74863-84-6 Usage
Description
Different sources of media describe the Description of 74863-84-6 differently. You can refer to the following data:
1. Argatroban is a new synthetic antithrombotic agent useful in maintenance
anticoagulation them
ischemic stroke and disseminated intravascular coagulation. In patients on hemodialysis, argatroban is su enor to heparin,
generating a more stable antithrombin effect. Other potential uses include progressing ischemic stroke and disseminated intravascular coagulation.
2. Argatroban is a reversible inhibitor of thrombin (IC50s = 0.01 and 0.09 μM for the free and clot-bound forms, respectively). It is selective for thrombin over factor Xa, trypsin, plasmin, and tissue plasminogen activator (Kis = 0.0045, 53, 0.19, 25.7, and 87.7 μM, respectively). It inhibits thrombin-induced platelet aggregation in washed isolated guinea pig platelets with an IC50 value of 0.077 μM. Argatroban (3.2 mg/kg, s.c.) decreases thrombus formation in a guinea pig model of iron chloride-induced arterial thrombosis. Formulations containing argatroban have been used in the prevention or treatment of thrombosis in patients with heparin-induced thrombocytopenia.
Originator
Mitsubishi Kasei; Daiichi (Japan)
Uses
Different sources of media describe the Uses of 74863-84-6 differently. You can refer to the following data:
1. anticoagulant;direct thrombine inhibitor
2. (2S,4S)-1-(2R)-Argatroban is an isomeric impurity of Argatroban (74863-84-6 #CAS), which is a synthetic thrombin inhibitor. Antithrombotic.
Brand name
Novastan (Mitsubishi
Chemical Corporation, Japan);Slonnon.
Therapeutic Function
Anticoagulant
Pharmacokinetics
Argatroban is administered subcutaneously because of the low lipophilicity of the drug. The drug is
bound to plasma protein and is metabolized via CYP3A4/5 to the aromatized metabolite and the two
hydroxylated metabolites. The M-1 metabolite retains 20 to 30% of the antithrombotic
activity. Coadministration of argatroban with inhibitors of CYP3A4 does not appear to produce
clinically significant effects. Argatroban is eliminated via biliary secretion into the feces.
Clinical Use
Argatroban has been approved for the prophylaxis and treatment of thrombosis in patients with HIT
(79). Argatroban is a peptidomimetic that binds selectively to the catalytic site of thrombin as a
univalent competitive DTI. Argatroban is available as a mixture of 21-R and 21-S
diastereomers (64:36), with the S-isomer approximately twice as potent as the R-isomer. The
drug is a reversible inhibitor of both free thrombin as well as clot-bound thrombin.
Drug interactions
Potentially hazardous interactions with other drugs
Analgesics: increased risk of haemorrhage with IV
diclofenac and ketorolac - avoid.
Antiplatelets and anticoagulants: increased risk of
bleeding complications.
Heparin: avoid concomitant administration.
Urokinase: may increase the risk of bleeding.
Thrombolytics: may increase risk of bleeding
complications; enhance effect of argatroban.
Metabolism
The metabolism of argatroban has not yet been fully
characterised. The metabolites identified (M-1, M-2, and
M-3) are formed by hydroxylation and aromatisation
of the 3-methyltetrahydroquinoline ring in the liver.
The main metabolite (M1) exerts 40-fold weaker
antithrombin effect than argatroban. Metabolites M-1,
M-2 and M-3 were detected in the urine, and M-1 was
detected in plasma and faeces.
Argatroban is excreted mainly in the faeces, presumably
through biliary secretion. Following intravenous infusion of [14C]-argatroban 21.8±5.8% of the dose was excreted
in urine and 65.4±7.1% in the faeces.
References
1) Kikumoto?et al. (1984),?Selective inhibition of thrombin by (2R,4R)-4-methyl-1-[N2-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)sulfonyl]-l-arginyl)]-2-piperidinecarboxylic acid; Biochemistry,?23?85
2) Jang?et al. (1990),?Prevention of platelet-rich arterial thrombosis by selective thrombin inhibition; Circulation,?81?219
3) Sugawara?et al. (2009),?Thrombin inhibition by argatroban ameliorates early brain injury and improves neurological outcomes after experimental subarachnoid hemorrhage in rats; Stroke,?40?1530
4) Schulze?et al. (2008),?The thrombin inhibitor Argatroban reduces breast cancer malignancy and metastasis via osteopontin-dependent and osteopontin-independent mechanisms; Breast Cancer Res. Treat.,?112?243
Check Digit Verification of cas no
The CAS Registry Mumber 74863-84-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,4,8,6 and 3 respectively; the second part has 2 digits, 8 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 74863-84:
(7*7)+(6*4)+(5*8)+(4*6)+(3*3)+(2*8)+(1*4)=166
166 % 10 = 6
So 74863-84-6 is a valid CAS Registry Number.
InChI:InChI=1/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-/m0/s1
74863-84-6Relevant articles and documents
Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides
van der Heijden, Gydo,van Schaik, Timo B.,Mouarrawis, Valentinos,de Wit, Martin J. M.,Velde, Christophe M. L. Vande,Ruijter, Eelco,Orru, Romano V. A.
supporting information, p. 5313 - 5325 (2019/06/10)
An efficient Ugi-type three-component reaction (U-3CR) for the synthesis of pipecolic amides is reported. The U-3CR between electronically diverse isocyanides, carboxylic acids and 4-substituted Δ1-piperideines proceeds in a highly diastereoselective fashion. The Δ1-piperideines are obtained by NCS-mediated oxidation of the corresponding 4-substituted piperidines, which in turn are generated by an efficient two-step procedure involving the alkylation of 4-picoline and subsequent catalytic hydrogenation of the pyridine ring. We demonstrate the utility of this U-3CR, in combination with the convertible isocyanide 2-bromo-6-isocyanopyridine, in the synthesis of the anticoagulant argatroban.
A short synthesis of argatroban: A potent selective thrombin inhibitor
Cossy, Janine,Belotti, Damien
, p. 1989 - 1992 (2007/10/03)
Argatroban was synthesized in seven steps from 4-methylpiperidine. The condensation of (±)-trans-benzyl 4-methylpipecolic acid ester with Nα-Boc-Nω-nitro-L-arginine led to two diastereomers that were separated. One of them is the precursor of argatroban.
Compositions containing argatroban analogs
-
, (2008/06/13)
An antithrombin composition in the form of a lipid emulsion which comprises, together with unsaturated fatty acid and an emulsifier, N2-arylsulfonyl-L-arginineamide of the following general formula (I): wherein R1 represents (2R,4R)-4-alkyl-2-carboxypiperidino group, R2 represents phenyl group or condensed polycyclic compound residue as defined below, said R2 optionally having one or more substituents selected from lower alkyl group, lower alkoxy group, or amino group substituted by lower alkyl group, said condensed polycyclic compound residue being a condensed polycyclic compound residue including a benzene ring, said benzene ring being bound to the sulfur atom of the sulfonyl group in the general formula (I), and said benzene ring being condensed with other ring which may be a heterocyclic ring, and said polycyclic compound residue having 7 - 14 carbon atoms in total,its hydrate and/or its salt is provided.
