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

Abstract

Upon irradiation with a 450 W high-pressure mercury lamp, the CB, cannabinoid antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-H-1-p yrazole-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, receptor (K-i = 48.0 +/- 2.7 nm). Copyright (C) 2003 John Wiley Sons, Ltd