Therapeutic amides

A pharmaceutical composition comprising an amide of the following formula I, or a pharmaceutically acceptable in vivo hydrolyzable ester of said amide, or a pharmaceutically acceptable salt of said amide or of said ester, ##STR4## wherein:

• E is selected from nitrogen and CZ wherein C is a ring carbon and Z is a substituent defined below, wherein:
• X is ArY wherein Y is a linking group, carbonyl, and Ar is selected from the group consisting of:
• six-membered heteroaryl rings containing 1-2 nitrogen atoms as the only heteroatoms;
• and
• five-membered heteroaryl rings containing from 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur;
• provided that Ar is not 4-pyridyl, or 5-pyrimidinyl;
• Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy;
• and
• R.sup.2 and R.sup.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.sup.2 and R.sup.3 are not both methyl;
• or
• together, with the carbon atom to which both R.sup.2 and R.sup.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;
• and a pharmaceutically acceptable diluent or carrier.

A method of treating urinary incontinence, comprising administering to a mammal in need of such treatment an effective amount of an amide of the following formula I, or a pharmaceutically acceptable in vivo hydrolyzable ester of said amide, or a pharmaceutically acceptable salt of said amide or of said ester, ##STR6## wherein:

• E is selected from nitrogen and CZ wherein C is a ring carbon and Z is a substituent defined below, wherein:
• X is ArY wherein Y is a linking group, carbonyl, and Ar is selected from the group consisting of:
• six-membered heteroaryl rings containing 1-2 nitrogen atoms as the only heteroatoms;
• and
• five-membered heteroaryl rings containing from 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur;
• provided that Ar is not 4-pyridyl or 5-pyrimidinyl;
• Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy;
• and
• R.sup.2 and R.sup.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.sup.2 and R.sup.3 are not both methyl;
• or
• together, with the carbon atom to which both R.sup.2 and R.sup.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.

An amide of the following formula I, ##STR8## wherein:

• E is selected from nitrogen and CZ wherein C is a ring carbon and Z is a substituent defined below, wherein:
• X is ArY wherein Y is a linking group, carbonyl, and Ar is selected from the group consisting of:
• six-membered heteroaryl rings containing 1-2 nitrogen atoms as the only heteroatoms;
• and
• five-membered heteroaryl rings containing from 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur;
• provided that Ar is not 4-pyridyl or 5-pyrimidinyl;
• Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy;
• and
• R.sup.2 and R.sup.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.sup.2 and R.sup.3 are not both methyl;
• or
• together, with the carbon atom to which both R.sup.2 and R.sup.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.