5-(2,3-Dihydro-1H-pyrrolizin-5-oyl)-2,3-dihyd ro-1H-pyrrolizine-1-alkanoic or carboxylic acids and use thereof as anti-inflammatory and analgesic agents
AssigneeMerck & Co., Inc.
InventorsTesfaye Biftu, Bruce E. Witzel, Peter L. Barker
Life of this patent
Estimating the term…
Abstract
New 5-(2,3-dihydro-1H-pyrrolizin-5-oyl)-, 5-(2,3-dihydro-1H-pyrrolo[2,1-b]thiazol-5-oyl)-, 5-(2,3-dihydro-1H-pyrrolo[2,1-b]imidazol-5-oyl)-, and 5-(2,3-dihydro-1H-pyrrolo[2,1-b]oxazol-5-oyl)-derivatives of substituted 2,3-dihydro-1H-pyrrolizine-1-alkanoic or carboxylic acids have been prepared. They are found to be effective inhibitors of platelet aggregation and are analgesic/anti-inflammatory agents with low ulcerogenic side effects.
Claims7
A compound of formula ##STR11## or a pharmaceutically acceptable salt thereof wherein:
- R is
- (a) H or C.sub.1-6 alkyl;
- (b) C.sub.2-4 alkenyl;
- (c) halo-C.sub.1-6 alkyl;
- or
- (d) phenyl-C.sub.1-3 alkyl;
- m is 0 or 1;
- R.sup.2 Z can be at any available position and R.sup.2 is R;
- q is 0 to 2;
- n is 0 to 1;
- R.sup.3 is hydroxy, C.sub.1-6 alkoxy or C.sub.1-6 (alkanoylaminoalkoxy);
- X is --CHR.sup.4 --;
- Y is --O--, --S--, Ch.sub.2 -- or H with the proviso that when Y is H, R is absent;
- and
- Z is --S--, --CH.sub.2 -- or halo with the proviso that when Z is halo, R.sup.2 is absent, R.sup.4 is hydrogen or C.sub.1-6 alkyl.
A pharmaceutical composition for treating inflammatory conditions, fever and pain in mammalian species comprising a non-toxic pharmaceutical carrier and an effective amount of a compound of formula ##STR12## or a pharmaceutically acceptable salt thereof wherein:
- R is
- (a) H or C.sub.1-6 alkyl;
- (b) C.sub.2-4 alkenyl;
- (c) halo-C.sub.1-6 alkyl;
- or
- (d) phenyl-C.sub.1-3 alkyl;
- m is 0 or 1;
- R.sup.2 Z can be at any available position and R.sup.2 is R;
- q is 0 to 2;
- n is 0 to 1;
- R.sup.3 is hydroxy, C.sub.1-6 alkoxy or C.sub.1-6 (alkanoylaminoalkoxy);
- X is --CHR.sup.4 --;
- Y is --O--, --S--, CH.sub.2 -- or H with the proviso that when Y is H, R is absent;
- and
- Z is --S--, --CH.sub.2 -- or halo with the proviso that when Z is halo, R.sup.2 is absent, R.sup.4 is hydrogen or C.sub.1-6 alkyl.
A method of treatment of inflammatory conditions, fever and pain which comprises the administration to a mammmalian species in need of such treatment an effective amount of a compound of formula ##STR13## or a pharmaceutically acceptable salt thereof wherein:
- R is
- (a) H or C.sub.1-6 alkyl;
- (b) C.sub.2-4 alkenyl;
- (c) halo-C.sub.1-6 alkyl;
- or
- (d) phenyl-C.sub.1-3 alkyl;
- m is 0 or 1;
- R.sup.2 Z can be at any available position and R.sup.2 is R;
- q is 0 to 2;
- n is 0 to 1;
- R.sup.3 is hydroxy, C.sub.1-6 alkoxy or C.sub.1-6 (alkanoylaminoalkoxy);
- X is --CHR.sup.4 --;
- Y is --O--, --S--, CH.sub.2 -- or H with the proviso that when Y is H, R is absent;
- and
- Z is --S--, --CH.sub.2 -- or halo with the proviso that when Z is halo, R.sup.2 is absent, R.sup.4 is hydrogen or C.sub.1-6 alkyl.
Dependencies are inferred from the claim text.