Potent immunosuppressive C32-O-arylethyl ether derivatives of ascomycin with reduced toxicity.
The synthesis of C32-O-arylethyl ether derivatives of ascomycin that possess equivalent immunosuppressant activity but reduced toxicity, compared to FK-506, is described.
Armstrong
H M
HM
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Wong
F
F
Holmes
M A
MA
Sinclair
P J
PJ
Goulet
M T
MT
Dumont
F J
FJ
Staruch
M J
MJ
Koprak
S
S
Peterson
L B
LB
Rosa
R
R
Wilusz
M B
MB
Wiederrecht
G J
GJ
Cryan
J G
JG
Wyvratt
M J
MJ
Parsons
W H
WH
D000284:Administration, Oral; D000818:Animals; D065095:Calcineurin Inhibitors; D004353:Drug Evaluation, Preclinical; D007035:Hypothermia / Q000139:chemically induced; D020104:Immunophilins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced; D018942:Macrolides / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D022021:Tacrolimus Binding Proteins; D018675:Toxicity Tests
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D018942:Macrolides; C058028:immunomycin; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins; D016559:Tacrolimus