# US 9,040,515 B2 · Aryl and heteroaryl fused lactams

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- Number: US 9,040,515 B2
- Document ID: US9040515B2
- Status: Granted
- Kind: B2
- Application number: 14/132,567
- Filed: 2013-12-18
- Published: 2014-06-26
- Granted: 2015-05-26
- Earliest claimed: 2012-12-21
- Assignees: Pfizer Inc.
- Applicants: Pfizer Inc.
- Inventors: Martin Paul Edwards; Robert Arnold Kumpf; Pei-Pei Kung; Indrawan James McAlpine; Sacha Ninkovic; Eugene Yuanjin Rui; Scott Channing Sutton; John Howard Tatlock; Martin James Wythes; Luke Raymond Zehnder
- Web page: https://patentgrep.com/patent/US9040515B2

## CPC

- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 401/14: containing three or more hetero rings
- C07D 403/14: containing three or more hetero rings
- C07D 405/14: containing three or more hetero rings
- C07D 407/14: containing three or more hetero rings
- C07D 413/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 413/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D 487/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention relates to compounds of general formula (I) in which R1, R2, U, V, L, M, R5, m, X, Y and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.

## Claims

### Claim 1

A compound of formula (II):
or a pharmaceutically acceptable salt thereof,
wherein:
U is N or CR3;
V is N or CR4;
R1 is C1-C8 alkyl, C1-C8 alkoxy, halo, —OH, —CN or —NR7R8, where each said C1-C8 alkyl or C1-C8 alkoxy is optionally substituted by one or more R21;
R2 is selected from the group consisting of H, C1-C8 alkyl, C1-C8 alkoxy, —OR6, —NR7R8, —C(O)NR7R8, —SO2NR7R8, —NR7SO2R8, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl, where each said C1-C8 alkyl or C1-C8 alkoxy is optionally substituted by one or more R22, and each said C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl or 5-12 membered heteroaryl is optionally substituted by one or more R32;
R3 is H, C1-C8 alkyl, C1-C8 alkoxy, halo, —OH, —CN or —NR7R8, where each said C1-C8 alkyl or C1-C8 alkoxy is optionally substituted by one or more R23;
R4 is selected from the group consisting of H, halo, C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, 5-12 membered heteroaryl, —(C1-C4 alkyl)Rz, —ORx, —CN, —C(O)Rx, —CO2Rx, —C(O)NRxRy, —SRx, —SORx, —SO2Rx, —SO2NRxRy, —NO2, —NRxRy, —NRxC(O)Ry, —NRxC(O)NRxRy, —NRxC(O)ORy, NRxSO2Ry, —NRxSO2NRxRy, —OC(O)Rx and —OC(O)NRxRy;
each Rx and Ry is independently selected from the group consisting of H, C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl; or Rx and Ry may be taken together with the N atom to which they are attached to form a 3-12 membered heterocyclyl or 5-12 membered heteroaryl ring, each optionally containing 1, 2 or 3 additional heteroatoms selected from O, N and S;
each Rz is independently selected from the group consisting of C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl; and
wherein each said C1-C8 alkyl in R4, Rx or Ry and each said C1-C4 alkyl in (C1-C4 alkyl)Rz is optionally substituted by one or more R24, and each said C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, or 5-12 membered heteroaryl in R4, Rx, Ry, Rz, or Rx and Ry taken together is optionally substituted by one or more R34;
each R5 is independently selected from the group consisting of halo, —OH, ═O, C1-C4 alkyl, C1-C4 alkoxy, —CN, —NR9R10 and —C(O)NR9R10, where each said C1-C4 alkyl or C1-C4 alkoxy is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, —OH, C1-C4 alkoxy, —CN, —NR9R10 and —C(O)NR9R10;
R6 is —(CR11R12)n—R13;
each R7 and R8 is independently selected from the group consisting of H, C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, and 5-12 membered heteroaryl; or
R7 and R8 may be taken together with the N atom to which they are attached to form a 3-12 membered heterocyclyl or 5-12 membered heteroaryl, each optionally containing 1, 2 or 3 additional heteroatoms selected from O, N and S;
where each said C1-C8 alkyl in R7 or R8 is optionally substituted by one or more R27, and each said C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, or 5-12 membered heteroaryl in R7, R8, or R7 and R8 taken together is optionally substituted by one or more R37;
each R9 and R10 is independently H or C1-C4 alkyl; or
R9 and R10 may be taken together with the N atom to which they are attached to form a 3-12 membered heterocyclyl or 5-12 membered heteroaryl, each optionally containing 1, 2 or 3 additional heteroatoms selected from O, N and S;
where each said C1-C4 alkyl in R9 or R10, and each said 3-12 membered heterocyclyl or 5-12 membered heteroaryl in R9 and R10 taken together is optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, —OH, ═O, C1-C4 alkyl, C1-C4 alkoxy, —CN, —NH2, —NH(C1-C4 alkyl) and —N(C1-C4 alkyl)2;
each R11 and R12 is independently H, halo or C1-C4 alkyl, where each said C1-C4 alkyl is optionally substituted by one or more R22;
R13 is selected from the group consisting of C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, and 5-12 membered heteroaryl, where each said C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl or 5-12 membered heteroaryl is optionally substituted by one or more R32;
m is 0 to 4;
n is 0 to 4;
each R21, R22, R23 and R24 is independently selected from the group consisting of halo, C1-C8 alkyl, —CN, ═O, —C(O)Re, —CO2Re, —C(O)NReRf, —ORe, —SRe, —SORe, —SO2Re, —SO2NReRf, —NO2, —NReRf, —NReC(O)Rf, —NReC(O)NReRf, —NReC(O)ORf—NReSO2Rf, —NReSO2NReRf, —OC(O)Re, —OC(O)NReRf, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl;
each Re and Rf is independently selected from the group consisting of H, C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl; or
Re and Rf may be taken together with the N atom to which they are attached to form a 3-12 membered heterocyclyl or 5-12 membered heteroaryl ring, each optionally containing 1, 2 or 3 additional heteroatoms selected from O, N and S;
wherein each said C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl or 5-12 membered heteroaryl in R24, Re, Rf, or Re and Rf taken together is optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, —OH, ═O, C1-C4 alkyl, C1-C4 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C4 alkoxy-C1-C6 alkyl, —CN, —NH2, —NH(C1-C4 alkyl) and —N(C1-C4 alkyl)2;
each R27 is independently selected from the group consisting of halo, —OH, C1-C4 alkoxy, —CN, —NR9R10, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl, where each said C1-C4 alkoxy, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl or 5-12 membered heteroaryl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, —OH, ═O, C1-C4 alkyl, C1-C4 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C4 alkoxy-C1-C6 alkyl, —CN, —NH2, —NH(C1-C4 alkyl) and —N(C1-C4 alkyl)2;
each R32, R34 and R37 is independently selected from the group consisting of halo, C1-C8 alkyl, —CN, ═O, —C(O)Rc, —CO2Rc, —C(O)NRcRd, —ORc, —SRc, —SORc, —SO2Rc, —SO2NRcRd, —NO2, —NRcRd, —NRcC(O)Rd, —NRcC(O)NRcRd, —NRcC(O)ORd, —NRcSO2Rd, —NRcSO2NRcRd, —OC(O)Rc, —OC(O)NRcRd, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl;
each Rc and Rd is independently selected from the group consisting of H, C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl; or
Rc and Rd may be taken together with the N atom to which they are attached to form a 3-12 membered heterocyclyl or 5-12 membered heteroaryl ring, each optionally containing 1, 2 or 3 additional heteroatoms selected from O, N and S;
wherein each said C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl or 5-12 membered heteroaryl in R32, R34, R37, Rc, Rd, or Rc and Rd taken together is optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, —OH, ═O, C1-C4 alkyl, C1-C4 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C4 alkoxy-C1-C6 alkyl, —CN, —NH2, —NH(C1-C4 alkyl) and —N(C1-C4 alkyl)2;
X and Z are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, 5-12 membered heteroaryl, halo, CN, —C(O)Ra, —CO2Ra, —C(O)NRaRb, —SRa, —SORa, —SO2Ra, —SO2NRaRb, —NO2, —NRaRb, —NRaC(O)Rb, —NRaC(O)NRaRb, —NRaC(O)ORa, —NRaSO2Rb, —NRaSO2NRaRb—ORa, —OC(O)Ra or —OC(O)NRaRb;
wherein each said C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, or 5-12 membered heteroaryl group is optionally substituted by one or more substituents independently selected from the group consisting of halo, —CN, —C(O)Ra, —CO2Ra, —C(O)NRaRb, —SRa, —SORa, —SO2Ra, —SO2NRaRb, —NO2, —NRaRb, —NRaC(O)Rb, —NRaC(O)NRaRb, —NRaC(O)ORa—NRaSO2Rb, —NRaSO2NRaRb, —ORa, —OC(O)Ra, —OC(O)NRaRb, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, and 5-12 membered heteroaryl;
each Ra and Rb is independently H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl or 5-12 membered heteroaryl, where each said C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl is optionally substituted by one or more substituents independently selected from the group consisting of halo, C1-C4 alkyl, —OR14, —NR142, —CO2R14, —C(O)NR142, —SO2R14 and —SO2NR142, where each R14 is independently H or C1-C4 alkyl; or
Ra and Rb may be taken together with the N atom to which they are attached to form a 3-12 membered heterocyclyl or 5-12 membered heteroaryl, each optionally containing 1, 2 or 3 additional heteroatoms selected from O, N and S, wherein said heterocyclyl or heteroaryl is optionally substituted by one or more substituents independently selected from the group consisting of halo, —OH, ═O, C1-C4 alkyl, C1-C4 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C4 alkoxy-C1-C6 alkyl, —CN, —NH2, —NH(C1-C4 alkyl) and —N(C1-C4 alkyl)2; and
Y is H, halo, —OH or C1-C4 alkoxy.

### Claim 2 (depends on 1)

The compound or salt of claim 1, wherein U is CR3 and V is CR4.

### Claim 3 (depends on 2)

The compound or salt of claim 2, wherein R3 is H and R4 is H or halo.

### Claim 4 (depends on 1)

The compound or salt of claim 1, wherein R1 is C1-C8 alkyl or halo.

### Claim 5 (depends on 1)

The compound or salt of claim 1, wherein R2 is 5-12 membered heteroaryl, where said 5-12 membered heteroaryl is optionally substituted by 1 to 3 R32.

### Claim 6 (depends on 1)

The compound or salt of claim 1, wherein R2 is OR6, where n is 0 or 1, and R13 is 3-12 membered heterocyclyl or 5-12 membered heteroaryl, where each said 3-12 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted by 1 to 3 R32.

### Claim 7 (depends on 1)

The compound or salt of claim 1, wherein X and Z are independently selected from the group consisting of H, C1-C8 alkyl and C3-C8 cycloalkyl, and Y is H.

### Claim 8

A compound of formula (II-A):
or a pharmaceutically acceptable salt thereof,
wherein:
R1 is C1-C8 alkyl, C1-C8 alkoxy, halo, —OH, —CN or —NR7R8, where each said C1-C8 alkyl or C1-C8 alkoxy is optionally substituted by one or more R21;
R2 is selected from the group consisting of H, C1-C8 alkyl, C1-C8 alkoxy, —OR6, —NR7R8, —C(O)NR7R8, —SO2NR7R8, —NR7SO2R8, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl, where each said C1-C8 alkyl or C1-C8 alkoxy is optionally substituted by one or more R22, and each said C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl or 5-12 membered heteroaryl is optionally substituted by one or more R32;
R3 is H, C1-C8 alkyl, C1-C8 alkoxy, halo, —OH, —CN or —NR7R8, where each said C1-C8 alkyl or C1-C8 alkoxy is optionally substituted by one or more R23;
R4 is selected from the group consisting of H, halo, C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, 5-12 membered heteroaryl, —(C1-C4 alkyl)Rz, —ORx, —CN, —C(O)Rx, —CO2Rx, —C(O)NRxRy, —SRx, —SORx, —SO2Rx, —SO2NRxRy, —NO2, —NRxRy, —NRxC(O)Ry, —NRxC(O)NRxRy, —NRxC(O)ORy, NRxSO2Ry, —NRxSO2NRxRy, —OC(O)Rx and —OC(O)NRxRy;
each Rx and Ry is independently selected from the group consisting of H, C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl; or Rx and Ry may be taken together with the N atom to which they are attached to form a 3-12 membered heterocyclyl or 5-12 membered heteroaryl ring, each optionally containing 1, 2 or 3 additional heteroatoms selected from O, N and S;
each Rz is independently selected from the group consisting of C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl; and
wherein each said C1-C8 alkyl in R4, Rx or Ry and each said C1-C4 alkyl in (C1-C4 alkyl)Rz is optionally substituted by one or more R24, and each said C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, or 5-12 membered heteroaryl in R4, Rx, Ry, Rz, or Rx and Ry taken together is optionally substituted by one or more R34;
each R5 is independently selected from the group consisting of halo, —OH, ═O, C1-C4 alkyl, C1-C4 alkoxy, —CN, —NR9R10 and —C(O)NR9R10, where each said C1-C4 alkyl or C1-C4 alkoxy is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, —OH, C1-C4 alkoxy, —CN, —NR9R10 and —C(O)NR9R10;
R6 is —(CR11R12)n—R13;
each R7 and R8 is independently selected from the group consisting of H, C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, and 5-12 membered heteroaryl; or
R7 and R8 may be taken together with the N atom to which they are attached to form a 3-12 membered heterocyclyl or 5-12 membered heteroaryl, each optionally containing 1, 2 or 3 additional heteroatoms selected from O, N and S;
where each said C1-C8 alkyl in R7 or R8 is optionally substituted by one or more R27, and each said C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, or 5-12 membered heteroaryl in R7, R8, or R7 and R8 taken together is optionally substituted by one or more R37;
each R9 and R10 is independently H or C1-C4 alkyl; or
R9 and R10 may be taken together with the N atom to which they are attached to form a 3-12 membered heterocyclyl or 5-12 membered heteroaryl, each optionally containing 1, 2 or 3 additional heteroatoms selected from O, N and S;
where each said C1-C4 alkyl in R9 or R10, and each said 3-12 membered heterocyclyl or 5-12 membered heteroaryl in R9 and R10 taken together is optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, —OH, ═O, C1-C4 alkyl, C1-C4 alkoxy, —CN, —NH2, —NH(C1-C4 alkyl) and —N(C1-C4 alkyl)2;
each R11 and R12 is independently H, halo or C1-C4 alkyl, where each said C1-C4 alkyl is optionally substituted by one or more R22;
R13 is selected from the group consisting of C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, and 5-12 membered heteroaryl, where each said C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl or 5-12 membered heteroaryl is optionally substituted by one or more R32;
m is 0 to 4;
n is 0 to 4;
each R21, R22, R23 and R24 is independently selected from the group consisting of halo, C1-C8 alkyl, —CN, ═O, —C(O)Re, —CO2Re, —C(O)NReRf, —ORe, —SRe, —SORe, —SO2Re, —SO2NReRf, —NO2, —NReRf, —NReC(O)Rf, —NReC(O)NReRf, —NReC(O)ORf—NReSO2Rf, —NReSO2NReRf, —OC(O)Re, —OC(O)NReRf, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl;
each Re and Rf is independently selected from the group consisting of H, C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl; or
Re and Rf may be taken together with the N atom to which they are attached to form a 3-12 membered heterocyclyl or 5-12 membered heteroaryl ring, each optionally containing 1, 2 or 3 additional heteroatoms selected from O, N and S;
wherein each said C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl or 5-12 membered heteroaryl in R24, Re, Rf, or Re and Rf taken together is optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, —OH, ═O, C1-C4 alkyl, C1-C4 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C4 alkoxy-C1-C6 alkyl, —CN, —NH2, —NH(C1-C4 alkyl) and —N(C1-C4 alkyl)2;
each R27 is independently selected from the group consisting of halo, —OH, C1-C4 alkoxy, —CN, —NR9R10, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl, where each said C1-C4 alkoxy, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl or 5-12 membered heteroaryl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, —OH, ═O, C1-C4 alkyl, C1-C4 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C4 alkoxy-C1-C6 alkyl, —CN, —NH2, —NH(C1-C4 alkyl) and —N(C1-C4 alkyl)2;
each R32, R34 and R37 is independently selected from the group consisting of halo, C1-C8 alkyl, —CN, ═O, —C(O)Rc, —CO2Rc, —C(O)NRcRd, —SRc, —SORc, —SO2Rc, —SO2NRcRd, —NO2, —NRcRd, —NRcC(O)Rd, —NRcC(O)NRcRd, —NRcC(O)ORd, —NRcSO2Rd, —NRcSO2NRcRd, —OC(O)Rc, —OC(O)NRcRd, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl;
each Rc and Rd is independently selected from the group consisting of H, C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl; or
Rc and Rd may be taken together with the N atom to which they are attached to form a 3-12 membered heterocyclyl or 5-12 membered heteroaryl ring, each optionally containing 1, 2 or 3 additional heteroatoms selected from O, N and S;
wherein each said C1-C8 alkyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl or 5-12 membered heteroaryl in R32, R34, R37, Rc, Rd, or Rc and Rd taken together is optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, —OH, ═O, C1-C4 alkyl, C1-C4 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C4 alkoxy-C1-C6 alkyl, —CN, —NH2, —NH(C1-C4 alkyl) and —N(C1-C4 alkyl)2;
X and Z are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, 5-12 membered heteroaryl, halo, CN, —C(O)Ra, —CO2Ra, —C(O)NRaRb, —SRa, —SORa, —SO2Ra, —SO2NRaRb, —NO2, —NRaRb, —NRaC(O)Rb, —NRaC(O)NRaRb, —NRaC(O)ORa, —NRaSO2Rb, —NRaSO2NRaRb—ORa, —OC(O)Ra or —OC(O)NRaRb;
wherein each said C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, or 5-12 membered heteroaryl group is optionally substituted by one or more substituents independently selected from the group consisting of halo, —CN, —C(O)Ra, —CO2Ra, —C(O)NRaRb, —SRa, —SORa, —SO2Ra, —SO2NRaRb, —NO2, —NRaRb, —NRaC(O)Rb, —NRaC(O)NRaRb, —NRaC(O)ORa—NRaSO2Rb, —NRaSO2NRaRb, —ORa, —OC(O)Ra, —OC(O)NRaRb, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl, and 5-12 membered heteroaryl;
each Ra and Rb is independently H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl or 5-12 membered heteroaryl, where each said C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, 3-12 membered heterocyclyl, C6-C12 aryl and 5-12 membered heteroaryl is optionally substituted by one or more substituents independently selected from the group consisting of halo, C1-C4 alkyl, —OR14, —NR142, —CO2R14, —C(O)NR142, —SO2R14 and —SO2NR142, where each R14 is independently H or C1-C4 alkyl; or
Ra and Rb may be taken together with the N atom to which they are attached to form a 3-12 membered heterocyclyl or 5-12 membered heteroaryl, each optionally containing 1, 2 or 3 additional heteroatoms selected from O, N and S, wherein said heterocyclyl or heteroaryl is optionally substituted by one or more substituents independently selected from the group consisting of halo, —OH, ═O, C1-C4 alkyl, C1-C4 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C4 alkoxy-C1-C6 alkyl, —CN, —NH2, —NH(C1-C4 alkyl) and —N(C1-C4 alkyl)2; and
Y is H, halo, —OH or C1-C4 alkoxy.

### Claim 9 (depends on 8)

The compound or salt of claim 8, wherein R1 is C1-C8 alkyl or halo.

### Claim 10 (depends on 8)

The compound or salt of claim 8, wherein R2 is 5-12 membered heteroaryl, where said 5-12 membered heteroaryl is optionally substituted by 1 to 3 R32.

### Claim 11 (depends on 10)

The compound or salt of claim 10, wherein each R32 is independently selected from the group consisting of halo, C1-C8 alkyl, —ORc, —SRc, —SO2Rc and —NRcRd, and each Rc and Rd is independently H or C1-C8 alkyl.

### Claim 12 (depends on 8)

The compound or salt of claim 8, wherein R2 is OR6, n is 0 or 1, and R13 is 3-12 membered heterocyclyl or 5-12 membered heteroaryl, where each said 3-12 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted by 1 to 3 R32.

### Claim 13 (depends on 12)

The compound or salt of claim 12, wherein each R32 is independently selected from the group consisting of halo and C1-C8 alkyl, where each said C1-C8 alkyl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, —OH, ═O, C1-C4 alkyl, C1-C4 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C4 alkoxy-C1-C6 alkyl, —CN, —NH2, —NH(C1-C4 alkyl) and —N(C1-C4 alkyl)2.

### Claim 14 (depends on 8)

The compound or salt of claim 8, wherein R3 is H and R4 is selected from the group consisting of H, halo, —CN and C1-C8 alkyl, where said C1-C8 alkyl is optionally substituted by 1 to 3 R24.

### Claim 15 (depends on 8)

The compound or salt of claim 8, wherein X and Z are independently selected from the group consisting of H, C1-C8 alkyl and C3-C8 cycloalkyl, and Y is H.

### Claim 16 (depends on 8)

The compound or salt of claim 8, wherein m is 0.

### Claim 17 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.