Heterocyclic amide derivatives and pharmaceutical use
AssigneeICI Americas Inc.
InventorsPeter R. Bernstein, Frederick J. Brown, Victor G. Matassa, Ying K. Yee
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Abstract
The invention concerns novel, pharmaceutically useful, amide derivatives of certain benzoheterocyclylalkanoic acids (and related tetrazoles and acylsulphonamides) of the formula I and salts thereof, wherein the radicals R.sup.1, R.sup.2, L, X, Y, Z, A.sup.1, Q, A.sup.2 and M have the meanings set out in the specification. The invention also includes pharmaceutical compositions incorporating a formula I compound or a salt thereof, a process for the manufacture of the said compound, together with intermediates for use in the latter process. ##STR1##
Claims15
A compound of formula I ##STR38## wherein the group >X--Y--Z-- is selected from the group consisting of:
- (c) >C.dbd.CRa--Zb--
- (d) >N--CRa.dbd.N--
- (f) >N--N.dbd.N--
- (g) >N--NRg--CO--
- (h) >N--N.dbd.C.ORd--
- wherein
- Ra is hydrogen or (1-4C)alkyl;
- Rd is hydrogen or (1-10C) alkyl optionally containing one or two double or triple bonds and in which a carbon atom may optionally be replaced by oxygen or sulphur, said (1-10C)alkyl additionally optionally bearing a substituent selected from the group consisting of (1-4C)alkoxy, cyano, carboxy, 1H-tetrazol-5-yl, carbamoyl, N-1-4C)carbamoyl, [N,N-di[(1-4C)alkyl]carbamoyl] N,N-di{(1-4C)alkyl}carbamoyl, and (1-4C)alkoxycarbonyl, or Rd is selected from the group consisting of (3-8C)cycloalkyl, (3-8C)cycloalkyl-(1-4C)alkyl, (2-6C)alkanoyl and phenyl-(1-4C)alkyl, the phenyl moiety of which may optionally bear a substituent selected from the group consisting of cyano, halogeno, (1-4C)alkyl, (1-4C)alkoxy and trifluoromethyl;
- Rg is (1-4C)alkyl;
- Zb is oxy or thio;
- the group R.sup.1.L-- stands for amidic radicals of the formula:
- R.sup.1.W.CO.NH-- or R.sup.1.W.CS.NH--, in which R.sup.1 is selected from the group consisting of (a) (2-10C)alkyl optionally containing 1 or more fluorine substituents;
- (b) phenyl-(1-6C)alkyl in which the (1-6C)alkyl moiety may optionally bear a fluoro or (1-4C)alkoxy substituent and in which the phenyl moiety may optionally bear a substituent selected from the group consisting of halogeno, (1-4C)alkyl, (1-4C)alkoxy and trifluoromethyl;
- and (c) (3-8C)cycloalkyl or (3-8C)cycloalkyl-(1-6C)alkyl, the cyclic moiety of any of which optionally may contain one unsaturated linkage and may optionally bear 1 or 2 (1-4C)alkyl substituents;
- W is oxy, thio, imino or a direct link to R.sup.1 ;
- R.sup.2 is hydrogen, halogeno, (1-4C)alkyl or (1-4C)alkoxy;
- Q is phenylene optionally bearing 1 or more substituents independently selected from the group consisting of halogeno, hydroxy, (1-4C)alkyl, (1-4C) alkoxy and trifluoromethyl;
- A.sup.1 is (1-2C)alkylene or vinylene;
- A.sup.2 is methylene, vinylene or a direct link to M;
- and
- M is an acidic group selected from the group consisting of carboxy, 1H-tetrazol-5-yl and an acylsulphonamide residue of the formula --CO.NH.SO.sub.m R.sup.3 in which m is the integer 1 or 1 and R.sup.3 is selected from the group consisting of (1-6C)alkyl, (3-8C)cycloalkyl, (6-12C)aryl, heteroaryl comprising 5-12 atoms at least one of which is carbon and at least one of which is selected from a group consisting of oxygen, sulfur and nitrogen, and (6-12C)aryl-(1-4C)alkyl, in any of which the aromatic or heteroaromatic moiety may bear 1 or 2 substituents selected from the group consisting of halogeno, (1-4C)alkyl, (1-4C)alkoxy, trifluoromethyl, nitro and amino;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.