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Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.

Guile, S D; Bantick, J R; Cheshire, D R; Cooper, M E; Davis, A M; Donald, D K; Evans, R; Eyssade, C; Ferguson, D D; Hill, S; Hutchinson, R; Ingall, A H; Kingston, L P; Martin, I; Martin, B P; Mohammed, R T; Murray, C; Perry, M W D; Reynolds, R H; Thorne, P V; Wilkinson, D J; Withnall, J.

Bioorg Med Chem Lett ; 16(8): 2260-5, 2006 Apr 15.

Article in English | MEDLINE | ID: mdl-16455256

ABSTRACT

A novel series of potent blockers of the monocarboxylate transporter, MCT1, is disclosed. From very potent but lipophilic lead compounds, systematic changes to all parts of the molecule, targeting reduction in log D, afforded compounds with significantly improved overall properties. These compounds show potent immunomodulatory activity.

Subject(s)

Aryl Hydrocarbon Hydroxylases/metabolism , Cytochrome P-450 Enzyme System/metabolism , Herpesviridae/drug effects , Immunologic Factors/pharmacology , Monocarboxylic Acid Transporters/antagonists & inhibitors , Symporters/antagonists & inhibitors , T-Lymphocytes/drug effects , Animals , Aryl Hydrocarbon Hydroxylases/immunology , Cytochrome P-450 CYP2C9 , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme System/immunology , Graft vs Host Disease/immunology , Herpesviridae/immunology , Herpesviridae/metabolism , Humans , Immunologic Factors/chemistry , Monocarboxylic Acid Transporters/immunology , Monocarboxylic Acid Transporters/metabolism , Symporters/immunology , Symporters/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism

ABSTRACT

Subject(s)

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