Therapeutic amides

Claim 1

A method of treating asthma comprising administering to a mammal in need of such treatment an effective amount of an amide of formula I: wherein: E is selected from nitrogen and CZ wherein C is a ring carbon and Z is a substituent defined below, wherein: when E is CZ, X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of: phenyl substituted with 0-2 substituents selected from halo, hydroxy, cyano, (1-4C)alkyl, and (1-4C)alkoxy, provided that the 4-position of said phenyl may be substituted by fluoro only, and that the said phenyl may not be 3,5-disubstituted; six-membered heteroaryl rings containing 1-2 nitrogen atoms as the only heteroatoms; five-membered heteroaryl rings containing from 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; provided that Ar is not 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl, 3-(1-4C)alkylphenyl, or 4-pyridyl when Y is carbonyl, and that Ar is not 5-pyrimidinyl when Y is sulfonyl or carbonyl; and Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; (B) X is cyano and Z is selected from the group consisting of phenylthio, phenylsulfinyl, and phenylsulfonyl the phenyl rings of which are substituted with 0-2 substituents selected from halo, hydroxy, cyano, nitro, (1-4C)alkyl, and (1-4C)alkoxy; when E is nitrogen, X is independently selected from any of the values for X given above in (A); R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring; or a pharmaceutically acceptable in vivo hydrolyzable ester of said amide; or a pharmaceutically acceptable salt of said amide or said ester.

Claim 2

A method of treating asthma comprising administering to a mammal in need of such treatment an effective amount of an amide of formula I: wherein: E is selected from nitrogen and CZ wherein C is a ring carbon and Z is a substituent defined below, wherein: when E is CZ, X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of: phenyl substituted with 0-2 substituents selected from halo, hydroxy, cyano, (1-4C)alkyl, and (1-4C)alkoxy, provided that the 4-position of said phenyl may be substituted by fluoro only, and that the said phenyl may not be 3,5-disubstituted; six-membered heteroaryl rings containing 1-2 nitrogen atoms as the only heteroatoms; five-membered heteroaryl rings containing from 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; provided that Ar is not 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl, 3-(1-4C)alkylphenyl, or 4-pyridyl when Y is carbonyl, and that Ar is not 5-pyrimidinyl when Y is sulfonyl or carbonyl; and Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; (B) X is cyano and Z is selected from the group consisting of phenylthio, phenylsulfinyl, and phenylsulfonyl the phenyl rings of which are substituted with 0-2 substituents selected from halo, hydroxy, cyano, nitro, (1-4C)alkyl, and (1-4C)alkoxy; when E is nitrogen, X is independently selected from any of the values for X given above in (A); R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring; or a pharmaceutically acceptable in vivo hydrolyzable ester of said amide; or a pharmaceutically acceptable salt of said amide or said ester.