Synthesis and Evaluation of Anti-inflammatory and Analgesic Activities of a Novel Series of Coumarin Mannich Bases

Abstract A novel series of coumarinyl Mannich bases (3a-l) have been synthesized by reacting 3-acetyl coumarin (1) with various substituted secondary amines (2a-l) in presence of paraformaldehyde. The structures of the newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and HRMS (high resolution mass spectral) data. Title compounds were screened for in vivo acute anti-inflammatory activity using the carrageenan-induced rat paw edema assay model. Among the compounds tested, 3-[3-(diethylamino) propanoyl]-2H-chromen-2-one (3a) and 3-[3-(piperidine-1-yl) propanoyl]-2H-chromen-2-one (3c) showed 63.1 and 66.7% inhibition, respectively, as compared to the standard drug diclofenac (CAS 15307–86–5, 68.8%). These potent compounds showed encouraging analgesic and antipyretic activities.

[1]  D. Hadjipavlou-Litina,et al.  Synthesis and antiinflammatory activity of coumarin derivatives. , 2005, Journal of medicinal chemistry.

[2]  D. Hadjipavlou-Litina,et al.  Synthesis and biological evaluation of novel coumarin derivatives with a 7-azomethine linkage. , 2004, Bioorganic & medicinal chemistry letters.

[3]  N. Karalı,et al.  Synthesis, Characterization and Primary Antituberculosis Activity Evaluation of 4-(3-Coumarinyl)-3-benzyl-4-thiazolin-2-one Benzylidenehydrazones , 2003 .

[4]  D. Secci,et al.  Synthesis of Coumarin-3-O-acylisoureas by Different Carbodiimides. , 1999 .

[5]  G. Engelhardt,et al.  Distinct isoforms (COX‐1 and COX‐2) of cyclooxygenase: possible physiological and therapeutic implications , 1996, Fundamental & clinical pharmacology.

[6]  C. Torrance,et al.  Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. , 1992, The New England journal of medicine.

[7]  K. S. Raghu,et al.  Synthesis and anti-inflammatory activity of 3-(benzylideneamino)coumarins in rodents. , 1992, Journal of pharmaceutical sciences.

[8]  J. Bijlsma,et al.  Treatment of endoscopy‐negative NSAID‐induced upper gastrointestinal symptoms with cimetidine: an international multicentre collaborative study , 1988, Alimentary pharmacology & therapeutics.

[9]  A. Awasthi,et al.  A Novel and Convenient Synthesis of Substituted Coumarins , 1987 .

[10]  J. Dimmock,et al.  Evaluation of some Mannich bases derived from substituted acetophenones against P-388 lymphocytic leukemia and on respiration in isolated rat liver mitochondria. , 1983, Journal of pharmaceutical sciences.

[11]  S. Yankell,et al.  Antipyretic testing of aspirin in rats. , 1972, Toxicology and applied pharmacology.

[12]  C A WINTER,et al.  Carrageenin-Induced Edema in Hind Paw of the Rat as an Assay for Antiinflammatory Drugs , 1962, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[13]  R. Pascal.  Textbook of Pathology , 1931, The Indian Medical Gazette.

[14]  E. De Clercq,et al.  Cytotoxic 1,4-bis(2-oxo-1-cycloalkylmethylene)benzenes and related compounds. , 2002, European journal of medicinal chemistry.

[15]  J. Vane,et al.  Mechanism of action of anti-inflammatory drugs. , 1996, Scandinavian journal of rheumatology. Supplement.

[16]  D. Egan,et al.  The pharmacology, metabolism, analysis, and applications of coumarin and coumarin-related compounds. , 1990, Drug metabolism reviews.

[17]  R. Koster,et al.  ACETIC ACID FOR ANALGESIC SCREENING , 1959 .