# US 7,465,726 B2 · Substituted pyrrolo[2.3-B]pyridines

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 7,465,726 B2
- Document ID: US7465726B2
- Status: Granted
- Kind: B2
- Application number: 11/194,158
- Filed: 2005-08-01
- Published: 2006-09-21
- Granted: 2008-12-16
- Earliest claimed: 2004-08-02
- Assignees: OSI Pharmaceuticals, Inc.
- Inventors: Saleh Ahmed; Oscar Barba; Jason Bloxham; Graham Dawson; William Gattrell; John Kitchin; Neil Anthony Pegg; Imaad Saba; Shazia Sadiq; Colin Peter Sambrook Smith; Don Smyth; Amo G. Steinig; Robin Wilkes; Bijoy Panicker; Paula Tavares; Matthew Cox; An-Hu Li; Hanqing Dong; Lifu Ma; Kenneth (‘Ken’) Foreman; Qinghua (‘Felix’) Weng; Kathryn Stolz
- Web page: https://patentgrep.com/patent/US7465726B2

## CPC

- C07D 471/02: in which the condensed system contains two hetero rings
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 487/02: in which the condensed system contains two hetero rings
- C07D 487/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Compounds represented by Formula (I): or stereoisomers or pharmaceutically acceptable salts thereof, are inhibitors of least two of the Abl, Aurora-A, Blk, c-Raf, cSRC, Src, PRK2, FGFR3, Flt3, Lck, Mek1, PDK-1, GSK3β, EGFR, p70S6K, BMX, SGK, CaMKII, Tie-2, IGF-1R, Ron, Ret, and KDR kinases in animals, including humans, for the treatment and/or prevention of various diseases and conditions such as cancer.

## Claims

### Claim 1

A compound represented by Formula I:
or a pharmaceutically acceptable salt thereof, wherein
X is C—CN;
Cy is
z is hetaryl, —C1-6alkyl-O—C1-6alkyl-, —C0-6alkyl-(heterocyclyl), —C0-6alkyl-(hetaryl), —C(O)—C0-6alkyl, —C(O)—C0-6alkyl-O—C0-6alkyl, —C(O)—C0-6alkyl-O—C1-6alkyl-O—C0-6alkyl, —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), —C(O)—C0-6alkyl-(heterocyclyl)-C(O)—C0-6alkyl, —C(O)—C0-6alkyl-(hetaryl), —S(O)2—C0-6alkyl, —S(O)2—N(C0-6alkyl)(C0-6alkyl), or —S(O)2—(hetaryl), wherein any of the alkyl, heterocyclyl, or hetaryl optionally is substituted with 1-6 independent halo, OH, —C0-6alkyl-O—C0-6alkyl, —C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), or —C0-6alkyl;
in which the wavy bond is the point of attachment, and wherein the piperazine or morpholine moieties are optionally substituted with 1-6 independent C0-6alkyl groups;
Y is —C(C0-6alkyl)(C0-6alkyl)-, —N(C0-6alkyl)-, —N(C0-6alkyl)-C1-6alkyl-, O, S, >N—C2-6alkyl-N—(C0-6alkyl)(C0-6alkyl), >N—C2-6alkyl-O—C0-6alkyl, >N—C1-6alkyl-C(O)—NH—C0-6alkyl, or >N—C2-6alkyl-N—C(O)—C1-6alkyl; and
R1 is aryl, hetaryl, or heterocyclyl, optionally substituted with 1-6 independent halo, —CN, —OH, —C0-6alkyl, —C3-10cycloalkyl, -haloC1-6alkyl, —C2-6alkynyl, —N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), —C1-6alkyl-C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —O—C0-6alkyl-(heterocyclyl), —C0-6alkyl-O—C0-6alkyl, —C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —O—C0-6alkyl-(hetaryl), —S(O)2—N(C0-6alkyl)(C0-6alkyl), aryl, hetaryl, or heterocyclyl substituents, or substituted with an oxo (═O) using a bond from the aryl, hetaryl, or heterocyclyl ring, wherein any of the substituents optionally is substituted with 1-6 independent halo, CN, OH, —C0-6alkyl-O—C0-6alkyl, —C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), or C0-6alkyl; or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein Cy is

### Claim 3 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is aryl optionally substituted with with 1-6 independent halo, —CN, —OH, —C0-6alkyl, -haloC1-6alkyl, —C2-6alkynyl, —N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —O—C0-6alkyl-(heterocyclyl), —O—C0-6alkyl-(hetaryl), —S(O)2—N(C0-6alkyl)(C0-6alkyl), aryl, hetaryl, or heterocyclyl substituents, or substituted with an oxo (═O) using a bond from the aryl ring, wherein any of the substituents optionally is substituted with 1-6 independent halo or C0-6alkyl.

### Claim 4 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is aryl optionally substituted with 1-6 independent halo, —CN, —OH, —C0-6alkyl, —C3-10cycloalkyl, -haloC1-6alkyl, —C2-6alkynyl, —N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), —C1-6alkyl-C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —O—C0-6alkyl-(heterocyclyl), —C0-6alkyl-O—C0-6alkyl, —C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —O—C0-6alkyl-(hetaryl), —S(O)2—N(C0-6alkyl)(C0-6alkyl), aryl, hetaryl, or heterocyclyl substituents, or substituted with an oxo (═O) using a bond from the aryl, hetaryl, or heterocyclyl ring, wherein any of the substituents optionally is substituted with 1-6 independent halo, CN, OH, —C0-6alkyl-O—C0-6alkyl, —C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), or C6alkyl.

### Claim 5 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is hetaryl optionally substituted with 1-6 independent halo, —CN, —OH, —C0-6alkyl, -haloC1-6alkyl, —C2-6alkynyl, —N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —O—C0-6alkyl-(heterocyclyl), —O—C0-6alkyl-(hetaryl), —S(O)2—N(C0-6alkyl)(C0-6alkyl), aryl, hetaryl, or heterocyclyl substituents, or substituted with an oxo (═O) using a bond from the hetaryl ring, wherein any of the substituents optionally is substituted with 1-6 independent halo or C0-6alkyl.

### Claim 6 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is hetaryl optionally substituted with 1-6 independent halo, —CN, —OH, —C0-6alkyl, —C3-10cycloalkyl, -haloC1-6alkyl, —C2-6alkynyl, —N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), —C1-6alkyl-C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —O—C0-6alkyl-(heterocyclyl), —C0-6alkyl-O—C0-6alkyl, —C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —O—C0-6alkyl-(hetaryl), —S(O)2—N(C0-6alkyl)(C0-6alkyl), aryl, hetaryl, or heterocyclyl substituents, or substituted with an oxo (═O) using a bond from the aryl, hetaryl, or heterocyclyl ring, wherein any of the substituents optionally is substituted with 1-6 independent halo, CN, OH, —C0-6alkyl-O—C0-6alkyl, —C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), or C0-6alkyl.

### Claim 7 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is heterocyclyl optionally substituted with 1-6 independent halo, —CN, —OH, —C0-6alkyl, -haloC1-6alkyl, —C2-6alkynyl, —N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —O—C0-6alkyl-(heterocyclyl), —O—C0-6alkyl-(hetaryl), —S(O)2—N(C0-6alkyl)(C0-6alkyl), aryl, hetaryl, or heterocyclyl substituents, or substituted with an oxo (═O) using a bond from the heterocyclyl ring, wherein any of the substituents optionally is substituted with 1-6 independent halo or C0-6alkyl.

### Claim 8 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is heterocyclyl optionally substituted with 1-6 independent halo, —CN, —OH, —C0-6alkyl, —C3-10cycloalkyl, -haloC1-6alkyl, —C2-6alkynyl, —N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), —C1-6alkyl-C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —O—C0-6alkyl-(heterocyclyl), —C0-6alkyl-O—C0-6alkyl, —C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —O—C0-6alkyl-(hetaryl), —S(O)2—N(C0-6alkyl)(C0-6alkyl), aryl, hetaryl, or heterocyclyl substituents, or substituted with an oxo (═O) using a bond from the aryl, hetaryl, or heterocyclyl ring, wherein any of the substituents optionally is substituted with 1-6 independent halo, CN, OH, —C0-6alkyl-O—C0-6alkyl, —C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), or C0-6alkyl.

### Claim 9 (depends on 1)

The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein Y—R1 is

### Claim 10 (depends on 1)

The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein Y is —N(C0-6alkyl)-.

### Claim 11

A compound represented by Formula I:
a pharmaceutically acceptable salt thereof, wherein
X is C—CN;
Cy is
Z is hetaryl, —C1-6alkyl-O—C1-6alkyl-, —C0-6alkyl-(heterocyclyl), —C0-6alkyl-(hetaryl), —C(O)—C0-6alkyl, —C(O)—C0-6alkyl-O—C0-6alkyl, —C(O)—C0-6alkyl-O—C1-6alkyl-O—C0-6alkyl, —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), —C(O)—C0-6alkyl-(heterocyclyl)-C(O)—C0-6alkyl, —C(O)—C0-6alkyl-(hetaryl), —S(O)2—C0-6alkyl, —S(O)2—N(C0-6alkyl)(C0-6alkyl), or —S(O)2—(hetaryl), wherein any of the alkyl, heterocyclyl, or hetaryl optionally is substituted with 1-6 independent halo, OH, —C0-6alkyl-O—C0-6alkyl, —C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), or —C0-6alkyl;
or z is
in which the wavy bond is the point of attachment, and wherein the piperazine or morpholine moieties are optionally substituted with 1-6 independent C0-6alkyl groups;
Y is —C(C0-6alkyl)(C0-6alkyl)-, —N(C0-6alkyl)-, —N(C0-6alkyl)-C1-6alkyl-, O, S, >N—C2-6alkyl-N—(C0-6alkyl)(C0-6alkyl), >N—C2-6alkyl-O—C0-6alkyl, >N—C1-6alkyl-C(O)—NH—C0-6alkyl, or >N—C2-6alkyl-N—C(O)—C1-6alkyl;
wherein R1 is selected from the following table:

### Claim 12

A compound represented by Formula I:
or a pharmaceutically acceptable salt thereof, wherein
X is C—CN;
Cy is
Y is —C(C0-6alkyl)(C0-6alkyl)-, —N(C0-6alkyl)-, —N(C0-6alkyl)-C1-6alkyl-, O, S, >N—C2-6alkyl-N—(C0-6alkyl)(C0-6alkyl), >N—C2-6alkyl-O—C0-6alkyl, >N—C1-6alkyl-C(O)—NH—C0-6alkyl, or >N—C2-6alkyl-N—C(O)—C1-6alkyl; and
R1 is aryl, hetaryl, or heterocyclyl, optionally substituted with 1-6 independent halo, —CN, —OH, —C0-6alkyl, —C3-10cycloalkyl, -haloC1-6alkyl, —C2-6alkynyl, —N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), —C1-6alkyl-C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —O—C0-6alkyl-(heterocyclyl), —C0-6alkyl-O—C0-6alkyl, —C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —O—C0-6alkyl-(hetaryl), —S(O)2—N(C0-6alkyl)(C0-6alkyl), aryl, hetaryl, or heterocyclyl substituents, or substituted with an oxo (═O) using a bond from the aryl, hetaryl, or heterocyclyl ring, wherein any of the substituents optionally is substituted with 1-6 independent halo, CN, OH, —C0-6alkyl-O—C0-6alkyl, —C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-N(C0-6alkyl)(C0-6alkyl), —C(O)—C0-6alkyl-(heterocyclyl), or C0-6alkyl;
wherein z is selected from the following table:

### Claim 13 (depends on 1)

The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein Y—R1 is

### Claim 14 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.