Synthesis and antiinflammatory and analgesic activity of 5-aroyl-6-(methylthio)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids and 1-methyl-4-(methylthio)-5-aroylpyrrole-2-acetic acids

Abstract

5-Aroyl-6-(methylthio)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carb oxylic acids and 1-methyl-4-(methylthio)-5-aroylpyrrole-2-acetic acids were synthesized and assayed as antiinflammatory and analgesic agents. The majority of these compounds exhibit a surprisingly low level of antiinflammatory activity (rat carrageenan paw) but have considerable potency as analgesics (mouse phenylquinone writing). For example, the p-tolyl-substituted bicyclic and monocyclic compounds 44 and 58 are 301 and 66 times more potent than aspirin (mouse writhing) but only 3.4 and 1.5 times more potent than phenylbutazone in the antiinflammatory screen (rat paw).

cis-1-(4-Bromophenyl)-6-ethyl-5-tosylperhydropyrrolo[3,4-b]pyrrole

“…Inhibitors of human cytomegalovirus (HCMV) protease have been designed, based on the 5-oxohexahydropyrrolo[3,2-b]pyrrole ring system (Borthwick et al, 2000). Pyrrolo[1,2-a]pyrrole compounds are used as anti-inflammatory and analgesic agents (Muchowski et al, 1989). Certain pyrrolo-[3,4-c]pyrroles act as potent and selective orphanin FQ/nociceptin (N/OFQ) receptor (NOP) agonists (Kolczewski et al, 2003).…”

2-(4-Methylphenyl)-5-(phenylsulfonyl)perhydro-1,3-thiazolo[3,4-a]pyrrolo[4,5-c]pyrrole

“…Inhibitors of human cytomegalovirus (HCMV) protease have been designed based on the 5-oxo-hexahydro-pyrrolo[3,2b]pyrrole ring system (Borthwick et al, 2000). Pyrrolo[1,2a]pyrrole compounds are used as anti-inflammatory and analgesic agents (Muchowski et al, 1989). Some of the pyrrolo[1,2-c]thiazole derivatives are used as platelet-activating factor (PAF) antagonists (Weissman et al, 1993;Le Naour et al, 1994).…”

5-(Phenylsulfonyl)perhydrothiazolo[3,4-a]pyrrolo[4,5-c]pyrrole

“…Pyrrolopyrrole compounds exbhit anti-inflammatory and analgesic activities (Rooks et al, 1982;Muchowski et al, 1989). Inhibitors of human cytomegalovirus (HCMV) protease have been designed based on the 5-oxo-hexahydropyrrolo[3,2b]pyrrole ring system (Borthwick et al, 2000).…”