Nitroso esters of .beta.-oxo-amides and aryl propionic acid derivatives of non-steroidal antiinflammatory drugs
AssigneeNitroMed, Inc.
InventorsDavid S. Garvey, L. Gordon Letts, H. Burt Renfroe, Sang William Tam
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Abstract
A compound comprising a non-steroidal antiinflammatory agent to which is directly or indirectly linked an NO group, a compound comprising an enolic anilide non-steroidal antiinflammatory agent to which is directly or indirectly linked an NO.sub.2 group, a pharmaceutical composition including the compounds and methods of treatment of pain and/or inflammation using the compounds and compositions are disclosed. Also disclosed is a composition comprising a non-steroidal antiinflammatory agent and a compound that donates, transfers or releases nitric oxide.
Claims29
An enolic anilide non-steroidal antiinflammatory drug having at least one NO.sub.2 group in the form of an enolic ether.
A composition comprising a compound of formula IV and a compound that donates, transfers or releases nitric oxide,
- wherein the compound of formula IV is:
- ##STR16## wherein R.sub.g is ##STR17## and X is:
- (1) --Y--(C(R.sub.b)(R.sub.c)).sub.p --T--NO, wherein Y is oxygen, sulfur or NR.sub.i, wherein R.sub.i is a hydrogen atom or a lower alkyl group;
- R.sub.b and R.sub.c are each independently a hydrogen atom, a lower alkyl group, a cycloalkyl group, an arylalkyl group, an aryl group or a heteroaryl group;
- p is an integer from 0 to 6;
- and T is a covalent bond, oxygen or sulfur;
- or
- (2) ##STR18## wherein W is a heterocyclic ring or NR.sub.h R.sub.i, wherein R.sub.h and R.sub.i are each independently a lower alkyl group, an aryl group or an alkenyl group.
A composition comprising a compound of formula III and a compound that donates, transfers or releases nitric oxide, wherein the compound of formula III is:
- ##STR19## wherein R.sub.e is hydrogen or lower alkyl;
- and R.sub.f is:
- ##STR20## wherein n is 0 or 1;
- and X is:
- (1) --Y--(C(R.sub.b)(R.sub.c)).sub.p --T--NO, wherein Y is oxygen, sulfur or NR.sub.i, wherein R.sub.i is a hydrogen atom or a lower alkyl group;
- R.sub.b and R.sub.c are each independently a hydrogen atom, a lower alkyl group, a cycloalkyl group, an arylalkyl group, an aryl group or a heteroaryl group;
- p is an integer from 0 to 6;
- and T is a covalent bond, oxygen or sulfur;
- or
- (2) ##STR21## wherein W is a heterocyclic ring or NR.sub.h R.sub.i, wherein R.sub.h and R.sub.i are each independently a lower alkyl group, an aryl group or an alkenyl group.
A method for treating inflammatory bowel disease in an animal in need thereof comprising administering to the animal a therapeutically effective amount of a composition comprising a compound of formula III and a pharmaceutically acceptable carrier, wherein the compound of formula III is:
- ##STR22## wherein R.sub.e is hydrogen or lower alkyl;
- and R.sub.f is:
- ##STR23## wherein n is 0 or 1;
- and X is:
- (1) --Y--(C(R.sub.b)(R.sub.c)).sub.p --T--NO, wherein Y is oxygen, sulfur or NR.sub.i, wherein R.sub.i is a hydrogen atom or a lower alkyl group;
- R.sub.b and R.sub.c are each independently a hydrogen atom, a lower alkyl group, a cycloalkyl group, an arylalkyl group, an aryl group or a heteroaryl group;
- p is an integer from 0 to 6;
- and T is a covalent bond, oxygen or sulfur;
- or
- (2) ##STR24## wherein W is a heterocyclic ring or NR.sub.h R.sub.i, wherein R.sub.h and R.sub.i are each independently a lower alkyl group, an aryl group or an alkenyl group.
Dependencies are inferred from the claim text.