Enantiomers of N‐[2‐(p‐methylbenzylmethylamino)propyl]propionanilide and of the N‐phenylpropyl analog have been prepared, and the S− (+)‐isomers were found to possess greater analgesic potency. When the number of methylene groups in the N‐aralkyl substituent is increased from one to three, the changes in the enantiomeric potency ratio which occur are considered as being reflective of a diminution in the stereoselectivity of the analgesic receptors. The decrease in stereoselectivity is attributed to differing modes of analgesic‐receptor binding.
Bibliographical noteFunding Information:
maceutical Chemistry,. College of Pharmacy, University of Minnesota, Minneapolis. Accepted for publication September 28, 1965. This investigation was supported by grant NB 05192 from the Institute of Neurological Diseases and Blindness, U. S. Public Health Service, Bethesda, Md. The authors express their appreciation to Dr. R. A. Hardy, Jr., and Dr. A. C. Osterberg, Lederle Laboratories, Pearl River, N. Y., for their cooperation and aid in connection with the analgesic testing. Previous paper: Portoghese, P. S., J.Med. Chrm., 8, 147 (1965).