N,N-Dialkylated 4-(4-arylsulfonylpiperazine-1-carbonyl)-benzamidines and 4-((4-arylsulfonyl)-2-oxo-piperazin-1-ylmethyl)-benzamidines as potent factor Xa inhibitors.
A class of N,N-dialkylated 4-(4-arylsulfonylpiperazine-1-carbonyl)-benzamidines and 4-((4-arylsulfonyl)-2-oxo-piperazin-1-ylmethyl)-benzamidines has been discovered as potent factor Xa inhibitors with desirable in vitro and in vivo anticoagulant activity, but with low oral bioavailability. The 5-chloroindole and 6-chlorobenzo[b]thiophene groups are optimal as the factor Xa S1 binding elements. The strategy of incorporating a side chain on the piperazine nucleus to enhance binding affinity has been examined.
Jia
Zhaozhong J
ZJ
Millennium Pharmaceuticals, Inc., 256 East Grand Ave, South San Francisco, CA 94080, USA. zjia@portola.com
Su
Ting
T
Zuckett
Jingmei F
JF
Wu
Yanhong
Y
Goldman
Erick A
EA
Li
Wenhao
W
Zhang
Penglie
P
Clizbe
Lane A
LA
Song
Yonghong
Y
Bauer
Shawn M
SM
Huang
Wenrong
W
Woolfrey
John
J
Sinha
Uma
U
Arfsten
Ann E
AE
Hutchaleelaha
Athiwat
A
Hollenbach
Stanley J
SJ
Lambing
Joseph L
JL
Scarborough
Robert M
RM
Zhu
Bing-Yan
BY
D001550:Benzamidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
D001550:Benzamidines; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors