ROCK inhibitor 3   

GtoPdb Ligand ID: 10425

Synonyms: Chiesi Rock inhibitor [2] | example 3 [WO2010032875A2] [3]
Compound class: Synthetic organic
Comment: Inhibitor 3 is a selectve and potent inhibitor of the Rho-associated kinases, ROCK1 and ROCK2. The chemical structure presented here was drawn from Cantoni et al., 2019 [1]. PubChem CID 46182713 presents the compound without specified stereochemistry.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 4
Topological polar surface area 103.26
Molecular weight 282.15
XLogP 1.35
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES COc1nc(NC2CCC(CC2)N)c(cc1C(=O)N)F
Isomeric SMILES COc1nc(N[C@@H]2CC[C@H](CC2)N)c(cc1C(=O)N)F
InChI InChI=1S/C13H19FN4O2/c1-20-13-9(11(16)19)6-10(14)12(18-13)17-8-4-2-7(15)3-5-8/h6-8H,2-5,15H2,1H3,(H2,16,19)(H,17,18)/t7-,8-
InChI Key IMZIJLMIOSQRGE-ZKCHVHJHSA-N
Bioactivity Comments
Inhibitor 3 produced a strong vasorelaxant effect in phenylephrine pre-contracted isolated rat pulmonary artery and aortic rings in vitro (IC50s of approximately 50 nM), and attenuated right ventricle systolic pressure elevation in the rat monocrotaline-induced pulmonary hypertension model [1]. Histological analyses showed that inhibitor 3 reduced pulmonary vascular remodeling in this experimental rodent model.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Rho associated coiled-coil containing protein kinase 2 Hs Inhibitor Inhibition 8.1 pIC50 - 1
pIC50 8.1 (IC50 7.8x10-9 M) [1]
Rho associated coiled-coil containing protein kinase 1 Hs Inhibitor Inhibition 8.0 pIC50 - 1
pIC50 8.0 (IC50 1x10-8 M) [1]