title: N,N-Dialkylated 4-(4-arylsulfonylpiperazine-1-carbonyl)-benzamidines and 4-((4-arylsulfonyl)-2-oxo-piperazin-1-ylmethyl)-benzamidines as potent factor Xa inhibitors.
abstract: 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.
authors.affiliation: Millennium Pharmaceuticals, Inc., 256 East Grand Ave, South San Francisco, CA 94080, USA. zjia@portola.com
authors.forename: Zhaozhong J
authors.initials: ZJ
authors.lastname: Jia
authors.forename: Ting
authors.initials: T
authors.lastname: Su
authors.forename: Jingmei F
authors.initials: JF
authors.lastname: Zuckett
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Wu
authors.forename: Erick A
authors.initials: EA
authors.lastname: Goldman
authors.forename: Wenhao
authors.initials: W
authors.lastname: Li
authors.forename: Penglie
authors.initials: P
authors.lastname: Zhang
authors.forename: Lane A
authors.initials: LA
authors.lastname: Clizbe
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Song
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Bauer
authors.forename: Wenrong
authors.initials: W
authors.lastname: Huang
authors.forename: John
authors.initials: J
authors.lastname: Woolfrey
authors.forename: Uma
authors.initials: U
authors.lastname: Sinha
authors.forename: Ann E
authors.initials: AE
authors.lastname: Arfsten
authors.forename: Athiwat
authors.initials: A
authors.lastname: Hutchaleelaha
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Hollenbach
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Lambing
authors.forename: Robert M
authors.initials: RM
authors.lastname: Scarborough
authors.forename: Bing-Yan
authors.initials: BY
authors.lastname: Zhu
mesh_terms: 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*
chemical_list: D001550:Benzamidines; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors