Identification of a novel spiropiperidine opioid receptor-like 1 antagonist class by a focused library approach featuring 3D-pharmacophore similarity

  • J Med Chem. 2006 Feb 9;49(3):847-9. doi: 10.1021/jm0509851.
Yasuhiro Goto  1 ,  Sachie Arai-Otsuki ,  Yukari Tachibana ,  Daisuke Ichikawa ,  Satoshi Ozaki ,  Hiroyuki Takahashi ,  Yoshikazu Iwasawa ,  Osamu Okamoto ,  Shoki Okuda ,  Hisashi Ohta ,  Takeshi Sagara
Affiliations
  • 1. Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Okubo 3, Tsukuba 300-2611, Japan.
PMID: 16451050 DOI: 10.1021/jm0509851
Abstract

A focused library approach identifying novel leads to develop a potent ORL1 antagonist is described. Beginning from a compound identified by random screening, an exploratory library that exhibited a diverse display of pharmacophores was designed. After evaluating ORL1 antagonistic activity, a highly focused library was designed based on 3D-pharmacophore similarity to known actives. A novel D-proline amide class was identified in this library and was found to possess potent ORL1 antagonistic activity.