# US 2023/0265083 A1 · Heterocycle CDK Inhibitors And Their Use Thereof

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- Number: US 2023/0265083 A1
- Document ID: US20230265083A1
- Status: Published application
- Kind: A1
- Application number: 18/041,223
- Filed: 2021-08-10
- Published: 2023-08-24
- Earliest claimed: 2020-08-10
- Assignees: Prelude Therapeutics Incorporated
- Applicants: Prelude Therapeutics Incorporated
- Inventors: Liang Lu; Andrew P. Combs; Chaofeng Dai; Raul A. Leal
- Web page: https://patentgrep.com/patent/US20230265083A1

## CPC

- A61P 35/00: Antineoplastic agents
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The disclosure is directed to, in part, to heterocycle CDK inhibitors, pharmaceutical compositions comprising the same, as well as methods of their use and preparation.

## Claims

### Claim 1

A compound, or a pharmaceutically acceptable salt or solvate thereof, having a formula of Formula (I), Formula (II-a), Formula (II-b), Formula (X), or Formula (XI):
wherein
X is O, S, or CR7R8;
Y is O, S, CR9R10, or NR4;
m is 1-3;
R2 and R3 is selected from H, D, halogen, oxo, CN, C1-3 alkyl, C1-3 alkoxy, C2-4 alkenyl, C2-4 alkynyl, C1-3 haloalkyl, and C1-3 haloalkoxy;
R4 is selected from H, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, and —C(O) C1-3 alkyl;
R1 is selected from C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-14 membered heteroaryl)-C1-4 alkyl, and (4-14 membered heterocycloalkyl)-C1-4 alkyl;
wherein R1 is optionally substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected Rb substituents;
each R5, R6, R7, R8, R9, and R10 are each independently selected from H, D, halo, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-11) aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-14 membered heteroaryl)-C1-4 alkyl, (4-14 membered heterocycloalkyl)-C1-4 alkyl, CN, NO2, ORa1, SRa1, NHORa1, C(O)Ra1, C(O)NRa1Ra1, C(O)ORa1, OC(O)Ra1, OC(O)NRa1Ra1, NHRa1, NRa1Ra1, NRa1C(O)Ra1, NRa1C(O)ORa1, NRa1C(O)NRa1Ra1, C(═NRa1)Ra1, C(═NRa1)NRa1Ra1, NRa1C(═NRa1)NRa1Ra1, NRa1C(═NOH)NRa1Ra1, NRa1C(═NCN)NRa1Ra1, NRa1S(O)Ra1, NRa1S(O)2Ra1, NRa1S(O)2NRa1Ra1, S(O)Ra1, NRa1S(O)(NRa1)Ra1, S(O)NRa1Ra1, S(O)2Ra1, SF5, P(O)Ra1Ra1, P(O)(ORa1)(ORa1), B(ORa1)2, and S(O)2NRa1Ra1;
wherein when R2, R3, R4, R5, R6, R7, R8, R9, or R10 is C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-11) aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-11) cycloalkyl-C1-4alkyl, (5-14 membered heteroaryl)-C1-4 alkyl, or (4-14 membered heterocycloalkyl)-C1-4 alkyl, then R2, R3, R4, R5, R6, R7, R8, R9, and R10 is optionally substituted with 1, 2, 3, 4 or 5 independently selected Rb substituents;
optionally R5 and R6 together with the carbon atom to which they are both attached form a C4-7 spirocyclic ring optionally substituted with 1, 2, 3, 4 or 5 independently selected Rb substituents;
optionally R4 and R5 together with the atoms to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl ring optionally substituted with 1, 2, 3, 4 or 5 independently selected Rb substituents;
optionally R4 and R6 together with the atoms to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl ring optionally substituted with 1, 2, 3, 4 or 5 independently selected Rb substituents;
optionally R7 and R8 together with the carbon atom to which they are both attached form a C3-C7 spirocyclic ring optionally substituted with 1, 2, 3, 4 or 5 independently selected Rb substituents,
optionally one of R5 and R6 and one of R7 and R8 together with the atoms to which they are attached form a 4-, 5-, 6-, or 7-membered cycloalkyl ring optionally substituted with 1, 2, 3, 4 or 5 independently selected Rb substituents; and
optionally one of R5 and R6 and one of R9 and R10 together with the atoms to which they are attached form a 4-, 5-, 6-, or 7-membered cycloalkyl ring optionally substituted with 1, 2, 3, 4 or 5 independently selected Rb substituents; and
wherein when m is 2 or 3, then two R5 or two R6 together with the atoms to which they are attached optionally form a 4-, 5-, 6-, or 7-membered cycloalkyl or heterocycloalkyl ring optionally substituted with 1, 2, 3, 4 or 5 independently selected Rb substituents;
each Ra1 is independently selected from H, D, C1-6 alkyl, C1-4haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-11) aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-4alkyl, C3-11) cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-14 membered heterocycloalkyl)-C1-4 alkyl;
wherein when Ra1 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl- or (4-14 membered heterocycloalkyl)-C1-4 alkyl, then Ra1 is optionally substituted with 1, 2, 3, 4, or 5 independently selected Rd substituents;
each Rb substituent is independently selected from D, halo, oxo, C1-4 alkyl, C1-6 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C6-10 aryl, C3-11) cycloalkyl, 5-10 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, (4-14 membered heterocycloalkyl)-C1-4 alkyl, CN, OH, NH2, NO2, NHORc, ORc, SRc, C(O)Rc, C(O)NRcRc, C(O)ORc, OC(O)Rc, OC(O)NRcRc, C(═NRc)NRcRc, NRcC(═NRc)NRcRc, NRcC(═NOH)NRcRc, NRcC(═NCN)NRcRc, SF5, P(O)RcRc, P(O)(ORc)(ORc), NHRc, NRcRc, NRcC(O)Rc, NRcC(O)ORc, NRcC(O)NRcRc, NRcS(O)Rc, NRcS(O)2Rc, NRcS(O)2NRcRc, S(O)Rc, NRcS(O)(NRc)Rc, S(O)NRcRc, S(O)2Rc, and S(O)2NRcRc;
wherein when Rb is C1-4 alkyl, C1-6 alkoxy, C1-4haloalkyl, C1-4 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl- or (4-14 membered heterocycloalkyl)-C1-4 alkyl, then Rb is optionally substituted with 1, 2, or 3 independently selected Rd substituents;
each Rc is independently selected from H, D, —OH, C1-6 alkyl, C1-6 alkoxy, C1-4 haloalkyl, C2-6alkenyl, C2-6 alkynyl, C6-11) aryl, C3-11) cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl;
wherein when Rc is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl- or (4-10 membered heterocycloalkyl)-C1-4 alkyl, then Rc is optionally substituted with 1, 2, 3, 4, or 5 independently selected Rf substituents;
each Rf is independently selected from halogen, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-11) aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-11) cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl, halo, CN, NHORg, ORg, SRg, C(O)Rg, C(O)NRgRg, C(O)ORg, OC(O)Rg, OC(O)NRgRg, NHRg, NRgRg, NRgC(O)Rg, NRgC(O)NRgRg, NRgC(O)ORg, C(═NRg)NRgRg, NRg C(═NRg)NRgRg, NRg C(═NOH)NRgRg, NRgC(═NCN)NRgRg, SF5, P(O)RgRg, P(O)(ORg)(ORg), S(O)Rg, NRgS(O)(NRg)Rg, S(O)NRgRg, S(O)2Rg, NRgS(O)2Rg, NRg S(O)2NRgRg, and S(O)2NRgRg;
wherein when Rf is C1-4alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl, then Rf is optionally substituted with 1, 2, 3, 4, or 5 independently selected Rn substituents;
each Rn is independently selected from C1-4 alkyl, C1-4 haloalkyl, halo, CN, Ro, NHORo, ORo, SRo, C(O)Ro, C(O)NRoRo, C(O)ORo, OC(O)Ro, OC(O)NRoRo, NHORo, NRoRo, NRoC(O)Ro, NRoC(O)NRoRo, NRoC(O)ORo, C(═NRo)NRoRo, NRoC(═NRo)NRoRo, NRoC(═NOH)NRoRo, NRoC(═NCN)NRoRo, SF5, P(O)RoRo, P(O)(ORo)(ORo), S(O)Ro, NRoS(O)(NRo)Ro, S(O)NRoRo, S(O)2Ro, NRoS(O)2Ro, NRoS(O)2NRoRo, and S(O)2NRoRo;
each Rd is independently selected from D, oxo, C1-6 alkyl, C1-6 haloalkyl, halo, C3-10 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl, CN, NH2, NHORe, ORe, SRe, C(O)Re, C(O)NReRe, C(O)ORe, OC(O)Re, OC(O)NReRe, NHRe, NReRe, NReC(O)Re, NReC(O)NReRe, NReC(O)ORe, C(═NRe)NReRe, NReC(═NRe)NReRe, NReC(═NOH)NReRe, NReC(═NCN)NReRe, SF5, P(O)ReRe, P(O)(ORe)(ORe), S(O)Re, NReS(O)(NRa1)Ra1, S(O)NReRe, S(O)2Re, NReS(O)2Re, NReS(O)2NReRe, and S(O)2NReRe,
wherein when Rd is C1-6alkyl, C3-11) cycloalkyl, C6-11) aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, or (4-10 membered heterocycloalkyl)-C1-4 alkyl, then Rd is optionally substituted with 1, 2, or 3 independently selected Rf substituents;
each Re is independently selected from H, D, CN, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-11) aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-11) cycloalkyl-C1-4alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl,
wherein when Re is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl- or (4-10 membered heterocycloalkyl)-C1-4 alkyl, then Re is optionally substituted with 1, 2 or 3 independently selected Rg substituents;
each Rg is independently selected from H, D, C1-6 alkyl, C1-4 haloalkyl, C2-6alkenyl, C2-6 alkynyl, C6-11) aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-11) cycloalkyl-C1-4alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl,
wherein when Rg is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl- or (4-10 membered heterocycloalkyl)-C1-4 alkyl, then Rg is optionally substituted with 1, 2 or 3 independently selected RP substituents;
each RP is independently selected from C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl, halo, CN, NHORr, ORr, SRr, C(O)Rr, C(O)NRrRr, C(O)ORr, OC(O)Rr, OC(O)NRrRr, NHRr, NRrRr, NRrC(O)Rr, NRrC(O)NRrRr, NRrC(O)ORr, C(═NRr)NRrRr, NRrC(═NRr)NRrRr, NRrC(═NOH)NRrRr, NRrC(═NCN)NRrRr, SF5, P(O)RrRr, P(O)(ORr)(ORr), S(O)Rr, NRrS(O)(NRr)Rr, S(O)NRrRr, S(O)2Rr, NRrS(O)2Rr, NRrS(O)2NRrRr, and S(O)2NRrRr;
each Ro or Rr is independently selected from H, D, C1-4 alkyl, C3-6cycloalkyl, C6-10 aryl, 5 or 6-membered heteroaryl, C1-4 haloalkyl, C2-4alkenyl, and C2-4 alkynyl,
wherein when Ro or Rr is C1-4 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5 or 6-membered heteroaryl, C2-4 alkenyl, and C2-4 alkynyl, then Ro or Rr is optionally substituted with 1, 2 or 3 independently selected Rq substituents;
each Rq is independently selected from D, OH, CN, —COOH, NH2, halo, C1-6alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-4 alkylthio, phenyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, —CONHR11, —NHC(O)R11, —OC(O)R11, C(O)OR11, —C(O)R11, —SO2R11, —NHSO2R11, —SO2NHR11 and NR11R11,
wherein when Rq is C1-6 alkyl, phenyl, 4-6 membered heterocycloalkyl or 5-6 membered heteroaryl, then Rq is optionally substituted with OH, CN, —COOH, NH2, C1-6 alkoxy, C3-6cycloalkyl or 4-6 membered heterocycloalkyl; and
each R11 is independently C1-6 alkyl.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein X is O.

### Claim 3 (depends on 2)

The compound of claim 2, or a pharmaceutically acceptable salt or solvate thereof, wherein m is 2.

### Claim 4 (depends on 1, 3)

The compound of claim 3, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has a formula of
wherein the variables are as defined in claim 1.

### Claim 5 (depends on 4)

The compound of claim 4, or a pharmaceutically acceptable salt or solvate thereof, wherein R5, R6, R7 and R8 are independently H or C1-6 alkyl.

### Claim 6 (depends on 4)

The compound of claim 4, or a pharmaceutically acceptable salt or solvate thereof, wherein both R7 and R8 are H.

### Claim 7 (depends on 4)

The compound of claim 4, or a pharmaceutically acceptable salt or solvate thereof, wherein R5 and R6 are independently H or C1-6 alkyl.

### Claim 8 (depends on 4)

The compound of claim 4, or a pharmaceutically acceptable salt or solvate thereof, wherein both R5 and R6 are CH3.

### Claim 9 (depends on 4)

The compound of claim 4, or a pharmaceutically acceptable salt or solvate thereof, wherein R5 is H.

### Claim 10 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is C3-10 cycloalkyl, C3-7 cycloalkyl C5-6 cycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 independently selected Rb substituents.

### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is
wherein n is 0 or 1 and Rb is as defined in claims 1-9.

### Claim 12 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Rb is NRcC(O)Rc, NRcC(O)NRcRc, NRCS(O)(NRc)Rc, or NRCS(O)2NRcRc.

### Claim 13 (depends on 12)

The compound of claim 12, or a pharmaceutically acceptable salt or solvate thereof, wherein the Rc in NRcC(O)Rc, NRcC(O)NRcRc, or NRcS(O)2NRcRc is independently H, C1-6 alkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, or (5-10 membered heteroaryl)-C1-4 alkyl; wherein when Rc is C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, or (5-10 membered heteroaryl)-C1-4 alkyl, then Rc is optionally substituted with 1, 2, 3, 4, or 5 independently selected Rf substituents.

### Claim 14 (depends on 13)

The compound of claim 13, or a pharmaceutically acceptable salt or solvate thereof, wherein the Rf substituents are independently halogen, CN, or ORg.

### Claim 15 (depends on 14)

The compound of claim 14, or a pharmaceutically acceptable salt or solvate thereof, wherein the Rg is independently H or C1-6 alkyl.

### Claim 16 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Rb is acetamido (—NHC(O)CH3), 3-hydroxybutanamido (—NHC(O)CH2CH(OH)CH3), propionamido (—NHC(O)CH2CH3), 2-methoxyacetamido (—NHC(O)CH2—OCH3), 2-cyanoacetamido (—NHC(O)CH2—CN), 1-hydroxycyclopropane-1-carboxamido,
2-(thiazol-4-yl)acetamido,
methylsulfonamido (—NSO2CH3), 3-methylureido (—NC(O)NHCH3), 3-methoxyureido (—NC(O)NHOCH3), 3,3-dimethylureido (—NC(O)N(CH3)2), or 3-ethylureido (—NC(O)NHCH2CH3), morpholine-4-carboxamido, i.e.,
or 4-methylpiperazine-1-carboxamide, i.e.,

### Claim 17 (depends on 1, 16)

The compound of claim 16, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound has a formula of
wherein the variables are as defined in claim 1.

### Claim 18 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R2 is H, halogen, or C1-6 alkyl.

### Claim 19 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R2 is Cl.

### Claim 20 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is CH3.

### Claim 21 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R3 is H or halogen.

### Claim 22 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R3 is F.

### Claim 23 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R3 is H

### Claim 24 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound have a formula of
wherein R4 is as defined in claim 1.

### Claim 25 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R4 is H, C1-6 alkyl, or C1-6 alkoxy.

### Claim 26 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R4 is H.

### Claim 27 (depends on 1)

The compound of claim 1, wherein the compound is selected from the group consisting of:
(1S,3R)-3-acetamido-N-(5-chloro-4-(indolin-4-yl)pyridin-2-yl)cyclohexane-1-carboxamide;
(1S,3R)-3-acetamido-N-(5-chloro-4-(2-methylindolin-4-yl)pyridin-2-yl)cyclohexane-1-carboxamide;
(1S,3R)-3-acetamido-N-(5-chloro-4-(1,2,3,4-tetrahydroquinolin-5-yl)pyridin-2-yl)cyclohexane-1-carboxamide;
(1S,3R)-3-acetamido-N-(5-chloro-4-(3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)pyridin-2-yl)cyclohexane-1-carboxamide;
(1S,3R)-3-acetamido-N-(5-chloro-4-(2,2-dimethylindolin-4-yl)pyridin-2-yl)cyclohexane-1-carboxamide;
(1S,3R)-3-(2-cyanoacetamido)-N-(4-(2,2-dimethylindolin-4-yl)-5-methylpyridin-2-yl)cyclohexane-1-carboxamide;
(1S,3R)-3-(2-cyanoacetamido)-N-(4-(3,3-dimethyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)-5-methylpyridin-2-yl)cyclohexane-1-carboxamide;
(1S,3R)-3-(2-cyanoacetamido)-N-(4-(3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)-5-methylpyridin-2-yl)cyclohexane-1-carboxamide;
(1S,3R)-3-acetamido-N-(5-chloro-4-(3,3-dimethyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)pyridin-2-yl)cyclohexane-1-carboxamide;
(1S,3R)—N-(5-chloro-4-(3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)pyridin-2-yl)-3-(2-cyanoacetamido)cyclohexane-1-carboxamide;
(1S,3R)—N-(5-chloro-4-(3,3-dimethyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)pyridin-2-yl)-3-(2-cyanoacetamido)cyclohexane-1-carboxamide;
(1S,3R)—N-(5-chloro-4-(6-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)pyridin-2-yl)-3-(2-cyanoacetamido)cyclohexane-1-carboxamide;
(1S,3R)—N-(5-chloro-4-(6-fluoro-3-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)pyridin-2-yl)-3-(2-cyanoacetamido)cyclohexane-1-carboxamide;
(1S,3R)-3-acetamido-N-(5-chloro-4-(2,2-dimethyl-2,3-dihydrobenzofuran-4-yl)pyridin-2-yl)cyclohexane-1-carboxamide; and
(1S,3R)—N-(5-chloro-4-(2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)pyridin-2-yl)-3-(2-cyanoacetamido)cyclohexane-1-carboxamide.

### Claim 28 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, and optionally a pharmaceutically acceptable excipient.

### Claim 29 (depends on 28)

The pharmaceutical composition of claim 28, wherein the pharmaceutical composition comprises an enantiomeric excess of at least 90% of one enantiomer of the compound, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 30 (depends on 28)

The pharmaceutical composition of claim 28, wherein the pharmaceutical composition comprises an enantiomeric excess of at least 95% of one enantiomer of the compound, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 31 (depends on 28)

The pharmaceutical composition of claim 28, wherein the pharmaceutical composition comprises an enantiomeric excess of at least 98% of one enantiomer of the compound, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 32 (depends on 28)

The pharmaceutical composition of claim 28, wherein the pharmaceutical composition comprises an enantiomeric excess of at least 99% of one enantiomer of the compound, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 33 (depends on 1)

A method of inhibiting a CDK enzyme comprising: contacting the CDK enzyme with an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 34 (depends on 33)

The method of claim 33, wherein the CDK enzyme is CDK9.

### Claim 35 (depends on 1)

A method of treating a disease or disorder associated with aberrant CDK activity in a subject or a subject in need thereof comprising administering to the subject, a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 36 (depends on 35)

The method of claim 35, wherein the disease or disorder associated with aberrant CDK activity is colon cancer, breast cancer, small-cell lung cancer, non-small-cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphoid leukemia, lymphoma, myeloma, acute myeloid leukemia, or pancreatic cancer.

### Claim 37 (depends on 1)

A method of treating cancer in a subject or a subject in need thereof comprising administering to the subject, a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 38 (depends on 37)

The method of claim 37, wherein the cancer is colon cancer, breast cancer, small-cell lung cancer, non-small-cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphoid leukemia, lymphoma, myeloma, acute myeloid leukemia, or pancreatic cancer.