1MUE

Thrombin-Hirugen-L405,426

1MUE の概要

• エントリーDOI: 10.2210/pdb1mue/pdb
• 関連するPDBエントリー: 1mu6 1mu8
• 分子名称: THROMBIN, HIRUDIN IIB, 2-(6-CHLORO-3-{[2,2-DIFLUORO-2-(1-OXIDO-2-PYRIDINYL)ETHYL]AMINO}-2-OXO-1(2H)-PYRAZINYL)-N-[(2-FLUOROPHENYL)METHYL]ACETAMIDE, ... (5 entities in total)
• 機能のキーワード: alpha thrombin-hirugen, blood clotting complex, hydrolase inhibitor complex, 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: 35836.11

構造登録者

Burgey, C.S.,Robinson, K.A.,Lyle, T.A.,Nantermet, P.G.,Selnick, H.G.,Isaacs, R.C.,Lewis, S.D.,Lucas, B.J.,Krueger, J.A.,Singh, R.,Miller-Stein, C.,White, R.B.,Wong, B.,Lyle, E.A.,Stranieri, M.T.,Cook, J.J.,McMasters, D.R.,Pellicore, J.M.,Pal, S.,Wallace, A.A.,Clayton, F.C.,Bohn, D.,Welsh, D.C.,Lynch, J.J.,Yan, Y.,Chen, Z.,Kuo, L.,Gardell, S.J.,Shafer, J.A.,Vacca, J.P. (登録日: 2002-09-23, 公開日: 2004-04-06, 最終更新日: 2024-10-16)

主引用文献

Burgey, C.S.,Robinson, K.A.,Lyle, T.A.,Nantermet, P.G.,Selnick, H.G.,Isaacs, R.C.,Lewis, S.D.,Lucas, B.J.,Krueger, J.A.,Singh, R.,Miller-Stein, C.,White, R.B.,Wong, B.,Lyle, E.A.,Stranieri, M.T.,Cook, J.J.,McMasters, D.R.,Pellicore, J.M.,Pal, S.,Wallace, A.A.,Clayton, F.C.,Bohn, D.,Welsh, D.C.,Lynch, J.J.,Yan, Y.,Chen, Z.,Kuo, L.,Gardell, S.J.,Shafer, J.A.,Vacca, J.P.
Pharmacokinetic optimization of 3-amino-6-chloropyrazinone acetamide thrombin inhibitors. Implementation of P3 pyridine N-oxides to deliver an orally bioavailable series containing P1 N-benzylamides.
Bioorg.Med.Chem.Lett., 13:1353-1357, 2003

PubMed Abstract: In this manuscript we demonstrate that a modification principally directed toward the improvement of the aqueous solubility (i.e., introduction a P3 pyridine N-oxide) of the previous lead compound afforded a new series of potent orally bioavailable P1 N-benzylamide thrombin inhibitors. An expedited investigation of the P1 SAR with respect to oral bioavailability, plasma half-life, and human liver microsome stability revealed 5 as the best candidate for advanced evaluation.

PubMed: 12657281
DOI: 10.1016/S0960-894X(03)00099-4

実験手法

X-RAY DIFFRACTION (2 Å)