Chemokine receptor CCR-5 inhibitors produced by Chaetomium globosum
Shu-Wei Yang1, Ronald Mierzwa, Joseph Terracciano
1Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA.
Abstract:
Two novel chemokine receptor CCR-5 inhibitors, Sch 210971 (1) and Sch 210972 (2), were isolated from the fungal fermentation broth of Chaetomium globosum by normal- and reversed-phase HPLC purifications. The structure determination of 1 and 2 was accomplished on the basis of UV, MS, and NMR spectral data analyses including COSY, NOESY, HMQC, and HMBC experiments. The structure and relative configuration of 2 were determined unequivocally by X-ray crystallographic analysis. The major component 2 demonstrated a potent inhibitory activity of IC(50) = 79 nM in the CCR-5 receptor in vitro binding assay.
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