ethyl 2-{[(1R)-1-cyclohexyl-2-[(2S)-2-[({4-[(Z)-N'-hydroxycarbamimidoyl]phenyl}methyl)carbamoyl]azetidin-1-yl]-2-oxoethyl]amino}acetate

• ChemBase编号: 4399
• 分子式: C24H35N5O5
• 平均质量: 473.5652
• 单一同位素质量: 473.26381925
• SMILES: O=C(N1[C@@H](CC1)C(=O)NCc1ccc(cc1)/C(=N/O)/N)[C@H](NCC(=O)OCC)C1CCCCC1
• Canonical SMILES: CCOC(=O)CN[C@@H](C(=O)N1CC[C@H]1C(=O)NCc1ccc(cc1)/C(=N/O)/N)C1CCCCC1
• InChI: InChI=1S/C24H35N5O5/c1-2-34-20(30)15-26-21(17-6-4-3-5-7-17)24(32)29-13-12-19(29)23(31)27-14-16-8-10-18(11-9-16)22(25)28-33/h8-11,17,19,21,26,33H,2-7,12-15H2,1H3,(H2,25,28)(H,27,31)/t19-,21+/m0/s1
• InChIKey: ZXIBCJHYVWYIKI-PZJWPPBQSA-N

名称和登记号

名称

• IUPAC标准名: ethyl 2-{[(1R)-1-cyclohexyl-2-[(2S)-2-[({4-[(Z)-N'-hydroxycarbamimidoyl]phenyl}methyl)carbamoyl]azetidin-1-yl]-2-oxoethyl]amino}acetate
• IUPAC传统名: ximelagatran
• 商标名: Exanta; Exarta
• 别名: H 376/95; ximelagatran; Ximelagatran

登记号

• CAS号: 192939-46-1
• PubChem SID: 160967831; 46509040
• PubChem CID: 9574101

理论计算性质

JChem

• Acid pKa: 9.638632
• 质子受体: 7
• 质子供体: 4
• LogD (pH = 5.5): 0.5353352
• LogD (pH = 7.4): 0.8611465
• Log P: 0.8693069
• 摩尔折射率: 126.5662 cm^3
• 极化性: 49.31325 Å^3
• 极化表面积: 146.35 Å^2
• 可自由旋转的化学键: 11
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 1.35
• LOG S: -3.75
• 溶解度: 8.45e-02 g/l

详细说明

DrugBank - DB04898

• Drug Groups: approved; withdrawn; investigational
• Description: Ximelagatran (Exanta? or Exarta?, H 376/95) is an anticoagulant that has been investigated extensively as a replacement for warfarin that would overcome the problematic dietary, drug interaction, and monitoring issues associated with warfarin therapy. In 2006, its manufacturer AstraZeneca announced that it would not attempt to market ximelagatran after reports of hepatotoxicity (liver damage) during trials, and to discontinue its distribution in countries where the drug had been approved.
• Indication: For the treatment of acute deep vein thrombosis.
• Toxicity: Hepatotoxicity (liver damage) was reported during trials.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Ximelagatran is a prodrug, being converted in vivo to the active agent melagatran. This conversion takes place in the liver and many other tissues through dealkylation and dehydroxylation (replacing the ethyl and hydroxyl groups with hydrogen).
• Absorption: Rapidly absorbed by the small intestine with an oral bioavailability of 20%.
• Half Life: 3-5 hours
• References: Eriksson H, Wahlander K, Gustafsson D, Welin LT, Frison L, Schulman S: A randomized, controlled, dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute deep vein thrombosis: THRIVE I. J Thromb Haemost. 2003 Jan;1(1):41-7. [Pubmed] ; Weitz JI: New anticoagulants for treatment of venous thromboembolism. Circulation. 2004 Aug 31;110(9 Suppl 1):I19-26. [Pubmed] ; Francis CW, Berkowitz SD, Comp PC, Lieberman JR, Ginsberg JS, Paiement G, Peters GR, Roth AW, McElhattan J, Colwell CW Jr: Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N Engl J Med. 2003 Oct 30;349(18):1703-12. [Pubmed] ; Bergqvist D, Solhaug JH, Holmdahl L, Eriksson UG, Andersson M, Boberg B, Ogren M: Pharmacokinetics, preliminary efficacy and safety of subcutaneous melagatran and oral ximelagatran : a multicentre study of thromboprophylaxis in elective abdominal surgery. Clin Drug Investig. 2004;24(3):127-36. [Pubmed] ; Koscielny J, Kiesewetter H, Jorg I, Harenberg J: Ximelagatran for treatment and prophylaxis of recurrent events in deep vein thrombosis. Clin Appl Thromb Hemost. 2007 Jul;13(3):299-307. [Pubmed]
• External Links: Wikipedia

参考文献

• Eriksson H, Wahlander K, Gustafsson D, Welin LT, Frison L, Schulman S: A randomized, controlled, dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute deep vein thrombosis: THRIVE I. J Thromb Haemost. 2003 Jan;1(1):41-7. Pubmed
• Weitz JI: New anticoagulants for treatment of venous thromboembolism. Circulation. 2004 Aug 31;110(9 Suppl 1):I19-26. Pubmed
• Francis CW, Berkowitz SD, Comp PC, Lieberman JR, Ginsberg JS, Paiement G, Peters GR, Roth AW, McElhattan J, Colwell CW Jr: Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N Engl J Med. 2003 Oct 30;349(18):1703-12. Pubmed
• Bergqvist D, Solhaug JH, Holmdahl L, Eriksson UG, Andersson M, Boberg B, Ogren M: Pharmacokinetics, preliminary efficacy and safety of subcutaneous melagatran and oral ximelagatran : a multicentre study of thromboprophylaxis in elective abdominal surgery. Clin Drug Investig. 2004;24(3):127-36. Pubmed
• Koscielny J, Kiesewetter H, Jorg I, Harenberg J: Ximelagatran for treatment and prophylaxis of recurrent events in deep vein thrombosis. Clin Appl Thromb Hemost. 2007 Jul;13(3):299-307. Pubmed