Chemo- and stereoselective synthesis of benzocycloheptene and 1-benzoxepin derivatives as alpha-sympathomimetic and anorexigenic agents.
The synthesis and pharmacological evaluation of cis- and trans-6-amino-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ols 4a-c and 5a-c and cis- and trans-4-amino-2,3,4,5-tetrahydro-1-benzoxepin-5-ols 4d-f and 5d-f were carried out. Chemo- and stereoselective synthesis of 5a-f was achieved by reduction of corresponding alpha-amino ketones 3a-f with LiAl(t-BuO)3H. cis-4-Amino-2,3,4,5-tetrahydro-1-benzoxepin-5-ol 4d and trans-4-amino-2,3,4,5-tetrahydro-1-benzoxepin-5-ol 5d exhibited marked anorexigenic activity in mice at a dose of LD50 800 and 500 mg/kg and ED50 75 and 55 mg/kg, respectively, while the analog cis-2,3-dihydroxy-6-amino-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol 8 showed typical alpha-sympathomimetic activity.
Tandon
Vishnu K
VK
Department of Chemistry, Lucknow University, Lucknow 226007, India. vishnutandon@yahoo.co.in
Singh
Kunwar A
KA
Awasthi
Anoop K
AK
Khanna
J M
JM
Lal
Bansi
B
Anand
Nitya
N
D000662:Amphetamines / Q000037:antagonists & inhibitors; D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D001567:Benzocycloheptenes / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D001584:Benzoxepins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D051379:Mice; D009765:Obesity / Q000188:drug therapy; D013237:Stereoisomerism; D013566:Sympathomimetics / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology
D000662:Amphetamines; D001067:Appetite Depressants; D001567:Benzocycloheptenes; D001584:Benzoxepins; D013566:Sympathomimetics