Back to results
US 7,351,834 B1Granted
ω-Carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
AssigneeBayer Pharmaceuticals Corporation
InventorsBernd Riedl, Jacques Dumas, Uday Khire, Timothy Lowinger, William Scott, Roger A. Smith, Jill E. Wood, Mary-Katherine Monahan, Reina Natero, Joel Renick, Robert Sibley
Life of this patent
Estimating the term…
Abstract
This invention relates to the use of a group of aryl ureas in treating raf mediated diseases, and pharmaceutical compositions for use in such therapy.
Claims41
A compound of Formula I:
- A—D—B (I)
- or a pharmaceutically acceptable salt thereof, wherein
- D is —NH—C(O)—NH—,
- A is a substituted moiety of the formula:
- —L—M—L1,
- wherein L is phenyl, optionally substituted by halogen, up to per-halo, and Wn, where n is 0-3;
- wherein each W is independently selected from the group consisting of C1-C5 linear or branched alkyl, C1-C5 linear or branched haloalkyl up to perhaloalkyl and C1-C3 alkoxy L1 is selected from pyridinyl substituted by —C(O)Rx, and
- optionally substituted with 1-3 additional substituents independently selected from the group consisting of R7 and halogen;
- wherein Rx is NRaRb and Ra and Rb are
- A) independently
- a) hydrogen,
- b) C1-C10 alkyl,
- c) C6 aryl,
- d) pyridinyl
- e) substituted C1-10 alkyl,
- f) substituted C6 aryl,
- g) substituted pyridinyl
- h) -phenylpiperazine(pyridinyl),
- i) -phenylmorpholinyl,
- j) -ethylmorpholinyl,
- k) -ethylpiperidyl,
- l) -methyl pyrrolidinyl,
- m) -methyl tetrahydrofuryl,
- or
- n) —C2H4NH(phenyl);
- where when Ra and Rb are a substituted group, they are substituted by
- a) halogen up to per halo,
- b) hydroxy,
- c) —N(CH3)2,
- d) C1-C10 alkyl,
- e) C1-C10 alkoxy,
- f) halosubstituted C1-6 alkyl, or
- g) —OSi(Pr-i)3;
- or
- B) Ra and Rb together form piperazine or a substituted piperazine with substituents selected from the group consisting of
- a) halogen,
- b) hydroxy,
- c) C1-10 alkyl,
- d) pyridinyl
- e) C1-10 alkoxy,
- f) C6 aryl,
- g) halo substituted C6 aryl, and
- h) N-(4-acetylphenyl);
- M is selected from the group consisting of oxygen and sulfur;
- and
- B is
- phenyl, substituted with 1-3 substituents independently selected from the group consisting of halogen and R7,
- and R7 is
- (a) C1-C6 linear or branched alkyl, optionally substituted with 1-3 halogen substituents;
- or
- (b) C1-C6 linear or branched alkoxy.
48 more elements
A compound of Formula I:
- A—D—B (I)
- or a pharmaceutically acceptable salt thereof, wherein
- D is —NH—C(O)—NH—,
- A is of the formula:
- —L—M—L1, wherein
- L is phenyl, optionally substituted with 1-3 substituents independently selected from the group consisting of C1-C5 linear or branched alkyl, C1-C5 linear or branched haloalkyl up to perhalo, C1-C3 alkoxy and halogen;
- L1 is pyridinyl, substituted by —C(O)Rx;
- wherein Rx is NRaRb and Ra and Rb are independently
- hydrogen,
- C1-C10 alkyl,
- C6 aryl,
- pyridinyl, substituted C1-10 alkyl,
- substituted C6 aryl, or
- substituted pyridinyl,
- where Ra and Rb are a substituted group, they are substituted by halogen up to per halo;
- and
- M is selected from the group consisting of oxygen and sulfur
- and
- B is phenyl, substituted with 1-3 substituents independently selected from the group consisting of R7 and halogen;
- and R7 is
- (a) C1-C6 linear or branched alkyl, optionally substituted with 1-3 halogen substituents;
- or
- (b) C1-C6 linear or branched alkoxy.
20 more elements
A compound of Formula I:
- A—D—B (I)
- or a pharmaceutically acceptable salt thereof, wherein
- D is —NH—C(O)—NH—,
- A is of the formula:
- —L—M—L1,
- L is phenyl,
- M is —O—,
- L1 is pyridinyl substituted by —C(O)Rx,
- wherein Rx is NRaRb and Ra and Rb are independently
- hydrogen,
- C1-C10 alkyl,
- C6 aryl,
- pyridinyl,
- substituted C1-10 alkyl,
- substituted C6 aryl, or
- substituted pyridinyl
- where Ra and Rb are a substituted group, they are substituted by halogen up to per halo,
- and
- B is a phenyl group substituted by trifluoromethyl or tert-butyl, and optionally additional substituents selected from the group consisting of halogen up to per halo, and Wn where n is 0-3, and each W is independently selected from the group consisting of
- C1-C10 alkyl,
- C1-C10 alkoxy,
- C6 aryl,
- pyridinyl,
- and substituted C1-C10 alkyl, substituted by one or more substituents independently selected from the group consisting of halogen up to per halo.
21 more elements
A compound of Formula I:
- A—D—B (I)
- or a pharmaceutically acceptable salt thereof, wherein
- D is —NH—C(O)—NH—,
- A is a substituted moiety of the formula:
- —L—M—L1,
- wherein L is phenyl, optionally substituted with chlorine or methyl substituents;
- L1 is pyridinyl, substituted with —C(O)NRaRb;
- wherein Ra and Rb independently are
- a) hydrogen
- b) methyl;
- c) ethyl;
- or
- d) propyl
- B is phenyl, substituted by tert-butyl or trifluoromethyl and optionally substituted with additional substituents independently selected from the group consisting of
- a) halogen, or
- b) methoxy.
13 more elements
A compound which is N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea of the formula X
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.