Monika Johar

Anticancer, Anti-inflammatory and Analgesic Activity Evaluation of Heterocyclic Compounds Synthesized by the Reaction of 4-Isothiocyanato-4-methylpentan-2-one with Substituted o-Phenylenediamines, o-Diaminopyridine and (Un)Substituted o

4,5-Dimethyl-1,2-phenylenediamine and 4-chloro-1,2-phenylenediamine react with 4-isothiocyanato-4-methylpentan-2-one (15) to give compounds (3a) and (3b), respectively. 3,4-Diaminobenzoic acid reacts similarly with (15) to give a mixture of compounds, possibly (2a) and (2b), which could be cyclized at pH ~5 to compound (3c). 3,4-Diaminopyridine reacted with (15) in DMF to give compounds (5) and (6), whereas condensation of 5,6-diaminopyrimidine and 4,5,6-triaminopyrimidine sulfate under similar conditions gave compounds (8a) and (8b), respectively. Compounds (8a) and (8b) at pH ~4 gave a mixture of compounds (9a), (10a) and (9b), (10b), respectively. Condensation of 4,5-diamino-6-hydroxy-2-mercaptopyrimidine, 4,5-diamino-2,6-dimercapto-pyrimidine and 5,6-diamino-1,3-dimethyluracil hydrate with (15) gave corresponding mercaptopyrimidines (12a), (12b) and (14), respectively. The evaluation of (3a–c), (8a,b), (12a,b) and (14) aganist a small panel of six cancer cell lines, consisting of prostate (DU145), colon (HT29), melanoma (LOX), breast (MCF, MCF7/ADR), ovarian (OVCAR3) and CNS (U251) is reported. The most active was compound (8b), against colon (HT29) (44.2 M). Anti-inflammatory and analgesic activity is also reported.

Anti-inflammatory, analgesic and antiamoebic activity evaluation of pyrimido[1,6-a]benzimidazole derivatives synthesized by the reaction of ketoisothiocyanates with mono and diamines.

(UN) substituted o-phenylenediamines 1a-g reacted with 3-isothiocyanatobutanal to give pyrimidobenzimidazole derivatives, 2a-g, respectively. Products 4, 6 and 8, 10 were obtained by condensation of 3-isothiocyanatobutanal with 2,3-diaminopyridine, 1,4-diaminobutane and 3-isothiocyanatopropanal with 4,5-dimethyl-1,2-phenylenediamine, o-nitroaniline, respectively. S-Methylation of 2f and 11b gave products 12a and 12b, respectively. Anti-inflammatory and analgesic activity evaluations of 2a-g and 12b were carried out at 50 mg kg(-1) p.o. Compound 2c exhibited good anti-inflammatory (46%) and mild analgesic activity (50%). Antiamoebic activity evaluations (using microdilution method) of 2a-g against Entamoeba-histolytica (strain HM1: IMSS) were carried out and compounds 2a, 2b, 2d and 2g exhibited good antiamoebic activity in vitro.

Heterocyclic compounds as inflammation inhibitors.

Clinical use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with significant toxicity particularly in the gastrointestinal tract and kidney. Various approaches such as formulation co-administration (of agents to protect the stomach), chemical manipulation and synthesis of new safer anti-inflammatory drugs reported in the literature to overcome the toxicity of NSAIDs have been summarized. As far as synthesis of new more effective and safer anti-inflammatory drugs is concerned, we have reported recent findings in the area of synthesis of heterocyclic compounds such as pyrimidines, imidazole, benzimidazole, thiazole, thiazolidine, acridine, thiourea, alkanoic acid derivatives and other related heterocyclic compounds and their role as inflammation inhibitors.

Synthesis and Anticancer, Antiinflammatory,and Analgesic Activity Evaluation of Some Sulfa Drug and Acridine Derivatives

Summary. Various sulfa drugs were condensed with 4-isothiocyanato-4-methyl-2-pentanone at pH∼3–5 by refluxing in methanol to give various substituted mercaptopyrimidines. On condensation with 9-chloro-2-substituted or -unsubstituted acridines, sulfathiazole gave the corresponding condensed products. N-Ethylaminoadenosine reacted with 9-chloroacridine to the coupled product. Condensation of sulfathiazole with 9-isothiocyanato-2,4-substituted or -unsubstituted acridines afforded the corresponding condensed compounds. The structures of all synthesized compounds were confirmed by spectroscopic methods. Anticancer, antiinflammatory, and analgesic activities of all compounds were investigated.

Synthesis, Anti-Inflammatory, Analgaesic and Anti-Amoebic Activity Evaluation of Some Pyrimidobenzimidazole and Pyrimidopyridoimidazole Derivatives

o-Phenylenediamine, 4-nitro-1,2-phenylenediamine, 3,4-diaminobenzophenone, 3,4-diaminotoluene, 4,5-dimethylphenylenediamine and 3,4-diaminobenzoic acid (1a–f) react with 4-isothiocyanatobutan-2-one to give the pyrimidobenzimidazole derivatives (2a–f) respectively. Condensation of 4-nitro-1,2-phenylenediamine with 4-isothiocyanatobutan-2-one at room temperature gave the thiourea derivative (3). o-Nitroaniline, on condensation with 4-isothiocyanatobutan-2-one at pH ca. 5 and under reflux conditions, gave the thiourea derivative (4). 2,3-Diaminopyridine, on condensation with 4-isothiocyanatobutan-2-one, gave product (5). Condensation of 2,3-diaminopyridine with 4-isothiocyanato-4-methylpentan-2-one using acetic acid as solvent gave compounds (6)–(8), whereas compounds (7) and (9) were isolated from the same reagents in dimethylformamide (DMF). 4-Isothiocyanato-4-methylpentan-2-one, on refluxing in acetic acid, gave compound (6). Anti-inflammatory activity evaluation was carried out at 100 mg/kg p.o. (paw oedema) for compounds (2a–f), (7) and (8). Compounds (2b), (2d) and (7) showed good anti-inflammatory and analgesic activities. Anti-amoebic activity evaluation of (2a–f) and (7) against Entamoeba histolytica (strain HM-1: IMSS) was carried out, and compound (2b) exhibited anti-amoebic activity similar to metronidazole in vitro.

SYNTHESIS OF AMIDINE AND BIS AMIDINE PERCURSORS

Abstract The reactions of substituted o-phenylene diamines, o-aminophenol, o-aminothiophenol, 3,4-diaminopyridine with p-cyanobenzaldehyde by refluxing in nitrobenzene gave corresponding benzimidazole, benzoxazole, benzthiazole and imidazopyridine derivatives Ia,b, II, III, and IV, respectively. Reaction of 4,5-diaminopyrimidine with p-cyanobenzaldehyde gave only Schiffs base it. V or V′ and not imidazopyrimidine derivative, 2,6-Pyridine dialdehyde on condensation with p-aminobenzonitrile give corresponding dicyano compound VI. In an attempt to couple p-aminobenzonitrile with 2,6- pyridine dicarboxylic acid using dicyclohexyl carbodiimide or 1,1′-carbonyl diimidazole, only intermediates VII & VIII were obtained, respectively and no coupled product wax formed.