4-(4-chloro-2-fluorophenyl)-2-(2-chloropyridin-4-yl)-1-(6-fluoro-1H-indazol-5-yl)-6-methyl-4H-pyrimidine-5-carboxamide

Names

[ Name ]:
4-(4-chloro-2-fluorophenyl)-2-(2-chloropyridin-4-yl)-1-(6-fluoro-1H-indazol-5-yl)-6-methyl-4H-pyrimidine-5-carboxamide

[Synonym ]:
4-(4-Chloro-2-fluorophenyl)-2-(2-chloro-4-pyridinyl)-N-(6-fluoro-1H-indazol-5-yl)-6-methyl-1,4-dihydro-5-pyrimidinecarboxamide
5-Pyrimidinecarboxamide, 4-(4-chloro-2-fluorophenyl)-2-(2-chloro-4-pyridinyl)-N-(6-fluoro-1H-indazol-5-yl)-1,4-dihydro-6-methyl-

Biological Activity

[Description]:

GSK-25 is a potent, selective and orally bioavailable ROCK1 inhibitor (IC50=7 nM). GSK-25 maintains good selectivity against a panel of 31 kinases (>100 fold), as well as RSK1 and p70S6K (RSK1: IC50=398 nM, p70S6K: IC50=1 μM). GSK-25 inhibits P450 profile (IC50s of 2.5, 5.2, 2.5 µM for CYP2C9, CYP2D6, CYP3A4, respectively)[1].

[Related Catalog]:

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Cell Cycle/DNA Damage >> ROCK

Signaling Pathways >> MAPK/ERK Pathway >> Ribosomal S6 Kinase (RSK)

Signaling Pathways >> Stem Cell/Wnt >> ROCK

Signaling Pathways >> TGF-beta/Smad >> ROCK

[Target]

ROCK1:7 nM (IC50)

RSK1:398 nM (IC50)

p70S6K:1000 nM (IC50)

[In Vivo]

GSK-25 (Rat aorta IC50=256 nM) is profiled in a spontaneously hypertensive rat (SHR) model of hypertension. At 30 mg/kg (p.o.), GSK-25 induces a 25 mmHg (t=3 hours) drop in blood pressure[1]. GSK-25 has promising oral bioavailability (49% in male Sprague-Dawley rats and 19% in monkey), good half-life (1.8 hours in rat and 2.2 hours in monkey)[1].

[References]

[1]. Sehon CA, et al. Potent, selective and orally bioavailable dihydropyrimidine inhibitors of Rho kinase (ROCK1) as potential therapeutic agents for cardiovascular diseases. J Med Chem. 2008 Nov 13;51(21):6631-4.

Chemical & Physical Properties

[ Density]:
1.6±0.1 g/cm3

[ Boiling Point ]:
751.7±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₄H₁₆Cl₂F₂N₆O

[ Molecular Weight ]:
513.326

[ Flash Point ]:
408.4±32.9 °C

[ Exact Mass ]:
512.073059

[ PSA ]:
101.25000

[ LogP ]:
4.18

[ Vapour Pressure ]:
0.0±2.5 mmHg at 25°C

[ Index of Refraction ]:
1.720