Bioorg Med Chem Lett 1998 Apr 21;8(8):935-8  

Studies on an immunosuppressive macrolactam, ascomycin: synthesis of a C-33 hydroxyl derivative.

Kawai M, Gunawardana IW, Mollison KW, Hsieh GC, Lane BC, Luly JR.

Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.

Ascomycin 2, a close analogue of the immunosuppressant FK506 1, was modified to incorporate a hydroxyl group at the C-33 position. This increased the aqueous solubility of ascomycin by a hundred-fold at pH 7.4 and by approximately 300-fold at pH 6.5. Ascomycin 3 also exhibited an excellent immunosuppressive activity in vitro, as tested in a human mixed lymphocyte proliferation (HuMLR) assay, and in vivo using a rat popliteal lymph node (rPLN) hyperplasia assay.

PMID: 9871515


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