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  • Discovery of 7-N-piperazinylthiazolo[5,4-d]pyrimidine analogues as a novel class of immunosuppressive agents with in vivo biological activity.

Discovery of 7-N-piperazinylthiazolo[5,4-d]pyrimidine analogues as a novel class of immunosuppressive agents with in vivo biological activity.

Journal of medicinal chemistry (2010-12-22)
Mi-Yeon Jang, Yuan Lin, Steven De Jonghe, Ling-Jie Gao, Bart Vanderhoydonck, Mathy Froeyen, Jef Rozenski, Jean Herman, Thierry Louat, Kristien Van Belle, Mark Waer, Piet Herdewijn
ABSTRACT

Herein we describe the synthesis and in vitro and in vivo activity of thiazolo[5,4-d]pyrimidines as a novel class of immunosuppressive agents, useful for preventing graft rejection after organ transplantation. This research resulted in the discovery of a series of compounds with potent activity in the mixed lymphocyte reaction (MLR) assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. The most potent congeners displayed IC(50) values of less than 50 nM in this MLR assay and hence are equipotent to cyclosporin A, a clinically used immunosuppressive drug. One representative of this series was further evaluated in a preclinical animal model of organ transplantation and showed excellent in vivo efficacy. It validates these compounds as new promising immunosuppressive drugs.

MATERIALS
Product Number
Brand
Product Description

Supelco
Cyclosporin A, VETRANAL®, analytical standard
Sigma-Aldrich
Cyclosporin A, from Tolypocladium inflatum, ≥95% (HPLC), solid
Sigma-Aldrich
Cyclosporin A, from Tolypocladium inflatum, BioReagent, for molecular biology, ≥95%
Sigma-Aldrich
Cyclosporin A, 97.0-101.5% (on dried basis)