Dasatinib

Base Information

• Chemical Name: Dasatinib
• CAS No.: 302962-49-8
• Molecular Formula: C22H26ClN7O2S
• Molecular Weight: 488.013
• Hs Code.: 29341000
• European Community (EC) Number: 801-607-0,638-874-6
• NSC Number: 759877,732517
• UNII: X78UG0A0RN
• DSSTox Substance ID: DTXSID4040979
• Wikipedia: Dasatinib
• Wikidata: Q419940
• NCI Thesaurus Code: C38713,C74556
• RXCUI: 475342,1546019
• Pharos Ligand ID: WHNTF247H22K
• Metabolomics Workbench ID: 43461
• ChEMBL ID: CHEMBL1421
• Mol file: 302962-49-8.mol

Synonyms:(18F)-N-(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide;354825, BMS;BMS 354825;BMS-354825;BMS354825;dasatinib;N-(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide;Sprycel

Chemical Property of Dasatinib

Chemical Property:

• Appearance/Colour: pale-yellow solid
• Melting Point: 275-286 °C
• PKA: 10.94±0.70(Predicted)
• PSA: 134.75000
• Density: 1.409 g/cm³
• LogP: 3.46240
• Storage Temp.: -20°C Freezer
• Solubility.: Soluble in DMSO (up to 200 mg/ml).
• XLogP3: 3.6
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 7
• Exact Mass: 487.1557220
• Heavy Atom Count: 33
• Complexity: 642

Purity/Quality:

99% ^*data from raw suppliers

Dasatinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC1=C(C(=CC=C1)Cl)NC(=O)C2=CN=C(S2)NC3=CC(=NC(=N3)C)N4CCN(CC4)CCO
• Recent ClinicalTrials: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
• Recent EU Clinical Trials: Safety and Impact of Dasatinib on Viral Persistence and Inflammation in People with HIV under Antiretroviral Treatment
• Recent NIPH Clinical Trials: A study of oral asciminib versus other TKIs in adult patients with newly diagnosed Ph+ CML-CP
• Uses: Suitable for treatment of chronic myeloid leukemia which is resistant or intolerant to the treating programs including imatinib mesylate.Dasatinib is used to treat a certain type of chronic myeloid leukemia (CML; a type of cancer of the white blood cells) as a first treatment and in people who can no longer benefit from other leukemia medications including imatinib (Gleevec) or in those who cannot take these medications because of side effects. Dasatinib is also used to treat a certain type of chronic CML in children. Dasatinib is also used to treat a certain type of acute lymphoblastic leukemia (ALL; a type of cancer of the white blood cells) in people who can no longer benefit from other leukemia medications or who cannot take these medications because of side effects. Dasatinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells.https://medlineplus.gov/druginfo/meds/a607063.html Dasatinib is a novel, potent and multi-targeted inhibitor that targets Abl, Src and c-Kit, with IC50 of ＜1 nM, 0.8 nM and 79 nM, respectively. Directly targets wild-type and mutant c-Abl kinase domains
• Drug Interactions: Dasatinib is a substrate and an inhibitor of CYP3A4. Therefore, there is a potential for interaction with other concomitantly administered drugs that are metabolized primarily by or modulate the activity of CYP3A4.Systemic exposure to dasatinib is increased if it is coadministered with drugs that are inhibitors of CYP 3A4 (e.g., clarithromycin, erythromycin, itraconazole, ketoconazole).If coadministered with drugs that induce CYP 3A4 (e.g., dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or Hypericum perforatum, also known as St. John’s Wort), dasatinib AUC is reduced. It was reduced by 82% when coadministered with rifampicin.Dasatinib AUC was reduced when coadministered with H2-blockers/protonpump inhibitors, or antacids. Concomitant administration of famotidin reduced dasatinib AUC by 61%, coadministration of aluminum hydroxide by 55%.Dasatinib is an inhibitor of CYP3A4. Substrates of CYP3A4 with a narrow therapeutic index should be administered with caution in patients receiving dasatinib. Drugs that rank among that list are alfentanil, astemizole, terfenadine, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloid (ergotamine, dihydroergotamine) (SprycelòBMS 2012).
• Description: Dasatinib, developed and marketed by Bristol Myers, is the first approved oral tyrosine kinase inhibitor which binds to multiple conformations of ABL kinase for the treatment of two leukemia indications: chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Dasatinib is a highly potent, ATPcompetitive ATPcompetitive kinase inhibitor which, at nanomolar concentrations, inhibits BCR-ABL, SRC family, c-KIT, EPHA2 and PDGFR-B.
• Clinical Use: #N/A
• Drug interactions: Potentially hazardous interactions with other drugsAntacids: absorption possibly reduced by antacids, give at least 2 hours apart.Antibacterials: metabolism accelerated by rifampicin - avoid.Antipsychotics: avoid with clozapine, increased risk of agranulocytosis.Antivirals: avoid with boceprevir.Ulcer healing drugs: avoid with histamine H2 antagonists; concentration reduced by proton pump inhibitors.

Technology Process of Dasatinib

There total 65 articles about Dasatinib which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 97.0%

1-(2-hydroxyethyl)piperazine (103-76-4) + 2-(6-chloro-2-methylpyrimidin-4-ylamino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide (302964-08-5) → dasatanib (302962-49-8)

Guidance literature:

With tetrabutylammomium bromide; In acetonitrile; at 30 - 80 ℃;

Reference yield: 96.4%

N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-acetoxyethyl)-1-piperazinyl]-2-methyl- 4-pyrimidinyl]amino]-5-thiazolecarboxamide (1245157-85-0) → dasatanib (302962-49-8)

Guidance literature:

With potassium carbonate; In methanol; water; at 60 - 65 ℃; for 3h; Solvent; Reagent/catalyst;

Reference yield: 95.3%

C20H24ClN5O4S + acetamidine hydrochloride (124-42-5) → dasatanib (302962-49-8)

Guidance literature:

With sodium methylate; In methanol; at 65 ℃; for 4h; Temperature; Cooling with ice;

upstream raw materials:

1-(2-hydroxyethyl)piperazine

2-(6-chloro-2-methylpyrimidin-4-ylamino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide

2-chloro-6-methylphenyl isocyanate

2-chloro-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide

Downstream raw materials:

N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)-1-piperazinyl)-2-methyl-4-pyrimidinyl)amino)-1,3-thiazole-5-carboxamide butanolate

dasatinib monohydrate

N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)-1-piperazinyl)-2-methyl-4-pyrimidinyl)amino)-1,3-thiazole-5-carboxamide maleic acid salt

N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)-1-piperazinyl)-2-methyl-4-pyrimidinyl)amino)-1,3-thiazole-5-carboxamide salicylic acid salt

Refernces

• 1、 Buchappa,Sagar Vijay Kumar,Durga Prasad,Aparna. "Scalable and impurity-free process for dasatinib: Src and BCR-Abl inhibitor". . p. 1621 - 1628. Retrieved 2018.
• 2、 -. "HALOGENATED-HETEROARYL AND OTHER HETEROCYCLIC KINASE INHIBITORS, AND USES THEREOF". Paragraph 0723; 0735-0736; 0737; 0739; 0793. . Retrieved 2021/11/04.
• 3、 -. "Preparation method of dasatinib hydrate". Paragraph 0027; 0033-0035. . Retrieved 2020/06/20.