New indole, aminoindole and pyranoindole derivatives with anti-inflammatory activity.
6-Methoxy-1-methyl-2,3-diphenyl indol-5-carboxaldehyde (2) was demethylated to give the 6-hydroxy derivative (3) which was cyclized to the pyrano[3,2-f]indole derivatives (4a-d) by the action of ethyl acetoacetate, diethyl malonate, malononitrile, ethyl cyanoacetate. When 4c was boiled in acetic acid, it gave 4d. Reduction of 4c by sodium borohydride yielded the orthoaminonitrile (5). Friedel Craft's acetylation of 1b yielded the 5-acetyl derivative (6), which reacted with hydrazine hydrate, o-toluidine and o-aminophenol to afford (7a-c). Demethylation of (1b) yielded the hydroxyl derivative (8), which differs from compound (9) obtained by demethylation of 6-methoxy-2,3-diphenyl-indole (1a). Friedel Craft's acetylation of 9 gave the 7-acetyl compound (10) which yielded the hydrazone (11). The reaction of primary aromatic amines, (i.e. p-nitroaniline, p-anisidine and p-bromo aniline) with 6-methoxy-1-methyl-2,3-diphenyl-indol-5-carboxaldehyde (2) gave the Schiff bases (12a-c). The latter compounds were reduced by sodium borohydride to yield the corresponding Mannich bases (13a-c). Treatment of 12a-c with thioglycolic acid led to the thiazolidin-4-one-derivatives (14a-c). When (12a-c) reacted with cyanoacetamide, the amino group was replaced by the active methylene to form the cyano compound (15). The structure was confirmed by reacting the carboxaldehyde (2) with cyanoacetamide to yield (15). Pharmacological screening was has been carried out to test the anti-inflammatory activity, ulcerogenecity, effect on the isolated rabbit intestine and the antispasmodic activity.
Natural Products Department, National Research Centre, Cairo, Egypt.
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Nakkady
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Fathy
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Hishmat
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Mahmond
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Ebeid
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D013055:Spectrophotometry, Infrared; D013276:Stomach Ulcer / Q000139:chemically induced
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles