3-BENZYLOXY-2-PHENYLPIPERIDINE NK1 ANTAGONISTS - THE INFLUENCE OF ALPHA-METHYL SUBSTITUTION

Authors
SWAIN CJ WILLIAMS BJ BAKER R CASCIERI MA CHICCHI G FORREST M HERBERT R KEOWN L LADDUWAHETTY T LUELL S MACINTYRE DE METZGER J MORTON S OWENS AP SADOWSKI S WATT AP
Citation
Cj. Swain et al., 3-BENZYLOXY-2-PHENYLPIPERIDINE NK1 ANTAGONISTS - THE INFLUENCE OF ALPHA-METHYL SUBSTITUTION, Bioorganic & medicinal chemistry letters, 7(23), 1997, pp. 2959-2962
Citations number
7
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
7
Issue
23
Year of publication
1997
Pages
2959 - 2962
Database
ISI
SICI code
0960-894X(1997)7:23<2959:3NA-TI>2.0.ZU;2-5
Abstract
In vitro metabolism studies on a series of 3,5-bis(trifluoromethyl)ben zyl ethers have identified 3,5-bis(trifluoromethyl)benzoic acid as a s ignificant metabolite possibly arising via oxidation of the benzylic p osition. A methyl group was introduced in an effort to suppress this r oute of metabolism. One diastereoisomer displayed an increase in affin ity and a marked improvement in duration of action. (C) 1997 Elsevier Science Ltd.