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

N-Methyl-N-[2-[[[2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-trifluoromethylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide, also known as PF-431396, is a pyrimidine-based dual inhibitor of proline-rich tyrosine kinase 2 (PYK2) and focal adhesion kinase (FAK) with IC50 values of 2 and 11 nM, respectively. It is a compound that has been developed to target specific nonreceptor tyrosine kinases, which play a role in various cellular processes, including cell adhesion, migration, and proliferation.

Uses

1. Used in Pharmaceutical Industry:
N-Methyl-N-[2-[[[2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-trifluoromethylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide is used as a dual PYK2/FAK inhibitor for studying its effects on various cellular processes and signaling pathways. It has been shown to promote osteoblast recruitment and activity, stimulating bone formation in ovariectomized rats, which could be beneficial for the development of treatments for osteoporosis and other bone-related conditions.
2. Used in Research Applications:
N-Methyl-N-[2-[[[2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-trifluoromethylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide is used as a research tool to study the roles of PYK2 and FAK in various cellular processes, such as cell adhesion, migration, and proliferation. It has been used to investigate the effects of PYK2/FAK inhibition on phosphorylation of Yes-associated protein (YAP) at Ser127 and the steady state of transcriptional coactivator with PDZ-binding motif (TAZ). Additionally, it has been utilized to study the effects of PYK2/FAK inhibition on protein kinase A activation in human sperm samples, which could provide insights into male fertility and reproductive health.

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.