C32-O-phenalkyl ether derivatives of the immunosuppressant ascomycin: a tether length study.
A tether length study of C32-O-phenalkyl ether derivatives of ascomycin was conducted wherein it was determined that a 2-carbon tether provides optimum in vitro immunosuppressive activity. Oxygen-bearing substituents along the 2-carbon tether can further increase the potency of this design.
Goulet
M T
MT
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Sinclair
P J
PJ
Wong
F
F
Staruch
M J
MJ
Dumont
F J
FJ
Cryan
J G
JG
Wiederrecht
G J
GJ
Wyvratt
M J
MJ
Parsons
W H
WH
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D020104:Immunophilins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D018942:Macrolides / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins
D007166:Immunosuppressive Agents; D018942:Macrolides; C058028:immunomycin; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins; D016559:Tacrolimus