42398-55-0

Basic information

• Product Name: 2-CHLOROPYRIMIDO[2,1-A]ISOQUINOLIN-4-ONE
• Synonyms: 2-CHLOROPYRIMIDO[2,1-A]ISOQUINOLIN-4-ONE
• CAS NO: 42398-55-0
• Molecular Formula: C₁₂H₇ClN₂O
• Molecular Weight: 230.64978
• Mol File: 42398-55-0.mol
• Article Data: 1

Chemical Properties

• Melting Point: 197-199 °C
• Boiling Point: 359.8°C at 760 mmHg
• Flash Point: 171.4°C
• Appearance: /
• Density: 1.42g/cm³
• Vapor Pressure: 2.31E-05mmHg at 25°C
• Refractive Index: 1.698
• PKA: -3.84±0.40(Predicted)
• CAS DataBase Reference: 2-CHLOROPYRIMIDO[2,1-A]ISOQUINOLIN-4-ONE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-CHLOROPYRIMIDO[2,1-A]ISOQUINOLIN-4-ONE(42398-55-0)
• EPA Substance Registry System: 2-CHLOROPYRIMIDO[2,1-A]ISOQUINOLIN-4-ONE(42398-55-0)

Safety Data

• Hazardous Substances Data: 42398-55-0(Hazardous Substances Data)

Usage

InChI:InChI=1/C12H7ClN2O/c13-10-7-11(16)15-6-5-8-3-1-2-4-9(8)12(15)14-10/h1-7H

Upstream product

• 1532-84-9 isoquinolin-1-ylamine 
• 23212-58-0 pyrimido[2,1-a]isoquinoline-2,4-dione 

Downstream Products

• 168425-64-7 2-(4-morpholinyl)-4H-pyrimido[2,1-a]isoquinolin-4-one 

Relevant articles and documents

Selective benzopyranone and pyrimido[2,1-α]isoquinolin-4-one inhibitors of DNA-dependent protein kinase: Synthesis, structure-activity studies, and radiosensitization of a human tumor cell line in vitro

A diverse range of chromen-2-one, chromen-4-one and pyrimidoisoquinolin-4- one derivatives was synthesized and evaluated for inhibitory activity against the DNA repair enzyme DNA-dependent protein kinase (DNA-PK), with a view to elucidating structure-activity relationships for potency and kinase selectivity. DNA-PK inhibitory activity varied widely over the series of compounds evaluated (IC50 values ranged from 0.19 to >10 μM), with excellent activity being observed for the 7,8-benzochromen-4-one and pyrimido[2,1-a] isoquinolin-4-one templates. By contrast, inhibitors based on the benzochromen-2-one (coumarin) or 2-aryl-7,8-benzochromen-4-one (flavone) scaffolds were less potent. Crucially, these studies revealed a very constrained structure-activity relationship at the 2-position of the benzopyranone and pyrimido[2,1-a]-isoquinolin-4-one pharmacophore, with only a 2-morpholino or 2-(2′-methylmorpholino) group being tolerated at this position. More detailed biological studies conducted with the most potent inhibitor NU7163 (48; IC50 = 0.19 μM) demonstrated ATP-competitive DNA-PK inhibition, with a Ki value of 24 nM, and 48 exhibited selectivity for DNA-PK compared with the related enzymes ATM, ATR, mTOR, and PI 3-K (p110alpha). Compound 48 sensitized the HeLa human tumor cell line to the cytotoxic effects of ionizing radiation in vitro, a dose modification factor of 2.3 at 10% survival being observed with an inhibitor concentration of 5 μM. This study identified these structural classes as novel DNA-PK inhibitors and delineated initial structure-activity relationships against DNA-PK.