IP Library › Patent Application 10579938

Patent Application

App. No. 10/579,938

Indolyl-thienopyrazinone derivatives useful for treating hyperproliferative disorders and diseases associated with angiogenesis

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US None
App. No.: 10/579,938

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

This invention relates to a compound of Formula (I): (I) and its use in treating hyper-proliferative disorders and diseases associated with angiogenesis.

Claims (179)

1 . A compound of Formula I

wherein

R 1 is selected from H, F, and Cl;

R 2 is selected from H, OH, CN, halo, C(O)R 5 , thienyl, pyrimidinyl, oxazolyl, furanyl,

(C 1 -C 3 )alkyl, (C 2 -C 6 )alkenyl and (C 2 -C 6 )alkynyl, each optionally substituted with up to two substituents selected from OH, halo, and

(C 1 -C 3 )alkoxy optionally substituted with (C 1 -C 3 )alkoxy,

(C 1 -C 6 )alkoxy optionally substituted with (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, pyrrolidinyl,

and N[(C 1 -C 3 )alkyl] 2 where each alkyl group is independently optionally substituted with a substituent selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy OH, halo,

and phenyl,

N[(C 1 -C 4 )alkyl] 2 where each alkyl group is independently optionally substituted with up to two substituents independently selected from OH, (C 1 -C 3 )alkyl, halo, (C 1 -C 3 )alkoxy, and phenyl,

pyridyl optionally substituted with up to two substituents independently selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, and halo,

phenyl optionally substituted with up to two substituents independently selected from (C 1 -C 3 )alkoxy, CN, halo,

C(O)N[(C 1 -C 3 )alkyl] 2 where each alkyl is optionally substituted with (C 1 -C 3 )alkoxy, and

pyrrolidinyl optionally substituted with N[(C 1 -C 3 )alkyl] 2 ;

R 3 is selected from H, halo, (C 1 -C 3 )alkyl, and (C 1 -C 3 )alkoxy;

R 4 is selected from H, F, and Cl;

R 5 is selected from OH, NHR 6 ,

N[(C 1 -C 3 )alkyl]R 7 where said alkyl is optionally substituted with up to one substituent selected from (C 1 -C 3 )alkyl and (C 1 -C 3 )alkoxy,

N[(C 1 -C 3 )alkyl] 2 where each alkyl is optionally substituted with up to two substituents independently selected from CN, OH, (C 1 -C 3 )alkoxy, N[(C 1 -C 3 )alkyl] 2 , pyridyl, phenyl, S(O) 2 (C 1 -C 3 )alkyl, tetrahydrofuryl, S(O) 2 -phenyl, (C 3 -C 6 )cycloalkyl, and

furyl optionally substituted with (C 1 -C 3 )alkyl,

N[(C 3 -C 6 )cycloalkyl](C 1 -C 3 )alkyl where said alkyl is substituted with up to two substituents independently selected from (C 1 -C 3 )alkoxy, OH, CN, N[(C 1 -C 4 )alkyl] 2 , S(O) 2 -phenyl, S(O) 2 (C 1 -C 3 )alkyl, phenyl, furyl, tetrahydrofuryl, (C 5 -C 6 )cycloalkyl, and pyridyl,

optionally substituted with up to two substituents independently selected from N[(C 1 -C 3 )alkyl] 2 , C(O)(C 1 -C 3 )alkyl, pyrrolidinyl, S(O) 2 (C 1 -C 3 )alkyl, S(O) 2 -phenyl,

oxo-dihydrobenzimidazolyl, pyrazinyl, C(O)NH 2 , C(O)NH-phenyl, C(O)-furanyl, C(O)NH(C 1 -C 3 )alkyl,

(C 1 -C 3 )alkyl optionally substituted with up to two substituents independently selected from OH, halo, (C 1 -C 3 )alkoxy,

pyrrolidinyl, C(O)-pyrrolidinyl,

and N[(C 1 -C 3 )alkyl] 2 ,

phenyl optionally substituted with up to two substituents independently selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, halo, CF 3 , and CN, and

pyridyl optionally substituted with (C 1 -C 3 )alkyl, CF 3 , and CN, and

pyrrolidinyl optionally substituted with up to two substituents independently selected from N[(C 1 -C 4 )alkyl] 2 , C(O)NH 2 , pyridyl, and

(C 1 -C 3 )alkyl optionally substituted with up to two substituents independently selected from (C 1 -C 3 )alkoxy, and pyrrolidinyl;

R 6 is selected from H,

(C 1 -C 4 )alkyl optionally substituted with up to two substituents independently selected from OH, halo, (C 1 -C 4 )alkoxy, NHC(O)(C 1 -C 3 )alkyl, S—(C 1 -C 3 )alkyl, benzimidazolyl, thienyl,

N[(C 1 -C 4 )alkyl) 2 ] where each alkyl is independently optionally substituted with up to two substituents independently selected from OH, (C 1 -C 3 )alkoxy, halo, and phenyl,

phenyl optionally substituted with up to two substituents independently selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, CN, halo, CF 3 , S(O) 2 (C 1 -C 3 )alkyl, S(O) 2 phenyl, and S(O) 2 NH 2 ,

pyridyl optionally substituted up to two times with CF 3 ,

indolyl optionally substituted up to two times with (C 1 -C 3 )alkyl,

imidazolyl optionally substituted up to two times with (C 1 -C 3 )alkyl,

furyl optionally substituted up to two times with (C 1 -C 4 )alkyl, and

pyrrolidinyl optionally substituted with up to two substituents independently selected from (C 1 -C 4 )alkoxy, (O), and

(C 1 -C 4 )alkyl optionally substituted with up to two substituents independently selected from OH, (C 1 -C 3 )alkoxy, and halo,

indolyl optionally substituted up to two times with (C 1 -C 3 )alkyl,

pyrazolyl optionally substituted with up to two substituents independently selected from (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, and

phenyl optionally substituted with up to two substituents independently selected from (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkyl, halo, CF 3 , and CN,

benzothiazolyl optionally substituted up to two times with (C 1 -C 4 )alkyl,

thiazolyl optionally substituted up to two times with (C 1 -C 4 )alkyl,

thiadiazolyl optionally substituted with up to two substituents independently selected from CF 3 , (C 3 -C 6 )cycloalkyl, and (C 1 -C 6 )alkyl,

phenyl optionally substituted with up to two substituents independently selected from CN, halo, CF 3 , N[(C 1 -C 4 )alkyl] 2 , indolyl,

(C 1 -C 4 )alkoxy, O-pyridyl optionally substituted with C(O)NH(C 1 -C 4 )alkyl,

(C 1 -C 4 )alkyl optionally substituted with up to two substituents independently selected from pyridyl, OH, halo, and phenyl, and

optionally substituted with up to two substituents independently selected from (C 1 -C 3 )alkyl, and (C 1 -C 4 )alkoxy,

pyridyl optionally substituted with phenoxy where said phenoxy is optionally substituted with up to two substituents independently selected from (C 1 -C 4 )alkyl and (C 1 -C 4 )alkoxy, and

indazolyl optionally substituted up to two times with (C 1 -C 4 )alkyl;

R 7 is selected from (C 1 -C 3 )alkoxy, pyrrolidinyl, tetrahydropyranyl,

pyridyl optionally substituted with up to two substituents independently selected from (C 1 -C 4 )alkyl and (C 1 -C 3 )alkoxy,

pyranyl optionally substituted with up to two substituents independently selected from (C 1 -C 4 )alkyl and (C 1 -C 3 )alkoxy,

piperidinyl optionally substituted with up to two substituents independently selected from (C 1 -C 3 )alkyl, and (C 1 -C 3 )alkoxy, and

phenyl optionally substituted with up to two substituents independently selected from (C 1 -C 3 )alkoxy, and (C 1 -C 3 )alkyl; and

X is selected from O, S, CH 2 and NH;

with the proviso that when R 1 is F or Cl, then R 4 must be H, and when R 4 is F or Cl, then R 1 must be H;

or a pharmaceutically acceptable salt thereof.

2 . A method of treating a disorder selected from a hyper-proliferative disorder and a disorder associated with angiogenesis, in a mammal in need thereof, comprising administering to said mammal an effective amount of a compound of Formula I