1493764-08-1

Basic information

• Product Name: UNC2881
• Synonyms: UNC2881;N-(4-(1H-iMidazol-1-yl)benzyl)-2-(butylaMino)-4-(((1r,4r)-4-hydroxycyclohexyl)aMino)pyriMidine-5-carboxaMide;N-(4-(1H-imidazol-1-yl)benzyl)-2-(butylamino)-4-((1r,4r)-4-hydroxycyclohexylamino)pyrimidine-5-carboxamide UNC2881;2-(Butylamino)-4-[(trans-4-hydroxycyclohexyl)amino]-N-[[4-(1H-imidazol-1-yl)phenyl]methyl]-5-pyrimidinecarboxamide;N-(4-(1H-Imidazol-1-yl)benzyl)-2-(butylamino)-4-(((1r,4r)-4-hydroxycyclohexyl)amino)pyrimidine
• CAS NO: 1493764-08-1
• Molecular Formula: C25H33N7O2
• Molecular Weight: 463.57522
• Product Categories: Inhibitors
• Mol File: 1493764-08-1.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• Density: 1.31±0.1 g/cm3(Predicted)
• Solubility: insoluble in H2O; insoluble in EtOH; ≥13.55 mg/mL in DMSO
• PKA: 12.70±0.46(Predicted)
• CAS DataBase Reference: UNC2881(CAS DataBase Reference)
• NIST Chemistry Reference: UNC2881(1493764-08-1)
• EPA Substance Registry System: UNC2881(1493764-08-1)

Safety Data

• Hazardous Substances Data: 1493764-08-1(Hazardous Substances Data)

Usage

Description

UNC2881 is an inhibitor of Mer (IC50 = 4.3 nM), a member of the TAM family of receptor tyrosine kinases. It is selective for Mer over the remaining TAM family members Axl and TYRO3 (IC50s = 360 and 250 nM, respectively). UNC2881 inhibits phosphorylation of Mer in 697 B-ALL acute lymphoblastic leukemia cells (IC50 = 21.9 nM). It inhibits platelet aggregation and ATP release induced by type I equine fibrillar collagen in isolated human platelet-rich plasma when used at a concentration of 3 μM.

Uses

UNC2881 is a specific Mer tyrosine kinase inhibitor. It inhibits collagen-stimulated platelet aggregation.

references

[1]. zhang w, mciver al, stashko ma, et al. discovery of mer specific tyrosine kinase inhibitors for the treatment and prevention of thrombosis. j med chem, 2013, 56(23): 9693-9700.

Upstream product

• 2972-52-3 2,4-dichloropyrimidine-5-carbonyl chloride 
• 65113-25-9 1-<4-(aminomethyl)phenyl>-1H-imidazole 
• 3177-20-6 2,4-dichloro-5-pyrimidinecarboxylic acid methyl ester 

Relevant articles and documents

Discovery of Mer specific tyrosine kinase inhibitors for the treatment and prevention of thrombosis

The role of Mer kinase in regulating the second phase of platelet activation generates an opportunity to use Mer inhibitors for preventing thrombosis with diminished likelihood for bleeding as compared to current therapies. Toward this end, we have discovered a novel, Mer kinase specific substituted-pyrimidine scaffold using a structure-based drug design and a pseudo ring replacement strategy. The cocrystal structure of Mer with two compounds (7 and 22) possessing distinct activity have been determined. Subsequent SAR studies identified compound 23 (UNC2881) as a lead compound for in vivo evaluation. When applied to live cells, 23 inhibits steady-state Mer kinase phosphorylation with an IC50 value of 22 nM. Treatment with 23 is also sufficient to block EGF-mediated stimulation of a chimeric receptor containing the intracellular domain of Mer fused to the extracellular domain of EGFR. In addition, 23 potently inhibits collagen-induced platelet aggregation, suggesting that this class of inhibitors may have utility for prevention and/or treatment of pathologic thrombosis.

PYRIMIDINE COMPOUNDS FOR THE TREATMENT OF CANCER

Described are compounds of Formula I or Formula II: wherein: ring A is a 5- or 6-membered heteroaryl group; dashed lines are optional double bonds; X is N or O; Y is a carbon atom or an S or N heteroatom in ring A in any suitable location; and substituents are as given herein. Compositions containing the same and methods of using the same in treating cancers such as acute lymphoblastic leukemia are also described.