2VH6

Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with biaryl P4 motifs

Summary for 2VH6

• Entry DOI: 10.2210/pdb2vh6/pdb
• Related: 1C5M 1EZQ 1F0R 1F0S 1FAX 1FJS 1G2L 1G2M 1HCG 1IOE 1IQE 1IQF 1IQG 1IQH 1IQI 1IQJ 1IQK 1IQL 1IQM 1IQN 1KSN 1KYE 1LPG 1LPK 1LPZ 1LQD 1MQ5 1MQ6 1MSX 1NFU 1NFW 1NFX 1NFY 1NL8 1P0S 1V3X 1WU1 1XKA 1XKB 1Z6E 2BMG 2BOH 2BOK 2BQ6 2BQ7 2BQW 2CJI 2FZZ 2G00 2GD4 2J2U 2J34 2J38 2J4I 2J94 2J95 2UWL 2UWO 2UWP 2VH0
• Descriptor: ACTIVATED FACTOR XA HEAVY CHAIN, ACTIVATED FACTOR XA LIGHT CHAIN, 2-(5-chlorothiophen-2-yl)-N-{(3S)-1-[3-fluoro-2'-(methylsulfonyl)biphenyl-4-yl]-2-oxopyrrolidin-3-yl}ethanesulfonamide, ... (4 entities in total)
• Functional Keywords: serine protease, egf-like domain, blood coagulation, polymorphism, glycoprotein, hydroxylation, gamma-carboxyglutamic acid, calcium, zymogen, complex, protease, hydrolase, cleavage on pair of basic residues
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 44318.47

Authors

Young, R.J.,Borthwick, A.D.,Brown, D.,Burns-Kurtis, C.L.,Campbell, M.,Chan, C.,Charbaut, M.,Chung, C.W.,Convery, M.A.,Kelly, H.A.,King, N.P.,Kleanthous, S.,Mason, A.M.,Pateman, A.J.,Patikis, A.N.,Pinto, I.L.,Pollard, D.R.,Senger, S.,Shah, G.P.,Toomey, J.R.,Watson, N.S.,Weston, H.E. (deposition date: 2007-11-19, release date: 2008-12-16, Last modification date: 2024-10-23)

Primary citation

Young, R.J.,Borthwick, A.D.,Brown, D.,Burns-Kurtis, C.L.,Campbell, M.,Chan, C.,Charbaut, M.,Chung, C.W.,Convery, M.A.,Kelly, H.A.,Paul King, N.,Kleanthous, S.,Mason, A.M.,Pateman, A.J.,Patikis, A.N.,Pinto, I.L.,Pollard, D.R.,Senger, S.,Shah, G.P.,Toomey, J.R.,Watson, N.S.,Weston, H.E.
Structure and Property Based Design of Factor Xa Inhibitors: Pyrrolidin-2-Ones with Biaryl P4 Motifs.
Bioorg.Med.Chem.Lett., 18:23-, 2008

PubMed Abstract: Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating biaryl P4 groups, producing highly potent inhibitors with encouraging oral pharmacokinetic profiles and significant but sub-optimal anticoagulant activities.

PubMed: 18054228
DOI: 10.1016/J.BMCL.2007.11.023

Experimental method

X-RAY DIFFRACTION (1.95 Å)