Tozasertib

Base Information

• Chemical Name: Tozasertib
• CAS No.: 639089-54-6
• Molecular Formula: C₂₃H₂₈N₈OS
• Molecular Weight: 464.594
• NSC Number: 745967
• UNII: 234335M86K
• DSSTox Substance ID: DTXSID10213609
• Nikkaji Number: J2.003.899C
• Wikipedia: Tozasertib
• Wikidata: Q6605919
• NCI Thesaurus Code: C98053
• Pharos Ligand ID: KRB1UUW78XD4
• ChEMBL ID: CHEMBL572878
• Mol file: 639089-54-6.mol

Synonyms:cyclopropane carboxylic acid N-(4-(4-(4-methylpiperazin-1-yl)-6-(5-methyl-2H-pyrazol-3-ylamino)pyrimidin-2-ylsulfanyl)phenyl)amide;MK-0457;MK0457;N-(4-((4-(4-methylpiperazin-1-yl)-6-((5-methyl-1H-pyrazol-3-yl)amino)pyrimidin-2-yl)sulfanyl)phenyl)cyclopropanecarboxamide;N-(4-((4-(4-methylpiperazin-1-yl)-6-((5-methyl-1H-pyrazol-3-yl)amino)pyrimidin-2-yl)sulfanyl)phenyl)cyclopropanecarboxamide lactate;N-(4-((4-(4-methylpiperazin-1-yl)-6-((5-methyl-1H-pyrazol-3-yl)amino)pyrimidin-2-yl)sulfanyl)phenyl)cyclopropanecarboxamide, (2S)-2-hydroxypropanoate;Tozasertib;tozasertib lactate;VE 465;VE-465;VX-680;VX-680 lactate;VX680;VX680 lactate

Chemical Property of Tozasertib

Chemical Property:

• Refractive Index: 1.708
• PKA: 14.09±0.70(Predicted)
• PSA: 127.37000
• Density: 1.4 g/cm³
• LogP: 3.65210
• Storage Temp.: 2-8°C
• Solubility.: Soluble in DMSO (up to 100 mg/ml).
• XLogP3: 3.4
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 7
• Exact Mass: 464.21067872
• Heavy Atom Count: 33
• Complexity: 650

Purity/Quality:

99% ^*data from raw suppliers

Tozasertib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=CC(=NN1)NC2=CC(=NC(=N2)SC3=CC=C(C=C3)NC(=O)C4CC4)N5CCN(CC5)C
• Recent ClinicalTrials: A VX-680 (an Aurora Kinase Inhibitor) Study in Patients With Advanced Cancer (0457-002)
• Recent EU Clinical Trials: A Phase II Study of MK-0457 in Patients With BCR-ABL T315I Mutant Chronic Myelogenous Leukemia and Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia
• Description: The Aurora kinases (A, B, and C) are a family of serine-threonine kinases that regulate various stages of mitotic function. With significant roles in cell cycle and cell division, Aurora kinase gene amplification and overexpression are linked to tumorigenesis. MK-0457 is a potent pan-Aurora kinase inhibitor but favors Aurora A (Ki = 0.6 nM) over Aurora B (Ki = 18 nM) or Aurora C (Ki = 4.6 nM). It shows selectivity against a panel of more than 190 different protein kinases. MK-0457 effectively inhibits proliferation of several different cell lines of clear cell renal carcinoma (IC50s = <10 μM) and blocks the growth of tumors in a rodent model of cancer (80 mg/kg), inhibiting histone H3 phosphorylation and increasing apoptosis. By depleting Aurora activity, MK-0457 disrupts bipolar spindle formation during mitosis, arresting cell cycle progression at the G2/M phase.
• Uses: Tozasertib is used as a multikinase inhibitor once used for cancer treatment.

Technology Process of Tozasertib

There total 2 articles about Tozasertib 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: 66.0%

1-methyl-piperazine (109-01-3) + N-[4-({4-chloro-6-[(3-methyl-1H-pyrazol-5-yl)amino]pyrimidin-2-yl}sulfanyl)phenyl]cyclopropane carboxamide (639090-55-4) → tozasertib (639089-54-6,1010423-95-6)

Guidance literature:

at 110 ℃; for 2h;

Reference yield:

(N-(4-mercaptophenyl)cyclopropylcarboxamide) (639090-54-3) → tozasertib (639089-54-6,1010423-95-6)

Guidance literature:

Multi-step reaction with 3 steps

1: water; ethyl acetate; tert-butyl alcohol / 1 h / 90 °C

2: N-ethyl-N,N-diisopropylamine / DMF (N,N-dimethyl-formamide); water; ethyl acetate / 4 h / 20 - 85 °C

3: water; ethyl acetate / 2 h / 110 °C

With N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide); water; ethyl acetate; tert-butyl alcohol;

Reference yield: 47.0%

tozasertib (639089-54-6,1010423-95-6) + methanesulfonic acid (75-75-2,98527-29-8) → cyclopropane carboxylic acid{4-[4-(4-methyl-piperazin-1-yl)-6-(5-methyl-2H-pyrazol-3-ylamino)-pyrimidin-2-ylsulphanyl]-phenyl}amide methanesulfonate

Guidance literature:

In ethanol; at 0 ℃; for 0.166667h; Heating / reflux;

upstream raw materials:

1-methyl-piperazine

N-[4-({4-chloro-6-[(3-methyl-1H-pyrazol-5-yl)amino]pyrimidin-2-yl}sulfanyl)phenyl]cyclopropane carboxamide

(N-(4-mercaptophenyl)cyclopropylcarboxamide)

Refernces

• 1、 -. "A NOVEL LACTIC ACID FORMULATION OF MK-0457 USEFUL FOR THE TREATMENT OF CANCER". Page/Page column 7. . Retrieved 2008/06/13.
• 2、 -. "PROCESSES FOR PREPARING SUBSTITUTED PYRIMIDINES AND PYRIMIDINE DERIVATIVES AS INHIBITORS OF PROTEIN KINASE". Page 46. . Retrieved 2008/06/13.