Letters in Drug Design & Discovery

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


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.


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

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