717907-76-1

Basic information

• Product Name: PF-562,271
• Synonyms: N-Methyl-N-{3-[({2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl}amino)methyl]pyridin-2-yl}methanesulfonamide;Methanesulfonamide, N-[3-[[[2-[(2,3-dihydro-2-oxo-1H-indol-5-yl)amino]-5-(trifluoromethyl)-4-pyrimidinyl]amino]methyl]-2-pyridinyl]-N-methyl-;N-Methyl-N-{3-[({2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-(trifluoromethyl)-4-pyrimidinyl}amino)methyl]-2-pyridinyl}methanesulfonamide
• CAS NO: 717907-76-1
• Molecular Formula: C₂₁H₂₀F₃N₇O₃S
• Molecular Weight: 328.681
• Mol File: 717907-76-1.mol
• Article Data: 6

Chemical Properties

• Density: 1.54 g/cm³
• CAS DataBase Reference: PF-562,271(CAS DataBase Reference)
• NIST Chemistry Reference: PF-562,271(717907-76-1)
• EPA Substance Registry System: PF-562,271(717907-76-1)

Safety Data

• Hazardous Substances Data: 717907-76-1(Hazardous Substances Data)

Upstream product

• 20876-36-2 5-amino-1,3-dihydro-2H-indol-2-one 
• 3932-97-6 2,4-dichloro-5-trifluoromethylpyrimidine 
• 54-20-6 5-trifluoromethyluracil 

Downstream Products

• 1095647-86-1 C₂₄H₂₃F₃N₆O₃S 
• 717906-29-1 PF-431396 
• 717907-75-0 PF-562,271 
• 939791-38-5 N-methyl-N-(3-((2-(2-oxoindolin-5-ylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)methanesulfonamide benzenesulfonate 
• 939791-40-9 N-methyl-N-(3-{[2-(2-oxo-2,3-dihydro-1H-indol-5-ylamino)-5-trifluoromethylpyrimidin-4-ylamino]methyl}pyridin-2-yl)methanesulfonamide tosylate 
• 939791-41-0 N-methyl-N-{3-[({2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-(trifluoromethyl)-4-pyrimidinyl}amino)methyl]-2-pyridinyl}methanesulfonamide hydrochloride 
• 1360460-87-2 5-(4-phenethyl-5-trifluoromethylpyrimidin-2-ylamino)-1,3-dihydro-indol-2-one 
• 1360450-91-4 5-{4-[2-(4-fluorophenyl)ethyl]-5-trifluoromethylpyrimidin-2-ylamino}-1,3-dihydro-indol-2-one 

Relevant articles and documents

Structure-kinetic relationship reveals the mechanism of selectivity of FAK inhibitors over PYK2

There is increasing evidence of a significant correlation between prolonged drug-target residence time and increased drug efficacy. Here, we report a structural rationale for kinetic selectivity between two closely related kinases: focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2). We found that slowly dissociating FAK inhibitors induce helical structure at the DFG motif of FAK but not PYK2. Binding kinetic data, high-resolution structures and mutagenesis data support the role of hydrophobic interactions of inhibitors with the DFG-helical region, providing a structural rationale for slow dissociation rates from FAK and kinetic selectivity over PYK2. Our experimental data correlate well with computed relative residence times from molecular simulations, supporting a feasible strategy for rationally optimizing ligand residence times. We suggest that the interplay between the protein structural mobility and ligand-induced effects is a key regulator of the kinetic selectivity of inhibitors of FAK versus PYK2.

Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): Structure-activity relationships and strategies for the elimination of reactive metabolite formation

The synthesis and SAR for a series of diaminopyrimidines as PYK2 inhibitors are described. Using a combination of library and traditional medicinal chemistry techniques, a FAK-selective chemical series was transformed into compounds possessing good PYK2 potency and 10- to 20-fold selectivity against FAK. Subsequent studies found that the majority of the compounds were positive in a reactive metabolite assay, an indicator for potential toxicological liabilities. Based on the proposed mechanism for bioactivation, as well as a combination of structure-based drug design and traditional medicinal chemistry techniques, a follow-up series of PYK2 inhibitors was identified that maintained PYK2 potency, FAK selectivity and HLM stability, yet were negative in the RM assay.

Pyrimidine derivatives for the treatment of abnormal cell growth

The present invention relates to a compound of the formula 1 wherein A and Ar are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.