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Letter

Indolin-2-ones with High in Vivo Efficacy in a Model for Multiple Sclerosis^§

Supporting Info

Laëtitia Bouérat,* Jef Fensholdt, Xifu Liang, Sophie Havez, Simon F. Nielsen, Jens R. Hansen, Simon Bolvig, and Christina Andersson*

LEO Pharma A/S, Industriparken, DK-2750 Ballerup, Denmark

J. Med. Chem., 2005, 48 (17), pp 5412–5414

DOI: 10.1021/jm0504151

Publication Date (Web): July 27, 2005

Dedicated to Lise and Ernst Binderup on the occasion of their retirement in December 2004.

To whom correspondence should be addressed. For L.B., Dept. of Marketing Healthcare: phone, (0045) 72262435; Fax, (0045) 44945823; e-mail: laetitia.bouerat@leo-pharma.com. For C.A., Dept. of Pharmacology: phone, (0045) 72263614; Fax, (0045) 72263335; e-mail, christina.andersson@leo-pharma.com.

Abstract

The known KDR inhibitor SU5416 and several analogues of the indolin-2-one family were surprisingly found to be highly efficacious in the EAE model, an established model for multiple sclerosis. The high in vivo effect could be correlated to in vitro inhibition of the pro-inflammatory cytokine IL-2. Activity following po administration was obtained with several analogues and via the use of prodrugs.

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Published In Issue August 25, 2005
Received May 2, 2005

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Letter

Indolin-2-ones with High in Vivo Efficacy in a Model for Multiple Sclerosis^§