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US 8,772,304 B2Granted
Benzimidazole inhibitors of leukotriene production
AssigneeBoehringer Ingelheim International GmbH
InventorsStephane De Lombaert, Weimin Liu, Ho Yin Lo, Peter Allen Nemoto
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Abstract
The present invention relates to compounds of formula (IA), (IB) and (IC): and pharmaceutically acceptable salts thereof, wherein R1-R7 are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.
Claims34
A compound of formula IA
- wherein:
- R1 is pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolopyridinyl, imidazopyridinyl, pyrazolopyridinyl or dihydropyrrolopyridinyl optionally substituted with oxo, wherein each heterocycle is optionally independently substituted with one to three groups selected from Ra, Rb and Rc;
- R2 is C1-C6 alkyl or C3-6 cycloalkyl optionally substituted with C1-3 alkyl;
- R3 is H, —OH, halogen, —CN, C1-6 alkoxy, —COOR8, —C(O)NR8R9 or 5-6 membered heteroaryl ring which is optionally substituted with C1-3 alkyl;
- R4, R5, and R6 are each independently selected from
- (a) —H,
- (b) —OH,
- (c) halogen,
- (d) —CN,
- (e) —CF3,
- (f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
- (g) C3-6cycloalkyl
- (h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1-6alkyl, or —OC3-6cycloalkyl
- (i) —S(O)nC1-6alkyl,
- (j) —S(O)2aryl
- (k) —S(O)2heterocycle
- (l) —CO2R8,
- (m) —SCF3,
- (n′) a5-6 membered heterocyclic ring;
- R8 and R9 are each independently selected from —H, C1-6alkyl, and 5-6 membered heterocyclic ring;
- Ra is selected from H, —NH2, —NH(C1-C6)alkyl, —NR10R11, —NH—C(O)C1-C6alkyl, NR11—C(O)C1-C6alkyl, —O(C1-C8)alkyl, —O(C3-C6)cycloalkyl, —S—(C1-C6)alkyl, —S(O)—C1-C6alkyl, —S(O)2—C1-C6alkyl, and —CH2—OH;
- Rb is selected from —H, —(C1-C6)alkyl, —O—(C1-C6)alkyl, —NH2, —CH2—OH, —C≡N, —CH2NH2 and —C(O)OCH3;
- Rc is selected from —H, —CH3 and —OH;
- R10and R11 are each independently selected from —H, C1-6alkyl-5-6 membered heterocyclyl, C1-6alkyl-5-6 membered heteroaryl optionally substituted with halogen and C1-6alkyl-aryl;
- n is 0, 1 or 2;
- or a pharmaceutically acceptable salt thereof.
23 more elements
A compound of formula IB
- wherein:
- R1 is pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolopyridinyl, imidazopyridinyl, pyrazolopyridinyl or dihydropyrrolopyridinyl optionally substituted with oxo, wherein each heterocycle is optionally independently substituted with one to three groups selected from Ra, Rb and Rc;
- R2 is C1-C6 alkyl or C3-6 cycloalkyl optionally substituted with C1-3 alkyl;
- R3 is H, —OH, halogen, —CN, C1-6 alkoxy, —COOR8, —C(O)NR8R9 or 5-6 membered heteroaryl ring which is optionally substituted with C1-3 alkyl;
- R5, R6, and R7 are each independently selected from
- (a) —H,
- (b) —OH,
- (c) halogen,
- (d) —CN,
- (e) —CF3,
- (f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
- (g) C3-6cycloalkyl
- (h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1 -6alkyl, or —OC3-6cycloalkyl
- (i) —S(O)nC1-6alkyl,
- (j) —S(O)2aryl
- (k) —S(O)2 heterocycle
- (l) —CO2R8,
- (m) —SCF3,
- (n′) a 5-6 membered heterocyclic ring;
- R8 and R9 are each independently selected from —H, C1-6alkyl, and 5-6 membered heterocyclic ring;
- Ra is selected from H, —NH2, —NH(C1-C6)alkyl, —NR10R11, —NH—C(O)C1-C6alkyl, NR11—C(O)C1-C6alkyl, —O(C1-C8)alkyl, —O(C3-C6)cycloalkyl, —S—(C1-C6)alkyl, —S(O)—C1-C6alkyl, —S(O)2—C1-C6alkyl, and —CH2—OH;
- Rb is selected from —H, —(C1-C6)alkyl, —O—(C1-C6)alkyl, —NH2, —CH2—OH, —C≡N, —CH2NH2 and —C(O)OCH3;
- Rc is selected from —H, —CH3 and, —OH;
- R10 and R11 are each independently selected from —H, C1-6alkyl, C1-6alkyl-5-6 membered heterocyclyl, C1-6alkyl-5-6 membered heteroaryl optionally substituted with halogen and C1-6alkyl-aryl;
- n is 0, 1 or 2;
- or a pharmaceutically acceptable salt thereof.
23 more elements
A compound of formula IC
- wherein:
- R1 is pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolopyridinyl, imidazopyridinyl, pyrazolopyridinyl or dihydropyrrolopyridinyl optionally substituted with oxo, wherein each heterocycle is optionally independently substituted with one to three groups selected from Ra, Rb and Rc;
- R2 is C1-C6 alkyl or C3-6 cycloalkyl optionally substituted with C1-3 alkyl;
- R3 is H, —OH, halogen, —CN, C1-6 alkoxy, —COOR8, —C(O)NR8R9 or 5-6 membered heteroaryl ring which is optionally substituted with C1-3 alkyl;
- R4, R6, and R7 are each independently selected from
- (a) —H,
- (b) —OH,
- (c) halogen,
- (d) —CN,
- (e) —CF3,
- (f) C1-6alkyl optionally substituted with one to three —OH, fluorine, C1-6alkoxyl —N(R8)(R9), or —C(O)N(R8)(R9),
- (g) C3-6 cycloalkyl
- (h) C1-6alkoxy optionally substituted with one to three —OH, fluorine, —OC1-6alkyl, or —OC3-6 cycloalkyl
- (i) —S(O)nC1-6alkyl,
- (j) —S(O)2aryl
- (k) —S(O)2 heterocycle
- (l) —CO2R8,
- (m) —SCF3,
- (n′) a 5-6 membered heterocyclic ring;
- R8 and R9 are each independently selected from —H, C1-6alkyl, and 5-6 membered heterocyclic ring;
- Ra is selected from H, —NH2, —NH(C1-C6)alkyl, —NR10R11, —NH—C(O)C1-C6alkyl, NR11—C(O)C1-C6alkyl, —O(C1-C8)alkyl, —O(C3-C6)cycloalkyl, —S—(C1-C6)alkyl, 13 S(O)—C1-C6alkyl, —S(O)2—C1-C6alkyl, and —CH2—OH;
- Rb is selected from —H, —(C1-C6)alkyl, —O—(C1-C6)alkyl, —NH2, —CH2—OH, —C≡N, —CH2NH2 and —C(O)OCH3;
- Rc is selected from —H, —CH3 and, —OH;
- R10 and R11 are each independently selected from —H, C1-6alkyl, C1-6alkyl-5-6 membered heterocyclyl, C1-6alkyl-5-6 membered heteroaryl optionally substituted with halogen and C1-6alkyl-aryl;
- n is 0, 1 or 2;
- or a pharmaceutically acceptable salt thereof.
23 more elements
A compound selected from a group consisting of:
- or pharmaceutically acceptable salts thereof.
Dependencies are inferred from the claim text.