Ispinesib

Base Information

• Chemical Name: Ispinesib
• CAS No.: 336113-53-2
• Molecular Formula: C₃₀H₃₃ClN₄O₂
• Molecular Weight: 517.071
• UNII: BKT5F9C2NI
• DSSTox Substance ID: DTXSID20187307
• Nikkaji Number: J2.576.501J
• Wikidata: Q27166496
• NCI Thesaurus Code: C38131
• Pharos Ligand ID: DPXJ9XAKF6U4
• Metabolomics Workbench ID: 149662
• ChEMBL ID: CHEMBL228814
• Mol file: 336113-53-2.mol

Synonyms:ispinesib;SB 715992;SB-715992;SB715992

Chemical Property of Ispinesib

Chemical Property:

• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.619
• Boiling Point: 707.986 °C at 760 mmHg
• PKA: 9.65±0.10(Predicted)
• Flash Point: 381.976 °C
• PSA: 81.22000
• Density: 1.216 g/cm³
• LogP: 6.29520
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility.: Chloroform (Slightly), Methanol (Slightly)
• XLogP3: 5.3
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 9
• Exact Mass: 516.2292040
• Heavy Atom Count: 37
• Complexity: 803

Purity/Quality:

99%, ^*data from raw suppliers

Ispinesib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=CC=C(C=C1)C(=O)N(CCCN)C(C2=NC3=C(C=CC(=C3)Cl)C(=O)N2CC4=CC=CC=C4)C(C)C
• Isomeric SMILES: CC1=CC=C(C=C1)C(=O)N(CCCN)[C@@H](C2=NC3=C(C=CC(=C3)Cl)C(=O)N2CC4=CC=CC=C4)C(C)C
• Recent ClinicalTrials: SB-715992 in Treating Patients With Locally Advanced, Recurrent, or Metastatic Liver Cancer
• Uses: Ispinesib is the first potent, highly specific small-molecule inhibitor of KSP tested for the treatment of human disease. Anticancer agent. The kinesin-like spindle protein Eg5 (also known as kinesin-5, kinesin family protein 11, or Kif11) is a motor protein that is essential for establishing a bipolar spindle during mitosis both in normal and tumor cells. Ispinesib is a cell-permeable, allosteric inhibitor of Eg5 (Ki app = 2.3 nM) with >10,000-fold selectivity for Eg5 over a range of other mitotic kinesins. It induces a monopolar spindle phenotype, leading to the activation of a spindle assembly checkpoint, mitotic arrest, and subsequent cell death (GI50s = 22-82 nM in colon, pancreas, prostrate, and lung cancer cells in vitro). At 10 mg/kg, ispinesib produces tumor regression of breast cancer cell xenografts in mice. It has also been used to halt the growth of treatment-resistant glioblastoma tumor-initiating cells, to prevent tumor initiation and self-renewal of a cancer stem cell population (EC50 = 1.15 nM), and to reduce glioma cell invasion.[Cayman Chemical]

Technology Process of Ispinesib

There total 36 articles about Ispinesib 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: 88.0%

(±)-tert-butyl (3-(N-(1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)-4-methylbenzamido)propyl)carbamate (1314917-44-6) → (±)-N-(3-aminopropyl)-N-(1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)-4-methylbenzamide (336115-13-0,336113-53-2)

Guidance literature:

With trifluoroacetic acid; In dichloromethane; at 20 ℃; for 2h; Inert atmosphere;

DOI:10.1016/j.bmc.2012.11.013

Reference yield: 87.0%

tert-butyl (3-(N-(1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)-4-methylbenzamido)propyl)carbamate (1417617-02-7) → (S)-ispinesib (336113-54-3,336113-53-2)

Guidance literature:

With trifluoroacetic acid; In dichloromethane; at 20 ℃; for 2h; Inert atmosphere;

DOI:10.1016/j.bmc.2012.11.013

Reference yield: 85.0%

tert-butyl (3-(N-(1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)-4-methylbenzamido)propyl)carbamate (587881-28-5) → (R)-ispinesib (336113-53-2)

Guidance literature:

With trifluoroacetic acid; In dichloromethane; at 20 ℃; for 2h; Inert atmosphere;

DOI:10.1016/j.bmc.2012.11.013

upstream raw materials:

(R)-tert-butyl (3-((1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)amino)propyl)carbamate

4-methyl-benzoyl chloride

2-Amino-4-chlorobenzoic acid

isopentanoyl chloride

Refernces

• 1、 Mossetti, Riccardo,Pirali, Tracey,Saggiorato, Desiree,Tron, Gian Cesare. "Imides: Forgotten players in the Ugi reaction. One-pot multicomponent synthesis of quinazolinones". . p. 6966 - 6968. Retrieved 2011/08/21.