Studies on an immunosuppressive macrolactam, ascomycin: synthesis of a C-33 hydroxyl derivative.
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.
Kawai
M
M
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Gunawardana
I W
IW
Mollison
K W
KW
Hsieh
G C
GC
Lane
B C
BC
Luly
J R
JR
D000818:Animals; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006965:Hyperplasia; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D008968:Molecular Conformation; D015394:Molecular Structure; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D007166:Immunosuppressive Agents; D007202:Indicators and Reagents; C058028:immunomycin; D016559:Tacrolimus