# US 2019/0169208 A1 · Macrocycle kinase inhibitors

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- Number: US 2019/0169208 A1
- Document ID: US20190169208A1
- Status: Published application
- Kind: A1
- Application number: 16/320,589
- Filed: 2017-07-27
- Published: 2019-06-06
- Earliest claimed: 2016-07-28
- Assignees: TP Therapeutics, Inc.
- Applicants: Tp Therapeutics, Inc.
- Inventors: Jingrong Jean CUI; Yishan LI; Evan W. ROGERS; Dayong ZHAI; Jane UNG
- Web page: https://patentgrep.com/patent/US20190169208A1

## CPC

- C07D 498/18: Bridged systems
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure relates to certain macrocyclic kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same to treat disease.

## Claims

### Claim 1

A compound of the formula I
or a pharmaceutically acceptable salt thereof, wherein
X1 and X2 are independently S, S(O), S(O)2, O or N(R10);
R1 is H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, —C(O)OR8 or —C(O)NR8R9; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2C6 alkynyl, C3-C6 cycloalkyl and C6-C10 aryl is independently optionally substituted by deuterium, halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, NHC(O)C1-C6 alkyl, —N(C1-C6 alkyl)C(O)C1-C6 alkyl, —NHC(O)NH2, —NHC(O)NHC1-C6 alkyl, —N(C1-C6 alkyl)C(O)NH2, —N(C1-C6 alkyl)C(O)NHC1-C6 alkyl, —NHC(O)N(C1-C6 alkyl)2, N(C1C6 alkyl)C(O)N(C1-C6 alkyl)2, —NHC(O)OC1-C6 alkyl, —N(C1-C6 alkyl)C(O)OC1-C6 alkyl, —NHS(O)(C1-C6 alkyl), —NHS(O)2(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)(C1-C6 alkyl), N(C1C6 alkyl)S(O)2(C1-C6 alkyl), —NHS(O)NH2, —NHS(O)2NH2, —N(C1-C6 alkyl)S(O)NH2, N(C1-C6 alkyl)S(O)2NH2, —NHS(O)NH(C1-C6 alkyl), —NHS(O)2NH(C1-C6 alkyl), NHS(O)N(C1-C6 alkyl)2, —NHS(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)NH(C1-C6 alkyl), N(C1-C6 alkyl)S(O)2NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)2N(C1-C6 alkyl)2, —CO2H, —C(O)OC1-C6 alkyl, —C(O)NH2, —C(O)NH(C1-C6 alkyl), C(O)N(C1-C6 alkyl)2, SC1-C6 alkyl, —S(O)C1-C6 alkyl, —S(O)2C1-C6 alkyl, S(O)NH(C1-C6 alkyl), —S(O)2NH(C1-C6 alkyl), —S(O)N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, P(C1-C6 alkyl)2, —P(O)(C1-C6 alkyl)2, C3-C6 cycloalkyl, or 3- to 7-membered heterocycloalkyl;
each R2 and R3 is independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, —C(O)OR8 or —C(O)NR8R9; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl and C6-C10 aryl is independently optionally substituted by deuterium, halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —NHC(O)C1-C6 alkyl, —N(C1-C6 alkyl)C(O)C1-C6 alkyl, —NHC(O)NH2, NHC(O)NHC1-C6 alkyl, —N(C1-C6 alkyl)C(O)NH2, —N(C1-C6 alkyl)C(O)NHC1-C6 alkyl, NHC(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)C(O)N(C1-C6 alkyl)2, —NHC(O)OC1-C6 alkyl, N(C1C6 alkyl)C(O)OC1-C6 alkyl, —NHS(O)(C1-C6 alkyl), —NHS(O)2(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)2(C1-C6 alkyl), —NHS(O)NH2, —NHS(O)2NH2, N(C1C6 alkyl)S(O)NH2, —N(C1-C6 alkyl)S(O)2NH2, —NHS(O)NH(C1-C6 alkyl), NHS(O)2NH(C1-C6 alkyl), —NHS(O)N(C1-C6 alkyl)2, —NHS(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)2NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)N(C1C6 alkyl)2, —N(C1-C6 alkyl)S(O)2N(C1-C6 alkyl)2, —CO2H, —C(O)OC1-C6 alkyl, C(O)NH2, C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl)2, —SC1-C6 alkyl, —S(O)C1-C6 alkyl, —S(O)2C1-C6 alkyl, —S(O)NH(C1-C6 alkyl), —S(O)2NH(C1-C6 alkyl), —S(O)N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, —P(C1-C6 alkyl)2, —P(O)(C1-C6 alkyl)2, C3-C6 cycloalkyl, or 3- to 7-membered heterocycloalkyl; or R2 and R3 taken together with the carbon atoms to which they are attached optionally form a C5-C7 cycloalkyl or a 5- to 7-membered heterocycloalkyl; or R2 and R6 taken together with the atoms to which they are attached optionally form a 5- to 7-membered heterocycloalkyl;
R4 is H, C1-C6 alkyl or 3- to 7-membered heterocycloalkyl, wherein each hydrogen atom in C1-C6 alkyl or 3- to 7-membered heterocycloalkyl is independently optionally substituted by halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —CO2H, C(O)OC1C6 alkyl, —C(O)NH2, —C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl)2, C3-C6 cycloalkyl, or monocyclic 5- to 7-membered heterocycloalkyl;
R5, R6 and R7 are each independently selected from the group consisting of H, fluoro, chloro, bromo, C1-C6 alkyl, —OH, —CN, OC1-C6 alkyl, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, —O—(C3-C6 cycloalkyl), —O-(3- to 7-membered heterocycloalkyl), 5- to 7 membered heteroaryl, C6-C10 aryl, and CF3; wherein each hydrogen atom in C1-C6 alkyl, OC1-C6 alkyl, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, —O—(C3-C6 cycloalkyl), —O-(3- to 7-membered heterocycloalkyl), 5- to 7 membered heteroaryl and C6-C10 aryl is independently optionally substituted by fluoro, chloro, bromo, —OH, CN, —OC1-C6 alkyl, —NH2, NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 7 membered heteroaryl, —CO2H, C(O)OC1C6 alkyl, C(O)NH2, —C(O)NH(C1-C6 alkyl) and —C(O)N(C1-C6 alkyl)2;
each R8 and R9 is independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl or heteroaryl;
each R10 is independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl or —OR8;
n is 1 or 2; and
provided that at least one of R5 or R7 is not H, and provided that the compound is not of the formula

### Claim at position 2

-3. (canceled)

### Claim 4 (depends on 1)

The compound of claim 1, having the formula Ia
or a pharmaceutically acceptable salt thereof, wherein
R1 is H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, —C(O)OR8 or —C(O)NR8R9; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2C6 alkynyl, C3-C6 cycloalkyl and C6-C10 aryl is independently optionally substituted by deuterium, halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, NHC(O)C1-C6 alkyl, —N(C1-C6 alkyl)C(O)C1-C6 alkyl, —NHC(O)NH2, —NHC(O)NHC1-C6 alkyl, —N(C1-C6 alkyl)C(O)NH2, —N(C1-C6 alkyl)C(O)NHC1-C6 alkyl, —NHC(O)N(C1-C6 alkyl)2, N(C1C6 alkyl)C(O)N(C1-C6 alkyl)2, —NHC(O)OC1-C6 alkyl, —N(C1-C6 alkyl)C(O)OC1-C6 alkyl, —NHS(O)(C1-C6 alkyl), —NHS(O)2(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)(C1-C6 alkyl), N(C1C6 alkyl)S(O)2(C1-C6 alkyl), —NHS(O)NH2, —NHS(O)2NH2, —N(C1-C6 alkyl)S(O)NH2, N(C1-C6 alkyl)S(O)2NH2, —NHS(O)NH(C1-C6 alkyl), —NHS(O)2NH(C1-C6 alkyl), NHS(O)N(C1-C6 alkyl)2, —NHS(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)NH(C1-C6 alkyl), N(C1-C6 alkyl)S(O)2NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)N(C1-C6alkyl)2, —N(C1-C6 alkyl)S(O)2N(C1-C6 alkyl)2, —CO2H, —C(O)OC1-C6 alkyl, —C(O)NH2, —C(O)NH(C1-C6 alkyl), C(O)N(C1-C6 alkyl)2, SC1-C6 alkyl, —S(O)C1-C6 alkyl, —S(O)2C1-C6 alkyl, S(O)NH(C1-C6 alkyl), —S(O)2NH(C1-C6 alkyl), —S(O)N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, P(C1-C6 alkyl)2, —P(O)(C1-C6 alkyl)2, C3-C6 cycloalkyl, or 3- to 7-membered heterocycloalkyl;
each R2 and R3 is independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, —C(O)OR8 or —C(O)NR8R9; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl and C6-C10 aryl is independently optionally substituted by deuterium, halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —NHC(O)C1-C6 alkyl, —N(C1-C6 alkyl)C(O)C1-C6 alkyl, —NHC(O)NH2, NHC(O)NHC1-C6 alkyl, —N(C1-C6 alkyl)C(O)NH2, —N(C1-C6 alkyl)C(O)NHC1-C6 alkyl, NHC(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)C(O)N(C1-C6 alkyl)2, —NHC(O)OC1-C6 alkyl, N(C1C6 alkyl)C(O)OC1-C6 alkyl, —NHS(O)(C1-C6 alkyl), —NHS(O)2(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)2(C1-C6 alkyl), —NHS(O)NH2, —NHS(O)2NH2, N(C1C6 alkyl)S(O)NH2, —N(C1-C6 alkyl)S(O)2NH2, —NHS(O)NH(C1-C6 alkyl), NHS(O)2NH(C1-C6 alkyl), —NHS(O)N(C1-C6 alkyl)2, —NHS(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)2NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)N(C1C6 alkyl)2, —N(C1-C6 alkyl)S(O)2N(C1-C6 alkyl)2, —CO2H, —C(O)OC1-C6 alkyl, C(O)NH2, C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl)2, —SC1-C6 alkyl, —S(O)C1-C6 alkyl, —S(O)2C1-C6 alkyl, —S(O)NH(C1-C6 alkyl), —S(O)2NH(C1-C6 alkyl), —S(O)N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, —P(C1-C6 alkyl)2, —P(O)(C1-C6 alkyl)2, C3-C6 cycloalkyl, or 3- to 7-membered heterocycloalkyl; or R2 and R3 taken together with the carbon atoms to which they are attached optionally form a C5-C7 cycloalkyl or a 5- to 7-membered heterocycloalkyl; or R2 and R6 taken together with the atoms to which they are attached optionally form a 5- to 7-membered heterocycloalkyl;
R4 is H, C1-C6 alkyl or 3- to 7-membered heterocycloalkyl, wherein each hydrogen atom in C1-C6 alkyl or 3- to 7-membered heterocycloalkyl is independently optionally substituted by halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —CO2H, C(O)OC1C6 alkyl, —C(O)NH2, —C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl)2, C3-C6 cycloalkyl, or monocyclic 5- to 7-membered heterocycloalkyl;
R5, R6 and R7 are each independently selected from the group consisting of H, fluoro, chloro, bromo, C1-C6 alkyl, —OH, —CN, OC1-C6 alkyl, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, —O—(C3-C6 cycloalkyl), —O-(3- to 7-membered heterocycloalkyl), 5- to 7 membered heteroaryl, C6-C10 aryl, and CF3; wherein each hydrogen atom in C1-C6 alkyl, OC1-C6 alkyl, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, —O—(C3-C6 cycloalkyl), —O-(3- to 7-membered heterocycloalkyl), 5- to 7 membered heteroaryl and C6-C10 aryl is independently optionally substituted by fluoro, chloro, bromo, —OH, CN, —OC1-C6 alkyl, —NH2, NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 7 membered heteroaryl, —CO2H, C(O)OC1C6 alkyl, C(O)NH2, —C(O)NH(C1-C6 alkyl) and —C(O)N(C1-C6 alkyl)2;
each R8 and R9 is independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl or heteroaryl;
each R10 is independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl or OR8;
n is 1 or 2;
provided that at least one of R5 or R7 is not H; and provided that the compound is not of the formula

### Claim 5

(canceled)

### Claim 6 (depends on 4)

The compound of claim 4, or a pharmaceutically acceptable salt thereof, wherein R7 is selected from the group consisting of fluoro, chloro, bromo, C1-C6 alkyl, OH, CN, OC1-C6 alkyl, 5- to 7 membered heteroaryl, and —CF3.

### Claim at position 6

-11. (canceled)

### Claim 12 (depends on 4)

The compound of claim 4, or a pharmaceutically acceptable salt thereof, wherein R5 is selected from the group consisting of fluoro, chloro, bromo, C1-C6 alkyl, OH, CN, OC1-C6 alkyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, —O—(C3-C6 cycloalkyl), —O-(3- to 7-membered heterocycloalkyl), 5- to 7 membered heteroaryl, C6-C10 aryl and CF3, wherein each hydrogen atom in C1-C6 alkyl, OC1-C6 alkyl, C3-C6 cycloalkyl, 3- to 7 membered heterocycloalkyl, —O—(C3-C6 cycloalkyl), —O-(3- to 7-membered heterocycloalkyl), 5- to 7 membered heteroaryl and C6-C10 aryl is independently optionally substituted by fluoro, chloro, bromo, —OH, —CN, OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C3C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 7 membered heteroaryl, —CO2H, C(O)OC1C6 alkyl, —C(O)NH2, C(O)NH(C1-C6 alkyl) and —C(O)N(C1-C6 alkyl)2.

### Claim at position 8

-20. (canceled)

### Claim 21 (depends on 4)

The compound of claim 4, or a pharmaceutically acceptable salt thereof, wherein R5 is 5- to 7 membered heteroaryl; wherein each hydrogen atom in 5- to 7 membered heteroaryl is independently optionally substituted by fluoro, chloro, bromo, —OH, CN, OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —CO2H, C(O)OC1C6 alkyl, C(O)NH2, C(O)NH(C1-C6 alkyl) and —C(O)N(C1-C6 alkyl)2.

### Claim at position 10

-26. (canceled)

### Claim 27 (depends on 1)

The compound of claim 1, having the formula Ib
or a pharmaceutically acceptable salt thereof, wherein
R1 is H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, —C(O)OR8 or —C(O)NR8R9; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2C6 alkynyl, C3-C6 cycloalkyl and C6-C10 aryl is independently optionally substituted by deuterium, halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, NHC(O)C1-C6 alkyl, —N(C1-C6 alkyl)C(O)C1-C6 alkyl, —NHC(O)NH2, —NHC(O)NHC1-C6 alkyl, —N(C1-C6 alkyl)C(O)NH2, —N(C1-C6 alkyl)C(O)NHC1-C6 alkyl, —NHC(O)N(C1-C6 alkyl)2, N(C1C6 alkyl)C(O)N(C1-C6 alkyl)2, —NHC(O)OC1-C6 alkyl, —N(C1-C6 alkyl)C(O)OC1-C6 alkyl, —NHS(O)(C1-C6 alkyl), —NHS(O)2(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)(C1-C6 alkyl), N(C1C6 alkyl)S(O)2(C1-C6 alkyl), —NHS(O)NH2, —NHS(O)2NH2, —N(C1-C6 alkyl)S(O)NH2, N(C1-C6 alkyl)S(O)2NH2, —NHS(O)NH(C1-C6 alkyl), —NHS(O)2NH(C1-C6 alkyl), NHS(O)N(C1-C6 alkyl)2, —NHS(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)NH(C1-C6 alkyl), N(C1-C6 alkyl)S(O)2NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)N(C1-C6alkyl)2, —N(C1-C6 alkyl)S(O)2N(C1-C6 alkyl)2, —CO2H, —C(O)OC1-C6 alkyl, —C(O)NH2, —C(O)NH(C1-C6 alkyl), C(O)N(C1-C6 alkyl)2, SC1-C6 alkyl, —S(O)C1-C6 alkyl, —S(O)2C1-C6 alkyl, S(O)NH(C1-C6 alkyl), —S(O)2NH(C1-C6 alkyl), —S(O)N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, P(C1-C6 alkyl)2, —P(O)(C1-C6 alkyl)2, C3-C6 cycloalkyl, or 3- to 7-membered heterocycloalkyl;
each R2 and R3 is independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, —C(O)OR8 or —C(O)NR8R9; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl and C6-C10 aryl is independently optionally substituted by deuterium, halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —NHC(O)C1-C6 alkyl, —N(C1-C6 alkyl)C(O)C1-C6 alkyl, —NHC(O)NH2, NHC(O)NHC1-C6 alkyl, —N(C1-C6 alkyl)C(O)NH2, —N(C1-C6 alkyl)C(O)NHC1-C6 alkyl, NHC(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)C(O)N(C1-C6 alkyl)2, —NHC(O)OC1-C6 alkyl, N(C1C6 alkyl)C(O)OC1-C6 alkyl, —NHS(O)(C1-C6 alkyl), —NHS(O)2(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)2(C1-C6 alkyl), —NHS(O)NH2, —NHS(O)2NH2, N(C1C6 alkyl)S(O)NH2, —N(C1-C6 alkyl)S(O)2NH2, —NHS(O)NH(C1-C6 alkyl), NHS(O)2NH(C1-C6 alkyl), —NHS(O)N(C1-C6 alkyl)2, —NHS(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)2NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)N(C1C6 alkyl)2, —N(C1-C6 alkyl)S(O)2N(C1-C6 alkyl)2, —CO2H, —C(O)OC1-C6 alkyl, C(O)NH2, C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl)2, —SC1-C6 alkyl, —S(O)C1-C6 alkyl, —S(O)2C1-C6 alkyl, —S(O)NH(C1-C6 alkyl), —S(O)2NH(C1-C6 alkyl), —S(O)N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, —P(C1-C6 alkyl)2, —P(O)(C1-C6 alkyl)2, C3-C6 cycloalkyl, or 3- to 7-membered heterocycloalkyl; or R2 and R3 taken together with the carbon atoms to which they are attached optionally form a C5-C7 cycloalkyl or a 5- to 7-membered heterocycloalkyl; or R2 and R6 taken together with the atoms to which they are attached optionally form a 5- to 7-membered heterocycloalkyl;
R4 is H, C1-C6 alkyl or 3- to 7-membered heterocycloalkyl, wherein each hydrogen atom in C1-C6 alkyl or 3- to 7-membered heterocycloalkyl is independently optionally substituted by halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —CO2H, C(O)OC1C6 alkyl, —C(O)NH2, —C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl)2, C3-C6 cycloalkyl, or monocyclic 5- to 7-membered heterocycloalkyl;
R5 and R6 are each independently selected from the group consisting of H, fluoro, chloro, bromo, C1-C6 alkyl, —OH, —CN, OC1-C6 alkyl, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, —O—(C3-C6 cycloalkyl), —O-(3- to 7-membered heterocycloalkyl), 5- to 7 membered heteroaryl, C6-C10 aryl, and CF3; wherein each hydrogen atom in C1-C6 alkyl, OC1-C6 alkyl, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, —O—(C3-C6 cycloalkyl), —O-(3- to 7-membered heterocycloalkyl), 5- to 7 membered heteroaryl and C6-C10 aryl is independently optionally substituted by fluoro, chloro, bromo, —OH, CN, —OC1-C6 alkyl, —NH2, NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 7 membered heteroaryl, —CO2H, C(O)OC1C6 alkyl, C(O)NH2, —C(O)NH(C1-C6 alkyl) and —C(O)N(C1-C6 alkyl)2;
R7 is selected from the group consisting of fluoro, chloro, bromo, C1-C6 alkyl, —OH, —CN, OC1-C6 alkyl, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, 5- to 7 membered heteroaryl, C6-C10 aryl, and CF3; wherein each hydrogen atom in C1-C6 alkyl, 5- to 7 membered heteroaryl and C6-C10 aryl is independently optionally substituted by fluoro, chloro, bromo, —OH, —CN, OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —CO2H, C(O)OC1C6 alkyl, C(O)NH2, —C(O)NH(C1-C6 alkyl) and —C(O)N(C1-C6 alkyl)2;
each R8 and R9 is independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl or heteroaryl;
each R10 is independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl or —OR8;
n is 1 or 2; and
provided that the compound is not of the formula

### Claim 28

(canceled)

### Claim 29 (depends on 27)

The compound of claim 27, or a pharmaceutically acceptable salt thereof, wherein R7 is selected from the group consisting of fluoro, chloro, bromo, C1-C6 alkyl, OH, CN, OC1-C6 alkyl, 5- to 7 membered heteroaryl, and CF3.

### Claim at position 14

-33. (canceled)

### Claim 34 (depends on 1)

The A compound of claim 1, having the formula Ic
or a pharmaceutically acceptable salt thereof, wherein
R1 is H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, —C(O)OR8 or —C(O)NR8R9; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2C6 alkynyl, C3-C6 cycloalkyl and C6-C10 aryl is independently optionally substituted by deuterium, halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, NHC(O)C1-C6 alkyl, —N(C1-C6 alkyl)C(O)C1-C6 alkyl, —NHC(O)NH2, —NHC(O)NHC1-C6 alkyl, —N(C1-C6 alkyl)C(O)NH2, —N(C1-C6 alkyl)C(O)NHC1-C6 alkyl, —NHC(O)N(C1-C6 alkyl)2, N(C1C6 alkyl)C(O)N(C1-C6 alkyl)2, —NHC(O)OC1-C6 alkyl, —N(C1-C6 alkyl)C(O)OC1-C6 alkyl, —NHS(O)(C1-C6 alkyl), —NHS(O)2(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)(C1-C6 alkyl), N(C1C6 alkyl)S(O)2(C1-C6 alkyl), —NHS(O)NH2, —NHS(O)2NH2, —N(C1-C6 alkyl)S(O)NH2, N(C1-C6 alkyl)S(O)2NH2, —NHS(O)NH(C1-C6 alkyl), —NHS(O)2NH(C1-C6 alkyl), NHS(O)N(C1-C6 alkyl)2, —NHS(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)NH(C1-C6 alkyl), N(C1-C6 alkyl)S(O)2NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)2N(C1-C6 alkyl)2, —CO2H, —C(O)OC1-C6 alkyl, —C(O)NH2, —C(O)NH(C1-C6 alkyl), C(O)N(C1-C6 alkyl)2, SC1-C6 alkyl, —S(O)C1-C6 alkyl, —S(O)2C1-C6 alkyl, S(O)NH(C1-C6 alkyl), —S(O)2NH(C1-C6 alkyl), —S(O)N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, P(C1-C6 alkyl)2, —P(O)(C1-C6 alkyl)2, C3-C6 cycloalkyl, or 3- to 7-membered heterocycloalkyl;
each R2 and R3 is independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C10 aryl, —C(O)OR8 or —C(O)NR8R9; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl and C6-C10 aryl is independently optionally substituted by deuterium, halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —NHC(O)C1-C6 alkyl, —N(C1-C6 alkyl)C(O)C1-C6 alkyl, —NHC(O)NH2, NHC(O)NHC1-C6 alkyl, —N(C1-C6 alkyl)C(O)NH2, —N(C1-C6 alkyl)C(O)NHC1-C6 alkyl, NHC(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)C(O)N(C1-C6 alkyl)2, —NHC(O)OC1-C6 alkyl, N(C1C6 alkyl)C(O)OC1-C6 alkyl, —NHS(O)(C1-C6 alkyl), —NHS(O)2(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)2(C1-C6 alkyl), —NHS(O)NH2, —NHS(O)2NH2, N(C1C6 alkyl)S(O)NH2, —N(C1-C6 alkyl)S(O)2NH2, —NHS(O)NH(C1-C6 alkyl), NHS(O)2NH(C1-C6 alkyl), —NHS(O)N(C1-C6 alkyl)2, —NHS(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)2NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)N(C1C6 alkyl)2, —N(C1-C6 alkyl)S(O)2N(C1-C6 alkyl)2, —CO2H, —C(O)OC1-C6 alkyl, C(O)NH2, C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl)2, —SC1-C6 alkyl, —S(O)C1-C6 alkyl, —S(O)2C1-C6 alkyl, —S(O)NH(C1-C6 alkyl), —S(O)2NH(C1-C6 alkyl), —S(O)N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, —P(C1-C6 alkyl)2, —P(O)(C1-C6 alkyl)2, C3-C6 cycloalkyl, or 3- to 7-membered heterocycloalkyl; or R2 and R3 taken together with the carbon atoms to which they are attached optionally form a C5-C7 cycloalkyl or a 5- to 7-membered heterocycloalkyl; or R2 and R6 taken together with the atoms to which they are attached optionally form a 5- to 7-membered heterocycloalkyl;
R4 is H, C1-C6 alkyl or 3- to 7-membered heterocycloalkyl, wherein each hydrogen atom in C1-C6 alkyl or 3- to 7-membered heterocycloalkyl is independently optionally substituted by halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —CO2H, C(O)OC1C6 alkyl, —C(O)NH2, —C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl)2, C3-C6 cycloalkyl, or monocyclic 5- to 7-membered heterocycloalkyl;
R5 is selected from the group consisting of fluoro, chloro, bromo, C1-C6 alkyl, —OH, —CN, OC1-C6 alkyl, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, —O—(C3-C6 cycloalkyl), —O-(3- to 7-membered heterocycloalkyl), 5- to 7-membered heteroaryl, C6-C10 aryl, and CF3; wherein each hydrogen atom in C1-C6 alkyl, —OC1-C6 alkyl, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, —O—(C3-C6 cycloalkyl), —O-(3- to 7-membered heterocycloalkyl), 5- to 7-membered heteroaryl and C6-C10 aryl is independently optionally substituted by fluoro, chloro, bromo, —OH, CN, —OC1-C6 alkyl, —NH2, NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C3C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 7 membered heteroaryl, —CO2H, C(O)OC1C6 alkyl, C(O)NH2, —C(O)NH(C1-C6 alkyl) and —C(O)N(C1-C6 alkyl)2;
R6 and R7 are each independently selected from the group consisting of H, fluoro, chloro, bromo, C1-C6 alkyl, —OH, —CN, OC1-C6 alkyl, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, 5- to 7 membered heteroaryl, C6-C10 aryl, and CF3; wherein each hydrogen atom in C1-C6 alkyl, 5- to 7 membered heteroaryl and C6-C10 aryl is independently optionally substituted by fluoro, chloro, bromo, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —CO2H, C(O)OC1C6 alkyl, C(O)NH2, —C(O)NH(C1-C6 alkyl) and —C(O)N(C1-C6 alkyl)2;
each R8 and R9 is independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl or heteroaryl;
each R10 is independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl; wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl or OR8; and
n is 1 or 2.

### Claim 35

(canceled)

### Claim 36 (depends on 34)

The compound of claim 34, or a pharmaceutically acceptable salt thereof, wherein R5 is selected from the group consisting of fluoro, chloro, bromo, C1-C6 alkyl, OH, CN, OC1-C6 alkyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, —O—(C3-C6 cycloalkyl), —O-(3- to 7 membered heterocycloalkyl), 5- to 7 membered heteroaryl, C6-C10 aryl and CF3, wherein each hydrogen atom in C1-C6 alkyl, OC1-C6 alkyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, —O—(C3-C6 cycloalkyl), —O-(3- to 7-membered heterocycloalkyl), 5- to 7 membered heteroaryl and C6-C10 aryl is independently optionally substituted by fluoro, chloro, bromo, —OH, —CN, OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1C6 alkyl)2, C3C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 7 membered heteroaryl, —CO2H, C(O)OC1C6 alkyl, C(O)NH2, C(O)NH(C1-C6 alkyl) and —C(O)N(C1-C6 alkyl)2.

### Claim at position 18

-50. (canceled)

### Claim 51 (depends on 4)

The compound of claim 4, or a pharmaceutically acceptable salt thereof, wherein R10 is H or C1-C6 alkyl.

### Claim 52 (depends on 27)

The compound of claim 27, or a pharmaceutically acceptable salt thereof, wherein R10 is H or C1-C6 alkyl.

### Claim 53 (depends on 34)

The compound of claim 34, or a pharmaceutically acceptable salt thereof, wherein R10 is H or C1-C6 alkyl.

### Claim 54

(canceled)

### Claim 55 (depends on 27)

The compound of claim 27, or a pharmaceutically acceptable salt thereof, wherein R2 is H or C1-C6 alkyl; wherein each hydrogen atom in C1-C6 alkyl is independently optionally substituted by deuterium, halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —NHC(O)C1-C6 alkyl, —N(C1-C6 alkyl)C(O)C1-C6 alkyl, NHC(O)NH2, NHC(O)NHC1-C6 alkyl, —N(C1-C6 alkyl)C(O)NH2, —N(C1-C6 alkyl)C(O)NHC1C6 alkyl, NHC(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)C(O)N(C1-C6 alkyl)2, NHC(O)OC1-C6 alkyl, N(C1C6 alkyl)C(O)OC1-C6 alkyl, —NHS(O)(C1-C6 alkyl), NHS(O)2(C1C6 alkyl), —N(C1-C6 alkyl)S(O)(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)2(C1-C6 alkyl), NHS(O)NH2, —NHS(O)2NH2, N(C1C6 alkyl)S(O)NH2, —N(C1-C6 alkyl)S(O)2NH2, NHS(O)NH(C1-C6 alkyl), NHS(O)2NH(C1-C6 alkyl), —NHS(O)N(C1-C6 alkyl)2, NHS(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)2NH(C1C6 alkyl), —N(C1-C6 alkyl)S(O)N(C1C6 alkyl)2, —N(C1-C6 alkyl)S(O)2N(C1-C6 alkyl)2, —CO2H, C(O)OC1-C6 alkyl, C(O)NH2, C(O)NH(C1-C6 alkyl), C(O)N(C1-C6 alkyl)2, —SC1-C6 alkyl, S(O)C1-C6 alkyl, S(O)2C1-C6 alkyl, —S(O)NH(C1-C6 alkyl), —S(O)2NH(C1-C6 alkyl), S(O)N(C1-C6 alkyl)2, S(O)2N(C1-C6 alkyl)2, —P(C1-C6 alkyl)2, —P(O)(C1-C6 alkyl)2, C3-C6 cycloalkyl, or 3- to 7 membered heterocycloalkyl.

### Claim 56 (depends on 34)

The compound of claim 34, or a pharmaceutically acceptable salt thereof, wherein R2 is H or C1-C6 alkyl; wherein each hydrogen atom in C1-C6 alkyl is independently optionally substituted by deuterium, halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —NHC(O)C1-C6 alkyl, —N(C1-C6 alkyl)C(O)C1-C6 alkyl, NHC(O)NH2, NHC(O)NHC1-C6 alkyl, —N(C1-C6 alkyl)C(O)NH2, —N(C1-C6 alkyl)C(O)NHC1C6 alkyl, NHC(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)C(O)N(C1-C6 alkyl)2, NHC(O)OC1-C6 alkyl, N(C1C6 alkyl)C(O)OC1-C6 alkyl, —NHS(O)(C1-C6 alkyl), NHS(O)2(C1C6 alkyl), —N(C1-C6 alkyl)S(O)(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)2(C1-C6 alkyl), NHS(O)NH2, —NHS(O)2NH2, N(C1C6 alkyl)S(O)NH2, —N(C1-C6 alkyl)S(O)2NH2, NHS(O)NH(C1-C6 alkyl), NHS(O)2NH(C1-C6 alkyl), —NHS(O)N(C1-C6 alkyl)2, NHS(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)NH(C1-C6 alkyl), —N(C1-C6 alkyl)S(O)2NH(C1C6 alkyl), —N(C1-C6 alkyl)S(O)N(C1C6 alkyl)2, —N(C1-C6 alkyl)S(O)2N(C1-C6 alkyl)2, —CO2H, C(O)OC1-C6 alkyl, C(O)NH2, C(O)NH(C1-C6 alkyl), C(O)N(C1-C6 alkyl)2, —SC1-C6 alkyl, S(O)C1-C6 alkyl, S(O)2C1-C6 alkyl, —S(O)NH(C1-C6 alkyl), —S(O)2NH(C1-C6 alkyl), S(O)N(C1-C6 alkyl)2, S(O)2N(C1-C6 alkyl)2, —P(C1-C6 alkyl)2, —P(O)(C1-C6 alkyl)2, C3-C6 cycloalkyl, or 3- to 7 membered heterocycloalkyl.

### Claim at position 25

-61.

### Claim 62 (depends on 27)

The compound of claim 27, or a pharmaceutically acceptable salt thereof, wherein R6 is selected from the group consisting of fluoro, chloro, bromo, C1-C6 alkyl, OH, —CN, OC1-C6 alkyl, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, 5- to 7 membered heteroaryl, C6C10 aryl, and CF3; wherein each hydrogen atom in C1-C6 alkyl, 5- to 7 membered heteroaryl and C6-C10 aryl is independently optionally substituted by halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —CO2H, —C(O)OC1C6 alkyl, C(O)NH2, C(O)NH(C1-C6 alkyl) and —C(O)N(C1-C6 alkyl)2.

### Claim 63 (depends on 34)

The compound claim 34, or a pharmaceutically acceptable salt thereof, wherein R6 is selected from the group consisting of fluoro, chloro, bromo, C1-C6 alkyl, OH, —CN, OC1-C6 alkyl, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, 5- to 7 membered heteroaryl, C6C10 aryl, and CF3; wherein each hydrogen atom in C1-C6alkyl, 5- to 7 membered heteroaryl and C6-C10 aryl is independently optionally substituted by halogen, —OH, —CN, —OC1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —CO2H, —C(O)OC1C6 alkyl, C(O)NH2, C(O)NH(C1-C6 alkyl) and —C(O)N(C1-C6 alkyl)2.

### Claim 64 (depends on 1)

The compound of claim 1, selected from the group consisting of
or a pharmaceutically acceptable salt thereof.

### Claim 65 (depends on 1)

The compound of claim 1, selected from the group consisting of
or a pharmaceutically acceptable salt thereof.

### Claim 66 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and optionally at least one diluent, carrier or excipient.

### Claim 67 (depends on 1)

A method of treating cancer, pain, neurological diseases, autoimmune diseases, or inflammation comprising administering to a subject in need of such treatment an effective amount of at least one compound of claim 1, or a pharmaceutically acceptable salt thereof.

### Claim at position 32

-83. (canceled)