1523406-39-4

Basic information

• Product Name: (S)-1-((5-chloropyridin-3-yl)methyl)-8-((R)-3-methylmorpholino)-2-(trifluoromethyl)-3,4-dihydro-1H-pyrimido[1,2-a]pyrimidin-6(2H)-one
• Synonyms: (S)-1-((5-chloropyridin-3-yl)methyl)-8-((R)-3-methylmorpholino)-2-(trifluoromethyl)-3,4-dihydro-1H-pyrimido[1,2-a]pyrimidin-6(2H)-one;SAR-405;(S)-1-((5-Chloropyridin-3-yl)methyl)-8-((R)-3-methylmorpholino)-2-(trifluoromethyl)-3,4-dihydr;(8S)-9-[(5-Chloro-3-pyridinyl)methyl]-6,7,8,9-tetrahydro-2-[(3R)-3-methyl-4-morpholinyl]-8-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-4-one
• CAS NO: 1523406-39-4
• Molecular Formula: C19H21ClF3N5O2
• Molecular Weight: 443.86
• Mol File: 1523406-39-4.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 526.5±60.0 °C(Predicted)
• Appearance: /
• Density: 1.51±0.1 g/cm3(Predicted)
• Solubility: ≥22.19 mg/mL in DMSO; insoluble in H2O; ≥32.25 mg/mL in EtOH with ultrasonic
• PKA: 3.29±0.20(Predicted)
• CAS DataBase Reference: (S)-1-((5-chloropyridin-3-yl)methyl)-8-((R)-3-methylmorpholino)-2-(trifluoromethyl)-3,4-dihydro-1H-pyrimido[1,2-a]pyrimidin-6(2H)-one(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-1-((5-chloropyridin-3-yl)methyl)-8-((R)-3-methylmorpholino)-2-(trifluoromethyl)-3,4-dihydro-1H-pyrimido[1,2-a]pyrimidin-6(2H)-one(1523406-39-4)
• EPA Substance Registry System: (S)-1-((5-chloropyridin-3-yl)methyl)-8-((R)-3-methylmorpholino)-2-(trifluoromethyl)-3,4-dihydro-1H-pyrimido[1,2-a]pyrimidin-6(2H)-one(1523406-39-4)

Safety Data

• Hazardous Substances Data: 1523406-39-4(Hazardous Substances Data)

Usage

Uses

SAR 405 is an anticancer agent and a phosphoinositide 3-kinase (PI3K) inhibitor.

Upstream product

• 1260585-11-2 (8S)-2-chloro-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one 
• 1260585-14-5 (2R,2S)-8-hydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydropyrimido[1,2-a]pyrimidin-6-one 
• 16075-42-6 2-amino-4-trifluoromethylpyrimidine 

Relevant articles and documents

Discovery of (2 S)-8-[(3 R)-3-Methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2 H -pyrimido[1,2- a ]pyrimidin-6-one: A novel potent and selective inhibitor of Vps34 for the treatment of solid tumors

Vps34 (the human class III phosphoinositide 3-kinase) is a lipid kinase involved in vesicle trafficking and autophagy and therefore constitutes an interesting target for cancer treatment. Because of the lack of specific Vps34 kinase inhibitors, we aimed to identify such compounds to further validate the role of this lipid kinase in cancer maintenance and progression. Herein, we report the discovery of a series of tetrahydropyrimidopyrimidinone derivatives. Starting with hit compound 1a, medicinal chemistry optimization led to compound 31. This molecule displays potent activity, an exquisite selectivity for Vps34 with excellent properties. The X-ray crystal structure of compound 31 in human Vps34 illustrates how the unique molecular features of the morpholine synthon bestows selectivity against class I PI3Ks. This molecule exhibits suitable in vivo mouse PK parameters and induces a sustained inhibition of Vps34 upon acute administration. Compound 31 constitutes an optimized Vps34 inhibitor that could be used to investigate human cancer biology.