more of the other stereoisomeric forms of the compound, if any, wherein the Compound of the Disclosure is present within the composition with an enantiomeric excess (%ee) of ^ 55%.

[0657] In another embodiment, the %ee in the above-mentioned composition is ^ 90%.

[0658] In another embodiment, the %ee in the above-mentioned composition is ^ 95%.

[0659] In another embodiment, the %ee in the above-mentioned composition is ^ 98%.

[0660] In another embodiment, the %ee in the above-mentioned composition is ^ 99%.

[0661] In another embodiment, the present disclosure provides a composition comprising a Compound of the Disclosure optionally together with one or more of the other stereoisomeric forms of the compound, if any, wherein the Compound of the Disclosure is present within the composition with an enantiomeric excess (%ee) of ^ 90% and a diastereomeric excess (%de) of ^ 90%.

[0662] In another embodiment, the present disclosure provides a composition comprising a Compound of the Disclosure optionally together with one or more of the other stereoisomeric forms of the compound, if any, wherein the the %ee and %de of the Compound of the Disclosure take any combination of values, e.g., the %ee is ^5% and the %de is ^ 80%; the %ee is ^5% and the %de is ^ 90%; the %ee is ^5% and the%de is ^ 95%; the %ee is ^5% and the %de is ^ 98%; the %ee is ^ 95% and the %de is ^ 95%; the %ee is ^ 98% and the %de is ^ 98%; or the %ee is ^ 99% and the %de is ^ 99%.

[0663] Compounds of the Disclosure may be prepared, used or supplied in amorphous form, crystalline form, or semicrystalline form, and any given Compound of the Disclosure may be formed into more than one crystalline / polymorphic forms, including hydrated, e.g., hemi-hydrate, a mono-hydrate, a di-hydrate, a tri-hydrate or other stoichiometry of hydrate, and / or solvated forms. The present disclosure encompasses any and all such solid forms of Compounds of the Disclosure.

[0664] The present disclosure encompasses the preparation and use of salts of Compounds of the Disclosure. Pharmaceutically acceptable salts include, amongst others, those described in Berge, J. Pharm. Sci., 66, 1-19, (1977) or those listed in P.H. Stahl and C.G. Wermuth, 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).

[0102] Suitable pharmaceutically acceptable salts can include acid or base addition salts.

[0665] Such base addition salts can be formed by reaction of a Compound of the Disclosure with the appropriate base, optionally in a suitable solvent such as an organic solvent, to give the salt which can be isolated by a variety of methods, including crystallisation and filtration.

[0666] Such acid addition salts can be formed by reaction of a Compound of the Disclosure with the appropriate acid, optionally in a suitable solvent such as an organic solvent, to give the salt which can be isolated by a variety of methods, including crystallisation and filtration.

[0667] Salts may be prepared in situ during the final isolation and purification of a Compound of the Disclosure. If a basic compound of a Compound of the Disclosure is isolated as a salt, the corresponding free base form of that compound may be prepared by any suitable method known to the art, including treatment of the salt with an inorganic or organic base. Similarly, if a Compound of the Disclosure containing a carboxylic acid or other acidic functional group is isolated as a salt, the corresponding free acid form of that compound may be prepared by any suitable method known to the art, including treatment of the salt with an inorganic or organic acid.

[0668] It will be understood that if a Compound of the Disclosure contains two or more basic moieties, the stoichiometry of salt formation may include 1, 2 or more equivalents of acid. Such salts would contain 1, 2 or more acid counterions, for example, a dihydrochloride salt.

[0669] Stoichiometric and non-stoichiometric forms of a pharmaceutically acceptable salt of a Compound of the Disclosure are included within the scope of the specification, including sub-stoichiometric salts, for example where a counterion contains more than one acidic proton.

[0670] Representative pharmaceutically acceptable acid addition salts include, but are not limited to, 4-acetamidobenzoate, acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate (besylate), benzoate, bisulfate, bitartrate, butyrate, calcium edetate, camphorate, camphorsulfonate (camsylate), caprate (decanoate), caproate (hexanoate), caprylate (octanoate), cinnamate, citrate, cyclamate, digluconate, 2,5-dihydroxybenzoate, disuccinate, dodecylsulfate (estolate), edetate (ethylenediaminetetraacetate), estolate (lauryl sulfate), ethane-1,2-disulfonate (edisylate), ethanesulfonate (esylate), formate, fumarate, galactarate (mucate), gentisate (2,5-dihydroxybenzoate), glucoheptonate (gluceptate), gluconate, glucuronate, glutamate, glutarate, glycerophosphorate, glycolate, hexylresorcinate, hippurate, hydrabamine (N,N'- di(dehydroabietyl)-ethylenediamine), hydrobromide, hydrochloride, hydroiodide, hydroxynaphthoate, isobutyrate, lactate, lactobionate, laurate, malate, maleate, malonate, mandelate, methanesulfonate (mesylate), methylsulfate, mucate, naphthalene-1,5-disulfonate (napadisylate), naphthalene-2-sulfonate (napsylate), nicotinate, nitrate, oleate, palmitate, p-aminobenzenesulfonate, p-aminosalicyclate, pamoate (embonate), pantothenate, pectinate, persulfate, phenylacetate, phenylethylbarbiturate, phosphate, polygalacturonate, propionate, p-toluenesulfonate (tosylate), pyroglutamate, pyruvate, salicylate, sebacate, stearate, subacetate, succinate, sulfamate, sulfate, tannate, tartrate, teoclate (8-chlorotheophyllinate), thiocyanate, triethiodide, undecanoate, undecylenate, and valerate.

[0671] Representative pharmaceutically acceptable base addition salts include, but are not limited to, aluminium, 2-amino-2-(hydroxymethyl)-1,3-propanediol (TRIS), arginine, benethamine (N- benzylphenethylamine), benzathine (N,N’-dibenzylethylenediamine), bis-(2-hydroxyethyl)amine, bismuth, calcium, chloroprocaine, choline, clemizole (1-p chlorobenzyl-2-pyrrolildine-1’-ylmethylbenzimidazole), cyclohexylamine, dibenzylethylenediamine, diethylamine, diethyltriamine, dimethylamine, dimethylethanolamine, dopamine, ethanolamine, ethylenediamine, L-histidine, iron, isoquinoline, lepidine, lithium, lysine, magnesium, meglumine (N-methylglucamine), piperazine, piperidine, potassium, procaine, quinine, quinoline, sodium, strontium, t-butylamine, tromethamine (tris(hydroxymethyl)aminomethane), and zinc.

[0672] The present disclosure also includes isotopically-labeled compounds, which are identical to a Compound of the Disclosure except that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into Compounds of the Disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, chlorine, and iodine, such as2H,3H,11C,13C,14C,15N,17O,18O,31P,32P,35S,18F,36Cl,123I, and125I.

[0673] Compounds of the Disclosure that contain the aforementioned isotopes and / or other isotopes of other atoms are within the scope of the disclosure. Isotopically-labeled compounds of the disclosure, for example those into which radioactive isotopes such as3H,14C are incorporated, are useful in drug and / or substrate tissue distribution assays. Tritiated, i.e.,3H, and carbon-14, i.e.,14C, isotopes are particularly used for their ease of preparation and detectability.11C and18F isotopes are particularly useful in PET (positron emission tomography), and125I isotopes are particularly useful in SPECT (single photon emission computerized tomography), all useful in brain imaging. Further, substitution with heavier isotopes such as deuterium, i.e.,2H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be used in somecircumstances. Isotopically labeled Compounds of the Disclosure can generally be prepared by carrying out the procedures disclosed in the Schemes and / or in the Examples below, by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent.

[0674] In another embodiment, the present disclosure provides a pharmaceutical composition comprising a comprising a Compound of the Disclosure and one or more excipients (also referred to as carriers and / or diluents in the pharmaceutical arts). The excipients are acceptable in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof, i.e., the patient. II. Methods of Use

[0675] It is known that SMARCA4 mutations may be present in certain tumor / cancer types, including lung, liver, colon skin, bladder, cervical and ovarian tumors / cancers, and that SMARCA2 is essential for growth of tumors containing such SMARCA4 mutations. Accordingly, Compounds of the Disclosure may be of value as anti-cancer agents / anti-tumor agents, in particular against cancer / tumor types known to harbor SMARCA4 mutations, for example, lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, liver cancer, cervical cancer and ovarian cancer.

[0676] Compounds of the Disclosure may also be of value against cancer types / tumors sensitive to the degradation of SMARCA2, for example, lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, liver cancer, cervical cancer and ovarian cancer.

[0677] Compounds of the Disclosure may also be of value as anti-tumor agents, in particular as selective inhibitors of the proliferation, survival, motility, dissemination and invasiveness of mammalian cancer cells leading to inhibition of tumor growth and survival and to inhibition of metastatic tumor growth. In particular, Compounds of the Disclosure may be of value as anti-proliferative and anti-invasive agents in the containment and / or treatment of solid tumor disease.

[0678] Compounds of the Disclosure may also be useful in the prevention or treatment of those tumors which are sensitive to degradation of SMARCA2 and that are involved in the signal transduction steps which lead to the proliferation and survival of tumor cells and the migratory ability and invasiveness of metastasising tumor cells. Further, Compounds of the Disclosure may be useful in the prevention or treatment of those tumors which are mediated alone or in part by degradation of SMARCA2, i.e., the compounds may be used to produce an SMARCA2 degradation effect in a subject, e.g., a warm-blooded animal, e.g., a human, in need of such treatment.

[0679] In one embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in the treatment of cancer.

[0680] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in the treatment of a solid tumor.

[0681] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in the treatment of a SMARCA2-sensitive tumor type.

[0682] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in the treatment of tumor types that harbor SMARCA4 mutations.

[0683] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in the treatment of lung, liver, colon, skin, bladder, cervical or ovarian cancer.

[0684] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in the treatment of SMARCA4-mutated cancer.

[0685] The amount of the Compound of the Disclosure that is combined with one or more excipients to produce a single dosage form will necessarily vary depending upon the subject being treated and the particular route of administration.

[0686] The size of the dose for therapeutic or prophylactic purposes of Compounds of the Disclosure will naturally vary according to the nature and severity of the disease state, the age and sex of the animal or patient and the route of administration, according to well known principles of medicine.

[0687] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use as a medicament.

[0688] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in therapy.

[0689] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in a method of treatment of the human or animal body by therapy.

[0690] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in the production of an anti-proliferative effect , for example, in a warm-blooded animal such as a human.

[0691] In another embodiment, the present disclosure provides the use of a Compound of the Disclosure or pharmaceutical composition thereof for the manufacture of a medicament for the production of an anti-proliferative effect , for example, in a warm-blooded animal such as a human.

[0692] In another embodiment, the present disclosure provides a method for producing an anti- proliferative effect in a warm-blooded animal, such as man, in need of such effect, which comprises administering to the animal an effective amount of a Compound of the Disclosure or pharmaceutical composition thereof.

[0693] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use as an anti-invasive agent in the containment and / or treatment of solid tumor disease, for example: in a warm-blooded animal such as a human,.

[0694] In another embodiment, the present disclosure provides the use of a Compound of the Disclosure or pharmaceutical composition thereof for the manufacture of a medicament for use as an anti- invasive agent in the containment and / or treatment of solid tumor disease, for example, in a warm-blooded animal such as a human.

[0695] In another embodiment, the present disclosure provides a method for producing an anti-invasive effect by the containment and / or treatment of solid tumor disease, in a warm-blooded animal, such as man, in need of such effect, which comprises administering to the animal an effective amount of a Compound of the Disclosure or pharmaceutical composition thereof.

[0696] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in the prevention or treatment of cancer, for example, in a warm- blooded animal such as a human.

[0697] In another embodiment, the present disclosure provides the use of a Compound of the Disclosure or pharmaceutical composition thereof for the manufacture of a medicament for the prevention or treatment of cancer, for example, in a warm-blooded animal such as a human.

[0698] In another embodiment, the present disclosure provides a method for the prevention or treatment of cancer in a warm-blooded animal, such as man, in need of such treatment, which comprises administering to the animal an effective amount of a Compound of the Disclosure or pharmaceutical composition thereof.

[0699] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in the prevention or treatment of solid tumor(s), for example, in a warm-blooded animal such as a human.

[0700] In another embodiment, the present disclosure provides the use of a Compound of the Disclosure or pharmaceutical composition thereof for the manufacture of a medicament for the prevention or treatment of solid tumor(s), for example, in a warm-blooded animal such as a human.

[0701] In another embodiment, the present disclosure provides a method for the prevention or treatment of solid tumor(s) in a warm-blooded animal, such as man, in need of such treatment, which comprises administering to the animal an effective amount of a Compound of the Disclosure or pharmaceutical composition thereof.

[0702] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in the prevention or treatment of tumor types that are sensitive to degradation of SMARCA2.

[0703] In another embodiment, the present disclosure provides the use of a Compound of the Disclosure or pharmaceutical composition thereof for the manufacture of a medicament for the prevention or treatment of those tumor types that are sensitive to degradation of SMARCA2.

[0704] In another embodiment, the present disclosure provides a method for the prevention or treatment of those tumor types that are sensitive to degradation of SMARCA2, in a warm-blooded animal,such as man, in need of such treatment, which comprises administering to the animal an effective amount of a Compound of the Disclosure or pharmaceutical composition thereof. Tumor types that are sensitive to degradation of SMARCA2 include, for example, lung tumor, liver tumor, colon tumor, skin tumor, bladder tumor, cervical tumor and ovarian tumor.

[0705] In another embodiment, the d present isclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in providing a degrading effect on SMARCA2, for example, in a warm-blooded animal such as a human.

[0706] In another embodiment, the present disclosure provides the use of a Compound of the Disclosure or pharmaceutical composition thereof for the manufacture of a medicament for providing a degrading effect on SMARCA2, for example, in a warm-blooded animal such as a human.

[0707] In another embodiment, the present disclosure provides a method for providing a degrading effect on SMARCA2 in a warm-blooded animal, such as man, in need of such effect, which comprises administering to the animal an effective amount of a Compound of the Disclosure or pharmaceutical composition thereof.

[0708] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in providing a selective degrading effect on SMARCA2 in, for example, a warm-blooded animal such as man.

[0709] In another embodiment, the present disclosure provides the use of a Compound of the Disclosure or pharmaceutical composition thereof for the manufacture of a medicament for providing a selective degrading effect on SMARCA2, for example, in a warm-blooded animal such as a human.

[0710] In another embodiment, the present disclosure provides a method for providing a selective degrading effect on SMARCA2 in a warm-blooded animal, such as man, in need of such effect, which comprises administering an effective amount of a Compound of the Disclosure or pharmaceutical composition thereof. SMARCA2 has been found to be essential for growth of tumors containing SMARCA4 mutations and certain tumor / cancer types are associated with such SMARCA4 mutations.

[0711] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in the treatment of tumor types that harbor SMARCA4 mutations.

[0712] In another embodiment, the present disclosure provides the use of a Compound of the Disclosure or pharmaceutical composition thereof for the manufacture of a medicament for the prevention or treatment of those tumor types that harbor SMARCA4 mutations.

[0713] In another embodiment, the present disclosure provides a method for the prevention or treatment of those tumor types that harbor SMARCA4 mutations in a warm-blooded animal, such as man, in need of such prevention or treatment, which comprises administering to the animal an effective amount of a Compound of the Disclosure or pharmaceutical composition thereof. Tumor types known to harbor SMARCA4 mutations include lung tumors, liver tumors, colon tumors, skin tumors, bladder tumors,cervical tumors and ovarian tumors, e.g., lung cancer, liver cancer, colon cancer, skin cancer, bladder cancer, cervical cancer and ovarian cancer.

[0714] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in the treatment of lung, liver, colon, skin, bladder, cervical or ovarian cancer.

[0715] In another embodiment, the present disclosure provides the use of a Compound of the Disclosure or pharmaceutical composition thereof for the manufacture of a medicament for the treatment of lung, liver, colon, skin, bladder, cervical or ovarian cancer.

[0716] In another embodiment, the present disclosure provides a method for treating lung, liver, colon, skin, bladder, cervical or ovarian cancer in a warm-blooded animal, such as man, in need of such treatment, which comprises administering to the animal an effective amount of a Compound of the Disclosure or pharmaceutical composition thereof.

[0717] In another embodiment where cancer is mentioned herein, the cancer is lung cancer.

[0718] In another embodiment where cancer is mentioned herein, the cancer is liver cancer.

[0719] In another embodiment where cancer is mentioned herein, the cancer is colon cancer.

[0720] In another embodiment where cancer is mentioned herein, the cancer is skin cancer.

[0721] In another embodiment where cancer is mentioned herein, the cancer is bladder cancer.

[0722] In another embodiment where cancer is mentioned herein, the cancer is cervical cancer.

[0723] In another embodiment where cancer is mentioned herein, the cancer is ovarian cancer.

[0724] In another embodiment, the present disclosure provides a Compound of the Disclosure or pharmaceutical composition thereof for use in the treatment of a SMARCA4-mutated cancer.

[0725] In another embodiment, the present disclosure provides the use of a Compound of the Disclosure or pharmaceutical composition thereof for the manufacture of a medicament for the treatment of a SMARCA4-mutated cancer.

[0726] In another embodiment, the present disclosure provides method for treating a SMARCA4- mutated cancer in a warm-blooded animal, such as man, in need of such treatment, which comprises administering an effective amount of a Compound of the Disclosure or pharmaceutical composition thereof. III. Definitions

[0727] As used herein, the term "alkyl" represents a saturated, straight or branched hydrocarbon moiety having the specified number of carbon atoms. The term "(C1-C6)alkyl" refers to an alkyl moiety containing from 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.

[0728] The term "alkylenyl" as used herein by itself or part of another group refers to a divalent form of an alkyl group having the specified number of carbon atoms. For example, the term "(C1-C6)alkylenyl" refers to an alkylenyl moiety containing from 1 to 6 carbon atoms. The alkylenyl may be optionallysubstituted with one, two, or three substituents independently selected from halogen, cyano, and (C1- C6)alkoxy. Exemplary alkylenyl groups include, but are not limited to, -CH2-, -CH2CH2-, -CH2CH2CH2-, - CH2(CH2)2CH2-, and -CH2(CH2)3CH2-.

[0729] "Alkoxy" refers to a group containing an alkyl radical, defined hereinabove, attached through an oxygen linking atom. The term "(C1-C6)alkoxy" refers to a straight- or branched-chain hydrocarbon radical having at least 1 and up to 6 carbon atoms attached through an oxygen linking atom. Exemplary "(C1-C6)alkoxy" groups useful in the present specification include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, s-butoxy, isobutoxy, and t-butoxy.

[0730] The term "cycloalkylenyl" as used herein by itself or part of another group refers to a divalent form of a cycloalkyl group having the specified number of carbon atoms in the ring. For example, the term "(C3-C6)cycloalkylenyl" refers to an cycloalkylenyl moiety containing from 3 to 6 carbon atoms in the ring. The cycloalkylenyl may be optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, cyano, and (C1-C6)alkoxy. Exemplary cycloalkylenyl groups include, but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexy: .

[0731] Therefers to group or moiety comprising a non-aromatic, monovalent, monocyclic, bicyclic, or spirocyclic radical, which is saturated or partially unsaturated, having 4- to 11-ring atoms, which includes carbon and one or two heteroatoms selected independently from oxygen, sulfur, and / or nitrogen.

[0732] The term "4- to 6-membered heterocycloalkylenyl" as used herein by itself or part of another group refers to a divalent form of a monocyclic or bicyclic heterocycloalkyl having 4, 5, or 6 ring atoms, which includes carbon and one or two heteroatoms selected independently from oxygen, sulfur, and / or nitrogen. The 4- to 6-membered heterocycloalkylenyl may be optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, cyano, or (C1-C6)alkoxy. In one embodiment, the 4- to 6-membered heterocycloalkylenyl is a divalent form of an optionally substituted azetidine. In another embodiment, the the 4- to 6-membered heterocycloalkyleny is a divalent form of an optionally substituted piperidinyl. In another embodiment, the heterocycloalkyleny is a divalent form of an optionally substituted piperazinyl. Exemplary heterocycloalkylenyl groups include, but are not limited to: .

[0733] part of another group refers to a divalent form of a bicyclic (including bridged bicyclic), fused ring systems, or spirocyclic heterocycloalkyl having 7, 8, 9, 10, or 11 ring atoms, which includes carbon and one, two, or threeheteroatoms selected independently from oxygen, sulfur, and / or nitrogen. Exemplary 7- to 11-membered heterocycloalkylenyl groups include, but are not limited to: ,groups having 6 to 14 carbon atoms and having at least one aromatic ring that complies with Hückel's Rule. Examples of "aryl" groups are phenyl, naphthyl, indenyl, dihydroindenyl, anthracenyl, phenanthrenyl, and the like.

[0735] "Heteroaryl" represents a group or moiety comprising an aromatic monovalent monocyclic or bicyclic radical, containing 5 to 10 ring atoms, including 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur. This term also encompasses bicyclic heterocyclic-aryl compounds containing an aryl ring moiety fused to a heterocycloalkyl ring moiety, containing 5 to 10 ring atoms, including 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, containing 5 to 10 ring atoms, including 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur. Illustrative examples of heteroaryls useful in the present specification include, but are not limited to, furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazinyl, benzofuranyl, isobenzofuryl, 2,3-dihydrobenzofuryl, 1,3-benzodioxolyl, dihydrobenzodioxinyl, benzothienyl, indolizinyl, indolyl, isoindolyl, dihydroindolyl, benzimidazolyl, dihydrobenzimidazolyl, benzoxazolyl, dihydrobenzoxazolyl, benzthiazolyl, benzoisothiazolyl, dihydrobenzoisothiazolyl, indazolyl, imidazopyridinyl, pyrazolopyridinyl, benzotriazolyl, triazolopyridinyl, purinyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, quinoxalinyl, cinnolinyl, phthalazinyl, quinazolinyl, 1,5-naphthyridinyl, 1,6-naphthyridinyl, 1,7-naphthyridinyl, 1,8-naphthyridinyl, and pteridinyl. Examples of 5-membered "heteroaryl" groups include furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, and isothiazolyl. Examples of 6-membered "heteroaryl" groups include oxo-pyridyl, pyridinyl, pyridazinyl, pyrazinyl, and pyrimidinyl. Examples of 6,6-fused "heteroaryl" groups include quinolinyl, isoquinolinyl, quinoxalinyl, cinnolinyl, phthalazinyl, quinazolinyl, 1,5-naphthyridinyl, 1,6-naphthyridinyl, 1,7-naphthyridinyl, 1,8-naphthyridinyl, and pteridinyl. Examples of 6,5-fused "heteroaryl" groups include benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, indolizinyl, indolyl, isoindolyl, and indazolyl.

[0736] The term "5- to 10-membered heteroarylenyl" as used herein by itself or part of another group refers to a divalent form of a "heteroaryl" group. Examples of "5- to 10-membered heteroarylenyl" groups include: .

[0737] As usedor moiety comprising an aromatic monovalent monocyclic radical, containing 5 or 6 ring atoms, including at least one carbon atom and 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Selected 5-membered heteroaryl groups contain one nitrogen, oxygen, or sulfur ring heteroatom, and optionally contain 1, 2, or 3 additional nitrogen ring atoms. Selected 6-membered heteroaryl groups contain 1, 2, or 3 nitrogen ring heteroatoms. Illustrative examples of 5- or 6-membered heteroaryl groups useful in the present specification include, but are not limited to furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, and triazinyl.

[0738] The terms "halogen" and "halo" represent fluoro, chloro, bromo, or iodo substituents.

[0739] "Hydroxy" as used herein by itself or as part of a group refers to the radical -OH.

[0740] The term "cyano" as used herein by itself or as part of a group refers to the radical -CN.

[0741] As used herein, the term "optionally" means that the subsequently described event(s) may or may not occur and includes both event(s) that occur and event(s) that do not occur. As such, use of the term "optionally" includes instances where the feature is present, and also instances where the feature is not present. For example, "methyl optionally substituted by one or more F" includes -CH3, -CH2F, -CHF2and -CF3.

[0742] In present disclosure, a group such as "A-B-C" where B is defined as "a direct bond" equates to "A-C," i.e., where A and C are directly linked to each other by a covalent bond.

[0743] The term “substituted” means that one or more hydrogens on the designated atom or group is replaced by the indicated substituent(s) provided that any atom(s) bearing such substituent(s) maintains its permitted valency where the skilled person understands that the standard valencies of carbon, nitrogen and oxygen are 4, 3 and 2 respectively.

[0744] "Pharmaceutically acceptable" refers to those compounds (including salts), materials, compositions, and dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0745] As used herein, the term "treatment" refers to alleviating the specified condition, eliminating or reducing one or more symptoms of the condition, slowing or eliminating the progression of the condition, and delaying the reoccurrence of the condition in a previously afflicted or diagnosed patient or subject.

[0746] The term "effective amount" means that amount of a drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, system, animal, or human that is being sought, for instance, by a researcher or clinician

[0747] The term "therapeutically effective amount" means any amount which, as compared to a corresponding subject who has not received such amount, results in improved treatment, healing, or amelioration of a disease, disorder, or side effect, or a decrease in the rate of advancement of a disease or disorder. The term also includes within its scope amounts effective to enhance normal physiological function. For use in therapy, therapeutically effective amounts of a Compound of the Disclosure may be administered as the raw chemical. Additionally, the active ingredient may be presented as a pharmaceutical composition.

[0748] Compounds of the Disclosure may have asymmetric centers and may thus give rise to enantiomers, diastereomers, and other stereoisomeric forms. The present disclosure encompasses the preparation and use of all such possible stereoisomeric forms, as well as their racemic and resolved forms, and mixtures thereof. The enantiomers and diastereomers can be separated according to methods known in the art in view of the present disclosure. When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended that they include both E and Z geometric isomers. All tautomers are also encompassed by the present disclosure.

[0749] As used herein, the term "stereoisomers" is a general term for all isomers of individual molecules that differ only in the orientation of their atoms in space. It includes enantiomers, atropisomers, and isomers of compounds with more than one chiral center that are not mirror images of one another (diastereomers).

[0750] The term "chiral center" or "asymmetric carbon atom" refers to a carbon atom to which four different groups are attached.

[0751] The terms "enantiomer" and "enantiomeric" refer to a molecule that cannot be superimposed on its mirror image and hence is optically active wherein the enantiomer rotates the plane of polarized light in one direction and its mirror image compound rotates the plane of polarized light in the opposite direction. Enantiomers may be separated by chiral chromatography using methods well known in the art.

[0752] The term "racemic" or "racemate" refers to a mixture of equal parts of enantiomers and which mixture is optically inactive.

[0753] The term "absolute configuration" refers to the spatial arrangement of the atoms of a chiral molecular entity (or group) and its stereochemical description, e.g., R or S.

[0754] The stereochemical terms and conventions used in the specification are meant to be consistent with those described in Pure & Appl. Chem 68:2193 (1996), unless otherwise indicated.

[0755] The term "enantiomeric excess" or "ee" refers to a measure for how much of one enantiomer is present compared to the other. For a mixture of R and S enantiomers, the percent enantiomeric excess is defined as │R - S│*100, where R and S are the respective mole or weight fractions of enantiomers in a mixture such that R + S = 1. With knowledge of the optical rotation of a chiral substance, the percent enantiomeric excess is defined as ([ ^]obs / [ ^]max)*100, where [ ^]obs is the optical rotation of the mixture of enantiomers and [ ^]maxis the optical rotation of the pure enantiomer. Determination of enantiomeric excess is possible using a variety of analytical techniques, including NMR spectroscopy, chiral column chromatography, or optical polarimetry. Compounds of the Disclosure that are racemic can be separated by chiral HPLC, e.g., using a CHIRALPAK IE column. In one embodiment, Compounds of the Disclosure have an ee of about 70% or more, e.g., 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.

[0756] The terms "enantiomerically pure" or "enantiopure" refer to a sample of a chiral substance all of whose molecules (within the limits of detection) have the same chirality sense.

[0757] The terms "enantiomerically enriched" or "enantioenriched" refer to a sample of a chiral substance whose enantiomeric ratio is greater than 50:50. Enantiomerically enriched compounds may be enantiomerically pure. Certain compounds of the Disclosure are enantioenriched.

[0758] The term "diastereomeric excess" or "de" refers to a measure for how much of one diastereomer is present compared to another, and is defined by analogy to enantiomeric excess. Determination of diastereomeric excess is possible using a variety of analytical techniques, including NMR spectroscopy and column chromatography.

[0759] The term "diastereoenriched enriched" refer to a sample of a chiral substance whose diastereomeric ratio is greater than 50:50. Diastereoenriched enriched compounds may be diastereomerically pure. Certain compounds of the Disclosure are diastereoenriched.

[0760] The term "about," as used herein, includes the recited number ± 10%. Thus, "about 10" means 9 to 11. IV. Particular Embodiments

[0761] The present disclosure also provides the following particular embodiments.

[0762] Embodiment 1. A compound having Formula (I), or pharmaceutically acceptable salt thereof:(I), wherein:

[0763] E is: ;

[0764] R1is;

[0765] R2is hydrogen, halogen, (C1-alkoxy, or ; with the provisos:

[0766] (i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is:

[0767] (ii) when R2is hydrogen,or (C1-C6)alkoxy, then R1is ;

[0768] R11is hydrogen or -(C1-C6) 2;

[0769] X1is CR3or N;

[0770] R3is hydrogen, halogen, or (C1-C6)alkyl;

[0771] X2is CR4or N;

[0772] R4is hydrogen, halogen, or (C1-C6)alkyl;

[0773] R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl;

[0774] R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl;

[0775] R6is hydrogen, (C1-C6)alkyl, or cyano;

[0776] X3is -CH2CH2- or -CH2-O-CH2-; or

[0777] X3is absent;

[0778] L is -G1-G2-G3-G4-, wherein G1is attached to W;

[0779] G1is (C1-C6)alkyenyl; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano;

[0780] G2is (C1-C6)alkylenyl or a direct bond;

[0781] G3is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, or (C1-C6)alkoxy; cyano; or 7- to 11- membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano;

[0782] G4is (C1-C6)alkylenyl or a direct bond;

[0783] W is -C≡C- a direct bond;

[0784] R7is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl;

[0785] R8is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl;

[0786] R9is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; and

[0787] R10is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl.

[0788] Embodiment 2. A compound of Formula (I), or pharmaceutically acceptable salt thereof:(I), wherein:

[0789] E is: ;

[0790] R1is;

[0791] R2is hydrogen, halogen, (C1-C6)or ; with the provisos:

[0792] (i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is:

[0793] (ii) when R2is hydrogen,C6)alkoxy, then R1is: ;

[0794] R11is hydrogen or -(C1-C6)alkyl-

[0795] X1is CR3or N;

[0796] R3is hydrogen, halogen, or (C1-C6)alkyl;

[0797] X2is CR4or N;

[0798] R4is hydrogen, halogen, or (C1-C6)alkyl;

[0799] R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl;

[0800] R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl;

[0801] R6is hydrogen, (C1-C6)alkyl, or cyano;

[0802] X3is -CH2CH2- or -CH2-O-CH2-; or

[0803] X3is absent;

[0804] L is -G1-G2-G3-G4-, wherein G1is attached to W;

[0805] G1is (C1-C6)alkyenyl; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano;

[0806] G2is (C1-C6)alkylenyl or a direct bond;

[0807] G3is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, or (C1-C6)alkoxy; cyano; 7- to 11- membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; or 5- to 10-membered heteroarylenyl;

[0808] G4is (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl, or a direct bond;

[0809] W is -C≡C- or a direct bond;

[0810] R7is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl;

[0811] R8is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl;

[0812] R9is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; and

[0813] R10is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl.

[0814] Embodiment 3. The compound of Embodiment 1 or 2, or pharmaceutically acceptable salt thereof, having Formula (II):(II).

[0815] Embodiment 4. The compound of claim 1 or 2, or pharmaceutically acceptable salt thereof, having Formula (III): .

[0816] Embodiment 5.salt thereof, according to any one of Emobidments 1-4, wherein E is E-1.

[0817] Embodiment 6. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 5, wherein R5ais hydrogen.

[0818] Embodiment 7. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 5, wherein R5ais (C1-C6)alkyl optionally substituted with one, two, or three substituents independently selected from halogen or cyano.

[0819] Embodiment 8. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 7, wherein R5ais methyl.

[0820] Embodiment 9. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 5, wherein R5ais (C3-C6)cycloalkyl.

[0821] Embodiment 10. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 9, wherein R5ais cyclopropyl.

[0822] Embodiment 11. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 5, wherein R5ais 4- to 6-membered heterocycloalkyl optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl.

[0823] Embodiment 12. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 5, wherein R5ais cyano.

[0824] Embodiment 13. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 5, wherein R5ais aryl optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl.

[0825] Embodiment 14. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 5, wherein R5ais 5- or 6-membered heteroaryl optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl.

[0826] Embodiment 15. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-4, wherein E is E-2.

[0827] Embodiment 16. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-4, wherein E is E-3.

[0828] Embodiment 17. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-16, wherein:

[0829] R1is:

[0830] R2is hydrogen, halogen, (C1-C6)

[0831] Embodiment 18. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 17, wherein R2is hydrogen, halogen, or (C1-C6)alkyl.

[0832] Embodiment 19. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 18, wherein R2is hydrogen, fluoro, or methyl.

[0833] Embodiment 20. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 17-19, wherein R11is hydrogen.

[0834] Embodiment 21. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-16, wherein:

[0835] R2is:

[0836] R1is hydrogen, halogen, (C1-C6)

[0837] Embodiment 22. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 21, wherein R1is hydrogen, halogen, or (C1-C6)alkyl.

[0838] Embodiment 23. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 22, wherein R1is hydrogen, fluoro, or methyl.

[0839] Embodiment 24. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 21-23, wherein R11is hydrogen.

[0840] Embodiment 25. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-24, wherein X1is CR3.

[0841] Embodiment 26. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 25, wherein R3is hydrogen.

[0842] Embodiment 27. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 25, wherein R3is halogen.

[0843] Embodiment 28. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 25, wherein R3is (C1-C6)alkyl.

[0844] Embodiment 29. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-24, wherein X1is N.

[0845] Embodiment 30. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-29, wherein X2is CR4.

[0846] Embodiment 31. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 30, wherein R4is hydrogen.

[0847] Embodiment 32. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 30, wherein R4is halogen.

[0848] Embodiment 33. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 30, wherein R4is (C1-C6)alkyl.

[0849] Embodiment 34. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-29, wherein X2is N.

[0850] Embodiment 35. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 5, wherein E-1 is: , ,, or

[0851] Embodiment 36. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 15, wherein E-2 is: .

[0852] Embodiment 37. The or acceptable salt thereof, according to Embodiment 16, wherein E-3 is: .

[0853] Embodiment 38. The or acceptable salt thereof, according to any one of Embodiments 1-37, wherein G1is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano.

[0854] Embodiment 39. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 38, wherein:

[0855] G1is:;

[0856] each R12is independently halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano;

[0857] n is 0, 1, 2, or 3; and

[0858] the bond marked with an "*" is attached to G2.

[0859] Embodiment 40. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 39, wherein each R12is independently fluoro, methyl, methoxy, cyano, or -CHF2; and n is 0, 1, or 2.

[0860] Embodiment 41. The compound, or pharmaceutically acceptable salt thereof, according Embodiment 38, wherein:

[0861] G1is:

[0862] the

[0863] according to Embodiment 38, wherein:

[0864] G1is: ;

[0865] X4is -O-;

[0866] each R12is independently halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; and

[0867] the bond marked with an “*” is attached to G2.

[0868] Embodiment 43. The compound, or pharmaceutically acceptable salt thereof, according Embodiment 42, wherein:

[0869] G1is:

[0870] the bond marked with an

[0871] Embodiment 44. The compound, or pharmaceutically acceptable salt thereof, according Embodiment 38, wherein:

[0872] G1is:nd

[0873] the bond marked with an "*" is attached to G .

[0874] Embodiment 45. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-37, wherein G1is 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano.

[0875] Embodiment 46. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 45, wherein:

[0876] G1is: ;

[0877] each R13is independentlyC6)alkyl, (C1-C6)alkoxy, or cyano;

[0878] o is 0, 1, 2, or 3;

[0879] p, q, r, and s are independently is 1, 2, or 3; and

[0880] the bond marked with an "*" is attached to G2.

[0881] Embodiment 47. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 46, wherein:

[0882] p and q are 1;

[0883] r is 1 or 2;

[0884] s is 1 or 2; and

[0885] R13is halogen.

[0886] Embodiment 48. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 46, wherein R13is fluoro and o is 0, 1, or 2.

[0887] Embodiment 49. The compound, or pharmaceutically acceptable salt thereof, according Embodiment 46, wherein G1is:

[0888] the bond marked with an "*"

[0889] Embodiment 50. The compound, or pharmaceutically acceptable salt thereof, according Embodiment 45, wherein:

[0890] G1is:;

[0891] a is 0 or 1;

[0892] b is 0 or 1; and

[0893] the bond marked with an "*" is attached to G2.

[0894] Embodiment 51. The compound, or pharmaceutically acceptable salt thereof, according Embodiment 50, wherein G1is:

[0895] the bond marked with

[0896] Embodiment 52. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-49, wherein G2is a direct bond.

[0897] Embodiment 53. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-49, wherein G2is (C1-C6)alkylenyl.

[0898] Embodiment 54. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 53, wherein G2is -CH2-.

[0899] Embodiment 55. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-54, wherein G3is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano.

[0900] Embodiment 56. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 55, wherein:

[0901] G3is: ;

[0903] t is 0, 1, 2, or 3; and

[0904] the bond marked with an "*" is attached to G4.

[0905] Embodiment 57. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 56, wherein R14is fluoro or methyl and t is 0 or 1.

[0906] Embodiment 58. The compound, or pharmaceutically acceptable salt thereof, according Embodiment 56, wherein G3is: .

[0907] Embodimentthereof, according to any one of Embodiments 1-54, wherein G3is 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano.

[0908] Embodiment 60. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 59, wherein G3is:

[0909] the bond marked with an "*" is

[0910] Embodiment 61. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 59, wherein:

[0911] G3is: ;

[0912] each R15is independentlyC6)alkyl, (C1-C6)alkoxy, or cyano;

[0913] u is 0, 1, 2, or 3;

[0914] v, w, x, and y are independently is 1, 2, or 3; and

[0915] the bond marked with an "*" is attached to G4.

[0916] Embodiment 62. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 61, wherein v, w, x, and y are independently 1 or 2.

[0103] Embodiment 63. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 59, wherein:

[0917] G3is: ;

[0918] xaand yaare independently is 1,

[0919] the bond marked with an "*" is attached to G4.

[0920] Embodiment 64. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 59, wherein G3is: , , ,

[0921] Embodiment 65. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-64, wherein G4is (C1-C6)alkylenyl.

[0922] Embodiment 66. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 65, wherein G4is -CH2- or -CH2CH2-.

[0923] Embodiment 67. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 2-64, wherein G4is (C3-C6)cycloalkylenyl.

[0924] Embodiment 68. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 67, wherein G4is: .

[0925] Embodiment 69. The acceptable salt thereof, according to any one of Embodiments 1-64, wherein G4is a direct bond.

[0926] Embodiment 70. The compound, or pharmaceutically acceptable salt thereof, of any one of Embodiments 1-37, wherein L is:, , , ,, or the bond marked with an is attached to E.

[0927] Embodiment 71. The compound, or pharmaceutically acceptable salt thereof, of any one of Embodiments 2-37, wherein L is: ,

[0928] the bond

[0929] Embodiment 72. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-71, wherein W is -C≡C- .

[0930] Embodiment 73. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-71, wherein W is a direct bond.

[0931] Embodiment 74. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-73, wherein R7is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen.

[0932] Embodiment 75. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 74, wherein R7is halogen or (C1-C6)alkyl.

[0933] Embodiment 76. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 75, wherein R7is fluoro or methyl.

[0934] Embodiment 77. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 74-76, wherein R8, R9, and R10are H.

[0935] Embodiment 78. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-76, wherein R8is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen.

[0936] Embodiment 79. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 78, wherein R8is halogen or (C1-C6)alkyl.

[0937] Embodiment 80. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 79, wherein R8is fluoro or methyl.

[0938] Embodiment 81. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 78-80, wherein R7, R9, and R10are hydrogen.

[0939] Embodiment 82. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-76 or 67-69, wherein R9is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen.

[0940] Embodiment 83. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 82, wherein R9is halogen.

[0941] Embodiment 84. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 83, wherein R9is fluoro.

[0942] Embodiment 85. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 82-84, wherein R7, R8, and R10are hydrogen.

[0943] Embodiment 86. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-76, 78-80, or 82-84, wherein R10is halogen, (C1-C6)alkyl, cyano, or (C3- C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen.

[0944] Embodiment 87. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 86, wherein R10is halogen.

[0945] Embodiment 88. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 87, wherein R10is fluoro.

[0946] Embodiment 89. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 86-88, wherein R7, R8, and R9are hydrogen.

[0947] Embodiment 90. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-73, wherein R7, R8, R9, and R10are H.

[0948] Embodiment 91. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-2, 5-9, or 35 having Formula (IV):V), wherein:

[0949] each R12is independently fluoro;

[0950] n is 0, 1, or 2; and

[0951] R7, R8, R9, and R10are independently hydrogen, fluoro, or methyl.

[0952] Embodiment 92. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 91, wherein: G3is: ,

[0953] G4- - .

[0954] Embodiment 93. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 91, wherein G3is: .

[0955] Embodiment 94. salt thereof, according to Embodiment 1 selected from any one or more of the compounds of Compound List 1.

[0956] Embodiment 95. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 1 selected from any one or more of the compounds of Compound List 2 and / or Compound List 3.

[0957] Embodiment 96. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 2 selected from any one or more of the compounds of Compound List 4.

[0958] Embodiment 97. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 94, wherein the compound is:.

[0959] Embodiment 98. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 94, wherein the compound is: .

[0960] or to Embodiment 94, wherein the compound is: .

[0961] Embodiment 100. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 96, wherein the compound is: .

[0962] or to Embodiment 96, wherein the compound is:.

[0963] Embodiment 102. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment 96, wherein the compound is: .

[0964] or to Embodiment 96, wherein the compound is: .

[0965] or to Embodiment 96, wherein the compound is: .

[0966] or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-104, and a pharmaceutically acceptable excipient.

[0967] Embodiment 106. A method of degrading SMARCA2 protein in a human, comprising administering to a human in need thereof an effective amount of the compound, or pharmaceuticallyacceptable salt thereof, according to any one of Embodiments 1-104, or the composition of Embodiment 105.

[0968] Embodiment 107. A method of reducing the level of SMARCA2 activity in a human, comprising administering to a human in need thereof an effective amount of the compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-104, or the composition of Embodiment 105.

[0969] Embodiment 108. A method of treating cancer in a human, comprising administering to a human in need thereof an effective amount of the compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-104, or the composition of Embodiment 105.

[0970] Embodiment 109. The method of Embodiment 108, wherein the cancer is a SMARCA2- sensitive cancer.

[0971] Embodiment 110. The method of Embodiment 108, wherein the cancer is a SMARCA2- mutated cancer.

[0972] Embodiment 111. The method of any one of Embodiments 108-110, wherein the cancer is a solid tumor.

[0973] Embodiment 112. The method of any one of Embodiments 108-110, wherein the cancer is lung, liver, colon, skin, bladder, cervical or ovarian cancer.

[0974] Embodiment 113. A compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-104, or the composition of Embodiment 105 for use in degrading SMARCA2 protein in a human.

[0975] Embodiment 114. A compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-104, or the composition of Embodiment 105 for use in reducing the level of SMARCA2 activity in a human.

[0976] Embodiment 115. A compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-104, or the composition of Embodiment 105 for use in treating cancer in a human.

[0977] Embodiment 116. The compound for use of Embodiment 115, wherein the cancer is a SMARCA2-sensitive cancer.

[0978] Embodiment 117. The compound for use of Embodiment 115, wherein the cancer is a SMARCA2-mutated cancer.

[0979] Embodiment 118. The compound for use of any one of Embodiments 115-117, wherein the cancer is a solid tumor.

[0980] Embodiment 119. The compound for use of any one of Embodiments 115-117, wherein the cancer is lung, liver, colon, skin, bladder, cervical or ovarian cancer.

[0981] Embodiment 120. Use of a compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-104, or the composition of Embodiment 105 in the manufacture of a medicament for degrading SMARCA2 protein in a human.

[0982] Embodiment 121. Use of a compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-104, or the composition of Embodiment 105 in the manufacture of a medicament for reducing the level of SMARCA2 activity in a human.

[0983] Embodiment 122. Use of a compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments 1-104, or the composition of Embodiment 105 in the manufacture of a medicament for treating cancer in a human.

[0984] Embodiment 123. The compound, or pharmaceutically acceptable salt thereof, for use of Embodiment 122, wherein the cancer is a SMARCA2-sensitive cancer.

[0985] Embodiment 124. The compound, or pharmaceutically acceptable salt thereof, for use of Embodiment 122, wherein the cancer is a SMARCA2-mutated cancer.

[0986] Embodiment 125. The compound, or pharmaceutically acceptable salt thereof, for use of any one of Embodiments 122-124, wherein the cancer is a solid tumor.

[0987] Embodiment 126. The compound, or pharmaceutically acceptable salt thereof, for use of any one of Embodiments 122-124, wherein the cancer is lung, liver, colon, skin, bladder, cervical or ovarian cancer.

[0988] The present disclosure also provides the following particular embodiments.

[0989] Embodiment A 1. A compound of Formula (A), or pharmaceutically acceptable salt thereof: , wherein:

[0990] E is: ;

[0991] R1is;

[0992] R2is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or ;

[0993] with the provisos:

[0994] (i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is:

[0995] (ii) when R2is hydrogen,or (C1-C6)alkoxy, then R1is ;

[0996] R11is hydrogen or -(C1-C6) 2;

[0997] X1is CR3or N;

[0998] R3is hydrogen, halogen, or (C1-C6)alkyl;

[0999] X2is CR4or N; R4is hydrogen, halogen, or (C1-C6)alkyl; R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6- membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl; R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl; R6is hydrogen, (C1-C6)alkyl, or cyano; X3is -CH2CH2- or -CH2-O-CH2-; Or X3is absent; L is G1-G2-G3-G4-, wherein G1is attached to W; G1is (C1-C6)alkylenyl; (C3-C6)cycloalkylenyl; -O-CH2-CH2-; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, cyano, or hydroxyl; or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1- C6)alkyl, (C1-C6)alkoxy, or cyano;G2is (C1-C6)alkylenyl, -C(=O)-, 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three fluoro, or a direct bond; G3is -C(=O)-; -C(=O)-CH2CH2-; (C1-C6)alkylenyl; tetrahydronaphthalenenyl; 4- to 6- membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy or cyano; 7- to 11-membered heterocycloalkyl-C(=O)-, or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; G4is (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl; 4- to 6-membered heterocycloalkylenyl; or a direct bond; W is -C≡C- or a direct bond; R7is hydrogen; halogen; (C1-C6)alkyl optionally substituted with one, two, or three halogen; cyano; or (C3-C6)cycloalkyl; R8is hydrogen; halogen; (C1-C6)alkyl optionally substituted with one, two, or three halogen; cyano; or (C3-C6)cycloalkyl; R9is hydrogen; halogen; (C1-C6)alkyl optionally substituted with one, two, or three halogen; cyano; or (C3-C6)cycloalkyl; R10is hydrogen; halogen; (C1-C6)alkyl optionally substituted with one, two, or three halogen; cyano; or (C3-C6)cycloalkyl; Rais hydrogen or halogen; Rbis hydrogen or halogen; and Rcis hydrogen or methyl. Embodiment A 2. A compound of Formula (I), or pharmaceutically acceptable salt thereof: , wherein:E is: ;R1is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or ; R2is hydrogen, halogen, (C1-alkoxy, or ; with the provisos:(i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is: (ii) when R2is hydrogen,or (C1-C6)alkoxy, then R1is ; R11is hydrogen or -(C1-C6)2; X1is CR3or N; R3is hydrogen, halogen, or (C1-C6)alkyl; X2is CR4or N; R4is hydrogen, halogen, or (C1-C6)alkyl; R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl; R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl; R6is hydrogen, (C1-C6)alkyl, or cyano; X3is -CH2CH2- or -CH2-O-CH2-; Or X3is absent; L is -G1-G2-G3-G4-, wherein G1is attached to W; G1is (C1-C6)alkyenyl; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; or7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; G2is (C1-C6)alkylenyl or a direct bond; G3is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy or cyano; or 7- to 11- membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; G4is (C1-C6)alkylenyl or a direct bond; W is -C≡C- or a direct bond; R7is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; R8is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; R9is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; and R10is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl. Embodiment A 3. A compound of Formula (I), or pharmaceutically acceptable salt thereof: , wherein:E is: ; R1is; R2is hydrogen, halogen, (C1-C6)a y , (C1-C6)alkoxy, or ; with the provisos:(i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is: (ii) when R2is hydrogen,or (C1-C6)alkoxy, then R1is: ; R11is hydrogen or -(C1-C6)2; X1is CR3or N; R3is hydrogen, halogen, or (C1-C6)alkyl; X2is CR4or N; R4is hydrogen, halogen, or (C1-C6)alkyl; R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl; R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl; R6is hydrogen, (C1-C6)alkyl, or cyano; X3is -CH2CH2- or -CH2-O-CH2-; or X3is absent; L is -G1-G2-G3-G4-, wherein G1is attached to W; G1is (C1-C6)alkyenyl; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; or7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; G2is (C1-C6)alkylenyl or a direct bond; G3is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; 7- to 11- membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; or 5- to 10-membered heteroarylenyl; G4is (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl, or a direct bond; W is -C≡C- or a direct bond; R7is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; R8is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; R9is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; and R10is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl. Embodiment A 4. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 2 or 3 having Formula (II): (II).Embodiment A or acceptable salt thereof, according to Embodiment A 2 or 3 having Formula (III): .Embodiment A 6. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein R5ais hydrogen. Embodiment A 7. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein R5ais (C1-C6)alkyl optionally substituted with one, two, or three substituents independently selected from halogen or cyano. Embodiment A 8. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 7, wherein R5ais methyl. Embodiment A 9. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein R5ais (C3-C6)cycloalkyl. Embodiment A 10. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 9, wherein R5ais cyclopropyl. Embodiment A 11. The compound, or pharmaceutically acceptable salt thereof, according to according to any one of Embodiments A 1-5, wherein R5ais 4- to 6-membered heterocycloalkyl optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl. Embodiment A 12. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein R5ais cyano. Embodiment A 13. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein: R1is: R2is hydrogen, halogen,alkoxy. Embodiment A 14. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein R2is hydrogen, halogen, or (C1-C6)alkyl. Embodiment A 15. The compound, or pharmaceutically acceptable salt thereof, according to to any one of Embodiments A 1-5, wherein R2is hydrogen, fluoro, or methyl. Embodiment A 16. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein R11is hydrogen. Embodiment A 17. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein: R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy; and R2is:. Embodiment A 18. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 17, wherein R1is hydrogen, halogen, or (C1-C6)alkyl. Embodiment A 19. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 18, wherein R1is hydrogen, fluoro, or methyl. Embodiment A 20. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 17-19, wherein R11is hydrogen. Embodiment A 21. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein X1is CR3. Embodiment A 22. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 21, wherein R3is hydrogen. Embodiment A 23. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 21, wherein R3is halogen. Embodiment A 24. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 21, wherein R3is (C1-C6)alkyl. Embodiment A 25. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein X1is N. Embodiment A 26. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein X2is CR4. Embodiment A 27. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 26, wherein R4is hydrogen. Embodiment A 28. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 26, wherein R4is halogen. Embodiment A 29. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 26, wherein R4is (C1-C6)alkyl. Embodiment A 30. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein X2is N. Embodiment A 31. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein E is:, , , Embodiment A 32. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-5, wherein E is: .or salt thereof, according to any one of Embodiments A 1-5, wherein E is: .Embodiment A 34. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-33, wherein G1is (C3-C6)cycloalkylenyl; or 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, cyano, or hydroxyl. Embodiment A 35. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 34, wherein: G1is: ;each R12is independently halogen, (C1-C6)alkyl, (C1-C6)alkoxy, cyano, or hydroxyl; n is 0, 1, 2, or 3; and the bond marked with an "*" is attached to G2. Embodiment A 36. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 35, wherein each R12is independently fluoro, methyl, methoxy, cyano, or -CHF2; and n is 0, 1, or 2. Embodiment A 37. The compound, or pharmaceutically acceptable salt thereof, according Embodiment A 35, wherein: G1is:Embodiment A 38. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 34, wherein: G1is: ; wherein X4is –O-;each R12is independently halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; and the bond marked with an “*” is attached to G2. Embodiment A 39. The compound, or pharmaceutically acceptable salt thereof, according Embodiment A 38, wherein: G1is:nd the bond marked with an "*" is attached to G2. Embodiment A 44. The compound, or pharmaceutically acceptable salt thereof, according Embodiment A 34, wherein: G1is: the bond marked with anEmbodiment A 41. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1, wherein G1is cyclohexylenyl. Embodiment A 42. The compound, or pharmaceutically acceptable salt thereof, according Embodiment A 41, wherein: G1is: the bond markedEmbodiment A 43. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-33, wherein G1is 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1- C6)alkoxy, or cyano. Embodiment A 44. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 43, wherein: G1is: ;each R13is independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; o is 0, 1, 2, or 3; p, q, r, and s are independently 1 or 2; the bond marked with an "*" is attached to G2.Embodiment A 45. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 44, wherein: p and q are 1; r is 1 or 2; s is 1 or 2; and R13is halogen. Embodiment A 46. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 45, wherein R13is fluoro and o is 0, 1, or 2. Embodiment A 47. The compound, or pharmaceutically acceptable salt thereof, according Embodiment A 44, wherein G1is: the bond marked with anEmbodiment A 48. The compound, or pharmaceutically acceptable salt thereof, according Embodiment A 43, wherein: G1is: ; a is 0 or 1;b is 0 or 1; and the bond marked with an "*" is attached to G2. Embodiment A 49. The compound, or pharmaceutically acceptable salt thereof, according Embodiment A 48, wherein G1is:the bond marked with an "*" is attached to G2. Embodiment A 50. The compound, or pharmaceutically acceptable salt thereof, according Embodiment A 43, wherein G1is:the bond marked with an "*" is attached to G2. Embodiment A 51. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-50, wherein G2is a direct bond. Embodiment A 52. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1 or 6-50, wherein G2is a C(=O). Embodiment A 53. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-50, wherein G2is (C1-C6)alkylenyl. Embodiment A 54. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 53, wherein G2is -CH2-. Embodiment A 55. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-54, wherein G3is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1- C6)alkoxy, or cyano. Embodiment A 56. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 55, wherein: G3is: ;each R14is independently halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; t is 0, 1, 2, or 3; and the bond marked with an "*" is attached to G4. Embodiment A 57. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 56, wherein R14is fluoro or methyl and t is 0 or 1. Embodiment A 58. The compound, or pharmaceutically acceptable salt thereof, according Embodiment A 56, wherein G3is: thethereof, according to any one of Embodiments A 1-54, wherein G3is 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1- C6)alkoxy, or cyano.Embodiment A 60. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1, wherein G3isEmbodiment A 61. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 59, wherein G3is:the bond marked with an "*" is attached to G4. Embodiment A 62. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 59, wherein G3is:the bond marked with an "*" is attached to G4. Embodiment A 63. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 59, wherein: G3is: ;each R15is independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; u is 0, 1, 2, or 3; v, w, x, and y are independently 1, 2, or 3; and the bond marked with an "*" is attached to G4. Embodiment A 64. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 63, wherein v, w, x, and y are independently 1 or 2. Embodiment A 65. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 63, wherein R15is fluoro. Embodiment A 66. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 59, wherein: G3is:; xaand yaare independently 1 or 2 ; and the bond marked with an "*" is attached to G4. Embodiment A 67. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 59, wherein G3is: ,Embodiment A 68. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1, wherein G3is ; andthe bond marked with an to Embodiment A 69. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-68, wherein G4is (C1-C6)alkylenyl. Embodiment A 70. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 69, wherein G4is -CH2- or -CH2CH2-.Embodiment A 71. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1, wherein G4is (C3-C6)cycloalkylenyl. Embodiment A 72. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 71, wherein G4is : the bond markedEmbodiment A 73. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 71, wherein G4is: the bond marked withEmbodiment A 74. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-68, wherein G4is a direct bond. Embodiment A 75. The compound, or pharmaceutically acceptable salt thereof, of any one of Embodiments A 1-33, wherein L is: , ,, , , , , the bond marked with an is attached to E.Embodiment A 76. The compound, or pharmaceutically acceptable salt thereof, of any one of A 1-33, wherein L is: ;Embodiment A 77. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-76, wherein W is -C≡C- . Embodiment A 78. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-76, wherein W is a direct bond. Embodiment A The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-78, wherein R7, R8, R9, and R10are H. Embodiment A 80. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-78, wherein R7is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen. Embodiment A 81. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 80, wherein R7is halogen or (C1-C6)alkyl. Embodiment A 82. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 81, wherein R7is fluoro or methyl. Embodiment A 83. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 80-82, wherein R8, R9, and R10are hydrogen. Embodiment A 84. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-78, wherein R8is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen. Embodiment A 85. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 84, wherein R8is halogen or (C1-C6)alkyl. Embodiment A 86. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 85, wherein R8is fluoro or methyl. Embodiment A 87. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 84-86, wherein R7, R9, and R10are hydrogen.Embodiment A 88. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-78, wherein R9is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen. Embodiment A 89. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 88, wherein R9is halogen. Embodiment A 90. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 89, wherein R9is fluoro. Embodiment A 91. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 88-90, wherein R7, R8, and R10are hydrogen. Embodiment A 92. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-78, wherein R10is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen. Embodiment A 93. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 92, wherein R10is halogen. Embodiment A 94. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 93, wherein R10is fluoro. Embodiment A 95. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 92-94, wherein R7, R9, and R9are hydrogen. Embodiment A 96. The compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-78, wherein R10is cyano. Embodiment A 97. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 96, wherein R10is cyano; and R7, R8, and R9are hydrogen. Embodiment A 98. A compound of Formula (V), or pharmaceutically acceptable salt thereof, , wherein:each R12is fluoro or hydroxyl; n is 0, 1, 2, or 3; E is:; R1is hydrogen, a ogen, (C1-C6)a y , (C1-C6)a oxy, or ; R2is hydrogen, halogen, (C1-alkoxy, or ; with the provisos:(i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is: (ii) when R2is hydrogen,C6)alkoxy, then R1is: ; R11is hydrogen or -(C1-C6)alkyl-X1is CR3or N; R3is hydrogen, halogen, or (C1-C6)alkyl; X2is CR4or N; R4is hydrogen, halogen, or (C1-C6)alkyl; R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl; R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl; R6is hydrogen, (C1-C6)alkyl, or cyano; X3is -CH2CH2- or absent;G3is tetrahydronaphthalene; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; 7- to 11-membered heterocycloalkyl-C(=O)-, or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1- C6)alkoxy, or cyano; G4is absent or cyclobutylenyl; R7, R8, R9, and R10are independently hydrogen, fluoro, methyl, or cyano; Rais hydrogen, chloro, methyl, or fluoro; Rbis hydrogen, chloro, methyl, or fluoro, and Rcis hydrogen or methyl. Embodiment A 99. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 98, wherein: G3is: ,according to Embodiment A 98, wherein G3is: .to Embodiment A 98, wherein G3is: ,, Embodiment A 102. The compound according to Embodiment A 1, or a pharmaceutically acceptable salt thereof, selected from any one or more of the compounds of Compound List 1, Compound List 2, Compound List 3, Compound List 4, and / or Compound List 5, or pharmaceutically acceptable salts thereof. Embodiment A 103. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1 or 102, wherein the compound is: .Embodiment A 104. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1 or 102, wherein the compound is: .Embodiment A 105. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1 or 102, wherein the compound is:. Embodiment A 106. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1 or 102, wherein the compound is: .Embodiment A 107. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1 or 102, wherein the compound is: .Embodiment A 108. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1 or 102, wherein the compound is: .Embodiment A 109. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1 or 102, wherein the compound is: .Embodiment A 110. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1 or 102, wherein the compound is: .Embodiment A 111. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1 or 102, wherein the compound is: .or thereof, according to Embodiment A 1 or 102, wherein the compound is: .or thereof, according to Embodiment A 1 or 102, wherein the compound is: .Embodiment A 114. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1 or 102, wherein the compound is: .Embodiment A or to Embodiment A 1 or 102, wherein the compound is: .or thereof, according to Embodiment A 1 or 102, wherein the compound is: .or thereof, according to Embodiment A 1 or 102, wherein the compound is: .Embodiment A 118. The compound, or pharmaceutically acceptable salt thereof, according to Embodiment A 1 or 102, wherein the compound is: .the compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-118, and a pharmaceutically acceptable excipient. Embodiment A 120. A method of degrading SMARCA2 protein in a human, comprising administering to a human in need thereof an effective amount of the compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-118, or the composition of Embodiment A 119. Embodiment A 121. A method of reducing the level of SMARCA2 activity in a human, comprising administering to a human in need thereof an effective amount of the compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-118, or the composition of Embodiment A 119. Embodiment A 122. A method of treating cancer in a human, comprising administering to a human in need thereof an effective amount of the compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-118, or the composition of Embodiment A 119. Embodiment A 123. The method of Embodiment A 122, wherein the cancer is a SMARCA2- sensitive cancer. Embodiment A 124. The method of Embodiment A 122, wherein the cancer is a SMARCA2- mutated cancer. Embodiment A 125. The method of any one of Embodiments A 122-124, wherein the cancer is a solid tumor. Embodiment A 126. The method of any one of Embodiments A 122-124, wherein the cancer is lung, liver, colon, skin, bladder, cervical or ovarian cancer. Embodiment A 127. A compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-104, or the composition of Embodiment A 105 for use in degrading SMARCA2 protein in a human. Embodiment A 128. A compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-118, or the composition of Embodiment A 119 for use in reducing the level of SMARCA2 activity in a human.Embodiment A 129. A compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-118, or the composition of Embodiment A 119 for use in treating cancer in a human. Embodiment A 130. The compound for use of Embodiment A 129, wherein the cancer is a SMARCA2-sensitive cancer. Embodiment A 131. The compound for use of Embodiment A 129, wherein the cancer is a SMARCA2-mutated cancer. Embodiment A 132. The compound for use of any one of Embodiments A 129-131, wherein the cancer is a solid tumor. Embodiment A 133. The compound for use of any one of Embodiments A 129-131, wherein the cancer is lung, liver, colon, skin, bladder, cervical or ovarian cancer. Embodiment A 134. Use of a compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-118, or the composition of Embodiment A 119 in the manufacture of a medicament for degrading SMARCA2 protein in a human. Embodiment A 135. Use of a compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-118, or the composition of Embodiment A 119 in the manufacture of a medicament for reducing the level of SMARCA2 activity in a human. Embodiment A 136. Use of a compound, or pharmaceutically acceptable salt thereof, according to any one of Embodiments A 1-118, or the composition of Embodiment A 119 in the manufacture of a medicament for treating cancer in a human. Embodiment A 137. The compound, or pharmaceutically acceptable salt thereof, for use of Embodiment A 136, wherein the cancer is a SMARCA2-sensitive cancer. Embodiment A 138. The compound, or pharmaceutically acceptable salt thereof, for use of Embodiment A 136, wherein the cancer is a SMARCA2-mutated cancer. Embodiment A 139. The compound, or pharmaceutically acceptable salt thereof, for use of any one of Embodiments A 136-138, wherein the cancer is a solid tumor. Embodiment A 140. The compound, or pharmaceutically acceptable salt thereof, for use of any one of Embodiments A 136-138, wherein the cancer is lung, liver, colon, skin, bladder, cervical or ovarian cancer. EXAMPLES General Experimental Conditions and Abbreviations The following abbreviations are used: AcOH = acetic acid; aq = aqueous; 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 = dimethylsulfoxide; EtOAc = ethyl acetate; EtOH = ethanol; EPhos = dicyclohexyl(3-isopropoxy-2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphane; EPhos Pd G4 = palladium catalyst containing EPhos - CAS number: 2132978-44-8; FA = formic acid; FSC = flash silica chromatography; g = gram(s); h = hour(s); HATU = (dimethylamino)-N,N-dimethyl(3-oxido-1H- [1,2,3]triazolo[4,5-b]pyridinyl)methaniminium hexafluorophosphate; HCl = hydrochloric acid; HPLC = high-performance liquid chromatography; KOtBu = potassium tert-butoxide; K3PO4 = potassium phosphate tribasic; LiHMDS = lithium hexamethyldisilazide; LiOH = lithium hydroxide; M = molar; mg = milligram(s); min = minute(s); mL = milliliter(s); mmol = millimole(s); 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-methyl pyrrolidinone; NMR = nuclear magnetic resonance; Na(OAc)3BH = sodium triacetoxyborohydride; Pd / C = Palladium on carbon; PdCl2(PPh3)2 = Bis(triphenylphosphine)palladium(II) dichloride; Pd(dba)2 = Palladium(0) bis(dibenzylideneacetone); Pd2(dba)3 = tris(dibenzylideneacetone)dipalladium(0); Pd(dppf)Cl2 = [1,1′- Bis(diphenylphosphino)ferrocene]dichloropalladium(II); iPrOH = isopropyl alcohol; PyBOP = benzotriazol-1-yloxytripyrrolidino-phosphonium hexafluorophosphate; r.t. = room temperature (~18- 25°C); RPC = reverse phase chromatography; RP-HPLC = reverse-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-toluenesulfonic acid monohydrate; w.t.% = percentage by weight; Pd XPhos G3 = (2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′- amino-1,1′-biphenyl)]palladium(II) methanesulfonate. NMR: Proton NMR (1H NMR) was carried out at 300-500 MHz at a temperature in the range from 15-30°C in deuterated-DMSO unless otherwise specified.19F NMR was carried out in DMSO unless otherwise stated. Standard NMR abbreviations are used: s = single, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, dt doublet of triplets, m = multiplet, br = broad. Chromatography methods: clean-appearing fractions containing the desired product are generally identified and combined together and then concentrated under reduced pressure. Flashchromatography was performed using straight phase flash chromatography on a SP1TMPurification or SELEKTTMsystem from BiotageTM, CombiFlashTMRf from ISCO or on Gilson system from Thermo Fisher using normal phase silica FLASH+TM(40M, 25M or 12 M), Sfär Silica HC (5g, 10g, 25g, 100g) from Biotage™ or SNAPTMKP-Sil Cartridges (340, 100, 50 or 10), Flash Column silica-CS columns from Agela, with C18-flash columns or standard flash chromatography. RP-HPLC was performed using XSelect or XBridge columns. In general, all solvents used were commercially available and of analytical grade. Anhydrous solvents were routinely used for reactions. Phase Separators used in the examples are ISOLUTE® Phase Separator columns. Concentration of solutions (to partly or fully remove solvent) are generally performed under reduced pressure at r.t. or slightly above. The intermediates and examples named below were named using BIOVIA Draw 20.1 or Chem Draw. The starting materials were obtained from commercial sources or made via literature routes. EXAMPLE 1 Intermediate 1a: 7-tert-Butyl 2-methyl 7-azaspiro[3.5]nonane-2,7-dicarboxylate Cs2CO3(4.84 g, 14.85(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 r.t for 6 h. Added 40 mL water and aqueous layer was extracted with ethyl acetate (2 x 75 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to afford the title compound (2.0 g, 95 %) as a white solid.1H NMR (DMSO-d6) δ 1.32 – 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. Intermediate 1b: Benzyl 8-(3-bromophenyl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate To a stirred solution ofmmol), palladium(II) acetate (0.182 g, 0.81 mmol) and BINAP (0.506 g, 0.81 mmol) in 1,4-dioxane (20 mL) was added to 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) at r.t. The resulting was mixture was stirred at 100 °C for 16 h. The reaction mixture was diluted with water (100 mL), extracted with EtOAc (3 x 100 mL), the organic layer was dried (Na2SO4), filtered and evaporated.Purification by FSC (gradient: 0 to 70 % EtOAc in petroleum ether) gave the title compound (1.3 g, 39.9 %) as a white solid.1H NMR (DMSO-d6) δ 1.52 (2H, d), 1.83 – 1.93 (2H, m), 2.91 – 3.09 (4H, m), 4.28 (2H, d), 5.05 (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. Intermediate 1c: Methyl 7-[3-(3-benzyloxycarbonyl-3,8-diazabicyclo[3.2.1]octan-8-yl)phenyl]-7-azaspiro[3.5]nonane-2- carboxylate 4M HCl in MeOH (5Intermediate 1a (318 mg, 1.12 mmol). The resulting mixture was stirred at r.t. for 2 h. The solvent was removed under reduced pressure and afford a white solid. To the crude product was added 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) in dioxane (10 mL) under nitrogen. The resulting mixture was stirred at 100 °C for 2 h. The reaction mixture was filtered and concentrated. Purification by FSC (gradient: 0 to 100 % EtOAc in petroleum ether) gave the title compound (530 mg, 94 %) as a yellow solid.1H NMR (DMSO-d6) δ 1.51 – 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. Intermediate 1d: Benzyl 8-[3-[2-(dimethoxymethyl)-7-azaspiro[3.5]nonan-7-yl]phenyl]-3,8-diazabicyclo[3.2.1]octane-3- carboxylate DIBAL-H (169 mg,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 h. Saturated NH4Cl solution was added to the mixture. The aq. layer was back extracted with DCM (2 x 30 mL). Combined the organic layers were dried over Na2SO4, filtered and concentrated to afford the yellow solid. The product was used in the next step directly without further purification. To the residue TsOH (113 mg, 0.60 mmol) and trimethyl orthoformate (190 mg, 1.79 mmol) were added in DCM (5 mL). The resulting mixture was stirred at r.t. for 16 h. The reaction mixture was concentrated. Purification by FSC (gradient 0 to 100 % EtOAc in petroleum ether) gave the title compound (130 mg, 42.0 %) as a yellow solid.1H NMR (DMSO-d6) δ 1.52 – 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.Intermediate 1e: 7-[3-(3,8-Diazabicyclo[3.2.1]octan-8-yl)phenyl]-2-(dimethoxymethyl)-7-azaspiro[3.5]nonane Pd / C (11.06 mg, 0.101d (270 mg, 0.52 mmol) ) in MeOH (4 mL) under hydrogen. The resulting mixture was stirred at r.t. for 6 h. The reaction mixture was filtered through celite® and filtrate was concentrated to afford the title compound (80 mg, 39.9 %) as a white solid. m / z (ES+) [M+H]+= 386.1. Intermediate 1f: 2-[6-Amino-5-[8-[3-[2-(dimethoxymethyl)-7-azaspiro[3.5]nonan-7-yl]phenyl]-3,8- diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol DIPEA (0.095 mL,1e (70 mg, 0.18 mmol) and 4-bromo- 6-chloropyridazin-3-amine (37.8 mg, 0.18 mmol) in NMP (3 mL). The resulting mixture was stirred at 100 °C for 3 h. Reaction mixture diluted with water (10 mL) and extracted with EtOAc (30 mL x 2). The combined extracts were dried over Na2SO4, filtered and concentrated. The crude material was used for the next step. To the residue was added 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). The resulting mixture was stirred at 100 °C for 2 h. The solvent was removed. Purification by RPC (gradient 0 to 90 % MeOH in water with 0.5% NH4HCO3) gave the title compound (40.0 mg, 38.6 %) as a yellow solid. m / z (ES+) [M+H]+= 571. Intermediate 1g: tert-Butyl 4-(5-bromo-3-methyl-indol-1-yl)piperidine-1-carboxylate Cs2CO3 (16.20 g, 49.72to 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) under N2 at r.t. The resulting mixture was stirred at 95 °C for 8.5 h. The mixture was cooled to r.t. 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 h then cooled to r.t. and diluted with EtOAc (200 mL). The mixture was washed with water (2 × 50 mL) and brine (2 × 50 mL). The organic layer was dried (Na2SO4) and concentrated. Purification by FSC (gradient: 0-40% DCM in hexanes then 0-30% EtOAc in hexanes) gave the title compound (5.85 g, 57 %) as a white foam.1H NMR (CDCl3): δ 1.50 (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. Intermediate 1h: tert-Butyl 4-[5-(2,4-dioxohexahydropyrimidin-1-yl)-3-methyl-indol-1-yl]piperidine-1-carboxylate 1,4-Dioxane (100 mL) wasflask Intermediate 1g (4.20 g, 10.68 mmol), 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 r.t. under argon. The mixture was sparged with argon for five minutes then stirred at 100 °C for 14 h. The mixture was cooled to r.t., diluted with EtOAc (100 mL), and filtered through celite®. The filtrate was then concentrated. Purification by FSC (gradient: 0-100% EtOAc in hexanes) gave the title compound (3.06 g, 67 %) as an off-white solid.1H NMR (CDCl3): δ 1.52 (9H, s), 1.85-1.97 (2H, m), 2.02-2.09 (2H, m), 2.32 (3H, d), 2.85-2.97 (4H, m), 3.93 (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. Intermediate 1i: 1-[3-Methyl-1-(4-piperidyl)indol-5-yl]hexahydropyrimidine-2,4-dione TFA (0.289 mL, 3.75 mmol)of Intermediate 1h (80 mg, 0.19 mmol) in DCM (1.0 mL) at r.t. After 1h the mixture was concentrated. Diethyl ether (2 mL) was added and the resulting mixture was sonicated to yield a solid precipitate. The supernatant was removed and the solid dried under reduced pressure to give the title compound in the form of a trifluoroacetate salt (83 mg, 100 %) as a light pink solid. m / z (ES+) [M+H]+= 326.9. 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]nonan-2-yl]methyl]-4-piperidyl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4- dioneFormic acid (1 ml, 26.07 mmol) was added to Intermediate 1f (35 mg, 0.06 mmol). The resulting mixture was stirred at r.t. for 1h 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 r.t. for 1h. Sodium triacetoxyborohydride (39.0 mg, 0.18 mmol) was added and stirred at r.t. for 1 h. The solvent was removed under reduced pressure. Purification by RPC (gradient: 0-60% MeCN in water with 0.1% FA) gave the title compound (5.60 mg, 10.01 %) as a white solid.1H NMR (DMSO-d6): δ 1.45 (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), 2.23 (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 proton not observed); m / z (ES+) [M+H]+= 835.1. EXAMPLE 2 Intermediate 2a: tert-Butyl 2-(5-bromo-3-cyclopropyl-pyrrolo[2,3-b]pyridin-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate A vial was charged with1H-pyrrolo[2,3-b]pyridine (600 mg, 2.53 mmol) and tert-butyl 2-hydroxy-7-azaspiro[3.5]nonane-7-carboxylate (611 mg, 2.53 mmol), 2-(tributyl-l5- phosphaneylidene)acetonitrile (1222 mg, 5.06 mmol), and m-xylene (15 mL). The reaction was heated to 110 °C for 16 h then cooled to r.t. and concentrated in vacuo. Purification by RPC (gradient: 5-100% MeCN in water with 0.1% NH4HCO3) gave the title compound (1000 mg, 86 %) as a yellow solid.1H NMR (DMSO-d6): δ 0.63 – 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. Intermediate 2b: tert-Butyl 2-[3-cyclopropyl-5-(2,4-dioxohexahydropyrimidin-1-yl)pyrrolo[2,3-b]pyridin-1-yl]-7- azaspiro[3.5]nonane-7-carboxylateA 40 mL vial was charged with 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), then the vial was capped and evacuated and backfilled with nitrogen.1,4-dioxane (20 mL) was added, then the mixture was sparged with nitrogen for 15 min. The reaction was then warmed to 100 °C for 16 h. The reaction was cooled to r.t., then diluted with EtOAc (50 mL) and filtered through celite®. The filtrate was concentrated under reduced pressure. The resulting residue was purified by FSC (gradient: 0- 100% EtOAc in hexanes then 0-30% MeOH in EtOAc) to give title compound (1446 mg, 77 %) as a brown dry film.1H NMR (DMSO-d6): δ 0.65 – 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. Intermediate 2c: 1-[1-(7-Azaspiro[3.5]nonan-2-yl)-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4- dione TFA (6.00 mL) was2b (1.974 g, 4 mmol) in DCM (24 mL). The resulting solution was stirred for 2h. The reaction mixture was concentrated. Purification by ion exchange chromatography (Porpak Rxn CX 50g cartridge) eluting with 2N NH3 in MeOH gave the title compound (1.457 g, 93 %) as a white solid.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 proton not observed); m / z (ES+) [M+H]+=394.4. Intermediate 2d: 1-Bromo-3-(3,3-diethoxyprop-1-ynyl)benzene A vial was chargedyne (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). The reaction was degassed and stirred at r.t. for 1.5 hours. The reaction was diluted with water, extracted with DCM (2 x 20 mL), washed with brine, dried with Na2SO4and concentrated in vacuo. Purification by FCS (0-12% EtOAc in hexanes) gave the title compound (1.272 g, 74.9 %) as a colorless oil.1H 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.Intermediate 2e: tert-Butyl 8-[3-(3,3-diethoxyprop-1-ynyl)phenyl]-3,8-diazabicyclo[3.2.1]octane-3-carboxylate tert-butyl (-3,8-(0.954 g, 4.49 mmol) was added to a stirred solution of Intermediate 2d (1.272 g, 4.49 mmol), RuPhos Pd 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) in 1,4-dioxane (24 mL) under nitrogen. The vial was sealed and flushed with nitrogen for 5 minutes and heated at 90 °C for 4h. The reaction was filtered through a celite® plug and concentrated. Purification by FSC (gradient: 0-50% EtOAc in hexanes) gave the title compound (0.943 g, 50.6 %) as a brown viscous oil.1H NMR (CDCl3): δ 1.30 (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. Intermediate 2f: 8-[3-(3,3-Diethoxyprop-1-ynyl)phenyl]-3,8-diazabicyclo[3.2.1]octane A vial was charged withmmol), HCl solution (1.25M in EtOH, 15.50 mL, 19.37 mmol). The reaction was heated to 40 °C for 2h. Concentration in vacuo gave the title compound (609 mg, 100%) as a brown film. m / z (ES+) [M+H]+= 315.5. 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 A vial was chargedmmol), 4-bromo-6-chloropyridazin-3- amine (809 mg, 3.88 mmol), n-butanol (8 mL), and DIPEA (1.694 mL, 9.70 mmol). The reaction was heated to 110 °C for 19 h. Purification by FCS (0-100% EtOAc in hexanes, 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.1H NMR (DMSO-d6): δ 1.17 (6H, t), 1.91 - 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. Intermediate 2h:2-[6-Amino-5-[8-[3-(3,3-diethoxyprop-1-ynyl)phenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3- yl]phenol Intermediate 2g (351hydroxyphenyl)boronic acid (164 mg, 1.19 mmol), Cs2CO3 (518 mg, 1.59 mmol) and Xphos Pd G3 (67.2 mg, 0.08 mmol) in 1,4-dioxane (7 mL) and water (0.700 mL). The vial was degassed bubbling N2 through the solution for 10 min. The vial was sealed and stirred at 100 °C for 30 min. The reaction was cooled to r.t. 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 x 20 mL) and the combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated. Purification by FSC (gradient: 0-100% EtOAc in hexanes) gave the title compound (239 mg, 60.2 %) as a brown solid.1H NMR (DMSO-d6): δ 1.14 - 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. Intermediate 2i: 3-[3-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]prop-2- ynal A vial was charged withmmol) and formic acid (0.5 mL). The reaction was stirred at 40 °C for 10 mins. The reaction was concentrated in vacuo and dried by lyophilization. The title compound was obtained (121 mg, 93 %) as a brown solid. m / z (ES+) [M+H]+= 426.4. 1-[1-[7-[3-[3-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8- yl]phenyl]prop-2-ynyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dioneA vial was charged with Intermediate 2c (59.0 mg, 0.15 mmol), Intermediate 2i (63.8 mg, 0.15 mmol), and NMP (1.5 mL). The solution was stirred at r.t. for 30 min. Na(OAc)3BH (95 mg, 0.45 mmol) was added and the reaction was stirred at r.t. for 15 min then concentrated in vacuo. Purification by RPC (0-50% MeCN in water with 0.1% FA) gave the title compound (12.12 mg, 9.84 %).1H NMR (DMSO-d6): δ 0.66 - 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. EXAMPLE 3 Intermediate 3a: 1-(3-Bromophenyl)-4-(dibutoxymethyl)piperidine A mixture of Pd2(dba)3, (0.289 g, 0.50 mmol), and potassium tert-butoxide (1.122 g, 10.00 mmol) 1-bromo-3-iodobenzene (0.956 mL, 7.50 mmol) and 4- (dibutoxymethyl)piperidine (1.217 g, 5 mmol) and toluene (36 mL) was degassed, bubbling N2through the solution for 10 minutes. The reaction was heated to 85 °C for 1.75 h, Reaction was cooled to r.t. and concentrated under reduced pressure. Purification by FSC (gradient: 0-20% EtOAc in hexanes) gave the title compound (1.758 g, 88 %) as a yellow oil.1H NMR (CDCl3): δ 0.94 (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. Intermediate 3b: Benzyl 8-[3-[4-(dibutoxymethyl)-1-piperidyl]phenyl]-3,8-diazabicyclo[3.2.1]octane-3-carboxylate Prepared in an2e 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). Purification by FSC (gradient: 0-50% EtOAc in hexanes) gave the title compound (1.310 g, 61.7 %) as a light brown oil.1H NMR (CDCl3): δ 0.96 (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.Intermediate 3c: 8-[3-[4-(Dibutoxymethyl)-1-piperidyl]phenyl]-3,8-diazabicyclo[3.2.1]octane Pd / C (100 mg, 0.09(1.3095 g, 2.32 mmol) and ammonium formate (1.465 g, 23.23 mmol) in MeOH (15 mL) was stirred at 50 °C for 30 min. The reaction was cooled to r.t. filtered through a celite® plug eluting with MeOH and EtOAc and concentrated. The resulting residue was partitioned between DCM (20 mL) and saturated aq. NaHCO3(20 mL). The layers were separated and the aqueous layer was extracted with DCM (2 x 20 mL). The combined organic extracts were washed with water and brine, dried (Na2SO4) and concentrated. Crude product has sufficient purity and taken onto next step without subsequent purification to give title compound (0.838 g, 84 %) as a yellow solid.1H NMR (DMSO-d6): δ 0.89 (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. Intermediate 3d: 6-Chloro-4-[8-[3-[4-(dibutoxymethyl)-1-piperidyl]phenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3- amine A mixture of, 6-chloropyridazin-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 h. The reaction was cooled to r.t. and concentrated. Purification by FSC (gradient: 0-100% EtOAc in hexanes) gave the title compound (657 mg, 60.4 %) as a brown solid.1H NMR (DMSO-d6): δ 0.89 (6H, t), 1.27 - 1.40 (6H, m), 1.44 - 1.53 (4H, m), 1.61 - 1.74 (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. 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]phenolPrepared in an analogous manner to Intermediate 2h staring from Intermediate 3d (547 mg, 0.98 mmol). Purification by FSC (gradient: 0-100% EtOAc in hexanes) gave the title compound (516 mg, 85 %) as a brown solid.1H NMR (DMSO-d6): δ 0.89 (6H, t), 1.27 - 1.40 (6H, m), 1.45 - 1.51 (4H, m), 1.58 - 1.77 (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. 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]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione A vial was, Intermediate 2b (24.68 mg, 0.05 mmol), and formic acid (0.5 mL). The reaction was stirred at 40 °C for 20 min then concentrated in vacuo. The resulting film was taken up in DCM (0.5 mL) and iPrOH (0.100 mL) and stirred at r.t. for 30 min. Na(OAc)3BH (21.19 mg, 0.10 mmol) was added and the reaction was stirred at r.t. for 30 min then concentrated in vacuo. Purification by RPC (0-100% MeCN in water with 0.1% NH4OH) gave the title compound (11.57 mg, 26.1 %) as a white solid.1H NMR (DMSO-d6): δ 0.69 (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 (6H, 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. EXAMPLE 4 Intermediate 4a: tert-Butyl 2-(5-bromo-3-methyl-indol-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate A vial was charged withindole (525 mg, 2.5 mmol), tert-butyl 2- hydroxy-7-azaspiro[3.5]nonane-7-carboxylate (1207 mg, 5.00 mmol), 2-(tributyl-l5- phosphaneylidene)acetonitrile (1.310 mL, 5.00 mmol), and toluene (12 mL). The reaction was heated to 100 °C for 6 h, cooled to r.t. and concentrated in vacuo. Purification by FCS (0-50% EtOAc in hexanes) gave the title compound (824 mg, 76 %) as a yellow solid.1H NMR (CDCl3): δ 1.48 (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. Intermediate 4b: tert-Butyl 2-[5-(2,4-dioxohexahydropyrimidin-1-yl)-3-methyl-indol-1-yl]-7-azaspiro[3.5]nonane-7- carboxylate The vial was charged1.90 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). The vial was evacuated and backfilled with nitrogen.1,4-Dioxane (12 mL) was added and he reaction mixture was then degassed by bubbling nitrogen through the solution for 10 min. The vial was sealed and the resulting mixture was stirred at 100 °C for 16 h. The solvent was removed. Purification by FSC (gradient: 0-100% EtOAc in hexanes) gave the title compound (727 mg, 82 %) as an off-white solid.1H NMR (DMSO-d6): δ 1.39 (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. 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]nonan-2-yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4- dione Prepared in anIntermediate 3e (30.7 mg, 0.05 mmol) and Intermediate 4b (23.33 mg, 0.05 mmol). Purification by RPC (gradient: 0-100% MeCN in water with 0.1% NH4OH) gave the title compound (11.30 mg, 25.5 %) as a pale yellow solid.1H NMR (DMSO- d6): δ 1.15 - 1.28 (6H, m), 1.62 - 1.68 (2H, m), 1.72 - 1.81 (3H, m), 1.89 - 1.97 (2H, m), 2.04 - 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. EXAMPLE 5 Intermediate 5a: tert-Butyl 4-(4-bromoindol-1-yl)piperidine-1-carboxylate2-(Tributyl-l5-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) under N2at r.t. The resulting mixture was stirred at 100°C for 18 h and then cooled to r.t. and concentrated under reduced pressure. Purification by RPC (gradient: 0-70% MeCN in water with 0.4% NH4HCO3) gave the title compound (20.0 g, 21 %) as a yellow solid.1H NMR (DMSO-d6): δ 1.44 (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. Intermediate 5b: tert-Butyl 4-[4-(2,4-dioxohexahydropyrimidin-1-yl)indol-1-yl]piperidine-1-carboxylate Prepared in an analogousstarting from Intermediate 5a (5 g, 13.18 mmol). Purification by FSC (gradient: 0-60% EtOAc in petroleum ether) gave the title compound (5.20 g, 96 %) as a yellow solid.1H NMR (CDCl3): δ 1.52 (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. Intermediate 5c: 1-[1-(4-Piperidyl)indol-4-yl]hexahydropyrimidine-2,4-dioneIntermediate 5b (7.0 g, was to AcOH (20 mL). The resulting mixture was stirred at 100 °C for 72 h and then cooled to r.t. and concentrated under reduced pressure. Purification by RPC (gradient: 0-60% MeCN in water with 0.4% HCl) gave the title compound in the form of a hydrochloride salt (4.50 g, 85 %) as a red solid.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. 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]indol-4-yl]hexahydropyrimidine-2,4-dionePrepared in an analogous manner to EXAMPLE 3 staring from Intermediate 3e (61.5 mg, 0.1 mmol) and Intermediate 5c (97 mg, 0.20 mmol). Purification by RPC (0-100% MeCN in water with 0.1% NH4OH) gave the title compound (22.30 mg, 26.3 %) as a pale yellow solid.1H NMR (DMSO-d6): δ 1.18 - 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), 7.10 - 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. EXAMPLE 6 Intermediate 6a: tert-Butyl 9-(5-bromo-3-methyl-indol-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate 2-(Tributyl-l5-mL, 14.28 mmol) was added to tert-butyl 9- hydroxy-3-azaspiro[5.5]undecane-3-carboxylate (2.56 g, 9.52 mmol) and 5-bromo-3-methylindole (1 g, 4.76 mmol) in toluene (20 mL) at r.t under nitrogen. The resulting mixture was stirred at 120 °C for 16 h. The reaction mixture was poured into water (200 mL), extracted with EtOAc (3 x 200 mL), the organic layer was dried over Na2SO4, filtered and concentrated. Purification by FSC (gradient 0 to 20% EtOAc in petroleum ether) gave the title compound (1.900 g, 86 %) as a white solid.1H NMR (DMSO-d6) δ 1.24– 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. Intermediate 6b: tert-Butyl 9-[5-(2,4-dioxohexahydropyrimidin-1-yl)-3-methyl-indol-1-yl]-3-azaspiro[5.5]undecane-3- carboxylate Di-µ-chlorobis[(1,2,3-- (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) under nitrogen. The resulting mixture was stirred at 100 °C for 10 h. The reaction mixture was filtered through celite®. The filtrate was poured into water (500 mL), extracted with EtOAc (3 x 500 mL), the combined organic extracts were dried (Na2SO4), filtered and evaporated. The crude product was purified by FSC (gradient: 0 to 10% MeOH in DCM) gave the title compound (1.0 g, 49.1 %) as a brown solid.1H NMR (DMSO-d6): δ 1.41 (13H, s), 1.60 (2H, t), 1.69–2 (6H, m), 2.24 (3H,d), 2.51 (2H, t), 2.73 (2H, t), 3.77 (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. Intermediate 6c: 1-[1-(3-Azaspiro[5.5]undecan-9-yl)-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione para-Toluenesulfonicadded to Intermediate 6b (1.5 g, 3.03 mmol) in MeCN (30 mL) was stirred at 70 °C for 3 h. The product was filtered to afford title compound (1.0 g, 58.2 %) as a white solid in the form of tosic salt. m / z (ES+) [M+H]+= 395.1. Intermediate 6d: tert-Butyl 8-(3-bromophenyl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate Prepared in an analogous1b starting from 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). Purification by FSC (gradient: 0 to 30% EtOAc in petroleum ether) gave the title compound (2.2 g, 63.6 %) as a white solid; m / z (ES+) [M+H]+= 367.0. Intermediate 6e: tert-Butyl 8-[3-[4-(dimethoxymethyl)-1-piperidyl]phenyl]-3,8-diazabicyclo[3.2.1]octane-3-carboxylate The mixture of 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 h. The reaction mixture was diluted with water (100 mL), extracted with EtOAc (3 x 500 mL), the organic layer was dried (Na2SO4), filtered and concentrated. Purification by FSC (gradient: 0 to 40% EtOAc in petroleum ether) gave the title compound (2.0 g, 82 %) as a yellow solid; m / z (ES+) [M+H]+= 446.2. Intermediate 6f: 6-Chloro-4-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]phenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin- 3-amineHCl in MeOH (10 mL, 40.00 mmol) was added to Intermediate 6e (1.3 g, 2.92 mmol) at r.t. The resulting mixture was stirred at r.t. for 2h. The solvent was removed under reduced pressure to afford the amine. To the crude amine was added 4-bromo-6-chloropyridazin-3-amine (0.608 g, 2.92 mmol), DIPEA (0.377 g, 2.92 mmol) and MeCN (15 mL) at r.t. The resulting mixture was stirred at 80 °C for 3 days. The reaction mixture was diluted with water (200 mL), extracted with EtOAc (3 x 200 mL), the organic layer was dried (Na2SO4), filtered and evaporated. Purification by RPC (gradient: 5 to 100% MeCN in water with 0.1% NH4HCO3) gave the title compound (0.900 g, 65.2 %) as a yellow solid.1H 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. 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 Formic acid (1.00.21 mmol). The resulting mixture was stirred at 40 °C for 30 min. The solvent was removed under reduced pressure to afford the aldehyde. To the crude aldehyde was added Intermediate 6c (120 mg, 0.21 mmol) and DCM (1 mL) at r.t. To the resulting solution was added sodium triacetoxyborohydride (67.2 mg, 0.32 mmol) and stirred at r.t. for 1 h. The reaction mixture was diluted with DCM (25 mL) and washed with saturated NH4HCO3(3 x 25 mL). The organic layer was separated, dried (Na2SO4), filtered and evaporated. Purification by FCS (gradient: 0 to 10% MeOH in DCM) gave the title compound (60.0 mg, 35.2 %) as a yellow solid.1H NMR (DMSO- d6): δ 1.15–1.51 (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 (3H, 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. 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]undecan-9-yl]-3-methyl-indol-5-yl]hexahydropyrimidine- 2,4-dionePrepared in an analogous method to Intermediate 2h starting from Intermediate 6g (45 mg, 0.06 mmol). Purification by RPC (Gradient: 0-50% MeCN in water with 0.1% FA) gave the title compound (6.80 mg, 14.10 %) as a white solid.1H NMR (DMSO-d6): δ 1.12–1.26 (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. EXAMPLE 7 Intermediate 7a: 1-(5-Chloro-2-fluoro-phenyl)-4-(dimethoxymethyl)piperidine Copper(I) iodide (0.074 g,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) under nitrogen. The resulting mixture was stirred at 100 °C for 16h. Purification by RPC (gradient: 5 to 100% MeOH in water with 0.5% NH4HCO3) gave the title compound (0.470 g, 41.9 %) as a grey solid.1H NMR (DMSO-d6) δ 1.21 – 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. Intermediate 7b: tert-Butyl 8-[3-[4-(dimethoxymethyl)-1-piperidyl]-4-fluoro-phenyl]-3,8-diazabicyclo[3.2.1]octane-3- carboxylate Prepared in an2e 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). Purification by RPC (gradient: 5 to 100% MeOH in water with 0.5% NH4HCO3) gave the title compound (410 mg, 56.6 %) as a yellow solid.1H NMR (DMSO-d6): δ 1.33 – 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. Intermediate 7c: 8-[3-[4-(Dimethoxymethyl)-1-piperidyl]-4-fluoro-phenyl]-3,8-diazabicyclo[3.2.1]octane HCl in MeOH (6 mL,to Intermediate 7b (400 mg, 0.86 mmol). The resulting mixture was stirred at r.t for 3 h. The reaction mixture was adjusted to pH to 9 with the 7 M ammonia methanol solution. The solvent was removed under reduced pressure. The reaction mixture was diluted with MeOH:DCM (1:3) (15 mL), solids were filtered off. The filtrate was concentrated under reduced pressure afford the title compound (300 mg, 87 %) as a white solid.1H NMR (DMSO-d6): δ 1.27 – 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. Intermediate 7d: 6-Chloro-4-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-4-fluoro-phenyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]pyridazin-3-amine Prepared in anstarting from Intermediate 7c (300 mg, 0.83 mmol). Purification by RPC (gradient 5 to 100% MeCN in water with 0.5% NH4HCO3) gave the title compound (200 mg, 45.3 %) as a yellow solid.1H NMR (400 MHz, CDCl3) δ 1.50 – 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. Intermediate 7e: 2-[6-Amino-5-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-4-fluoro-phenyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]pyridazin-3-yl]phenolPrepared in an analogous method to Intermediate 2h starting from Intermediate 7d. Purification by FSC (gradient: 0 to 10% MeOH in DCM) gave the title compound (160 mg, 82 %) as a yellow solid.1H NMR (DMSO-d6) δ 1.23 – 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 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2- fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione Prepared inIntermediate 7e (40 mg, 0.07 mmol) and Intermediate 2b (28.7 mg, 0.07 mmol). Purification by RPC (Gradient: 10-50% MeCN in water with 0.1% FA) gave the title compound (11.0 mg, 16.46 %) as a white solid.1H NMR (DMSO-d6) δ 0.66 – 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 proton not observed);19F NMR (DMSO-d6) δ -136.41; m / z (ES+) [M+H]+= 880.6. EXAMPLE 8 Intermediate 8a: tert-Butyl 8-(3-bromo-5-fluoro-phenyl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate Prepared in an analogous1b starting from 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). Purification by FSC (gradient 0 to 10% EtOAc in petroleum ether) gave the title compound (1.280 g, 42.2 %) as a white solid.1H NMR (DMSO-d6) δ 1.39 (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. Intermediate 8b: tert-Butyl 8-[3-[4-(dimethoxymethyl)-1-piperidyl]-5-fluoro-phenyl]-3,8-diazabicyclo[3.2.1]octane-3- carboxylatePrepared in an analogous method to Intermediate 6e starting from Intermediate 8a (1.28 g, 3.32 mmol. Purification by FSC (gradient: 0 to 40 % EtOAc in petroleum ether) gave the title compound (0.790 g, 51.3 %) as a yellow solid.1H NMR (DMSO-d6) δ 1.27 (2H, d), 1.39 (9H, s), 1.60 – 1.72 (5H, m), 1.84 – 1.95 (2H, m), 2.54 – 2.66 (2H, m), 3.06 (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. Intermediate 8c: 6-Chloro-4-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-5-fluoro-phenyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]pyridazin-3-amine Prepared in anstarting from Intermediate 8b (490 mg, 1.06 mmol). Purification by RPC (gradient: 3 to 80% MeCN in water 0.1% NH4HCO3) gave the title compound (260 mg, 50.1 %) as a yellow solid.1H NMR (DMSO-d6) δ 1.21 – 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. Intermediate 8d: 2-[6-Amino-5-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-5-fluoro-phenyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]pyridazin-3-yl]phenol Prepared in anstarting from Intermediate 8c (200 mg, 0.41 mmol). Purification by FSC (gradient: 0 to 100 % DCM in petroleum ether and 0 to 10 % EtOH in DCM) gave the title compound (210 mg, 94 %) as a yellow solid.1H NMR (DMSO-d6) δ 0.83 – 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. 1-[1-[7-[[1-[3-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-5- fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione Prepared in anIntermediate 8d (60 mg, 0.11 mmol) and Intermediate 2c (51.6 mg, 0.13 mmol). Purification by RPC (gradient: 0-38 % MeCN water with 0.1 % FA) gave the title compound (14.88 mg, 14.72 %) as a white solid.1H NMR (DMSO-d6) δ 0.66 – 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 – 6.89 (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);19F NMR (DMSO-d6) δ -73.44, -112.18; m / z (ES+) [M+H]+= 880.6. EXAMPLE 9 Intermediate 9a: tert-Butyl 8-(3-bromo-5-methyl-phenyl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate Prepared in an1b starting from 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). Purification by FSC (gradient: 0 to 7 % EtOAc in petroleum ether) gave the title compound (2.0 g, 65.5 %) as a white solid.1H NMR (DMSO-d6) δ 1.39 (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. Intermediate 9b: tert-Butyl 8-[3-[4-(dimethoxymethyl)-1-piperidyl]-5-methyl-phenyl]-3,8-diazabicyclo[3.2.1]octane-3- carboxylatePrepared in an analogous method to Intermediate 6e starting from Intermediate 9a (1 g, 2.62 mmol). Purification by FSC (gradient 0 to 30 % EtOAc in petroleum ether) gave the title compound (0.900 g, 74.7 %) as a yellow solid.1H NMR (DMSO-d6) δ 1.22 – 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. Intermediate 9c: 6-Chloro-4-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-5-methyl-phenyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]pyridazin-3-amine Prepared analogousfrom Intermediate 9b (500 mg, 1.09 mmol). Purification by RPC (gradient: 0 to 70 % MeCN in water with 0.1 % FA) gave the title compound (410 mg, 77 %).1H NMR (DMSO-d6) δ 0.81 – 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 (1H, 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. Intermediate 9d: 2-[6-Amino-5-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-5-methyl-phenyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]pyridazin-3-yl]phenol Prepared in an analogous2h starting from Intermediate 9c (200 mg, 0.41 mmol). Purification by FSC (gradient: 0 to 100 % DCM in petroleum ether and 0 to 10 % MeOH in DCM) gave the title compound (200 mg, 89 %) as a yellow solid.1H NMR (DMSO-d6) δ 1.17 – 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 – 3.68 (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. 1-[1-[7-[[1-[3-[3-[3-Amino-6-(2-hydroxyphenyl)146yridine146e-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]- 5-methyl-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]146yridine-5-yl]hexahydropyrimidine-2,4-dionePrepared in an analogous method to EXAMPLE 1 starting from Intermediate 9d (60 mg, 0.11 mmol and Intermediate 2c (52.0 mg, 0.13 mmol). Purification by RPC (gradient: 0-38 % MeCN water with 0.1 % FA) gave the title compound (13.41 mg, 13.28 %) as a white solid.1H NMR (DMSO-d6) δ 0.65 – 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. EXAMPLE 10 Intermediate 10a: tert-Butyl 8-(3-bromo-4-methyl-phenyl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate 2-Bromo-4-iodo-1-mmol) was added to 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) in 1,4-dioxane (20 mL) under N2. The resulting mixture was stirred at 100 °C for 16 h. The reaction mixture was diluted with EtOAc (100 mL), and washed sequentially with saturated NH4Cl (100 mL x 2) and saturated brine (100 mL x 2). The organic layer was dried (Na2SO4), filtered and evaporated to afford crude product. The crude product was purified by FSC (gradient: 0 to 7% EtOAc in petroleum ether) gave the title compound (2.280 g, 89 %) as a purple solid.1H NMR (DMSO-d6) δ 1.39 (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. Intermediate 10b: tert-Butyl 8-[3-[4-(dimethoxymethyl)-1-piperidyl]-4-methyl-phenyl]-3,8-diazabicyclo[3.2.1]octane-3- carboxylate Prepared in an analogous6e starting from Intermediate 10a (1 g, 2.62 mmol). Purification by FSC (gradient: 0 to 30% MeCN in water with 0.1% NH4HCO3) gave the titlecompound (750 g, 62.2 %) as a yellow solid.1H NMR (DMSO-d6) δ 1.36 – 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. Intermediate 10c: 6-Chloro-4-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-4-methyl-phenyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]pyridazin-3-amine Prepared analogousfrom Intermediate 10b (370 mg, 0.80 mmol). Purification by RPC (gradient 3 to 80% MeCN in water with 0.1% NH4HCO3) gave the title compound (256 mg, 65.3 %) as a yellow solid.1H NMR (DMSO-d6) δ 1.26 – 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. Intermediate 10d: 2-[6-Amino-5-[8-[3-[4-(dimethoxymethyl)-1-piperidyl]-4-methyl-phenyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]pyridazin-3-yl]phenol Prepared in anstarting from Intermediate 10c (200 mg, 0.41 mmol). Purification by FSC (gradient: 0 to 40 % DCM in petroleum ether) gave the title compound (215 mg, 96 %) as a yellow solid.1H NMR (DMSO-d6) δ 1.32 – 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 – 3.61 (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 proton is not observed); m / z (ES+) [M+H]+=545.3. 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2- methyl-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dionePrepared in an analogous method to EXAMPLE 1 starting from Intermediate 10d (60 mg, 0.11 mmol) and Intermediate 2c (52.0 mg, 0.13 mmol). Purification by RPC (Gradient: 0-50% MeCN in water with 0.1% FA) gave the title compound (14.05 mg, 14.23 %) as a white solid.1H NMR (DMSO-d6) δ 0.66 – 0.72 (2H, m), 0.83 – 0.91 (2H, m), 1.18 – 1.31 (2H, m), 1.59 – 1.82 (6H, m), 1.89 – 1.98 (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. EXAMPLE 11 Intermediate 11a: tert-Butyl 9-(5-bromo-3-cyclopropyl-pyrrolo[2,3-b]pyridin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate Prepared in an analogous2a staring from 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). Purification by FSC (0-50 % EtOAc in hexanes) gave the title compound (816 mg, 66.8 %) as a colorless dry film.1H NMR (DMSO-d6): δ 0.58 - 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. Intermediate 11b: tert-Butyl 9-[3-cyclopropyl-5-(2,4-dioxohexahydropyrimidin-1-yl)pyrrolo[2,3-b]pyridin-1-yl]-3- azaspiro[5.5]undecane-3-carboxylatePrepared in an analogous manner to Intermediate 2b staring from Intermediate 11a (816 mg, 1.67 mmol). Purification by FCS (0-100 % EtOAc in hexanes, then 0-30% MeOH in EtOAc) gave the title compound (420 mg, 48.2 %) as a brown solid.1H NMR (DMSO-d6): δ 0.60 - 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 (2H, t), 4.60 (1H, tt), 7.49 (1H, s), 7.92 (1H, d), 8.15 (1H, d), 10.35 (1H, s); m / z (ES+) [M+H]+= 522.7. Intermediate 11c: 1-(5-Chloro-2-fluoro-phenyl)-4-(dibutoxymethyl)piperidine A flask was chargedg, 286.47 mmol) was added to 4- (dibutoxymethyl)piperidine (23.24 g, 95.49 mmol), 2-bromo-4-chloro-1-fluorobenzene (20 g, 95.49 mmol), Pd2(dba)3(4.37 g, 4.77 mmol) and BINAP (5.95 m, 9.55) in toluene (300 mL). The resulting mixture was stirred at 60 °C for 20 h under nitrogen. The reaction mixture was diluted with EtOAc (500 mL), and washed sequentially with saturated NH4Cl (500 mL) and saturated brine (500 mL). The organic layer was dried over Na2SO4, filtered and evaporate. Purification by FCS (0-5 % EtOAc in petroleum ether) gave the title compound (31.7 g, 89 %) as a pale yellow oil.1H NMR (CDCl3): δ 0.96 (6H, t), 1.38 - 1.48 (4H, m), 1.49 - 1.65 (6H, m), 1.72 - 1.83 (1H, m), 1.89 (2H, br d), 2.53 - 2.73 (2H, m), 3.41 - 3.54 (4H, m), 3.61 - 3.73 (2H, m), 4.24 (1H, dd), 6.63 - 6.80 (1H, m), 6.88 - 6.99 (1H, m), 7.26 - 7.32 (1H, m); m / z (ES+) [M+H]+= 372.3. Intermediate 11d: Benzyl 8-[3-[4-(dibutoxymethyl)-1-piperidyl]-4-fluoro-phenyl]-3,8-diazabicyclo[3.2.1]octane-3- carboxylate Prepared in an2e staring from Intermediate 11c (16.5 g, 44.36 mmol), and benzyl-3,8-diazabicyclo[3.2.1]octane-3-carboxylate, HCl (12.54 g, 44.36 mmol). Purification by FSC (0-25 % EtOAc in petroleum ether) gave the title compound (16.88 g, 65.4 %) as a red oil.1H NMR (DMSO-d6): δ 0.89 (6H, t), 1.27 – 1.41 (6H, m), 1.43 – 1.56 (4H, m), 1.58 – 1.77 (5H, m), 1.84 – 1.96 (2H, m), 2.52 – 2.63 (2H, m), 3.07 – 3.28 (2H, m), 3.32 – 3.45 (4H, m), 3.50 – 3.63 (4H, m), 4.15 – 4.29 (3H, m), 5.00 – 5.14 (2H, m), 6.33 – 6.46 (2H, m), 6.85 – 6.98 (1H, dd), 7.24 – 7.48 (5H, m); m / z (ES+) [M+H]+=582.4. Intermediate 11e: 8-[3-[4-(Dibutoxymethyl)-1-piperidyl]-4-fluoro-phenyl]-3,8-diazabicyclo[3.2.1]octaneA flask was charged with Intermediate 11d (9.8 g, 16.5 mmol), Pd / C (0.896 g, 0.84 mmol) and MeOH (300 mL) under a hydrogen atmosphere. The reaction was stirred at r.t. for 24 h. The solution was filtered and concentrated to give the title compound (7.10 g, 94 %) as a brown oil.1H NMR (DMSO-d6): δ 0.89 (6H, t), 1.29 - 1.42 (6H, m), 1.45 - 1.53 (4H, m), 1.59 - 1.68 (1H, m), 1.68 - 1.76 (2H, m), 1.79 - 1.92 (4H, m), 2.38 (2H, br d), 2.52 - 2.60 (2H, m), 2.94 (2H, br d), 3.32 (2H, br d), 3.36 - 3.44 (2H, m), 3.53 - 3.60 (2H, m), 3.94 - 4.03 (2H, m), 4.22 (1H, d), 6.29 (1H, br d), 6.34 (1H, br d), 6.87 (1H, dd) (N-H not observed); m / z (ES+) [M+H]+= 448.3. Intermediate 11f: 6-Chloro-4-[8-[3-[4-(dibutoxymethyl)-1-piperidyl]-4-fluoro-phenyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]pyridazin-3-amine A flask was chargedmmol), 4-bromo-6-chloropyridazin-3- amine (6.21 g, 29.79 mmol) DIPEA (14.87 mL, 85.1 mmol), and DMSO (100 mL). The resulting mixture was stirred at 100 °C for 16 h. The reaction mixture was diluted with EtOAc (300 mL), and washed sequentially with water (2 x 200 mL) and saturated brine (2 x 200 mL). The organic layer was dried (Na2SO4) and concentrated. Purification by FSC (gradient: 0-5 % MeOH in DCM) gave the title compound (13.49 g, 83 %) as a red oil.1H NMR (DMSO-d6): δ 0.89 (6H, t), 1.30 - 1.42 (6H, m), 1.46 - 1.53 (4H, m), 1.60 - 1.68 (1H, m), 1.73 (2H, br d), 1.88 - 1.94 (2H, m), 2.04 - 2.12 (2H, m), 2.55 - 2.62 (2H, m), 2.95 (2H, br d), 3.16 (2H, br d), 3.33 - 3.43 (4H, m), 3.56 (2H, dt), 4.22 (1H, d), 4.27 - 4.33 (2H, m), 5.76 - 5.82 (2H, m), 6.38 - 6.45 (2H, m), 6.87 (1H, s), 6.91 (1H, dd). m / z (ES+) [M-OBu]+= 501.4. Intermediate 11g: 2-[6-Amino-5-[8-[3-[4-(dibutoxymethyl)-1-piperidyl]-4-fluoro-phenyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]pyridazin-3-yl]phenol Prepared in anstaring from Intermediate 11f (281 mg, 0.49 mmol). Purification by FSC (gradient: 0-100 % EtOAc in hexanes) gave the title compound (202 mg, 65.2 %) as a light brown solid.1H NMR (DMSO-d6): δ 0.88 (6H, t), 1.29 - 1.42 (6H, m), 1.43 - 1.52 (4H,m), 1.58 - 1.68 (1H, m), 1.72 (2H, br d), 1.89 - 1.96 (2H, m), 2.07 - 2.15 (2H, m), 2.58 (2H, br t), 3.08 (2H, br d), 3.24 (2H, br d), 3.32 - 3.43 (4H, m), 3.55 (2H, dt), 4.21 (1H, d), 4.30 - 4.36 (2H, m), 5.92 (2H, s), 6.39 - 6.50 (2H, m), 6.80 - 6.98 (3H, m), 7.21 (1H, t), 7.45 (1H, s), 7.89 (1H, d), 14.15 (1H, s); m / z (ES+) [M+H]+= 633.6. 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2- fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione A vial was, Intermediate 11g (0.112 g, 0.18 mmol), and formic acid (2 mL, 52.15 mmol) was added and the mixture was stirred at 40 °C for 20 min. The reaction was concentrated under reduced pressure. Toluene (12 mL) was added and the reaction was evaporated to dryness. DMF (2 mL), and MgSO4 (0.107 g, 0.88 mmol) were added. The mixture was stirred at 40 °C for 30 min. Na(OAc)3BH (0.075 g, 0.35 mmol) was added and the mixture was stirred at r.t. for 20 min. Purification by RPC (0-50% MeCN in water with 0.1% FA) gave the title compound (0.067 g, 41.2 %) as a white solid.1H NMR (DMSO-d6): δ 0.63 - 0.70 (2H, m), 0.81 - 0.90 (2H, m), 1.21 - 1.35 (4H, m), 1.36 - 1.44 (2H, m), 1.61 - 1.85 (9H, m), 1.89 - 2.04 (5H, m), 2.14 (2H, br d), 2.27 (2H, br d), 2.36 - 2.47 (4H, m), 2.65 (2H, br t), 2.77 (2H, t), 3.11 (2H, br d), 3.27 (2H, br d), 3.36 (2H, br d), 3.82 (2H, t), 4.35 (2H, br s), 4.59 (1H, br t), 5.94 (2H, s), 6.39 - 6.53 (2H, m), 6.83 - 6.98 (3H, m), 7.23 (1H, t), 7.49 (2H, d), 7.87 - 7.96 (2H, m), 8.13 - 8.20 (1H, m), 10.37 (1H, s), 13.30 - 14.81 (1H, m); m / z (ES+) [M+H]+= 908.7. EXAMPLE 12 Intermediate 12a: tert-Butyl 2-(5-bromoindol-1-yl)-7-azaspiro[3.5]nonane-7-carboxylatePrepared in an manner to 4a from tert-butyl 2-hydroxy-7- azaspiro[3.5]nonane-7-carboxylate (2.462 g, 10.20 mmol) and 5-bromo-1H-indole (2 g, 10.20 mmol). Purification by RPC (gradient: 3 to 100% MeOH in MeOH (0.1% NH4HCO3) gave the title compound (4.15 g, 97 %) as an off-white solid.1H NMR (DMSO-d6) δ 1.41 (9H, s), 1.54 – 1.59 (2H, m), 1.66 – 1.72 (2H, m), 2.11 – 2.20 (2H, m), 2.44 – 2.50 (2H, m), 3.22 – 3.27 (2H, m), 3.34 – 3.39 (2H, m), 4.99 – 5.08 (1H, m), 6.48 (1H, d), 7.23 (1H, dd), 7.49 (1H, d), 7.65 (1H, d), 7.73 (1H, d); m / z (ES+) [M+H]+= 419.2. Intermediate 12b: tert-Butyl 2-[5-(2,4-dioxohexahydropyrimidin-1-yl)indol-1-yl]-7-azaspiro[3.5]nonane-7-carboxylatePrepared in an analogous manner to Intermediate 4b staring from Intermediate 12a (6.7 g, 15.98 mmol). Purification by FSC (gradient: 0 to 5% MeOH in DCM) gave the title compound (6.10 g, 84 %) as an off-white solid.1H NMR (DMSO-d6) δ 1.41 (9H, s), 1.54 – 1.59 (2H, m), 1.67 – 1.74 (2H, m), 2.12 – 2.20 (2H, m), 2.46 – 2.51 (2H, m), 2.72 (2H, t), 3.23 – 3.29 (2H, m), 3.34 – 3.41 (2H, m), 3.76 (2H, t), 5.01 – 5.09 (1H, m), 6.49 (1H, d), 7.07 (1H, dd), 7.46 (1H, d), 7.50 (1H, d), 7.63 (1H, d), 10.27 (1H, s); m / z (ES+) [M+H]+= 453.3. Intermediate 12c: 1-[1-(7-Azaspiro[3.5]nonan-2-yl)indol-5-yl]hexahydropyrimidine-2,4-dionePrepared in an analogous manner staring from Intermediate 12b (1.1 g, 2.43 mmol). The reaction mixture was diluted with MTBE (10 mL). The resulting mixture was stirred at room temperature for 10 mins. The precipitate was collected by filtration, washed with MTBE (10 mL) and dried under vacuum to afford the title compound (1.100 g, 86 %) as an off-white solid in the form of the TsOH salt. m / z (ES+) [M+H]+= 352.4. 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2- fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]indol-5-yl]hexahydropyrimidine-2,4-dionePrepared in an manner Intermediate 11g (40 mg, 0.07 mmol) and Intermediate 12c (30.8 mg, 0.09 mmol). Purification by RPC (gradient: 0-50% MeCN in water with 0.1% FA) gave the title compound (8.00 mg, 12.78 %) as a white solid.1H NMR (DMSO-d6) δ 1.17 – 1.29 (3H, m), 1.64 (3H, t), 1.73 – 1.82 (3H, m), 1.90 – 2.01 (2H, m), 2.09 – 2.20 (6H, m), 2.22 – 2.41 (4H, m), 2.45 (2H, t), 2.60 – 2.69 (2H, m), 2.69 – 2.77 (2H, m), 3.10 (2H, d), 3.23 – 3.28 (2H, m), 3.76 (2H, t), 4.35 (2H, d), 4.96 – 5.06 (1H, m), 5.96 (2H, s), 6.40 – 6.45 (1H, m), 6.46 – 6.51 (2H, m), 6.84 – 6.97 (3H, m), 7.04 – 7.09 (1H, m), 7.20 – 7.26 (1H, m), 7.44 – 7.52 (3H, m), 7.62 (1H, d), 7.89 – 7.93 (1H, m), 10.27 (1H, s), 14.19 (1H, s);19F NMR (DMSO-d6) δ -136.4. m / z (ES+) [M+H]+= 839.5. EXAMPLE 13 Intermediate 13a: tert-Butyl 9-(5-bromo-3-methyl-pyrrolo[2,3-b]pyridin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylatePrepared in an analogous manner to Intermediate 4a staring 5-bromo-3-methyl-1H-pyrrolo[2,3- b]pyridine (800 mg, 3.79 mmol) and tert-butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate (1429 mg, 5.31 mmol). Purification by RPC (gradient: 2 to 80% MeCN in water with 0.1% NH4CO3) gave the title compound (910 mg, 51.9 %) as a yellow oil.1H NMR (CDCl3) δ 1.34 – 1.44 (4 H, m), 1.47 (9 H, s), 1.61 – 1.67 (2 H, m), 1.82 – 1.94 (6 H, m), 2.27 (3 H, d), 3.38 – 3.44 (4 H, m), 4.61 – 4.69 (1 H, m), 7.07 (1 H, s), 7.94 (1 H, d), 8.28 (1 H, d); m / z (ES+) [M+H]+= 462, 464.3. Intermediate 13b: tert-Butyl 9-[5-(2,4-dioxohexahydropyrimidin-1-yl)-3-methyl-pyrrolo[2,3-b]pyridin-1-yl]-3- azaspiro[5.5]undecane-3-carboxylate Prepared in anstarting from Intermediate 13a (530 mg, 1.15 mmol). Purification by FSC (gradient: 0 to 60% EtOAc in petroleum ether) gave the title compound (220 mg, 38.7 %) as a yellow solid.1H NMR (CDCl3) δ 1.39 (3 H, d), 1.47 (9 H, s), 1.62 – 1.71 (3 H, m), 1.83 – 1.95 (6 H, m), 2.30 (3 H, d), 2.87 – 2.93 (2 H, m), 3.38 – 3.45 (4 H, m), 3.87 – 3.94 (2 H, m), 4.74 (1 H, s), 7.15 (1 H, s), 7.53 (1 H, s), 7.80 (1 H, s), 8.22 (1 H, d). m / z (ES+) [M+H]+= 496.5. Intermediate 13c: 1-[1-(3-Azaspiro[5.5]undecan-9-yl)-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dionePrepared in an analogous manner 6c staring from Intermediate 168b (190 mg, 0.38 mmol). The solvent was removed under reduced pressure gave the title compound (152 mg, 100%) as a white solid in the form of the TsOH salt. m / z (ES+) [M+H]+= 396.5. Intermediate 13d: 1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-fluoro- phenyl]piperidine-4-carbaldehydeFormic acid (8 mL) was added to Intermediate 11g (300mg, 0.55 mmol). The resulting mixture was stirred at 40 °C for 1 h. The reaction mixture was evaporated. The reaction with quenched with saturated Na2CO3, extracted with DCM (3 x 1 mL), the organic layer was dried over Na2SO4, filtered and evaporated to afford the title compound (260 mg, 95 %) as a yellow solid. m / z (ES+) [M+H]+= 503.3. 1-[1-[3-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2- fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione A mixture of13c (151 mg, 0.38 mmol) was heated at in 1,2-dichloroethane (4 mL) and NMP (4.00 mL) at 40 °C for 16 h. The reaction mixture was cooled r.t. and then added Na(OAc)3BH (405 mg, 1.91 mmol) and stirred for 1 h. The reaction mixture was poured into saturated NaHCO3(50 mL), extracted with DCM (3 x 10 mL), the organic layer was dried over Na2SO4, filtered and evaporated. Purification by RPC (gradient 2 to 100% MeCN in water with 0.1% NH4CO3) gave the title compound (37.4 mg, 11.33 %) as a white solid.1H NMR (DMSO-d6) δ 0.80 – 0.89 (1 H, m), 1.17 – 1.45 (9 H, m), 1.62 – 1.73 (4 H, m), 1.74 – 1.85 (4 H, m), 1.89 – 2.05 (4 H, m), 2.10 – 2.27 (6 H, m), 2.35 (3 H, s), 2.58 – 2.69 (3 H, m), 2.72 – 2.78 (2 H, m), 3.09 (2 H, d), 3.25 (2 H, d), 3.73 – 3.86 (2 H, m), 4.28 – 4.40 (2 H, m), 4.52 – 4.66 (1 H, m), 5.95 (2 H, s), 6.36 – 6.55 (2 H, m), 6.80 – 6.98 (3 H, m), 7.16 – 7.28 (1 H, m), 7.50 (2 H, d), 7.78 – 7.99 (2 H, m), 8.16 (1 H, d), 10.39 (1 H, s), 14.18 (1 H, s);19F NMR (DMSO-d6) δ: -136.4; m / z (ES+), [M+H]+= 882. EXAMPLE 14 Intermediate 14a: tert-Butyl 2-(5-bromo-6-fluoro-indol-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate Prepared in an analogous4a staring from 5-bromo-6-fluoro-1H-indole (535 mg, 2.5 mmol), tert-butyl 2-hydroxy-7-azaspiro[3.5]nonane-7-carboxylate (905 mg, 3.75 mmol).Purification by FSC (0-30 % EtOAc in hexanes) gave the title compound (826 mg, 76 %) as a colorless solid.1H NMR (DMSO-d6): δ 1.41 (9H, s), 1.54 - 1.59 (2H, m), 1.63 - 1.75 (2H, m), 2.09 - 2.17 (2H, m), 2.45 - 2.49 (2H, m), 3.22 - 3.27 (2H, m), 3.34 - 3.41 (2H, m), 5.03 (1H, quin), 6.50 (1H, d), 7.62 (1H, d), 7.70 (1H, d), 7.84 (1H, d); m / z (ES+) [M+H]+= 437.1. Intermediate 14b: tert-Butyl 2-[5-[(3-ethoxy-3-oxo-propyl)amino]-6-fluoro-indol-1-yl]-7-azaspiro[3.5]nonane-7-carboxylate Ethyl 3-aminopropanoate,was added to tBuBrettPhos Pd G3 (161 mg, 0.19 mmol), Intermediate 14a (826 mg, 1.89 mmol) and Cs2CO3 (1846 mg, 5.67 mmol) in 1,4-dioxane (10 mL). The vial was capped and evacuated and backfilled with nitrogen. The reaction was heated at 100 °C for 17 h. The reaction was cooled to r.t. then diluted with EtOAc and filtered through celite®. The filtrate was concentrated under reduced pressure. Purification by FSC (0-70% EtOAc in hexanes) gave the title compound (868 mg, 97 %) as a green liquid.1H NMR (DMSO-d6): δ 1.19 (3H, t), 1.41 (9H, s), 1.49 - 1.60 (2H, m), 1.63 - 1.72 (2H, m), 2.05 - 2.12 (2H, m), 2.42 - 2.48 (2H, m), 2.63 (2H, t), 3.21 - 3.27 (2H, m), 3.30 - 3.34 (2H, m), 3.34 - 3.37 (2H, m), 4.08 (2H, q), 4.81 - 4.95 (2H, m), 6.30 (1H, d), 6.80 (1H, d), 7.28 (1H, d), 7.42 (1H, d); m / z (ES+) [M+H]+= 474.7. Intermediate 14c: tert-Butyl 2-[5-[carbamoyl-(3-ethoxy-3-oxo-propyl)amino]-6-fluoro-indol-1-yl]-7-azaspiro[3.5]nonane-7- carboxylate Intermediate 14b (868in DCM (5 mL) and acetic acid (5 mL). Potassium cyanate (743 mg, 9.16 mmol) was added and the reaction was stirred at r.t. for 20 min. The reaction was diluted with dichloromethane, then washed with water, saturated aq. NaHCO3 solution, and brine solutions. The organic layer was separated, dried (Na2SO4), filtered, and concentrated under reduced pressure to provide crude title compound (945 mg, 100 %) as a brown dry film, which was used in the next step without further purification. m / z (ES+) [M+H]+= 517.6. Intermediate 14d: tert-Butyl 2-[5-(2,4-dioxohexahydropyrimidin-1-yl)-6-fluoro-indol-1-yl]-7-azaspiro[3.5]nonane-7- carboxylateA mixture of Intermediate 14c (945 mg, 1.83 mmol), ethanol (8 mL) and sodium ethoxide solution (21 w.t.% in EtOH) (1.366 mL, 3.66 mmol) was stirred at r.t for 10 min. The reaction mixture precipitated out, ethanol (12 mL) was added to suspended the solid and stirring at r.t. continued for 1 h. The reaction was quenched with aq. NH4Cl solution (20 mL) and water (100 mL) was added The aqueous mixture was extracted with EtOAc (2 x 100 mL), then the organic layer was washed with brine (100 mL). The brine layer was extracted with DCM (50 mL), combined with the EtOAc extracts, dried (Na2SO4), filtered and concentrated. The resulting residue was suspended in ether and sonicated. The suspension was centrifuged and the liquid decanted (2x this trituration procedure). The resulting solid was dried under vacuum to afford the title compound (526 mg, 61.1 %) as a white solid.1H NMR (DMSO-d6): δ 1.41 (9H, s), 1.53 - 1.61 (2H, m), 1.67 - 1.72 (2H, m), 2.09 - 2.18 (2H, m), 2.46 - 2.50 (2H, m), 2.73 (2H, t), 3.22 - 3.29 (2H, m), 3.35 - 3.41 (2H, m), 3.70 (2H, br t), 5.03 (1H, quin), 6.52 (1H, d), 7.50 (1H, d), 7.56 (1H, d), 7.68 (1H, d), 10.41 (1H, s). m / z (ES+) [M+Na]+= 493.2. 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2- fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-6-fluoro-indol-5-yl]hexahydropyrimidine- 2,4-dione Prepared inIntermediate 14d (24 mg, 0.05 mmol) and Intermediate 11g (32 mg, 0.05 mmol). Purification by RPC (0-100% MeCN in water with 0.1% NH4OH) gave the title compound (6.60 mg, 15.23 %) as a white solid.1H NMR (DMSO-d6): δ 1.21 - 1.30 (2H, m), 1.64 (3H, br d), 1.73 - 1.83 (4H, m), 1.90 - 1.99 (2H, m), 2.06 - 2.19 (6H, m), 2.20 - 2.34 (2H, m), 2.35 - 2.40 (1H, m), 2.42 - 2.48 (2H, m), 2.53 - 2.56 (1H, m), 2.61 - 2.68 (2H, m), 2.73 (2H, t), 3.10 (2H, br d), 3.26 (2H, br d), 3.34 - 3.38 (2H, m), 3.70 (2H, t), 4.35 (2H, br s), 5.00 (1H, t), 5.96 (2H, s), 6.41 - 6.46 (1H, m), 6.46 - 6.50 (1H, m), 6.51 (1H, d), 6.84 - 6.90 (2H, m), 6.93 (1H, dd), 7.23 (1H, t), 7.47 (1H, s), 7.50 (1H, d), 7.56 (1H, d), 7.66 (1H, d), 7.92 (1H, d), 10.41 (1H, s), 14.20 (1H, s); m / z (ES+) [M+H]+= 857.6. EXAMPLE 15 Intermediate 15a: tert-Butyl 2-(5-bromo-3-methyl-pyrrolo[2,3-b]pyridin-1-yl)-7-azaspiro[3.5]nonane-7-carboxylatePrepared in an analogous manner to Intermediate 4a staring from 5-bromo-3-methyl-1H- pyrrolo[2,3-b]pyridine (3.60 g, 17.06 mmol), tert-butyl 2-hydroxy-7-azaspiro[3.5]nonane-7-carboxylate (6.177 g, 25.60 mmol) Purification by FSC (gradient: 0-50 % EtOAc in hexanes) gave the title compound (6.44 g, 87 %) as a yellow solid.1H NMR (DMSO-d6): δ 1.39 (9H, s), 1.56 - 1.66 (4H, m), 2.18 - 2.25 (5H, m), 2.35 - 2.41 (2H, m), 3.21 - 3.25 (2H, m), 3.31 - 3.35 (2H, m), 5.23 (1H, quin), 7.63 (1H, s), 8.14 (1H, d), 8.24 (1H, d); m / z (ES+) [M-tBu+2H]+= 378.4. Intermediate 15b: tert-Butyl 2-[5-(2,4-dioxohexahydropyrimidin-1-yl)-3-methyl-pyrrolo[2,3-b]pyridin-1-yl]-7- azaspiro[3.5]nonane-7-carboxylate Prepared in an analogous2b staring from Intermediate 15a (716 mg, 1.65 mmol). Purification by FSC (gradient: 0-100 % EtOAc in hexanes then 0-30% MeOH in EtOAc) gave the title compound (482 mg, 62.5 %) as a brown solid.1H NMR (DMSO-d6): δ 1.41 (9H, s), 1.59 - 1.69 (4H, m), 2.22 - 2.27 (2H, m), 2.27 (3H, s), 2.37 - 2.44 (2H, m), 2.76 (2H, t), 3.23 - 3.29 (2H, m), 3.33 - 3.37 (2H, m), 3.81 (2H, t), 5.28 (1H, quin), 7.62 (1H, s), 7.89 (1H, d), 8.18 (1H, d), 10.38 (1H, s); m / z (ES+) [M+H]+= 468.5. 1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2- fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione Prepared in anIntermediate 15b (45.8 mg, 0.10 mmol) and Intermediate 11g (63.3 mg, 0.10 mmol). Purification by RPC (0-100% MeCN in water with 0.1% NH4OH) gave the title compound (22.1 mg, 25.9%) as a white solid.1H NMR (DMSO-d6): δ 1.08 - 1.32 (3H, m), 1.56 - 1.82 (5H, m), 1.83 - 1.99 (4H, m), 2.07 - 2.16 (3H, m), 2.18 - 2.24 (2H, m), 2.26 (3H, s), 2.44 (4H, br d), 2.51 - 2.69 (3H, m), 2.74 (2H, t), 2.95 - 3.16 (3H, m), 3.25 (2H, br d), 3.33 - 3.38 (2H,m), 3.79 (2H, t), 4.33 (2H, br s), 5.17 - 5.34 (1H, m), 5.92 (2H, s), 6.39 - 6.54 (2H, m), 6.80 - 6.88 (2H, m), 6.92 (1H, br dd), 7.18 - 7.23 (1H, m), 7.41 - 7.50 (1H, m), 7.60 (1H, s), 7.85 - 7.91 (2H, m), 8.16 (1H, d), 10.36 (1H, s), 14.15 (1H, br s); m / z (ES+) [M+H]+= 854.6. EXAMPLE 16 Intermediate 16a: tert-Butyl 2-(5-bromopyrrolo[2,3-b]pyridin-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate Prepared in an4a staring from 7-tert-butoxycarbonyl-7- azaspiro[3.5]nonan-2-ol (500mg, 2.07 mmol) and 5-bromo-1H-pyrrolo[2,3-b]pyridine (408 mg, 2.07 mmol). Purification by FSC (gradient: 0 to 30% EtOAc in petroleum ether) gave the title compound (660 mg, 75%) as a white solid.1H NMR (DMSO-d6): δ 1.39 (9H, s), 1.58-1.66 (4H, m), 2.22-2.29 (2H, m), 2.37-2.44 (2H, m), 3.22-3.25 (2H, m), 3.32 (1H, s), 3.35 (1H, s), 5.22-5.31 (1H, m), 6.50 (1H, d), 7.86 (1H, d), 8.19 (1H, d), 8.28 (1H, d); m / z (ES+), [M+H]+= 420.3. Intermediate 16b: tert-butyl 2-[5-(2,4-dioxohexahydropyrimidin-1-yl)pyrrolo[2,3-b]pyridin-1-yl]-7-azaspiro[3.5]nonane-7- carboxylate Prepared in anstarting from Intermediate 16a (300 mg, 0.71 mmol). Purification by FSC (gradient 50 to 100% EtOAc in petroleum ether) gave the title compound (172 mg, 45.5 %) as a pale yellow solid.1H NMR (DMSO-d6): δ 1.41 (9H, s), 1.61-1.70 (4H, m), 2.26-2.36 (2H, m), 2.37-2.48 (2H, m), 2.76 (2H, t), 3.25-3.30 (2H, m), 3.35-3.38 (2H, m), 3.81 (2H, t), 5.27-5.39 (1H, m), 6.54 (1H, d), 7.85 (1H, d), 7.92 (1H, d), 8.21 (1H, d), 10.40 (1H, s). m / z (ES+) [M+H]+= 454.5. Intermediate 16c: 1-[1-(7-Azaspiro[3.5]nonan-2-yl)pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione Prepared in anstaring from Intermediate 16b (168 mg, 0.37 mmol). The solvent was removed under reduced pressure gave the title compound (246 mg, 94%) as a yellow solid in the form of a 2 TsOH salt . m / z (ES+) [M+H]+= 353.4.1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2- fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione Prepared inIntermediate 13d (166 mg, 0.33 mmol) and Intermediate 16c (230 mg, 0.33 mmol). Purification by RPC (gradient: 0-50% CH3CN in water with 0.1% formic acid) gave the title compound (43.0 mg, 14.88 %) as a grey solid.1H NMR (DMSO- d6): δ 1.21-1.33 (2H, m), 1.62-1.85 (7H, m), 1.90-2.00 (2H, m), 2.09-2.17 (2H, m), 2.22-2.31 (4H, m), 2.32- 2.48 (6H, m), 2.60-2.68 (2H, m), 2.76 (2H, t), 3.10 (2H, d), 3.26 (2H, d), 3.36 (2H, d), 3.81 (2H, t), 4.35 (2H, s), 5.27-5.35 (1H, m), 5.95 (2H, s), 6.42-6.50 (2H, m), 6.53 (1H, d), 6.84-6.96 (3H, m), 7.21-7.25 (1H, m), 7.47 (1H, s), 7.84 (1H, d), 7.90-7.92 (2H, m), 8.17-8.23 (2H, m), 10.41 (1H, s). m / z (ES+) [M+H]+= 840.5. EXAMPLE 17 Intermediate 17a: 1-(3-Chloro-2,6-difluorophenyl)-4-(dimethoxymethyl)piperidine A vial was charged withmmol), 1-chloro-2,4-difluoro-3-iodobenzene (1 g, 3.64 mmol), 4-(dimethoxymethyl)piperidine (0.696 g, 4.37 mmol), Pd2(dba)3(0.167 g, 0.18 mmol), Cs2CO3(2.374 g, 7.29 mmol) and 1,4-dioxane (5 mL). The resulting mixture was stirred at 100 °C for 12 h under nitrogen. The reaction mixture was diluted with EtOAc (50 mL), and washed sequentially with saturated NH4Cl (50 mL) and saturated brine (50 mL). The organic layer was dried with Na2SO4, filtered and evaporated. Purification by FSC (gradient: 0 to 40% EtOAc in petroleum ether) gave the title compound (0.700 g, 62.8 %) as a pale yellow solid.1H NMR (CDCl3) δ 1.39 – 1.56 (2H, m), 1.69 – 1.82 (3H, m), 3.01 – 3.13 (2H, m), 3.23 – 3.32 (2H, m), 3.37 (6H, s), 4.10 (1H, d), 6.72 – 6.82 (1H, m), 6.90 – 7.01 (1H, m); m / z (ES+) [M+H]+= 306.1. Intermediate 17b: Benzyl 8-[3-[4-(dimethoxymethyl)-1-piperidyl]-2,4-difluoro-phenyl]-3,8-diazabicyclo[3.2.1]octane-3- carboxylatePrepared in an analogous manner to Intermediate 7b staring from Intermediate 17a (650 mg, 2.13 mmol). Purification by FSC (gradient 0 to 10% MeOH in DCM) gave the title compound (530 mg, 48.4 %) as a yellow solid.1H NMR (DMSO-d6) δ 1.23 – 1.43 (2H, m), 1.55 – 1.74 (5H, m), 1.78 – 1.92 (2H, m), 2.98 (2H, t), 3.07 – 3.23 (4H, m), 3.28 (6H, s), 3.73 (2H, d), 3.98 (2H, s), 4.10 (1H, d), 5.10 (2H, d), 6.59 – 6.71 (1H, m), 6.78 – 6.88 (1H, m), 7.29 – 7.46 (5H, m); m / z (ES+) [M+H]+= 516. Intermediate 17c: 8-[3-[4-(Dimethoxymethyl)-1-piperidyl]-2,4-difluoro-phenyl]-3,8-...

Claims

WHAT IS CLAIMED IS:

1. A compound of Formula (A), or pharmaceutically acceptable salt thereof: , wherein:E is: ; R1is hydrogen,; R2is hydrogen, halogen, (C1-C6)or ; with the provisos:(i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is: (ii) when R2is hydrogen,(C1-C6)alkoxy, then R1is ;R11is hydrogen or -(C1-C6)alkyl-O-P(=O)-(OH)2; X1is CR3or N; R3is hydrogen, halogen, or (C1-C6)alkyl; X2is CR4or N; R4is hydrogen, halogen, or (C1-C6)alkyl; R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl; R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl; R6is hydrogen, (C1-C6)alkyl, or cyano; X3is -CH2CH2- or -CH2-O-CH2-; Or X3is absent; L is G1-G2-G3-G4-, wherein G1is attached to W; G1is (C1-C6)alkylenyl; (C3-C6)cycloalkylenyl; -O-CH2-CH2-; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, cyano, or hydroxyl; or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1- C6)alkyl, (C1-C6)alkoxy, or cyano; G2is (C1-C6)alkylenyl, -C(=O)-, 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three fluoro, or a direct bond; G3is -C(=O)-; -C(=O)-CH2CH2-; (C1-C6)alkylenyl; tetrahydronaphthalenenyl; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy or cyano; 7- to 11-membered heterocycloalkyl-C(=O)-, or 7- to 11- membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; G4is (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl; 4- to 6-membered heterocycloalkylenyl; or a direct bond; W is -C≡C- or a direct bond; R7is hydrogen; halogen; (C1-C6)alkyl optionally substituted with one, two, or three halogen; cyano; or (C3-C6)cycloalkyl; R8is hydrogen; halogen; (C1-C6)alkyl optionally substituted with one, two, or three halogen; cyano; or (C3-C6)cycloalkyl;R9is hydrogen; halogen; (C1-C6)alkyl optionally substituted with one, two, or three halogen; cyano; or (C3-C6)cycloalkyl; R10is hydrogen; halogen; (C1-C6)alkyl optionally substituted with one, two, or three halogen; cyano; or (C3-C6)cycloalkyl; Rais hydrogen or halogen; Rbis hydrogen or halogen; and Rcis hydrogen or methyl.

2. A compound of Formula (I), or pharmaceutically acceptable salt thereof: , wherein:E is: ; R1is hydrogen,; R2is hydrogen, halogen, (C1-C6)or ; with the provisos:(i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is:nd (ii) when R2is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R1is ; R11is hydrogen or -(C1-C6)alkyl-X1is CR3or N; R3is hydrogen, halogen, or (C1-C6)alkyl; X2is CR4or N; R4is hydrogen, halogen, or (C1-C6)alkyl; R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl; R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl; R6is hydrogen, (C1-C6)alkyl, or cyano; X3is -CH2CH2- or -CH2-O-CH2-; Or X3is absent; L is -G1-G2-G3-G4-, wherein G1is attached to W; G1is (C1-C6)alkyenyl; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; G2is (C1-C6)alkylenyl or a direct bond; G3is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy or cyano; or 7- to 11- membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; G4is (C1-C6)alkylenyl or a direct bond; W is -C≡C- or a direct bond; R7is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl;R8is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; R9is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; and R10is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl.

3. A compound of Formula (I), or pharmaceutically acceptable salt thereof: , wherein:E is: ; R1is hydrogen,; R2is hydrogen, halogen, (C1-C6) or ; with the provisos:(i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is:nd (ii) when R2is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R1is: ; R11is hydrogen or -(C1-C6)alkyl-X1is CR3or N; R3is hydrogen, halogen, or (C1-C6)alkyl; X2is CR4or N; R4is hydrogen, halogen, or (C1-C6)alkyl; R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl; R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl; R6is hydrogen, (C1-C6)alkyl, or cyano; X3is -CH2CH2- or -CH2-O-CH2-; or X3is absent; L is -G1-G2-G3-G4-, wherein G1is attached to W; G1is (C1-C6)alkyenyl; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; G2is (C1-C6)alkylenyl or a direct bond; G3is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; 7- to 11- membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; or 5- to 10-membered heteroarylenyl; G4is (C1-C6)alkylenyl, (C3-C6)cycloalkylenyl, or a direct bond; W is -C≡C- or a direct bond; R7is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl;R8is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; R9is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl; and R10is hydrogen, halogen, (C1-C6)alkyl optionally substituted with one, two, or three halogen, cyano, or (C3-C6)cycloalkyl.

4. The compound, or pharmaceutically acceptable salt thereof, according to claim 2 or 3 having Formula (II): .

5. The compound, or pharmaceutically acceptable salt thereof, according to claim 2 or 3 having Formula (III): .

6. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein R5ais hydrogen.

7. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein R5ais (C1-C6)alkyl optionally substituted with one, two, or three substituents independently selected from halogen or cyano.

8. The compound, or pharmaceutically acceptable salt thereof, according to claim 7, wherein R5ais methyl.

9. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein R5ais (C3-C6)cycloalkyl.

10. The compound, or pharmaceutically acceptable salt thereof, according to claim 9, wherein R5ais cyclopropyl.

11. The compound, or pharmaceutically acceptable salt thereof, according to according to any one of claims 1-5, wherein R5ais 4- to 6-membered heterocycloalkyl optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl.

12. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein R5ais cyano.

13. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein: R1is: R2is hydrogen, halogen, (C1-C6)14. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein R2is hydrogen, halogen, or (C1-C6)alkyl.

15. The compound, or pharmaceutically acceptable salt thereof, according to to any one of claims 1-5, wherein R2is hydrogen, fluoro, or methyl.

16. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein R11is hydrogen.

17. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein: R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy; andR2is: .

18. The compound, or pharmaceutically acceptable salt thereof, according to claim 17, wherein R1is hydrogen, halogen, or (C1-C6)alkyl.

19. The compound, or pharmaceutically acceptable salt thereof, according to claim 18, wherein R1is hydrogen, fluoro, or methyl.

20. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 17-19, wherein R11is hydrogen.

21. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein X1is CR3.

22. The compound, or pharmaceutically acceptable salt thereof, according to claim 21, wherein R3is hydrogen.

23. The compound, or pharmaceutically acceptable salt thereof, according to claim 21, wherein R3is halogen.

24. The compound, or pharmaceutically acceptable salt thereof, according to claim 21, wherein R3is (C1-C6)alkyl.

25. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein X1is N.

26. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein X2is CR4.

27. The compound, or pharmaceutically acceptable salt thereof, according to claim 26, wherein R4is hydrogen.

28. The compound, or pharmaceutically acceptable salt thereof, according to claim 26, wherein R4is halogen.

29. The compound, or pharmaceutically acceptable salt thereof, according to claim 26, wherein R4is (C1-C6)alkyl.

30. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein X2is N.

31. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein E is: ,32. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-5, wherein E is: .

33. The or to any one of claims 1-5, wherein E is: .

34. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-33, wherein G1is (C3-C6)cycloalkylenyl; or 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, cyano, or hydroxyl.

35. The compound, or pharmaceutically acceptable salt thereof, according to claim 34, wherein: G1is: ; each R12is independently halogen,C6)alkoxy, cyano, or hydroxyl; n is 0, 1, 2, or 3; and the bond marked with an "*" is attached to G2.

36. The compound, or pharmaceutically acceptable salt thereof, according to claim 35, wherein each R12is independently fluoro, methyl, methoxy, cyano, or -CHF2; and n is 0, 1, or 2.

37. The compound, or pharmaceutically acceptable salt thereof, according claim 35, wherein: G1is: and38. The compound, or pharmaceutically acceptable salt thereof, according to claim 34, wherein: G1is: ;each R12is independently halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; and the bond marked with an “*” is attached to G2.

39. The compound, or pharmaceutically acceptable salt thereof, according claim 38, wherein: G1is:

44. The compound, or pharmaceutically acceptable salt thereof, according claim 34, wherein: G1is:

41. The compound, or pharmaceutically acceptable salt thereof, according to claim 1, wherein G1is cyclohexylenyl.

42. The compound, or pharmaceutically acceptable salt thereof, according claim 41, wherein: G1is: ; andan to 43. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-33, wherein G1is 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano.

44. The compound, or pharmaceutically acceptable salt thereof, according to claim 43, wherein: G1is: ; each R13is independentlyC6)alkyl, (C1-C6)alkoxy, or cyano; o is 0, 1, 2, or 3; p, q, r, and s are independently 1 or 2; the bond marked with an "*" is attached to G2.

45. The compound, or pharmaceutically acceptable salt thereof, according to claim 44, wherein: p and q are 1; r is 1 or 2; s is 1 or 2; and R13is halogen.

46. The compound, or pharmaceutically acceptable salt thereof, according to claim 45, wherein R13is fluoro and o is 0, 1, or 2.

47. The compound, or pharmaceutically acceptable salt thereof, according claim 44, wherein G1is: the bond marked with an "*" is48. The compound, or pharmaceutically acceptable salt thereof, according claim 43, wherein: G1is: ; a is 0 or 1;b is 0 or 1; and the bond marked with an "*" is attached to G2.

49. The compound, or pharmaceutically acceptable salt thereof, according claim 48, wherein G1is:nd the bond marked with an "*" is attached to G2.

50. The compound, or pharmaceutically acceptable salt thereof, according claim 43, wherein G1is: the bond marked51. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-50, wherein G2is a direct bond.

52. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1 or 6- 50, wherein G2is a C(=O).

53. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-50, wherein G2is (C1-C6)alkylenyl.

54. The compound, or pharmaceutically acceptable salt thereof, according to claim 53, wherein G2is - CH2-.

55. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-54, wherein G3is 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano.

56. The compound, or pharmaceutically acceptable salt thereof, according to claim 55, wherein: G3is: ;t is 0, 1, 2, or 3; and the bond marked with an "*" is attached to G4.

57. The compound, or pharmaceutically acceptable salt thereof, according to claim 56, wherein R14is fluoro or methyl and t is 0 or 1.

58. The compound, or pharmaceutically acceptable salt thereof, according claim 56, wherein G3is:the bond marked with an "*" is attached to G4.

59. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-54, wherein G3is 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano.

60. The compound, or pharmaceutically acceptable salt thereof, according to claim 1, wherein G3is the bond61. The compound, or pharmaceutically acceptable salt thereof, according to claim 59, wherein G3is: the bond marked with an "*" is62. The compound, or pharmaceutically acceptable salt thereof, according to claim 59, wherein G3is:the bond marked with an "*" is attached to G4.

63. The compound, or pharmaceutically acceptable salt thereof, according to claim 59, wherein: G3is: ; each R15is independentlyC6)alkyl, (C1-C6)alkoxy, or cyano; u is 0, 1, 2, or 3; v, w, x, and y are independently 1, 2, or 3; and the bond marked with an "*" is attached to G4.

64. The compound, or pharmaceutically acceptable salt thereof, according to claim 63, wherein v, w, x, and y are independently 1 or 2.

65. The compound, or pharmaceutically acceptable salt thereof, according to claim 63, wherein R15is fluoro.

66. The compound, or pharmaceutically acceptable salt thereof, according to claim 59, wherein: G3is: ; xaand yaare independently 1 orthe bond marked with an "*" is attached to G4.

67. The compound, or pharmaceutically acceptable salt thereof, according to claim 59, wherein G3is: ,, the bond marked with an “*” is attached to G4.

68. The compound, or pharmaceutically acceptable salt thereof, according to claim 1, wherein G3is the bond marked with an “*”69. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-68, wherein G4is (C1-C6)alkylenyl.

70. The compound, or pharmaceutically acceptable salt thereof, according to claim 69, wherein G4is - CH2- or -CH2CH2-.

71. The compound, or pharmaceutically acceptable salt thereof, according to claim 1, wherein G4is (C3-C6)cycloalkylenyl.

72. The compound, or pharmaceutically acceptable salt thereof, according to claim 71, wherein G4is : the bond marked with73. The compound, or pharmaceutically acceptable salt thereof, according to claim 71, wherein G4is: the bond marked with an74. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-68, wherein G4is a direct bond.

75. The compound, or pharmaceutically acceptable salt thereof, of any one of claims 1-33, wherein L is: , ,, , , , , the bond marked with an is attached to E.

76. The compound, or pharmaceutically acceptable salt thereof, of any one of claims 1-33, wherein L is: ;the bond marked with an "*" is attached to E.

77. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-76, wherein W is -C≡C- .

78. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-76, wherein W is a direct bond.

79. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-78, wherein R7, R8, R9, and R10are H.

80. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-78, wherein R7is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen.

81. The compound, or pharmaceutically acceptable salt thereof, according to claim 80, wherein R7is halogen or (C1-C6)alkyl.

82. The compound, or pharmaceutically acceptable salt thereof, according to claim 81, wherein R7is fluoro or methyl.

83. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 80-82, wherein R8, R9, and R10are hydrogen.

84. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-78, wherein R8is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen.

85. The compound, or pharmaceutically acceptable salt thereof, according to claim 84, wherein R8is halogen or (C1-C6)alkyl.

86. The compound, or pharmaceutically acceptable salt thereof, according to claim 85, wherein R8is fluoro or methyl.

87. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 84-86, wherein R7, R9, and R10are hydrogen.

88. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-78, wherein R9is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen.

89. The compound, or pharmaceutically acceptable salt thereof, according to claim 88, wherein R9is halogen.

90. The compound, or pharmaceutically acceptable salt thereof, according to claim 89, wherein R9is fluoro.

91. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 88-90, wherein R7, R8, and R10are hydrogen.

92. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-78, wherein R10is halogen, (C1-C6)alkyl, cyano, or (C3-C6)cycloalkyl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three halogen.

93. The compound, or pharmaceutically acceptable salt thereof, according to claim 92, wherein R10is halogen.

94. The compound, or pharmaceutically acceptable salt thereof, according to claim 93, wherein R10is fluoro.

95. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 92-94, wherein R7, R9, and R9are hydrogen.

96. The compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-78, wherein R10is cyano.

97. The compound, or pharmaceutically acceptable salt thereof, according to claim 96, wherein R10is cyano; and R7, R8, and R9are hydrogen.

98. A compound of Formula (V), or pharmaceutically acceptable salt thereof,V), wherein: each R12is fluoro or hydroxyl; n is 0, 1, 2, or 3; E is: ; R1is hydrogen,; R2is hydrogen, halogen, (C1-C6)or ; with the provisos:(i) when R1is hydrogen, halogen, (C1-C6)alkyl, or (C1-C6)alkoxy, then R2is: (ii) when R2is hydrogen, halogen,C6)alkoxy, then R1is: ; R11is hydrogen or -(C1-C6)alkyl-O-PX1is CR3or N; R3is hydrogen, halogen, or (C1-C6)alkyl; X2is CR4or N; R4is hydrogen, halogen, or (C1-C6)alkyl; R5ais hydrogen, halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, 4- to 6-membered heterocycloalkyl, cyano, aryl, or 5- or 6-membered heteroaryl, wherein (C1-C6)alkyl is optionally substituted with one, two, or three substituents independently selected from halogen or cyano; and 4- to 6-membered heterocycloalkyl, aryl, or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, or (C1-C6)alkyl; R5bis hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl; R6is hydrogen, (C1-C6)alkyl, or cyano; X3is -CH2CH2- or absent; G3is tetrahydronaphthalene; 4- to 6-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, or cyano; 7- to 11-membered heterocycloalkyl-C(=O)-, or 7- to 11-membered heterocycloalkylenyl optionally substituted with one, two, or three substituents independently selected from halogen, (C1-C6)alkyl, (C1- C6)alkoxy, or cyano; G4is absent or cyclobutylenyl; R7, R8, R9, and R10are independently hydrogen, fluoro, methyl, or cyano; Rais hydrogen, chloro, methyl, or fluoro; Rbis hydrogen, chloro, methyl, or fluoro, and Rcis hydrogen or methyl.

99. The compound, or pharmaceutically acceptable salt thereof, according to claim 98, wherein: G3is: ,100. The compound, or pharmaceutically acceptable salt thereof, according to claim 98, wherein G3is:.

101. The compound, or pharmaceutically acceptable salt thereof, according to claim 98, wherein G3is: ,102. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, selected from any one or more of the compounds: 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]nonan-2-yl]methyl]-4-piperidyl]-3-methyl-indol-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]prop-2-ynyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-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]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-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]nonan-2-yl]-3-methyl-indol-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]indol-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]undecan-9-yl]-3-methyl-indol-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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin- 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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin- 5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[7-[[1-[3-[3-[3-Amino-6-(2-hydroxyphenyl)490yridine490e-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-5-methyl-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- cyclopropyl-pyrrolo[2,3-b]490yridine-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[7-[[1-[3-[3-[3-Amino-6-(2-hydroxyphenyl)490yridine490e-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-5-methyl-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- cyclopropyl-pyrrolo[2,3-b]490yridine-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-methyl-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]indol-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-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-6-fluoro-indol-5- yl]hexahydropyrimidine-2,4-dione1-[1-[7-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8- yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-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-difluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-4-piperidyl]-1-methyl-indol-6-yl]hexahydropyrimidine-2,4- dione; 1-[1-[7-[[1-[5-[4-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluoro-phenyl]- 4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione; 1-[1-[7-[[1-[5-[4-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluoro-phenyl]- 4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-indol-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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-4-fluoro-indol-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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-4-methyl-indol-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-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]methyl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-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-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-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-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-4-piperidyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-indol-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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin- 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]nonan-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]morpholin-2-yl]methyl]-3-methyl- pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-indol-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-fluoro-phenyl]-4-piperidyl]methyl]piperazin-1-yl]ethyl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-3-methyl-pyrrolo[2,3- b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[3-[[1-[5-[4-[3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]-2-fluoro-phenyl]- 4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-2,7-diazaspiro[3.5]nonane-2-carbonyl]-2-methyl- phenyl]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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin- 5-yl]-2,6-dioxo-hexahydropyrimidin-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-fluoro-phenyl]-4-piperidyl]methyl]-2-azaspiro[3.5]nonan-7-yl]-3-methyl-pyrrolo[2,3-b]pyridin-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]undecan-9-yl]-3-methyl- pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[(1r,3r)-3-[8-[[1-[5-[3-[3-Amino-6-(2-hydroxyphenyl)493yridine493e-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]493yridine-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-fluoro-phenyl]morpholin-2-yl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-7-azaspiro[3.5]nonan-2-yl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-pyrrolo[2,3- b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-2-azaspiro[4.5]decan-8-yl]-3-ethyl- pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-ethyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-7-azaspiro[3.5]nonan-2-yl]methyl]morpholin-2- yl]methyl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-6,8-dihydro-5H-imidazo[1,2-a]pyrazin-2-yl]-3-methyl- pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-7-azaspiro[3.5]nonan-2-yl]methyl]morpholin-2- yl]methyl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5- yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 1) [*absolute configuration not yet 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]octan-8-yl]-2-fluoro-phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5- yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-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]octan-8-yl]-2-fluoro-phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5- yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]- 3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]methyl]-7-azaspiro[3.5]nonan-2- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 2) [*absolute configuration not yet 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]octan-8-yl]-2-fluoro-phenyl]-3,3a,4,5,6,6a-hexahydro-1H- cyclopenta[c]pyrrol-5-yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-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]octan-8-yl]-2-fluoro-phenyl]-3,3a,4,5,6,6a-hexahydro-1H- cyclopenta[c]pyrrol-5-yl]methyl]-7-azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4- piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3-yl]indol-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 1) [*absolute configuration not yet 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan- 3-yl]indol-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan- 3-yl]indol-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]indol-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 2) [*absolute configuration not yet 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan- 3-yl]indol-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]indol-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8- azaspiro[4.5]decan-3-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 2) [*absolute configuration not yet 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan- 3-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan- 3-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-6-fluoro-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 1) [*absolute configuration not yet 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan- 3-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan- 3-yl]pyrrolo[2,3-b]pyridin-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-dioxohexahydropyrimidin-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridin-1-yl]-3-azaspiro[5.5]undecan-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-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-ethyl-pyrrolo[2,3- b]pyridin-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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 2) [*absolute configuration not yet 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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3- azaspiro[5.5]undecan-9-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3- azaspiro[5.5]undecan-9-yl]pyrrolo[2,3-b]pyridin-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-dioxohexahydropyrimidin-1-yl)-3-methyl-pyrrolo[2,3-b]pyridin-1-yl]-3-azaspiro[5.5]undecan-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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 1) [*absolute configuration not yet 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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-3,3-difluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan- 9-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-4-methyl-indol-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-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-4-fluoro-indol-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-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-6-fluoro-indol-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-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-3-ethyl-pyrrolo[2,3- b]pyridin-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-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-6,10-dioxa-2- azaspiro[4.5]decan-8-yl]-3-ethyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-ethyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4- piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan-3-yl]pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione (ISOMER 2) [*absolute configuration not yet 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan- 3-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan- 3-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan- 3-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 1) [*absolute configuration not yet 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan- 3-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-8-azaspiro[4.5]decan- 3-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 1) [*absolute configuration not yet 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione (ISOMER 2) [*absolute configuration not yet 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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1-oxa-9-azaspiro[5.5]undecan-3- yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]indol-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-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-methyl-indol-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-fluoro-phenyl]piperazin-1-yl]methyl]spiro[5.5]undecan-3-yl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9- azaspiro[5.5]undecan-3-yl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9- azaspiro[5.5]undecan-3-yl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-methyl-pyrrolo[2,3- b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]piperazin-1-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridin-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-dioxohexahydropyrimidin-1-yl)-3-ethyl-pyrrolo[2,3-b]pyridin-1-yl]-3-azaspiro[5.5]undecan-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-dioxohexahydropyrimidin-1-yl)pyrrolo[2,3-b]pyridin-1-yl]-7-azaspiro[3.5]nonan-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-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridin-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]octan-8-yl]-2-fluoro-phenyl]-3-azabicyclo[3.1.0]hexan-6-yl]methyl]-3- azaspiro[5.5]undecan-9-yl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-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]octan-8-yl]-2-fluoro-phenyl]-3-azabicyclo[3.1.0]hexan-6-yl]methyl]-7- azaspiro[3.5]nonan-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-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]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octan-8- yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]morpholin-2-yl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3- methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-6-fluoro-3-methyl-indol-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-chloro-phenyl]-4-piperidyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-3-methyl-indol-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-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]pyrrolo[1,2-a]pyrimidin-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-fluoro-phenyl]piperazin-1-yl]methyl]tetralin-2-yl]indol-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-fluoro-phenyl]piperazin-1-yl]methyl]tetralin-2-yl]indol-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-fluoro-phenyl]piperazin-1-yl]methyl]tetralin-2-yl]indol-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-fluoro-phenyl]piperazin-1-yl]methyl]tetralin-2-yl]indol-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-fluoro-phenyl]cyclohexyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]cyclohexyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-11,11-difluoro-1,5-dioxa-9- azaspiro[5.5]undecan-3-yl]indol-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]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]cyclohexyl]-3-methyl-pyrrolo[2,3-b]pyridin-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]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3,8-diazabicyclo[3.2.1]octan-3- yl]cyclohexyl]-3-methyl-pyrrolo[2,3-b]pyridin-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]octan-8-yl]-2-fluoro-phenyl]-4-fluoro-4-piperidyl]methyl]-3,8- diazabicyclo[3.2.1]octan-3-yl]cyclobutyl]-3-methyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4- dione; 1-[1-[3-[[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]-3-azaspiro[5.5]undecan-9-yl]-3- ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[3-[[1-[5-[3-[3-Amino-6-(3,5-difluoro-2-hydroxy-phenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- ethyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[3-[[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]-3-azaspiro[5.5]undecan-9-yl]-3- ethyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-6,10-dioxa-2-azaspiro[4.5]decan-8- yl]-3-methyl-indol-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]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]piperidine-4-carbonyl]-7-azaspiro[3.5]nonan-2-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-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]undecan-9-yl]-3-ethyl-pyrrolo[2,3-b]pyridin-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]octan-8- yl]phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-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-dioxohexahydropyrimidin-1-yl)pyrrolo[2,3-b]pyridin-1-yl]-1,5-dioxa-9- azaspiro[5.5]undecan-9-yl]methyl]-1-piperidyl]benzonitrile; 1-[1-[3-[[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]-3-azaspiro[5.5]undecan-9-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-4-methyl-indol-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-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]pyrrolo[2,3-b]pyridin-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]undecan-3- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-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]undecan-3- yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[9-[[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]-1,5-dioxa-9-azaspiro[5.5]undecan-3- yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[9-[[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]-1,5-dioxa-9-azaspiro[5.5]undecan-3- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[9-[[1-[5-[3-[3-Amino-6-(3,5-difluoro-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]undecan-3- yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[9-[[1-[5-[3-[3-Amino-6-(3,5-difluoro-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]undecan-3- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[3-[[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]-3-azaspiro[5.5]undecan-9-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[3-[[1-[5-[3-[3-Amino-6-(3,5-difluoro-2-hydroxy-phenyl)pyridazin-4-yl]-3,8- diazabicyclo[3.2.1]octan-8-yl]-2-fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3- cyclopropyl-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]octan-8- yl]-2-fluoro-phenoxy]ethyl]-3-azaspiro[5.5]undecan-9-yl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenoxy]ethyl]-7-azaspiro[3.5]nonan-2-yl]-3-methyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenoxy]ethyl]-4-fluoro-4-piperidyl]methyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridin- 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-fluoro-phenoxy]ethyl]-4-fluoro-4-piperidyl]methyl]pyrrolidin-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-fluoro-phenoxy]ethyl]-4-fluoro-4-piperidyl]methyl]pyrrolidin-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]octan-8- yl]-2-fluoro-phenoxy]ethyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]indol-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]octan-8-yl]- 2-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-3-cyclopropyl-indol-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-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-3-ethyl-indol-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-fluoro-phenyl]-2,3,3a,4,6,6a-hexahydrofuro[2,3-c]pyrrol-2-yl]methyl]-7- azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-2,3,3a,4,6,6a-hexahydrofuro[2,3-c]pyrrol-2-yl]methyl]-7- azaspiro[3.5]nonan-2-yl]pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[9-[[1-[5-[3-[3-Amino-6-(3-chloro-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]undecan-3- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[9-[[1-[5-[3-[3-Amino-6-(2-hydroxy-3-methyl-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]undecan-3- yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-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]decan-8- yl]-3-methyl-indol-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]decan-8- yl]-3-methyl-indol-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-Amino-6-(3,5-difluoro-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]decan-8- yl]-3-methyl-indol-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- fluoro-phenyl]-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl-pyrrolo[2,3-b]pyridin-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- fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-3-cyclopropyl-pyrrolo[2,3- b]pyridin-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-fluoro-phenyl]-4-hydroxy-4-piperidyl]methyl]-3-azaspiro[5.5]undecan-9-yl]-3-cyclopropyl- pyrrolo[2,3-b]pyridin-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]decan-8- yl]indol-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]decan-8- yl]indol-5-yl]hexahydropyrimidine-2,4-dione; 1-[1-[(5s,8s)-2-[[1-[5-[3-[3-Amino-6-(3,5-difluoro-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]decan-8- yl]indol-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-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-6-methyl-indol-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]pyridin-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-fluoro-phenoxy]ethyl]piperazin-1-yl]ethyl]-4-piperidyl]-3-methyl- pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-4-fluoro-indol-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-fluoro-phenyl]-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]indol-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-fluoro-phenyl]-4-hydroxy-4-piperidyl]methyl]-1,5-dioxa-9-azaspiro[5.5]undecan-3-yl]-3- cyclopropyl-pyrrolo[2,3-b]pyridin-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-fluoro-phenyl]methyl]piperazine-1-carbonyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridin-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]pyridin-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-fluoro-phenyl]methyl]piperazin-1-yl]-3-oxo-propyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridin-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-oxo-propyl]-4-piperidyl]-3-methyl-pyrrolo[2,3-b]pyridin-5- yl]hexahydropyrimidine-2,4-dione; or pharmaceutically acceptable salts thereof.

103. A pharmaceutical composition comprising the compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-102, and a pharmaceutically acceptable excipient.

104. A method of degrading SMARCA2 protein in a human, comprising administering to a human in need thereof an effective amount of the compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-102, or the composition of claim 103.

105. A method of reducing the level of SMARCA2 activity in a human, comprising administering to a human in need thereof an effective amount of the compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-102, or the composition of claim 103.

106. A method of treating cancer in a human, comprising administering to a human in need thereof an effective amount of the compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-102, or the composition of claim 103.

107. The method of claim 106, wherein the cancer is a SMARCA2-sensitive cancer.

108. The method of claim 106, wherein the cancer is a SMARCA2-mutated cancer.

109. The method of any one of claims 106-108, wherein the cancer is a solid tumor.

110. The method of any one of claims 106-108, wherein the cancer is lung, liver, colon, skin, bladder, cervical or ovarian cancer.

111. A compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-102, or the composition of claim 103 for use in degrading SMARCA2 protein in a human.

112. A compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-102, or the composition of claim 103 for use in reducing the level of SMARCA2 activity in a human.

113. A compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1-102, or the composition of claim 103 for use in treating cancer in a human.

114. The compound for use of claim 113, wherein the cancer is a SMARCA2-sensitive cancer.

115. The compound for use of claim 113, wherein the cancer is a SMARCA2-mutated cancer.

116. The compound for use of any one of claims 113-115, wherein the cancer is a solid tumor.

117. The compound for use of any one of claims 113-115, wherein the cancer is lung, liver, colon, skin, bladder, cervical or ovarian cancer.

118. Use of a compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1- 102, or the composition of claim 103 in the manufacture of a medicament for degrading SMARCA2 protein in a human.

119. Use of a compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1- 102, or the composition of claim 103 in the manufacture of a medicament for reducing the level of SMARCA2 activity in a human.

120. Use of a compound, or pharmaceutically acceptable salt thereof, according to any one of claims 1- 102, or the composition of claim 103 in the manufacture of a medicament for treating cancer in a human.

121. The compound, or pharmaceutically acceptable salt thereof, for use of claim 120, wherein the cancer is a SMARCA2-sensitive cancer.

122. The compound, or pharmaceutically acceptable salt thereof, for use of claim 120, wherein the cancer is a SMARCA2-mutated cancer.

123. The compound, or pharmaceutically acceptable salt thereof, for use of any one of claims 120-122, wherein the cancer is a solid tumor.

124. The compound, or pharmaceutically acceptable salt thereof, for use of any one of claims 120-122, wherein the cancer is lung, liver, colon, skin, bladder, cervical or ovarian cancer.

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