1012883-12-3

Basic information

• Product Name: C₁₆H₁₇Cl₃N₄O₄
• Synonyms: C₁₆H₁₇Cl₃N₄O₄
• CAS NO: 1012883-12-3
• Molecular Weight: 435.694
• Mol File: 1012883-12-3.mol

Chemical Properties

• CAS DataBase Reference: C₁₆H₁₇Cl₃N₄O₄(CAS DataBase Reference)
• NIST Chemistry Reference: C₁₆H₁₇Cl₃N₄O₄(1012883-12-3)
• EPA Substance Registry System: C₁₆H₁₇Cl₃N₄O₄(1012883-12-3)

Safety Data

• Hazardous Substances Data: 1012883-12-3(Hazardous Substances Data)

Upstream product

• 59997-51-2 trimethylacetylacetonitrile 
• 1012883-10-1 3-tert-butyl-1-(3-nitrophenyl)-1H-pyrazol-5-amine hydrochloride 
• 17341-93-4 2,2,2-Trichloroethyl chloroformate 

Downstream Products

• 1446981-10-7 N-(4-(4-(3-(1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl)-ureido)phenylamino)quinazolin-6-yl)-4-(dimethylamino)butanamide 
• 1446981-12-9 N-(4-(4-(3-(1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl)-ureido)phenylamino)quinazolin-6-yl)-3-(4-methylpiperazin-1-yl)propanamide trifluoroacetic acid 
• 1446981-14-1 N-(4-(4-(3-(1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl)ureido)-phenylamino)quinazolin-6-yl)-3-morpholinopropanamide trifluoroacetic acid 
• 1446981-18-5 1-(1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl)-3-methylurea 
• 1446981-24-3 C₄₀H₄₂N₆O₅ 
• 1446981-04-9 1-(3-tert-butyl-1-(3-nitrophenyl)-1H-pyrazol-5-yl)-3-(4-(6-nitroquinazolin-4-ylamino)phenyl)urea 
• 1446981-23-2 C₂₅H₃₂N₆O₃ 
• 1446981-05-0 1-(3-tert-butyl-1-(3-nitrophenyl)-1H-pyrazol-5-yl)-3-(4-(quinazolin-4-ylamino)phenyl)urea 
• 1446981-06-1 1-(1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl)-3-(4-(6-aminoquinazolin-4-ylamino)phenyl)urea 
• 1446981-07-2 1-(1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl)-3-(4-(quinazolin-4-ylamino)phenyl)urea 
• 1446981-09-4 N-(4-(4-(3-(1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl)ureido)phenylamino)quinazolin-6-yl)propionamide 
• 1446981-21-0 tert-butyl 4-(3-(3-tert-butyl-1-(3-nitrophenyl)-1H-pyrazol-5-yl)ureido)phenylcarbamate 
• 1446981-17-4 1-(3-tert-butyl-1-(3-nitrophenyl)-1H-pyrazol-5-yl)-3-methylurea 
• 1446981-22-1 tert-butyl 3-(3-(3-tert-butyl-1-(3-nitrophenyl)-1H-pyrazol-5-yl)-ureido)phenylcarbamate 

Relevant articles and documents

Targeting gain of function and resistance mutations in Abl and KIT by hybrid compound design

Mutations in the catalytic domain at the gatekeeper position represent the most prominent drug-resistant variants of kinases and significantly impair the efficacy of targeted cancer therapies. Understanding the mechanisms of drug resistance at the molecular and atomic levels will aid in the design and development of inhibitors that have the potential to overcome these resistance mutations. Herein, by introducing adaptive elements into the inhibitor core structure, we undertake the structure-based development of type II hybrid inhibitors to overcome gatekeeper drug-resistant mutations in cSrc-T338M, as well as clinically relevant tyrosine kinase KIT-T670I and Abl-T315I variants, as essential targets in gastrointestinal stromal tumors (GISTs) and chronic myelogenous leukemia (CML). Using protein X-ray crystallography, we confirm the anticipated binding mode in cSrc, which proved to be essential for overcoming the respective resistances. More importantly, the novel compounds effectively inhibit clinically relevant gatekeeper mutants of KIT and Abl in biochemical and cellular studies.