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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Bridged Piperazines and Piperidines as CCR1 Antagonists with Oral Activity in Models of Arthritis and Multiple Sclerosis

Author(s): Laszlo Revesz, Birgit Bollbuck, Thomas Buhl, Janet Dawson, Roland Feifel, Richard Heng, Peter Hiestand, Helmut Sparrer, Achim Schlapbach, Rudolf Waelchli and Pius Loetscher

Volume 3 , Issue 10 , 2006

Page: [689 - 694] Pages: 6

DOI: 10.2174/157018006778631866

Price: $65

Abstract

CCR1 antagonists were prepared by coupling bridged piperazines and bridged piperidines with 2- acetylamino-4-chloro-5-methoxy cinnamic acid. Compound 2 of the series showed the desired equal potency against human, mouse and rat CCR1 (IC50= 20; 22; 28nM), exhibited a superior pharmacokinetic profile and inhibited the clinical grades in rat acute experimental autoimmune encephalomyelitis and knee swelling in rat antigen induced arthritis at doses of 2 x 30 and 2 x 15 mg/kg p.o.

Keywords: Rheumatoid arthritis, Multiple sclerosis, CCR1, Antagonist, Bridged piperazine


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