Synthesis of pharmacologically active indoles.
Formylation of 6-methoxy-1-methyl and 5-methyl,2,3-diphenyl-1H-indole (Ib and IX) gave the 5- and 6- carboxaldehyde derivatives (II and X) respectively, which were treated with ethyl cyanoacetate to form the corresponding 2-cyano-3-substituted acrylic acid ethyl ester (III and XI). The latter compounds reacted with hydrazine hydrate, urea and thiourea to form the corresponding 5-amino-4-substituted 2,4,dihydropyrazol-3- one (IV), 6-indolyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile s (V and XII) and 6-indolyl-4-oxo-2-thixo-1,2,3,4-tetrahydropyrimidine-5-ca rbonitriles (VI and XIII). Reaction of the 5- and 6-carboxaldehyde derivatives with malononitrile afforded the 2-substituted malononitrile derivatives (VII and XIV). VII and XIV reacted readilly with aromatic ketones to give the 2-amino4,6-disubstituted nicotinonitriles (VIII a,b and XVa,b). The biological activity of compounds Ia, Ib, II, III, IX and X was tested for antiinflammatory, ulcerogenic and antispasmodic activities.
Hishmat
O H
OH
Natural Products Department, National Research Centre, Cairo Egypt.
Ebeid
M Y
MY
Nakkady
S S
SS
Fathy
M M
MM
Mahmoud
S S
SS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D010276:Parasympatholytics / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; D010276:Parasympatholytics