Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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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, Pius Loetscher.

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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Article Details

VOLUME: 3
ISSUE: 10
Year: 2006
Page: [689 - 694]
Pages: 6
DOI: 10.2174/157018006778631866
Price: $58