2WYG

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

Summary for 2WYG

• Entry DOI: 10.2210/pdb2wyg/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 2JKH 2UWL 2UWO 2UWP 2VH0 2VH6 2VVC 2VVU 2VVV 2VWL 2VWM 2VWN 2VWO 2W26 2W3I 2W3K 2WYJ
• Descriptor: ACTIVATED FACTOR XA HEAVY CHAIN, FACTOR X LIGHT CHAIN, (E)-2-(5-CHLOROTHIOPHEN-2-YL)-N-[(3S)-1-{4-[(1R)-1-(DIMETHYLAMINO)ETHYL]-2-FLUOROPHENYL}-2-OXOPYRROLIDIN-3-YL]ETHENESULFONAMIDE, ... (4 entities in total)
• Functional Keywords: blood clotting, serine protease, egf-like domain, blood coagulation, hydrolase, hydroxylation, zymogen
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 44233.39

Authors

Kleanthous, S.,Borthwick, A.D.,Brown, D.,Burns-Kurtis, C.L.,Campbell, M.,Chaudry, L.,Chan, C.,Clarte, M.,Convery, M.A.,Harling, J.D.,Hortense, E.,Irving, W.R.,Irvine, S.,Pateman, A.J.,Patikis, A.,Pinto, I.L.,Pollard, D.R.,Roethka, T.J.,Senger, S.,Shah, G.P.,Stelman, G.J.,Toomey, J.R.,Watson, N.S.,Whittaker, C.,Zhou, P.,Young, R.J. (deposition date: 2009-11-16, release date: 2010-12-01, Last modification date: 2023-12-20)

Primary citation

Kleanthous, S.,Borthwick, A.D.,Brown, D.,Burns-Kurtis, C.L.,Campbell, M.,Chaudry, L.,Chan, C.,Clarte, M.,Convery, M.A.,Harling, J.D.,Hortense, E.,Irving, W.R.,Irvine, S.,Pateman, A.J.,Patikis, A.,Pinto, I.L.,Pollard, D.R.,Roethka, T.J.,Senger, S.,Shah, G.P.,Stelman, G.J.,Toomey, J.R.,Watson, N.S.,Whittaker, C.,Zhou, P.,Young, R.J.
Structure and Property Based Design of Factor Xa Inhibitors: Pyrrolidin-2-Ones with Monoaryl P4 Motifs
Bioorg.Med.Chem.Lett., 20:618-, 2010

PubMed Abstract: Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa inhibitors, incorporating neutral and basic monoaryl P4 groups, ultimately producing potent inhibitors with effective levels of anticoagulant activity and extended oral pharmacokinetic profiles. However, time dependant inhibition of Cytochrome P450 3A4 was a particular issue with this series.

PubMed: 20006499
DOI: 10.1016/J.BMCL.2009.11.077

Experimental method

X-RAY DIFFRACTION (1.88 Å)