# US 10,246,433 B2 · Aryl and heteroaryl fused lactams

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- Number: US 10,246,433 B2
- Document ID: US10246433B2
- Status: Granted
- Kind: B2
- Application number: 15/585,880
- Filed: 2017-05-03
- Published: 2017-08-17
- Granted: 2019-04-02
- 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/US10246433B2

## 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-A):
or a pharmaceutically acceptable salt thereof,
wherein:
R1 is C1-C4 alkyl or halo;
R2 is 5-12 membered heteroaryl, where said 5-12 membered heteroaryl is optionally substituted by 1 to 3 R32 groups;
R3 is H;
R4 is H or halo;
m is 0;
R5 is absent;
each R32 is independently selected from the group consisting of —Cl, —F, —OH, —CH3, —CH2CH3, —CF3, —CH2OH, —CH2OCH3, —OCH3, —OC2H5, —OCF3, —CN, —C(O)NH2, —C(O)NHCH3, —C(O)N(CH3)2, —NHC(O)CH3, —NH2, —NHCH3, —N(CH3)2, cyclopropyl, 4-6 membered heterocyclyl, phenyl and 5-6 membered heteroaryl, where said 4-6 membered heterocyclyl, phenyl or 5-6 membered heteroaryl are optionally substituted by 1 to 3 halo, C1-C4 alkyl or C1-C4 alkoxy, which are independently selected;
X and Z are independently C1-C4 alkyl; and
Y is H.

### Claim 2 (depends on 1)

The compound or salt of claim 1, wherein R1 is chloro.

### Claim 3 (depends on 1)

The compound or salt of claim 1, wherein R2 is 5-12 membered heteroaryl selected from the group consisting of pyrazolyl, isoxazoyl and triazolyl, where said 5-12 membered heteroaryl is optionally substituted by 1 to 3 R32 groups.

### Claim 4 (depends on 3)

The compound or salt of claim 3, wherein each R32 is independently selected from the group consisting of —CH3 and —CH2CH3.

### Claim 5 (depends on 1)

The compound or salt of claim 1, wherein R4 is halo.

### Claim 6 (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.

### Claim 7 (depends on 1)

A method for the treatment of abnormal cell growth in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 7)

The method of claim 7, wherein the abnormal cell growth is cancer.

### Claim 9 (depends on 7)

The method of claim 7, wherein the subject is human.

### Claim 10

A compound that is 5-bromo-8-chloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one, or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 10)

A pharmaceutical composition comprising the compound of claim 10, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

### Claim 12 (depends on 10)

The compound of claim 10 that is 5-bromo-8-chloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one.

### Claim 13 (depends on 10)

A pharmaceutically acceptable salt of the compound of claim 10 that is 5-bromo-8-chloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one.

### Claim 14 (depends on 12)

A pharmaceutical composition comprising the compound of claim 12, and a pharmaceutically acceptable carrier or excipient.

### Claim 15 (depends on 13)

A pharmaceutical composition comprising the pharmaceutically acceptable salt of claim 13, and a pharmaceutically acceptable carrier or excipient.

### Claim 16

A compound of formula (II-A):
or a pharmaceutically acceptable salt thereof, wherein:
R1 is C1-C4 alkyl or halo;
R2 is a 5-6 membered heteroaryl, optionally substituted by 1 to 3 R32 groups;
R3 is H;
R4 is H or halo;
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; or
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;
m is 0 and R5 is absent;
X and Z are independently C1-C4 alkyl; and
Y is H.