Antifungal rapamycin analogues with reduced immunosuppressive activity.
Several 1,2,3,4-tetrahydro- and 7-N-hydroxycarbamate derivatives of the natural product rapamycin were prepared and assayed for their immunosuppressive and antifungal profiles. Substitutions at the 7-position indicate the possibility of a differentiated immunosuppressive to antifungal profile, whereas 40-position variants of the tetrahydro-analogues did not show similar differentiated activity.
Dickman
D A
DA
Infectious and Immunological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064, USA.
Ding
H
H
Li
Q
Q
Nilius
A M
AM
Balli
D J
DJ
Ballaron
S J
SJ
Trevillyan
J M
JM
Smith
M L
ML
Seif
L S
LS
Kim
K
K
Sarthy
A
A
Goldman
R C
RC
Plattner
J J
JJ
Bennani
Y L
YL
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001702:Biopharmaceutics; D002175:Candida / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D015398:Signal Transduction; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D020123:Sirolimus