苯二氮卓的故事.pdf

Journal ofMedkina1 Chemistry 0 Copyright 1978 by the American Chemical Society Volume 22, Number 1 January 1979 The Benzodiazepine Story’ Leo H. Sternbach Research Dioision, Hoffmann-La Roche Inc., Nutley, New Jersey 07110. Received September 5, 1978 Before starting with my lecture proper, I would like to then known tranquilizers were intensively studied by express my deep felt thanks to the Medicinal Chemistry several groups of investigators, e.g., meprobamate (Mil- Division of the American Chemical Society for choosing town) at Wallace Laboratories, reserpine by the Ciba me to receive this prestigious award. It is indeed an honor, research group, and chlorpromazine by the SKF research gives me great satisfaction, and makes me very happy. team. In this lecture, I would like to tell you about the chain We therefore considered it more attractive to pursue the of events that started with the synthesis of a new chemical second approach and be guided mainly by our interest in entity and culminated in the discovery of a new class of synthetic chemical bench work. The class of compounds biologically active agents. Specifically, I shall discuss the we were seeking would be expected to fulfill the following development of the group of centrally acting 1,4-benzo- criteria: (1) be relatively unexplored, (2) be readily ac- diazepines that began with the discovery of a pharma- cessible, (3) give the possibility of a multitude of variations cologically active compound, which received the generic and transformations, (4) offer some challenging chemical name chlordiazepoxide and is the active ingredient of problems, and (5) “look” as if it could lead to biologically Librium. active products. Our search led us to the benzheptox- The story starts in the mid 1950s when the tranquilizers, diazines, compounds I