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

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

Uses

Used in Pharmaceutical Industry:
UNC2881 is used as a specific Mer tyrosine kinase inhibitor for inhibiting collagen-stimulated platelet aggregation. This application is particularly relevant in the development of therapeutic strategies for conditions involving abnormal platelet function or clotting disorders.
Additionally, due to its inhibitory effects on Mer in leukemia cells, UNC2881 may also be used as a potential therapeutic agent in the treatment of certain types of leukemia, specifically 697 B-ALL acute lymphoblastic leukemia. Its ability to inhibit Mer phosphorylation could contribute to the development of targeted cancer therapies.

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.

THERAPUETIC USES OF SELECTED PYRIMIDINE COMPOUNDS WITH ANTI-MER TYROSINE KINASE ACTIVITY

Uses of pyrimidines with anti-Mer tyrosine kinase activity as anti-infective agents, immunostimulatory and immunomodulatory agents, anti-cancer agents (including against MerTK -/- tumors and ITD and TKD mutant forms of Acute Myeloid Leukemia (AML)), and as adjunctive agents in combination with chemotherapeutic, radiation or other standard of care for neoplasms.

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.