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

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

Volume: 3 Issue: 10

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

Affiliation:

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

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.

Cite this article as:

Revesz Laszlo, Bollbuck Birgit, Buhl Thomas, Dawson Janet, Feifel Roland, Heng Richard, Hiestand Peter, Sparrer Helmut, Schlapbach Achim, Waelchli Rudolf and Loetscher Pius, Bridged Piperazines and Piperidines as CCR1 Antagonists with Oral Activity in Models of Arthritis and Multiple Sclerosis, Letters in Drug Design & Discovery 2006; 3 (10) . https://dx.doi.org/10.2174/157018006778631866

DOI https://dx.doi.org/10.2174/157018006778631866	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X