Aurora kinase inhibitors for inhibiting mitotic progression

Patent metadata

Field	Value
Publication number	US-10836766-B2
Application number	US-201815996166-A
Country	US
Kind code	B2
Filing date	Jun 1, 2018
Priority date	Nov 16, 2006
Publication date	Nov 17, 2020
Grant date	Nov 17, 2020

Abstract

The present invention relates to compounds and methods for the treatment of cancer. In particular, the invention provides potent inhibitors of Aurora A kinase, pharmaceutical compositions comprising the compounds, and methods of using the compounds for the treatment of cancer.

First claim

What is claimed:

1. A method for inhibiting Aurora kinase activity in a cell, comprising contacting a cell with a compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
R a is selected from the group consisting of C 1-3 aliphatic, C 1-3 fluoroaliphatic, —R 1 , —T—R 1 , —R 2 , and —T—R 2 ;
T is a C 1-3 alkylene chain optionally substituted with fluoro;
R 1 is an optionally substituted aryl, heteroaryl, or heterocyclyl group;
R 2 is selected from the group consisting of halo, —C≡C—R 3 , —CH═CH—R 3 , —N(R 4 ) 2 , and —OR 5 ;
R 3 is hydrogen or an optionally substituted aliphatic, aryl, heteroaryl, or heterocyclyl group;
each R 4 independently is hydrogen or an optionally substituted aliphatic, aryl, heteroaryl, or heterocyclyl group; or two R 4 on the same nitrogen atom, taken together with the nitrogen atom form an optionally substituted 5- to 6-membered heteroaryl or 4- to 8-membered heterocyclyl ring having, in addition to the nitrogen atom, 0-2 ring heteroatoms selected from N, 0, and S;
R 5 is hydrogen or an optionally substituted aliphatic, aryl, heteroaryl, or heterocyclyl group; and
R b is selected from the group consisting of fluoro, chloro, —CH 3 , —CF 3 , —OH, —OCH 3 , —OCF 3 , —OCH 2 CH 3 , and —OCH 2 CF 3 .

2. The method of claim 1 , wherein:
R a is selected from the group consisting of C 1-3 aliphatic, C 1-3 fluoroaliphatic, —R 1 and —R 2 ;
R 1 is a 5- or 6-membered aryl or heteroaryl optionally substituted with one substituent selected from the group consisting of halo and C 1-3 aliphatic;
R 2 is selected from the group consisting of halo, —C≡C—R 3 , —CH═CH—R 3 , and —OR 5 ;
R 3 is hydrogen, C 1-3 aliphatic or —CH 2 OCH 3 R 5 is hydrogen or C 1-3 aliphatic; and
R b is selected from the group consisting of fluoro, —OH, —OCH 3 , —OCF 3 , and —OCH 2 CF 3 .

3. The method of claim 1 , wherein:
R a is halo, C 1-3 aliphatic, C 1-3 fluoroaliphatic, —OH, —O(C 1-3 aliphatic), —O(C 1-3 fluoroaliphatic), or —C≡C—R 3 , —CH═CH—R 3 ; and R 3 is hydrogen, C 1-3 aliphatic, or —CH 2 —OCH 3 ; or
R a is a phenyl, furyl, pyrrolidinyl, or thienyl ring optionally substituted with one substituent selected from the group consisting of halo and C 1-3 aliphatic.

4. The method of claim 3 , wherein:
R a is selected from the group consisting of chloro, fluoro, C 1-3 aliphatic, C 1-3 fluoroaliphatic, —OCH 3 , —C≡C—CH 3 , —C≡C—CH 2 OCH 3 , —CH═CH 2 , —CH═CHCH 3 , N-methylpyrrolidinyl, thienyl, methylthienyl, furyl, methylfuryl, phenyl, fluorophenyl, and tolyl.

5. The method of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

Assignees

• Millennium Pharm Inc
• Millenium Pharmaceuticals Inc

Inventors

• Claiborne Christopher F
• Sells Todd B
• Stroud Stephen G

Classifications

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title