1489389-18-5

Basic information

• Product Name: CCT245737
• Synonyms: CCT245737
• CAS NO: 1489389-18-5
• Molecular Formula: C16H16F3N7O
• Molecular Weight: 379.3397496
• EINECS: -0
• Mol File: 1489389-18-5.mol

Chemical Properties

• Boiling Point: 547.2±50.0 °C(Predicted)
• Appearance: /
• Density: 1.44±0.1 g/cm3(Predicted)
• PKA: 8.56±0.40(Predicted)
• CAS DataBase Reference: CCT245737(CAS DataBase Reference)
• NIST Chemistry Reference: CCT245737(1489389-18-5)
• EPA Substance Registry System: CCT245737(1489389-18-5)

Safety Data

• Hazardous Substances Data: 1489389-18-5(Hazardous Substances Data)

Usage

Uses

CCT245737 is a CHK inhibitor.

Upstream product

• 135065-64-4 tert-butyl (2R)-2-({[(4-methylphenyl)sulfonyl]oxy}methyl)morpholine-4-carboxylate 
• 135065-71-3 (R)-2-hydroxymethylmorpholine-4-carboxylic acid tert-butyl ester 
• 113305-94-5 2-amino-5-cyanopyrazine 
• 505084-58-2 2-chloro-5-(trifluoromethyl)pyridine-4-carboxylic acid 
• 1061358-78-8 2-chloro-5-(trifluoromethyl)pyridin-4-amine 
• 148638-76-0 tert-butyl (2S)-2-({[(4-methylphenyl)sulfonyl]oxy}methyl)morpholine-4-carboxylate 
• 135065-76-8 tert-butyl (2S)-2-(hydroxymethyl)morpholine-4-carboxylate 
• 503455-76-3 (R)-tert-butyl 2-(((methylsulfonyl)oxy)methyl)morpholine-4-carboxylate 

Relevant articles and documents

METHODS FOR SYNTHESIS OF CHK1 INHIBITORS

The present technology relates to processes, compounds, compositions, and methods useful for coupling reactions. Also, the present disclosure provides for novel intermediates, compositions of matter, and processes relating to the Chk1 inhibitor, SRA737.

Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737)

Multiparameter optimization of a series of 5-((4-aminopyridin-2-yl)amino)pyrazine-2-carbonitriles resulted in the identification of a potent and selective oral CHK1 preclinical development candidate with in vivo efficacy as a potentiator of deoxyribonucleic acid (DNA) damaging chemotherapy and as a single agent. Cellular mechanism of action assays were used to give an integrated assessment of compound selectivity during optimization resulting in a highly CHK1 selective adenosine triphosphate (ATP) competitive inhibitor. A single substituent vector directed away from the CHK1 kinase active site was unexpectedly found to drive the selective cellular efficacy of the compounds. Both CHK1 potency and off-target human ether-a-go-go-related gene (hERG) ion channel inhibition were dependent on lipophilicity and basicity in this series. Optimization of CHK1 cellular potency and in vivo pharmacokinetic-pharmacodynamic (PK-PD) properties gave a compound with low predicted doses and exposures in humans which mitigated the residual weak in vitro hERG inhibition.

5-[[4-[[MORPHOLIN-2-YL]METHYLAMINO]-5-(TRIFLUOROMETHYL)-2-PYRIDYL]AMINO]PYRAZINE-2-CARBONITRILE AND THERAPEUTIC USES THEREOF

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to 5-[[4-[[morpholin-2-yl]methylamino]-5- (trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile compounds (referred to her