Synthesis of bicyclic biaryls as glucose-6-phosphatase inhibitors.
Biaryls, 7-naphthyl-5-s-amino-2,3-dihydrobenzo[b]thiophene-4-carbonitriles (3a-e), 8-(1-naphthyl)-6-s-amino-isothiochroman-5-carbonitriles (6a-d), 4-(1-naphthyl)-2-s-aminobezocycloalkene-1-carbonitriles (6e-j), 8-naphthyl-6-s-amino-2-ethyl-1,2,3,4-tetrahydro-isoquinoline-5-carbonitrle (6k-n), 1-naphthyl-3-s-amino-10H-9-thia-phenantherene-4-carbonitriles (8a-e) and 1-(1-naphthyl)-3-s-amino-9,10-dihydrophenantherene-4-carbonitriles (8f-i) have been prepared through carbanion induced ring transformation reactions of 6-naphthyl-3-cyano-4-s-amino-2H-pyran-2-ones (1) from respective ketones (2, 5, and 7). These compounds have been evaluated for their glucose-6-phosphatase inhibitory activity and only 6a, c, j, m, c, d, h displayed significant inhibition of the glucose-6-phosphatase.
Farhanullah
Division of Medicinal Chemistry, Central Drug Research Institute, Lucknow-226001, India.
Tripathi
Brajendra K
BK
Srivastava
Arvind K
AK
Ram
Vishnu Ji
VJ
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D001643:Bridged Bicyclo Compounds; D004791:Enzyme Inhibitors; D006841:Hydrocarbons, Aromatic; D005952:Glucose-6-Phosphatase