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Structure elucidation of a novel ring‐constrained biaryl pyrazole CB 1 cannabinoid receptor antagonist
Author(s) -
Francisco Ma. Elena Y.,
Burgess Jason P.,
George Clifford,
Bailey Gregory S.,
Gilliam Anne F.,
Seltzman Herbert H.,
Thomas Brian F.
Publication year - 2003
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.1174
Subject(s) - chemistry , pyrazole , stereochemistry , cannabinoid , phenanthridine , ring (chemistry) , molecule , crystal structure , yield (engineering) , nuclear magnetic resonance spectroscopy , antagonist , cannabinoid receptor , crystallography , receptor , organic chemistry , biochemistry , materials science , metallurgy
Upon irradiation with a 450 W high‐pressure mercury lamp, the CB 1 cannabinoid antagonist N ‐(piperidinyl)‐5‐(4‐chlorophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1 H ‐pyrazole‐3‐carboxamide (SR14‐1716; 1 ) undergoes a photocyclization reaction to yield a single reaction product. This product, 2 , the structure of which is based on a pyrazolo[1,5‐ f ]phenanthridine ring system, was established by two‐dimensional NMR techniques (COSY, HSQC, HMBC and ROESY), and was later confirmed by single‐crystal x‐ray diffraction analysis. The crystal structure shows two independent molecules of 3 and a half molecule of the 1,2‐dichloroethane solvate. Compound 2 has reasonably high affinity for the CB 1 receptor ( K i = 48.0 ± 2.7 n M ). Copyright © 2003 John Wiley & Sons, Ltd.