Rapamycin analogs with reduced systemic exposure.
The synthesis and biological activities of rapamycin (I) analogs modified at the C-40 position are reported. Emphasis placed on compounds that potentially have an improved safety profile on account of their shorter in vivo half-life when compared with rapamycin.
Wagner
Rolf
R
Abbott Laboratories, Global Pharmaceutical Research and Development, Abbott Park, IL 60064, USA. rolf.wagner@abbott.com
Mollison
Karl W
KW
Liu
Luping
L
Henry
Cynthia L
CL
Rosenberg
Teresa A
TA
Bamaung
Nwe
N
Tu
Noah
N
Wiedeman
Paul E
PE
Or
Yatsun
Y
Luly
Jay R
JR
Lane
Benjamin C
BC
Trevillyan
James
J
Chen
Yung-Wu
YW
Fey
Thomas
T
Hsieh
Gin
G
Marsh
Kennan
K
Nuss
Merrill
M
Jacobson
Peer B
PB
Wilcox
Denise
D
Carlson
Richard P
RP
Carter
George W
GW
Djuric
Stevan W
SW
D000818:Animals; D018501:Antirheumatic Agents / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000633:toxicity; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000031:analogs & derivatives*
D018501:Antirheumatic Agents; D020123:Sirolimus