(2R,4R)-1-[(2S)-5-[(diaminomethylidene)amino]-2-[(3R)-3-methyl-1,2,3,4-tetrahydroquinoline-8-sulfonamido]pentanoyl]-4-methylpiperidine-2-carboxylic acid

• ChemBase编号: 163
• 分子式: C23H36N6O5S
• 平均质量: 508.63414
• 单一同位素质量: 508.24678928
• SMILES: S(=O)(=O)(N[C@H](C(=O)N1[C@H](C[C@@H](CC1)C)C(=O)O)CCCN=C(N)N)c1c2NC[C@@H](Cc2ccc1)C
• Canonical SMILES: NC(=NCCC[C@@H](C(=O)N1CC[C@H](C[C@@H]1C(=O)O)C)NS(=O)(=O)c1cccc2c1NC[C@@H](C2)C)N
• InChI: InChI=1S/C23H36N6O5S/c1-14-8-10-29(18(12-14)22(31)32)21(30)17(6-4-9-26-23(24)25)28-35(33,34)19-7-3-5-16-11-15(2)13-27-20(16)19/h3,5,7,14-15,17-18,27-28H,4,6,8-13H2,1-2H3,(H,31,32)(H4,24,25,26)/t14-,15-,17+,18-/m1/s1
• InChIKey: KXNPVXPOPUZYGB-XYVMCAHJSA-N

名称和登记号

名称

• IUPAC标准名: (2R,4R)-1-[(2S)-5-[(diaminomethylidene)amino]-2-[(3R)-3-methyl-1,2,3,4-tetrahydroquinoline-8-sulfonamido]pentanoyl]-4-methylpiperidine-2-carboxylic acid
• IUPAC传统名: (2R,4R)-1-[(2S)-5-[(diaminomethylidene)amino]-2-[(3R)-3-methyl-1,2,3,4-tetrahydroquinoline-8-sulfonamido]pentanoyl]-4-methylpiperidine-2-carboxylic acid
• 别名: argatroban; Argatroban

登记号

• CAS号: 74863-84-6
• PubChem SID: 160963626; 46507650
• PubChem CID: 152951

理论计算性质

JChem

• Acid pKa: 3.0738177
• 质子受体: 9
• 质子供体: 5
• LogD (pH = 5.5): -0.9708456
• LogD (pH = 7.4): -0.9700008
• Log P: -0.96971005
• 摩尔折射率: 133.5362 cm^3
• 极化性: 51.34015 Å^3
• 极化表面积: 180.21 Å^2
• 可自由旋转的化学键: 8
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 0.19
• LOG S: -3.36
• 溶解度: 2.21e-01 g/l

分子性质

理化性质

• 疏水性(logP): 1

详细说明

DrugBank - DB00278

• Drug Groups: approved; investigational
• Description: Argatroban is a direct, selective thrombin inhibitor. The American College of Cardiologists (ACC) recommend using bivalirudin or argatroban in patients who have had, or at risk for, heparin induced thrombocytopenia (HIT) and are undergoing percutaneous coronary intervention. Argatroban is a non-heparin anticoagulant shown to both normalize platelet count in patients with HIT and prevent the formation of thrombi. Parental anticoagulants must be stopped and a baseline activated partial thromboplastin time must be obtained prior to administering argatroban.
• Indication: Argatroban is indicated for prevention and treatment of thrombosis caused by heparin induced thrombocytopenia (HIT). It is also indicated for use in patients with, or at risk for, HIT who are undergoing percutaneous coronary intervention.
• Pharmacology: Argatroban is a synthetic direct thrombin inhibitor derived from L-arginine indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia. Argatroban is a direct thrombin inhibitor that reversibly binds to the thrombin active site. Argatroban does not require the co-factor antithrombin III for antithrombotic activity. Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation. Argatroban is highly selective for thrombin with an inhibitory constant (K_i) of 0.04 µM. At therapeutic concentrations, Argatroban has little or no effect on related serine proteases (trypsin, factor Xa, plasmin, and kallikrein).; Argatroban is capable of inhibiting the action of both free and clot-associated thrombin.
• Toxicity: Excessive bleeding
• Affected Organisms: Humans and other mammals
• Biotransformation: Liver via hydroxylation and aromatization of the 3-methyltetrahydroquinoline ring. Age and gender do not substantially affect the pharmacodynamic or pharmacokinetic profile of argatroban.
• Absorption: Bioavailability is 100% (intravenous).
• Half Life: 39 and 51 minutes
• Protein Binding: 54%
• Elimination: Argatroban is excreted primarily in the feces (65%), presumably through biliary secretion; 22% is eliminated via urine.
• Distribution: * 174 mL/kg; * 12.18 L [70-kg adult]
• Clearance: * 5.1 L/kg/hr [infusion doses up to 40?mcg/kg/min]
• References: Di Nisio M, Middeldorp S, Buller HR: Direct thrombin inhibitors. N Engl J Med. 2005 Sep 8;353(10):1028-40. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

参考文献

• Di Nisio M, Middeldorp S, Buller HR: Direct thrombin inhibitors. N Engl J Med. 2005 Sep 8;353(10):1028-40. Pubmed