Conformation of 2,9-dimethyl-3'-hydroxy-5-phenyl-6,7-genzomorphan and its relation to other analgetics and enkephalin

X-ray crystallographic data for 2,9-dimethyl-3'-hydroxy-5-phenyl-6,7-benzomorphan (I) as its p-bromobenzoyl ester are presented. The structure of I is compared with that of morphine, meperidine, alpha-allylprodine, methadone, and moramide as well as with a proposed structure of the enkephalins. A quantitative relationship is found between in vitro opiate receptor binding potency and in vivo analgesia for analgesics of diverse structure, including I. A new view of the analgetic pharmacophore is presented. Programs for the TI Programmable 59 calculator are described for conversion of X-ray crystallographic data to rectangular coordinates with reorientation of the molecule and for the calculation of torsion angles.