Structure elucidation of a novel ring-constrained biaryl pyrazole CB1 cannabinoid receptor antagonist

Upon irradiation with a 450 W high‐pressure mercury lamp, the CB1 cannabinoid antagonist N‐(piperidinyl)‐5‐(4‐chlorophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐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 CB1 receptor (Ki = 48.0 ± 2.7 nM). Copyright © 2003 John Wiley & Sons, Ltd.