717906-29-1

Basic information

• Product Name: N-Methyl-N-[2-[[[2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-trifluoromethylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide
• Synonyms: N-Methyl-N-[2-[[[2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-trifluoromethylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide;N-[2-[[[2-[(2,3-Dihydro-2-oxo-1H-indol-5-yl)aMino]-5-(trifluoroMethyl)-4-pyriMidinyl]aMino]Methyl]phenyl]-N-MethylMethanesulfonaMide;N-methyl-N-(2-((2-(2-oxoindolin-5-ylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)phenyl)methanesulfonamide;N-Methyl-N-[2-[[[2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-trifluoromethylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide PF-431396;N-[2-[[[2-[(2,3-dihydro-2-oxo-1H-indol-5-yl)amino]-5-(trifluoromethyl)-4-pyrimidinyl]amino]methyl]phenyl]-N-methyl-Methanesulfonamide hydrate;PF-431396 hydrate;PF 431396, >=98%;N-Methyl-N-(2-(((2-((2-oxoindolin-5-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)p
• CAS NO: 717906-29-1
• Molecular Formula: C22H21F3N6O3S
• Molecular Weight: 506.5
• Product Categories: Dual focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2) inhibitor.;Amines;Aromatics;Inhibitors;Intermediates & Fine Chemicals;Pfizer compounds;Pharmaceuticals
• Mol File: 717906-29-1.mol
• Article Data: 2

Chemical Properties

• Appearance: off-white to blue-gray/
• Density: 1.506
• Storage Temp.: 2-8°C
• Solubility: DMSO: ≥10mg/mL
• PKA: 13.66±0.20(Predicted)
• CAS DataBase Reference: N-Methyl-N-[2-[[[2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-trifluoromethylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-Methyl-N-[2-[[[2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-trifluoromethylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide(717906-29-1)
• EPA Substance Registry System: N-Methyl-N-[2-[[[2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-trifluoromethylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide(717906-29-1)

Safety Data

• Hazard Codes: T
• Statements: 25-36
• Safety Statements: 26-45
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 717906-29-1(Hazardous Substances Data)

Usage

Description

Proline-rich tyrosine kinase 2 (PYK2) and focal adhesion kinase (FAK) are nonreceptor tyrosine kinases that constitute the focal adhesion kinase subfamily. PYK2 is expressed in both bone-forming osteoblasts and bone-resorbing osteoclasts where it has a positive role in osteoclast maturation and bone resorption. PF-431396 is a pyrimidine-based dual inhibitor of FAK and PYK2 (IC50s = 2 and 11 nM, respectively). In ovariectomized rats, it has been shown to increase bone formation, promoting osteoblast recruitment and activity.

Uses

Different sources of media describe the Uses of 717906-29-1 differently. You can refer to the following data:
1. PF 431396 is a dual focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2) inhibitor (IC50 values are 2 and 11 nM respectively). Promotes osteoblast recruitment and activity, and stimulates bone formation in ovariectomized rats.
2. PF-431396 hydrate has been used as a dual inhibitor of proline-rich tyrosine kinase 2 (PYK2) / focal adhesion kinase (FAK) inhibitor to study its effects on phosphorylation of Yes-associated protein (YAP) at Ser127 and steady state of transcriptional coactivator with PDZ-binding motif (TAZ) . It has also been used as a PYK2/FAK inhibitor to study its effects on protein kinase A activation in human sperm samples .

Biochem/physiol Actions

PF-431396 is a potent inhibitor of PYK2 and FAK kinases (IC50 = 11 and 1.5 nM, respectively). PF-431396 increases bone formation and protects against bone loss in ovariectomized rats.

InChI:InChI=1S/C22H21F3N6O3S/c1-31(35(2,33)34)18-6-4-3-5-13(18)11-26-20-16(22(23,24)25)12-27-21(30-20)28-15-7-8-17-14(9-15)10-19(32)29-17/h3-9,12H,10-11H2,1-2H3,(H,29,32)(H2,26,27,28,30)

Upstream product

• 717907-76-1 5-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-2,3-dihydro-1H-indol-2-one 
• 869371-40-4 N-[2-(aminomethyl)phenyl]-N-methylmethanesulfonamide 

Relevant articles and documents

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.