Welcome to LookChem.com Sign In|Join Free

CAS

  • or

503612-47-3

Post Buying Request

503612-47-3 Suppliers

Recommended suppliersmore

  • Product
  • FOB Price
  • Min.Order
  • Supply Ability
  • Supplier
  • Contact Supplier

503612-47-3 Usage

Description

Apixaban, also known by its brand name Eliquis, is an orally bioavailable, highly selective, and reversible inhibitor of Factor Xa, a crucial enzyme in the coagulation cascade responsible for blood clot formation. It was developed through a series of innovative medicinal chemistry discoveries and modifications to razaxaban, resulting in a potent and well-balanced compound with low volume of distribution (Vdss). Apixaban is characterized as a pyrazolopyridine derivative with substitutions at positions 1 and 6, and it is used for the prevention and treatment of thromboembolic diseases.

Uses

Used in Orthopedic Surgery:
Apixaban is used as an antithrombotic agent for the prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective hip or knee replacement surgery. Its selective inhibition of Factor Xa helps reduce the risk of blood clot formation without inducing adverse bleeding events.
Used in Atrial Fibrillation:
Apixaban is used as an antithrombotic agent for preventing blood clot formation in patients with atrial fibrillation. Its oral bioavailability and selective inhibition of Factor Xa make it an effective treatment option for reducing the risk of stroke and other thromboembolic complications associated with this condition.
Used in Venous Thrombosis:
Apixaban is used as an antithrombotic agent in a rabbit model of venous thrombosis, demonstrating its potential for treating thromboembolic disorders by inhibiting the coagulation cascade and reducing blood clot formation.
Used in Aortic Heterotopic Valve Replacement:
In a porcine model of aortic heterotopic valve replacement, apixaban is used to prevent thrombus formation without causing adverse bleeding events. Its selective inhibition of Factor Xa makes it a valuable option for managing thromboembolic risks in patients undergoing valve replacement surgeries.

Indications and Usage

Apixaban is a new form of oral anticoagulant drug developed by Bristol Myers Squibb and Pfizer. It is a new form of oral Xa factor inhibitor, and its commercial name is Eliquis. Apixaban is used to treat adult patients undergoing elective hip or knee replacement surgery to prevent venous thromboembolism (VTE)

Mechanisms of Action

Apixaban is an oral selective activated Xa factor inhibitor and can prevent thrombin generation and thrombosis.

Clinical Research

Apixaban is the third new oral anticoagulant to go on sale, following dabigatran and rivaroxaban, and it has already been approved in Europe for preventing venous thromboembolism in patients undergoing elective hip or knee replacement surgery. Out of these three oral anticoagulants approved in Europe, compared to the current standard preventative treatment against venous thromboembolism, enoxaparin, rivaroxaban excelled in the record experiment, and apixaban excelled in the advance experiment. Rivaroxaban’s curative effects were slightly superior, but it caused more severe bleeding than apixaban. Researchers attributed these differences to medication time, as rivaroxaban was taken 6-8 hours after surgery in the record experiment, while apixaban was used 18 hours after surgery in the advance experiment. These drugs have better curative effect when used closer to time of surgery, but also have an increased bleeding risk. Clinical research showed that compared to a daily subdermal injection of 40mg enoxaparin, 2 oral 2.5mg dosages of apixaban had better preventative effects against venous thromboembolism following hip or knee replacement surgery and did not increase bleeding risk.

Drug Interactions

1.A double inhibitor of strong CYP3A4 and P-gp increases apixaban’s blood levels: decrease Eliquis dosage to 2.5mg or avoid simultaneous usage. 2.A inductor of strong CYP3A4 and P-gp can decrease apixaban’s blood levels: avoid simultaneous usage.

Warnings and Precautions

Breastfeeding mothers should stop usage or stop breastfeeding. Use during pregnancy is not advised. Use while experiencing severe liver damage is not advised.

Originator

Bristol Myers Squibb Company (United States)

Clinical Use

Apixaban is an oral anticoagulant with highly selective inhibition of factor Xa. It was approved by the European Medicines Agency (EMA) for the treatment of venous thromboembolic events and first marketed in Germany under the brand name Eliquis in June 2011. Apixaban was co-developed by Bristol-Myers Squibb and Pfizer and represents the first approved drug for this indication since warfarin over 50 years ago.

Synthesis

Although several convenient preparations of apixaban (BMS-562247) have been reported, the most likely process-scale route is described in the scheme. The starting material 4-iodoaniline (14) was acylated with 5-bromovaleryl chloride (15) and triethylamine followed by cyclization under basic conditions to give lactam 16 in 49% yield. Intermediate 16 was then reacted with phosphorus pentachloride to provide the a,a-dichlorinated lactam 17 in 87% yield.30 This dichloride was reacted with excess morpholine to affect an alkylation–elimination sequence to afford enaminolactam 18 in 86% yield. N-Arylation of this iodide with valerolactam 19 using a copper (I) catalyst resulted in a 77% yield of the desired p-bispiperidone 20. Interestingly, sequential exposure of 20 to a nitrile imine generated from the treatment of ethyl 2-chloro-2-(2,4-methoxyphenyl)-hydrazono) acetate 21 with base resulted in a [3+2] dipolarcycloadditon reaction. Upon acidification with 4 N HCl, pyrazole 22 was furnished in 67% over two steps. Conversion of the ester within 22 to the corresponding amide was achieved via a mixture of formamide and sodium methoxide to give apixaban (III) in 71% yield. It is important to note that intermediate 21 was prepared from commercially available 4-methoxyaniline (23) by sequential diazotization and condensation with ethyl 2-chloroacetoacetate (24).

in vitro

apixabanhas exhibited a high degree of potency, selectivity, and efficacy on factor xa with ki of 0.08 nm and 0.17 nm for human factor xa and rabbit factor xa, respectively [1]. apixaban prolonged the clotting times of normal human plasma with the concentrations (ec2x) of 3.6, 0.37, 7.4 and 0.4 μm, which are required respectively to double the prothrombin time (pt), modified prothrombin time (mpt), activated partial thromboplastin time (aptt) and heptest. besides, apixaban showed the highest potency in human and rabbit plasma, but less potency in rat and dog plasma in both the pt and aptt assays [3].

in vivo

apixaban exihibited the excellent pharmacokinetics with very low clearance (cl: 0.02 l kg-1h-1), and low volume of distribution (vdss: 0.2 l/kg) in the dog. besides, apixaban also showed a moderate half-life with t1/2 of 5.8 hours and good oral bioavailability (f: 58%) [1]. in the arteriovenous-shunt thrombosis (avst), venous thrombosis (vt) and electrically mediated carotid arterial thrombosis (ecat) rabbit models, apixaban produced antithrombotic effects with ec50 of 270 nm, 110 nm and 70 nm in a dose-dependent manner[3]. apixaban significantly inhibited factor xa activity with an ic50 of 0.22 μm in rabbit ex vivo[4]. in chimpanzee, apixaban also showed small volume of distribution (vdss: 0.17 l kg-1), low systemic clearance (cl: 0.018 l kg-1h-1), and good oral bioavailability (f: 59%) [5].

Drug interactions

Potentially hazardous interactions with other drugs Analgesics: increased risk of haemorrhage with IV diclofenac and ketorolac - avoid. Antibacterials: avoid with clarithromycin and telithromycin; concentration possibly reduced by rifampicin - avoid if treating DVT/PE. Anticoagulants: increased risk of haemorrhage with other anticoagulants - avoid. Antidepressants: concentration possibly reduced by St John’s wort - avoid if treating DVT/PE. Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin, phenobarbital, phenytoin and primidone - avoid if treating DVT/ PE with carbamazepine. Antifungals: concentration increased by ketoconazole - avoid; avoid with itraconazole, posaconazole and voriconazole. Antivirals: avoid with atazanavir, boceprevir, darunavir, fosamprenavir, indinavir, lopinavir, ritonavir, saquinavir, telaprevir and tipranavir. Cobicistat: avoid concomitant use.

Metabolism

Apixaban is metabolised in the liver mainly via the P450 cytochromes CYP3A4 and CYP3A5. Apixaban has multiple routes of elimination. Of the administered apixaban dose in humans, approximately 25% was recovered as metabolites, with the majority recovered in faeces. Renal excretion of apixaban accounts for approximately 27% of total clearance. There are also additional contributions from biliary and direct intestinal excretion.

References

https://en.wikipedia.org/wiki/Apixaban https://www.drugbank.ca/drugs/DB06605

Check Digit Verification of cas no

The CAS Registry Mumber 503612-47-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 5,0,3,6,1 and 2 respectively; the second part has 2 digits, 4 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 503612-47:
(8*5)+(7*0)+(6*3)+(5*6)+(4*1)+(3*2)+(2*4)+(1*7)=113
113 % 10 = 3
So 503612-47-3 is a valid CAS Registry Number.
InChI:InChI=1/C25H25N5O4/c1-34-19-11-9-18(10-12-19)30-23-20(22(27-30)24(26)32)13-15-29(25(23)33)17-7-5-16(6-8-17)28-14-3-2-4-21(28)31/h5-12H,2-4,13-15H2,1H3,(H2,26,32)

503612-47-3SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 20, 2017

Revision Date: Aug 20, 2017

1.Identification

1.1 GHS Product identifier

Product name apixaban

1.2 Other means of identification

Product number -
Other names 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5-dihydropyrazolo[3,4-c]pyridine-3-carboxamide

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:503612-47-3 SDS

503612-47-3Upstream product

503612-47-3Downstream Products

Post a RFQ

Enter 15 to 2000 letters.Word count: 0 letters

Attach files(File Format: Jpeg, Jpg, Gif, Png, PDF, PPT, Zip, Rar,Word or Excel Maximum File Size: 3MB)

1

What can I do for you?
Get Best Price

Get Best Price for 503612-47-3