SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS FOR A SERIES OF SUBSTITUTED PYRROLIDINE NK1 NK2 RECEPTOR ANTAGONISTS/

Authors
BURKHOLDER TP KUDLACZ EM MAYNARD GD LIU XG LE TB WEBSTER ME HORGAN SW WENSTRUP DL FREUND DW BOYER F BRATTON L GROSS RS KNIPPENBERG RW LOGAN DE JONES BK CHEN TM GEARY JL CORRELL MA POOLE JC MANDAGERE AK THOMPSON TN HWANG KK
Citation
Tp. Burkholder et al., SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS FOR A SERIES OF SUBSTITUTED PYRROLIDINE NK1 NK2 RECEPTOR ANTAGONISTS/, Bioorganic & medicinal chemistry letters, 7(19), 1997, pp. 2531-2536
Citations number
23
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
7
Issue
19
Year of publication
1997
Pages
2531 - 2536
Database
ISI
SICI code
0960-894X(1997)7:19<2531:SASFAS>2.0.ZU;2-H
Abstract
We recently described the synthesis and characterization of MDL 105,21 2, a non peptide tachykinin antagonist with high affinity for NK1 and NK2 receptors.(1) Here we report the synthesis and structure-activity relationships for a series of analogs of MDL 105,212 with regards to: NK1 and NK2 receptor binding affinity, physical-chemical characterizat ion; in vitro absorption potential; in vitro metabolic stability; and efficacy in a capsaicin-challenge conscious guinea pig model after ora l administration. (C) 1997 Elsevier Science Ltd.