Document Detail

Discovery of potent, selective, orally active benzoxazepine-based Orexin-2 receptor antagonists.
MedLine Citation:
PMID:  21917455     Owner:  NLM     Status:  Publisher    
During our efforts to identify a series of potent, selective, orally active human Orexin-2 Receptor (OX2R) antagonists, we elucidated structure-activity relationship (SAR) on the 7-position of a benzoxazepine scaffold by utilizing Hammett σ(p) and Hansch-Fujita π value as aromatic substituent constants. The attempts led to the discovery of compound 1m, possessing good in vitro potency with over 100-fold selectivity against OX1R, good metabolic stability in human and rat liver microsome, good oral bioavailability in rats, and in vivo antagonistic activity in rats by oral administration.
Tatsuhiko Fujimoto; Jun Kunitomo; Yoshihide Tomata; Keiji Nishiyama; Masato Nakashima; Mariko Hirozane; Shin-Ichi Yoshikubo; Keisuke Hirai; Shogo Marui
Related Documents :
15766725 - The application of nuclear magnetic resonance-based metabonomics to the dominant-submis...
7071605 - Oxytocin induces maternal behavior in virgin female rats.
20799285 - Impulsive rats are less maternal.
21622965 - Left ventricle structural remodelling in the prediabetic goto-kakizaki rat.
10669485 - Recurrent excitatory connectivity in the dentate gyrus of kindled and kainic acid-treat...
3644825 - Direct radioimmunoassay of rat urinary kallikrein: its application to the determination...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-30
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  -     ISSN:  1464-3405     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-9-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Medicinal Chemistry Research Laboratories, Takeda Pharmaceutical Company, 26-1, Muraokahigashi 2-Chome, Fujisawa, Kanagawa 251-1238, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Design, synthesis and SAR of indazole and benzoisoxazole containing 4-azetidinyl-1-aryl-cyclohexanes...
Next Document:  Test-retest reliability and descriptive statistics of geometric measurements based on plantar pressu...