Structure and activity relationships of tartrate-based TACE inhibitors.
The syntheses and structure-activity relationships of the tartrate-based TACE inhibitors are discussed. The optimization of both the prime and non-prime sites led to compounds with picomolar activity. Several analogs demonstrated good rat pharmacokinetics.
Li
Dansu
D
Department of Medicinal Chemistry, Merck Research Laboratories, Cambridge, 320 Bent Street, Cambridge, MA 02141, United States. dansu.li@spcorp.com
Popovici-Muller
Janeta
J
Belanger
David B
DB
Caldwell
John
J
Dai
Chaoyang
C
David
Maria
M
Girijavallabhan
Vinay M
VM
Lavey
Brian J
BJ
Lee
Joe F
JF
Liu
Zhidan
Z
Mazzola
Rob
R
Rizvi
Razia
R
Rosner
Kristin E
KE
Shankar
Bandarpalle
B
Spitler
Jim
J
Ting
Pauline C
PC
Vaccaro
Henry
H
Yu
Wensheng
W
Zhou
Guowei
G
Zhu
Zhaoning
Z
Niu
Xiaoda
X
Sun
Jing
J
Guo
Zhuyan
Z
Orth
Peter
P
Chen
Shiying
S
Kozlowski
Joseph A
JA
Lundell
Daniel J
DJ
Madison
Vincent
V
McKittrick
Brian
B
Piwinski
John J
JJ
Shih
Neng-Yang
NY
Shipps
Gerald W
GW
Siddiqui
M Arshad
MA
Strickland
Corey O
CO
D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship; D013644:Tartrates / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
D011480:Protease Inhibitors; D013644:Tartrates; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat