1MU8

thrombin-hirugen_l-378,650

1MU8 の概要

• エントリーDOI: 10.2210/pdb1mu8/pdb
• 関連するPDBエントリー: 1MU6 1MUE
• 分子名称: THROMBIN, HIRUDIN IIB, 2-(6-CHLORO-3-{[2,2-DIFLUORO-2-(2-PYRIDINYL)ETHYL]AMINO}-2-OXO-1(2H)-PYRAZINYL)-N-[(2-FLUORO-3-METHYL-6-PYRIDINYL)METHYL]ACETAMIDE, ... (5 entities in total)
• 機能のキーワード: thrombin-hirugen, blood clotting, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted, extracellular space: P00734 P00734; Secreted: P28506
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 35816.72

構造登録者

Burgey, C.S.,Robinson, K.A.,Lyle, T.A.,Sanderson, P.E.,Lewis, S.D.,Lucas, B.J.,Krueger, J.A.,Singh, R.,Miller-Stein, C.,White, R.B.,Wong, B.,Lyle, E.A.,Williams, P.D.,Coburn, C.A.,Dorsey, B.D.,Barrow, J.C.,Stranieri, M.T.,Holahan, M.A.,Sitko, G.R.,Cook, J.J.,McMasters, D.R.,McDonough, C.M.,Sanders, W.M.,Wallace, A.A.,Clayton, F.C.,Bohn, D.,Leonard, Y.M.,Detwiler Jr., T.J.,Lynch Jr., J.J.,Yan, Y.,Chen, Z.,Kuo, L.,Gardell, S.J.,Shafer, J.A.,Vacca, J.P.J. (登録日: 2002-09-23, 公開日: 2004-04-06, 最終更新日: 2024-11-20)

主引用文献

Burgey, C.S.,Robinson, K.A.,Lyle, T.A.,Sanderson, P.E.,Lewis, S.D.,Lucas, B.J.,Krueger, J.A.,Singh, R.,Miller-Stein, C.,White, R.B.,Wong, B.,Lyle, E.A.,Williams, P.D.,Coburn, C.A.,Dorsey, B.D.,Barrow, J.C.,Stranieri, M.T.,Holahan, M.A.,Sitko, G.R.,Cook, J.J.,McMasters, D.R.,McDonough, C.M.,Sanders, W.M.,Wallace, A.A.,Clayton, F.C.,Bohn, D.,Leonard, Y.M.,Detwiler Jr., T.J.,Lynch Jr., J.J.,Yan, Y.,Chen, Z.,Kuo, L.,Gardell, S.J.,Shafer, J.A.,Vacca, J.P.J.
Metabolism-directed optimization of 3-aminopyrazinone acetamide thrombin inhibitors. Development of an orally bioavailable series containing P1 and P3 pyridines.
J.Med.Chem., 46:461-473, 2003

PubMed Abstract: Recent efforts in the field of thrombin inhibitor research have focused on the identification of compounds with good oral bioavailability and pharmacokinetics. In this manuscript we describe a metabolism-based approach to the optimization of the 3-(2-phenethylamino)-6-methylpyrazinone acetamide template (e.g., 1) which resulted in the modification of each of the three principal components (i.e., P1, P2, P3) comprising this series. As a result of these studies, several potent thrombin inhibitors (e.g., 20, 24, 25) were identified which exhibit high levels of oral bioavailability and long plasma half-lives.

PubMed: 12570369
DOI: 10.1021/jm020311f

実験手法

X-RAY DIFFRACTION (2 Å)