4-(4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide Chemical Properties

storage temp. 

Store at -20°C

solubility 

DMSO:57.67(Max Conc. mg/mL);157.83(Max Conc. mM)
Ethanol:3.0(Max Conc. mg/mL);8.21(Max Conc. mM)

form 

A crystalline solid

color 

Light yellow to khaki

InChI

1S/C19H16FN5O2/c1-10-16(17(24-19(27)22-10)11-2-4-13(20)5-3-11)18(26)23-14-6-7-15-12(8-14)9-21-25-15/h2-9,17H,1H3,(H,21,25)(H,23,26)(H2,22,24,27)

InChIKey

HEAIGWIZTYAQTC-UHFFFAOYSA-N

SMILES

O=C(NC1=CC=C(NN=C2)C2=C1)C3=C(C)NC(NC3C4=CC=C(F)C=C4)=O

Safety Information

WGK Germany 

WGK 3

Storage Class

11 - Combustible Solids

4-(4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide Usage And Synthesis

Uses

GSK180736A is potent Rho-associated coiled-coil kinase 1 (ROCK1) inhibitor with an IC50 of 100 nM. GSK180736A is also a selective and ATP-competitive G protein-coupled receptor kinase 2 (GRK2) inhibitor with an IC50 of 0.77 μM.

Biological Activity

GSK180736A (GSK180736) is a Rho-related, coiled-coil protein kinase inhibitor that binds to GRK2 (G protein-coupled receptor kinase 2) with logIC50 of -6.6. The selectivity for GRK2 is more than 400-fold higher than that for GRK1 and GRK5.

in vitro

GSK180736A inhibits GRK2 with IC50 of 770 nM, 300-fold more potent than GRK5. It is a weak PKA inhibitor with IC50=30 μM; it is a potent ROCK1 inhibitor (IC50=100 nM).

target

IC 50

ROCK1: 100 nM (IC₅₀); GRK2: 770 nM (IC₅₀)

References

[1] Waldschmidt HV, et al. Structure-Based Design, Synthesis, and Biological Evaluation of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors. J Med Chem. 2016 Apr 28;59(8):3793-807. DOI:10.1021/acs.jmedchem.5b02000