IP Library › Granted Patent US 7,429,584
Granted Patent B2
US 7,429,584 · App. 10/515,605 · Granted Sep 30, 2008

Furo[2.3-b]pyridine derivatives for the treatment of hyper-proliferative disorders

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Quick Facts
Patent No.
US 7,429,584
App. No.
10/515,605
Granted
Sep 30, 2008
Kind
B2
Abstract

This invention relates to a compound of Formula (I) wherein Y is CH or N; Ar 1 is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each selected independently from (C 1 -C 3 )alkoxy halo, OH, CF 3 , CN, NO 2 and (C 1 -C 3 )alkyl, said alkyl being optionally substituted with CF 3 ; Ar 2 is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each independently selected from halo, OH, CN, NO 2 , CF 3 , (C 1 -C 6 )alkoxy, NR 1 R 1 , S(O) 2 R 2 , C(O)R 3 , and (C 1 -C 6 )alkyl optionally substituted with R 4 , and its use in treating hyper-proliferative disorders.

Claims (62)

1. A compound of Formula I

wherein

Y is CH;

Ar 1 is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each selected independently from (C 1 -C 3 )alkoxy, halo, OH, CF 3 , CN, NO 2 and (C 1 -C 3 )alkyl, said alkyl being optionally substituted with CF 3 ;

Ar 2 is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each independently selected from halo, OH, CN, NO 2 , CF 3 , (C 1 -C 6 )alkoxy, NR 1 R 1 , S(O) 2 R 2 , C(O)R 3 , and (C 1 -C 6 )alkyl optionally substituted with R 4 ;

wherein at least one of Ar 1 and Ar 2 is not unsubstituted phenyl and wherein when Ar 1 or Ar 2 is substituted phenyl, said phenyl is not substituted with only 1 (C 1 -C 3 )alkyl substituent;

R 1 is selected from H, S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl, C(O)(C 1 -C 3 )alkyl where said alkyl is optionally substituted with NR 5 R 5 , and (C 1 -C 3 )alkyl where said alkyl is optionally substituted with 1 or 2 substituents each selected independently from OH and (C 1 -C 3 )alkoxy,

with the proviso that in any NR 1 R 1 group when one R 1 is S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 -C 3 )alkyl then the other R 1 must be other than S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 -C 3 )alkyl;

R 2 is selected from (C 1 -C 3 )alkyl, pyrrolidinyl, and NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH;

R 3 is selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, morpholinyl, pyrrolidinyl, piperidinyl, and NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH, (C 1 -C 3 )alkoxy or N[(C 1 -C 3 )alkyl] 2 ;

R 4 is selected from OH, CN, CF 3 , (C 1 -C 3 )alkoxy, C(O)NR 5 R 5 , NR 5 R 5 , and piperidinyl; and

R 5 is selected from H, (C 1 -C 3 )alkyl, C(O)(C 1 -C 3 )alkyl, S(O) 2 (C 1 -C 3 )alkyl and piperidinyl,

with the proviso that in any NR 5 R 5 group when one R 5 is C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1 -C 3 )alkyl, then the other R 5 must be other than C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1 -C 3 )alkyl; and

excluding (3 -amino-6-phenylfuro[2,3 -b]pyridin-2-yl)(4-nitrophenyl)methanone,

or a pharmaceutically acceptable salt thereof.

2. A compound of claim 1 wherein Ar 1 is optionally substituted phenyl.

3. A compound of Formula I

wherein

Y is CH;

Ar 1 is pyridyl optionally substituted with 1 or 2 substituents each selected independently from (C 1 -C 3 )alkoxy, halo, OH, CF 3 , CN, NO 2 and (C 1 -C 3 )alkyl, said alkyl being optionally substituted with CF 3 ;

Ar 2 is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each independently selected from halo, OH, CN, NO 2 , CF 3 , (C 1 -C 6 )alkoxy, NR 1 R 1 , S(O) 2 R 2 , C(O)R 3 , and (C 1 -C 6 )alkyl optionally substituted with R 4 :

R 1 is selected from H, S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl, C(O)(C 1 -C 3 )alkyl where said alkyl is optionally substituted with NR 5 R 5 , and (C 1 -C 3 )alkyl where said alkyl is optionally substituted with 1 or 2 substituents each selected independently from OH and (C 1 -C 3 )alkoxy,

with the proviso that in any NR 1 R 1 group when one R 1 is S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 -C 3 )alkyl then the other R 1 must be other than S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 -C 3 )alkyl;

R 2 is selected from (C 1 -C 3 )alkyl, pyrrolidinyl, and NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH;

R 3 is selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, morpholinyl, pyrrolidinyl, piperidinyl, and NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH, (C 1 -C 3 )alkoxy or N[(C 1 -C 3 )alkyl] 2 ;

R 4 selected from OH, CN, CF 3 , (C 1 -C 3 )alkoxy, C(O)NR 5 R 5 , NR 5 R 5 , and piperidinyl; and

R 5 is selected from H, (C 1 -C 3 )alkyl, C(O)(C 1 -C 3 )alkyl, S(O) 2 (C 1 -C 3 )alkyl and piperidinyl,

with the proviso that in any NR 5 R 5 group when one R 5 is C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1 -C 3 )alkyl, then the other R 5 must be other than C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1-C 3 )alkyl

or a pharmaceutically acceptable salt thereof.

4. A compound of claim 1 wherein Ar 2 is optionally substituted phenyl.

5. A compound of Formula I

wherein

Y is CH;

Ar 1 is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each selected independently from (C 1 -C 3 )alkoxy, halo, OH, CF 3 , CN, NO 2 and (C 1 -C 3 )alkyl, said alkyl being optionally substituted with CF 3 ;

Ar 2 is pyridyl optionally substituted with 1 or 2 substituents each independently selected from halo, OH, CN, NO 2 , CF 3 , (C 1 -C 6 )alkoxy, NR 1 R 1 , S(O) 2 R 2 , C(O)R 3 , and (C 1 -C 6 )alkyl optionally substituted with R 4 ;

R 1 is selected from H, S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl, C(O)(C 1 -C 3 )alkyl where said alkyl is optionally substituted with NR 5 R 5 , and (C 1 -C 3 )alkyl where said alkyl is optionally substituted with 1 or 2 substituents each selected independently from OH and (C 1 -C 3 )alkyl;

with the proviso that in any NR 1 R 1 group when one R 1 is S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 C 3 )alkyl then the other R 1 must be other than S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 -C 3 )alkyl;

R 2 is selected from (C 1 -C 3 )alkyl, pyrrolidinyl, and NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH;

R 3 is selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, morpholinyl, pyrrolidinyl, piperidinyl, and NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH, (C 1 -C 3 )alkoxy or N[(C 1 -C 3 )alkyl] 2 ;

R 4 is selected from OH, CN, CF 3 , (C 1 -C 3 )alkoxy, C(O)NR 5 R 5 , NR 5 R 5 , and piperidinyl; and

R 5 is selected from H, (C 1 -C 3 )alkyl, C(O)(C 1 -C 3 )alkyl, S(O) 2 (C 1 -C 3 )alkyl and piperidinyl, with the proviso that in any NR 5 R 5 group when one R 5 is C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1 -C 3 )alkyl, then the other R 5 must be other than C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1 -C 3 )alkyl

or a pharmaceutically acceptable salt thereof.

6. A compound of claim 5 wherein Ar 1 is optionally substituted phenyl.

7. A compound of claim 2 wherein Ar 2 is optionally substituted phenyl.

8. A compound of claim 3 wherein Ar 2 is optionally substituted phenyl.

9. A compound of claim 3 wherein Ar 2 is optionally substituted pyridyl.

10. A pharmaceutical composition comprising a compound of Formula I

wherein

Y is CH;

Ar 1 is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each selected independently from (C 1 -C 3 )alkoxy, halo, OH, CF 3 , CN, NO 2 and (C 1 -C 3 )alkyl, said alkyl being optionally substituted with CF 3 ;

Ar 2 is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each independently selected from halo, OH, CN, NO 2 , CF 3 , (C 1 -C 6 )alkoxy, NR 1 R 1 , S(O) 2 R 2 , C(O)R 3 , and (C 1 -C 6 )alkyl optionally substituted with R 4 ;

wherein at least one of Ar 1 and Ar 2 is not unsubstituted phenyl and wherein when Ar 1 or Ar 2 is substituted phenyl, said phenyl is not substituted with only 1 (C 1 -C 3 )alkyl substituent;

R 1 is selected from H, S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl, C(O)(C 1 -C 3 )alkyl where said alkyl is optionally substituted with NR 5 R 5 , and (C 1 -C 3 )alkyl where said alkyl is optionally substituted with 1 or 2 substituents each selected independently from OH and (C 1 -C 3 )alkoxy,

with the proviso that in any NR 1 R 1 group when one R 1 is S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 -C 3 )alkyl then the other R 1 must be other than S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 -C 3 )alkyl;

R 2 is selected from (C 1 -C 3 )alkyl, pyrrolidinyl, and NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH;

R 3 is selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, morpholinyl, pyrrolidinyl, piperidinyl, and NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH, (C 1 -C 3 )alkoxy or N[(C 1 -C 3 )alkyl] 2 ;

R 4 is selected from OH, CN, CF 3 , (C 1 -C 3 )alkoxy, C(O)NR 5 R 5 , NR 5 R 5 , and piperidinyl; and

R 5 is selected from H, (C 1 -C 3 )alkyl, C(O)(C 1 -C 3 )alkyl, S(O) 2 (C 1 -C 3 )alkyl and piperidinyl,

with the proviso that in any NR 5 R 5 group when one R 5 is C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1 -C 3 )alkyl, then the other R 5 must be other than C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1 -C 3 )alkyl; and

excluding, (3-amino-6-phenylfuro[2,3-b]pyridin-2-yl)(4-nitrophenyl)methanone,

or a pharmaceutically acceptable salt thereof,

and a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 27, 2009
From: BAYER PHARMACEUTICALS CORPORATION
To: BAYER HEALTHCARE LLC
Reel/Frame 023027/0804 →