911417-87-3

Basic information

• Product Name: ROCK inhibitor 2
• Synonyms: ROCK inhibitor 2;KD-025;SLx 2119;SLx2119;SLx-2119;2-[3-[4-[(1H-Indazol-5-yl)amino]quinazolin-2-yl]phenoxy]-N-isopropylacetamide;KD025 (SLx-2119);SLx-2119(KD-025)
• CAS NO: 911417-87-3
• Molecular Formula: C26H24N6O2
• Molecular Weight: 452.50776
• Product Categories: API
• Mol File: 911417-87-3.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 682.6±55.0 °C(Predicted)
• Appearance: /
• Density: 1.318±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C(protect from light)
• Solubility: Soluble in DMSO (25 mg/ml)
• PKA: 13?+-.0.40(Predicted)
• Stability: Stable for 1 year as supplied from date of purchase. Solutions in DMSO may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: ROCK inhibitor 2(CAS DataBase Reference)
• NIST Chemistry Reference: ROCK inhibitor 2(911417-87-3)
• EPA Substance Registry System: ROCK inhibitor 2(911417-87-3)

Safety Data

• Hazardous Substances Data: 911417-87-3(Hazardous Substances Data)

Usage

Description

KD 025 is an inhibitor of Rho-associated kinase 2 (ROCK2; IC50 = 0.105 μM). It is selective for ROCK2 over ROCK1 (IC50 = 24 μM). KD 025 (10 μM) decreases the expression of connective tissue growth factor (CTGF) and induces remodeling of the actin cytoskeleton in isolated human ileal fibrotic smooth muscle cells. It inhibits heat-killed C. albicans- or S. epidermidis-induced production of IL-17 in isolated human peripheral blood mononuclear cells (PBMCs) when used at concentrations ranging from 1.25 to 10 μM. KD 025 (100 and 200 mg/kg) reduces infarct volume in a mouse model of cerebral ischemia induced by transient middle cerebral artery occlusion (MCAO). It decreases disease severity in a mouse model of sclerodermatous chronic graft versus host disease (GVHD) when administered at a dose of 150 mg/kg. Formulations containing KD 025 have been used in the treatment of chronic GVHD.

Uses

KD 025 is an inhibitor of Rho-associated protein kinase II (ROCK-II), a serine/threonine kinase that regulates the formation of actin stress fibers and focal adhesions, smooth muscle contraction, and gene expression (1, 2). KD025 has been shown to reduce infarct volume after transient middle cerebral artery occlusion (2).

References

Boerma et al. (2008) Comparative gene expression profiling in three primary human cell lines after treatment with a novel inhibitor of Rho kinase or atorvastatin; Blood Coagul. Fibrinolysis.?19 709 Zanin-Zhorov et al. (2014) Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism; Natl. Acad. Sci. USA?111 16814 Flynn et al. (2016) Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism; 127 2144 Jagasia et al. (2021) ROCK2 Inhibition with Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease; Clin. Invest.?39 1888 Diep et al. (2018) Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells; Rep.?8 2477 Diep et al. (2019) KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells; Adipocyte?9 114 Wei et al. (2020) ROCK2 inhibition enhances the thermogenic program in white and brown fat tissue in mice; FASEB J.?34 474 Tran and Chun (2021) ROCK2-Specific Inhibitor KD025 Suppresses Adipocyte Differentiation by Inhibiting Casein Kinase 2; Molecules?26 4747

Upstream product

• 56071-04-6 2-(3-methoxyphenyl)quinazolin-4(3H)-one 
• 28144-70-9 anthranilic acid amide 
• 1711-05-3 m-anisoyl chloride 
• 911417-61-3 tert-butyl 5-(2-(3-(2-tert-butoxy-2-oxoethoxy)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate 
• 911417-25-9 tert-butyl 5-(2-(3-acetoxyphenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate 
• 911417-26-0 tert-butyl 5-(2-(3-hydroxyphenyl)-quinazolin-4-ylamino)-1H-indazole-1-carboxylate 
• 911417-24-8 3-(4-chloroquinazolin-2-yl)phenyl acetate 
• 371947-93-2 3-(4-oxo-3,4-dihydroquinazolin-2-yl)phenyl acetate 
• 330657-87-9 N-(2-carbamoylphenyl)-3-methoxybenzamide 
• 911417-23-7 2-(3-hydroxylphenyl)quinazolin-4(3H)-one 
• 75726-96-4 2-bromo-N-isopropylacetamide 
• 19335-11-6 1H-indazol-5-ylamine 
• 911417-62-4 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)acetic acid 
• 75-31-0 isopropylamine 

Relevant articles and documents

Synthesis method of SLx-2119

The invention belongs to the field of drug synthesis, and particularly, discloses a synthesis method of SLx-2119, wherein the synthesis method comprises the steps: firstly, with isopropylamine and bromoacetyl bromide as raw materials, preparing 2-bromo-N-isopropyl acetamide I, and then successively carrying out nucleophilic substitution reaction and ester hydrolysis reaction with 3-methyl hydroxybenzoate, carrying out amination reaction, cyclization reaction and chlorination reaction with 2-aminobenzamide, and finally carrying out nucleophilic substitution reaction with 5-aminoindazole, to prepare the SLx-2119. The use of expensive dihydroxy phenyl borate, Pd(dppf)Cl2, 2,4-dihydrogen quinazoline and other reagents is avoided, so the costs are reduced; the use of heavy metal palladium is also avoided, so the synthesis method has the advantages of no heavy metal pollution, environmental friendliness, raw materials without heavy metal residues, short reaction route, high yield and low cost, and is beneficial for industrialized production.

RHO KINASE INHIBITORS

The present invention relates to inhibitors of ROCKl and R0CK2, which may be selective for R0CK2, and methods of modulating the pharmacokinetic and/or pharmacodynamic properties of such compounds. Also provided are methods of inhibiting ROCKl and/or R0CK2. Also provided are treatments combining inhibitors of ROCKl and/or R0CK2 with statins.