BnSO2-D-Phe-Phe(3,4-diF)-Arg(Mtr)-thiazol-2-yl | 603137-79-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: BnSO2-D-Phe-Phe(3,4-diF)-Arg(Mtr)-thiazol-2-yl
• 英文别名: (2R)-N-[(2S)-1-[[(2S)-5-[[amino-[(4-methoxy-2,3,6-trimethylphenyl)sulfonylamino]methylidene]amino]-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-3-(3,4-difluorophenyl)-1-oxopropan-2-yl]-2-(benzylsulfonylamino)-3-phenylpropanamide
• CAS: 603137-79-7
• 化学式: C₄₄H₄₉F₂N₇O₈S₃
• 分子量: 938.11
• InChiKey: AEWUWQCCIXDTBO-AGSXMJPOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  64
• 可旋转键数：
  22
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  273
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  BnSO2-D-Phe-Phe(3,4-diF)-Arg(Mtr)-thiazol-2-yl 在 茴香硫醚 、 三氟乙酸 作用下， 生成 (R)-N-{(S)-2-(3,4-Difluoro-phenyl)-1-[(S)-4-guanidino-1-(thiazole-2-carbonyl)-butylcarbamoyl]-ethyl}-3-phenyl-2-phenylmethanesulfonylamino-propionamide
  参考文献：
  名称：

  Polymer-Assisted solution-Phase (PASP) parallel synthesis of an α-Ketothiazole library as tissue factor VIIa inhibitors

  摘要：

  A solution-phase synthesis of an alpha-ketothiazole library of the general form D-Phe-L-AA-L-Arg-alpha-ketothiazole is described. The five-step synthesis is accomplished using a combination of polymeric reagents and polymer-assisted solution-phase purification protocols, including reactant-sequestering resins, reagent-sequestering resins, and tagged reagents. The multi-step synthesis affords the desired alpha-ketothiazole products in excellent purities and yields. A variety Of L-amino acid inputs were used to probe the S2 pocket of the tissue factor (TF) Vila enzyme to influence both potency and selectivity. An X-ray crystal structure of compound 10e bound to the TF/VIIa complex was obtained that explains the observed selectivity. The alpha-ketothiazoles were found to be potent, reversible-covalent inhibitors of tissue factor VIIa, with some analogues demonstrating selectivity versus thrombin. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00398-6
• 作为产物：
  描述：

  BOC-L-3,4-二氟苯丙氨酸 在 盐酸 、 carbodiimide resin 、 戴斯-马丁氧化剂 作用下， 以 1,4-二氧六环 为溶剂， 生成 BnSO2-D-Phe-Phe(3,4-diF)-Arg(Mtr)-thiazol-2-yl
  参考文献：
  名称：

  Polymer-Assisted solution-Phase (PASP) parallel synthesis of an α-Ketothiazole library as tissue factor VIIa inhibitors

  摘要：

  A solution-phase synthesis of an alpha-ketothiazole library of the general form D-Phe-L-AA-L-Arg-alpha-ketothiazole is described. The five-step synthesis is accomplished using a combination of polymeric reagents and polymer-assisted solution-phase purification protocols, including reactant-sequestering resins, reagent-sequestering resins, and tagged reagents. The multi-step synthesis affords the desired alpha-ketothiazole products in excellent purities and yields. A variety Of L-amino acid inputs were used to probe the S2 pocket of the tissue factor (TF) Vila enzyme to influence both potency and selectivity. An X-ray crystal structure of compound 10e bound to the TF/VIIa complex was obtained that explains the observed selectivity. The alpha-ketothiazoles were found to be potent, reversible-covalent inhibitors of tissue factor VIIa, with some analogues demonstrating selectivity versus thrombin. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00398-6

文献信息

• Polymer-Assisted Solution-Phase Library Synthesis and Crystal Structure of α-Ketothiazoles as Tissue Factor VIIa Inhibitors
  作者：John J. Parlow、Thomas A. Dice、Rhonda M. Lachance、Thomas J. Girard、Anna M. Stevens、Roderick A. Stegeman、William C. Stallings、Ravi G. Kurumbail、Michael S. South

  DOI：10.1021/jm030130t

  日期：2003.9.1

  A solution-phase synthesis of an alpha-ketothiazole library of the general form D-Phe-L-AA-Arg-alpha-ketothiazole is described. The five-step synthesis is accomplished using a combination of polymeric reagents and polymer-assisted solution-phase purification concepts, including reactant-sequestering resins, reagent-sequestering resins, and tagged reagents. The multistep synthesis affords desired alpha-ketothiazole products in excellent purities and yields. A variety of L-amino acid inputs were used to probe the S-2 pocket of tissue Factor VIIa enzyme to influence both potency and selectivity. An X-ray crystal structure of compound 10k bound to the TF/ VIIa complex was obtained that explains the observed selectivity. The alpha-ketothiazoles were found to be potent, reversible-covalent inhibitors of tissue Factor VIIa, with some analogues demonstrating selectivity over thrombin.
• Polymer-Assisted solution-Phase (PASP) parallel synthesis of an α-Ketothiazole library as tissue factor VIIa inhibitors
  作者：Michael S South、Thomas A Dice、Thomas J Girard、Rhonda M Lachance、Anna M Stevens、Roderick A Stegeman、William C Stallings、Ravi G Kurumbail、John J Parlow

  DOI：10.1016/s0960-894x(03)00398-6

  日期：2003.7

  A solution-phase synthesis of an alpha-ketothiazole library of the general form D-Phe-L-AA-L-Arg-alpha-ketothiazole is described. The five-step synthesis is accomplished using a combination of polymeric reagents and polymer-assisted solution-phase purification protocols, including reactant-sequestering resins, reagent-sequestering resins, and tagged reagents. The multi-step synthesis affords the desired alpha-ketothiazole products in excellent purities and yields. A variety Of L-amino acid inputs were used to probe the S2 pocket of the tissue factor (TF) Vila enzyme to influence both potency and selectivity. An X-ray crystal structure of compound 10e bound to the TF/VIIa complex was obtained that explains the observed selectivity. The alpha-ketothiazoles were found to be potent, reversible-covalent inhibitors of tissue factor VIIa, with some analogues demonstrating selectivity versus thrombin. (C) 2003 Elsevier Science Ltd. All rights reserved.