(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 ID: 163
• Molecular Formular: C23H36N6O5S
• Molecular Mass: 508.63414
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: (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 Traditional name: (2R,4R)-1-[(2S)-5-[(diaminomethylidene)amino]-2-[(3R)-3-methyl-1,2,3,4-tetrahydroquinoline-8-sulfonamido]pentanoyl]-4-methylpiperidine-2-carboxylic acid
• Synonyms: argatroban; Argatroban

Database IDs

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

CALCULATED PROPERTIES

JChem

• Acid pKa: 3.0738177
• H Acceptors: 9
• H Donor: 5
• LogD (pH = 5.5): -0.9708456
• LogD (pH = 7.4): -0.9700008
• Log P: -0.96971005
• Molar Refractivity: 133.5362 cm^3
• Polarizability: 51.34015 Å^3
• Polar Surface Area: 180.21 Å^2
• Rotatable Bonds: 8
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 0.19
• LOG S: -3.36
• Solubility (Water): 2.21e-01 g/l

PROPERTIES

Physical Property

• Hydrophobicity(logP): 1

DETAILS

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

REFERENCES

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