title: Synthesis of biologically active N-methyl derivatives of amidines and cyclized five-membered products of amidines with oxalyl chloride.
abstract: A series of substituted N-methylisonicotinamidine (2a-f), N-methylpyrazine-2-carboxamidine (2g-i) derivatives were synthesized by reaction of amidine derivatives (1a-i) with methyl iodide in presence of triethylamine. Five-membered condensed dihydroimidazolylbenzenesulfonamide derivatives (3a-i) were obtained by the reaction of amidine derivatives (1a-i) with acylating agent oxalyl chloride. All the compounds, i.e. 2a-i and 3a-i were purified by crystallization. Structures of all the synthesized compounds are supported by correct IR, (1)H NMR, mass spectral and analytical data. Anti-inflammatory activity evaluation was carried out using carrageenan-induced paw oedema assay and compounds 2e, 3a and 3d exhibited good anti-inflammatory activity (44%, 31% and 37% activity at 50 mg/kg p.o., respectively). Analgesic activity evaluation was carried out using acetic acid writhing assay and compounds 2a and 3f gave 75% activity each at 100 mg/kg p.o.; on the other hand compounds 3a and 3d exhibited 60% analgesic activity each at 50 mg/kg p.o. Compounds 3a and 3d exhibited good anti-inflammatory and analgesic activities.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Roorkee (IIT R), Roorkee-247667, Uttarakhand, India. sondifcy@iitr.ernet.in
authors.forename: Sham M
authors.initials: SM
authors.lastname: Sondhi
authors.forename: Monica
authors.initials: M
authors.lastname: Dinodia
authors.forename: Shubhi
authors.initials: S
authors.lastname: Jain
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000284:Administration, Oral; D000578:Amidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002351:Carrageenan; D002712:Chlorides / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003500:Cyclization; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D008297:Male; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010070:Oxalates / Q000737:chemistry*; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000578:Amidines; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002712:Chlorides; D010070:Oxalates; D002351:Carrageenan; C092266:oxalyl chloride