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 :
12369255 - Female wistar rats tested during late proestrus or during pregnancy and ovariectomized ...
8728545 - Affiliation in periadolescent rats: behavioral and corticosterone response to social re...
22231835 - Adhd animal model characterization: transcriptomics and proteomics analyses.
3754145 - Food intake, aggression, and fear behavior in the mother rat: control by neural systems...
6872155 - Carcinogenesis and aging. ii. modifying effect of aging on metabolism of methyl(acetoxy...
25237595 - Rat sightings in new york city are associated with neighborhood sociodemographics, hous...
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...