Synthesis and appetite suppressant activity of 1-aryloxy-2-substituted aminomethyltetrahydronaphthalenes as conformationally rigid analogues of fluoxetine.
Several 1-aryloxy-2-substituted aminomethyltetrahydronaphthalenes (7-21) as conformationally rigid analogues of fluoxetine were synthesized and evaluated for their anorexigenic and antidepressant activities. For SAR studies the related acyclic analogues (22-27) were also prepared. Out of the 21 synthesized compounds, 10 compounds (9, 10, 11, 15, 16, 18, 21, 22, 23 and 27) exhibited significant anorexigenic activity (at 75 micromol/kg). Interestingly, all the compounds (7-20, 22-26) were devoid of antidepressant effect, except for compounds 21 and 27 in which the antidepressant activity was retained. Compound 16 emerged as the most active compound of the series with better anorexigenic activity (97.92%) compared to fluoxetine (76.25%) and even with a clinically used drug sibutramine, thus providing a new structural lead for appetite suppressants.
Bhandari
Kalpana
K
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, India. bhandarikalpana@rediffmail.com
Srivastava
Shipra
S
Shankar
Girija
G
Nath
Chandishwar
C
D001067:Appetite Depressants / Q000138:chemical synthesis* / Q000494:pharmacology*; D005473:Fluoxetine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D001067:Appetite Depressants; D009281:Naphthalenes; D005473:Fluoxetine