Identification of a novel spiropiperidine opioid receptor-like 1 antagonist class by a focused library approach featuring 3D-pharmacophore similarity.
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.
Goto
Yasuhiro
Y
Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Okubo 3, Tsukuba 300-2611, Japan.
Arai-Otsuki
Sachie
S
Tachibana
Yukari
Y
Ichikawa
Daisuke
D
Ozaki
Satoshi
S
Takahashi
Hiroyuki
H
Iwasawa
Yoshikazu
Y
Okamoto
Osamu
O
Okuda
Shoki
S
Ohta
Hisashi
H
Sagara
Takeshi
T
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D015394:Molecular Structure; D009292:Narcotic Antagonists; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000819:agonists / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D000094942:Nociceptin Receptor
D009292:Narcotic Antagonists; D010880:Piperidines; D011957:Receptors, Opioid; D013141:Spiro Compounds; D011392:Proline; C056291:prolinamide; D000094942:Nociceptin Receptor