GSK269962A

Base Information

• Chemical Name: GSK269962A
• CAS No.: 850664-21-0
• Molecular Formula: C₂₉H₃₀N₈O₅
• Molecular Weight: 570.608
• UNII: F89KMM7TE2
• ChEMBL ID: CHEMBL220241
• DSSTox Substance ID: DTXSID40582496
• Nikkaji Number: J3.437.789H
• Pharos Ligand ID: G9Y4VV8DSQ35
• Wikidata: Q27077891
• Mol file: 850664-21-0.mol

Synonyms:GSK 269962A;GSK-269962A;GSK269962A;N-(3-((2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-1H-imidazo(4,5-c)pyridin-6-yl)oxy)phenyl)-4-((2-(4-morpholinyl)ethyl)oxy)benzamide

Chemical Property of GSK269962A

Chemical Property:

• Melting Point: 125 - 127°C
• PSA: 155.68000
• Density: 1.45
• LogP: 4.43110
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 2.2
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 11
• Rotatable Bond Count: 10
• Exact Mass: 570.23391609
• Heavy Atom Count: 42
• Complexity: 860

Purity/Quality:

97% ^*data from raw suppliers

GSK269962 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCN1C2=CC(=NC=C2N=C1C3=NON=C3N)OC4=CC=CC(=C4)NC(=O)C5=CC=C(C=C5)OCCN6CCOCC6
• Description: Two Rho-associated kinases (ROCKS), ROCK1 and ROCK2, act downstream of the G protein Rho to regulate cytoskeletal stability. The ROCKs play important roles in diverse cellular functions including cell adhesion and proliferation, smooth muscle contraction, and stem cell renewal. GSK269962 is a selective ROCK inhibitor with IC50 values of 1.6 and 6 nM for ROCK1 and ROCK2, respectively. It displays greater than 30-fold selectivity for ROCK against a panel of serine/threonine kinases. GSK269962 has been shown to block the generation of inflammatory cytokines in lipopolysaccharide-stimulated monocytes and to induce vasorelaxation in preconstricted rat aorta (IC50 = 35 nM). Oral administration of 1-30 mg/kg GSK269962 can dose-dependently lower blood pressure in spontaneously hypertensive rats.
• Uses: GSK 269962 is a potent and selective Rho kinase (ROCK) inhibitor.

Technology Process of GSK269962A

There total 17 articles about GSK269962A which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 83.0%

4-[2-(morpholin-4-yl)ethoxy]benzoyl chloride + 4-{6-[(3-aminophenyl)oxy]-1-ethyl-1H-imidazo[4,5-c]pyridin-2-yl}-furazan-3-amine (850663-66-0) → GSK269962A (850664-21-0,925213-63-4)

Guidance literature:

With pyridine; In dichloromethane; at 70 ℃;

DOI:10.1021/jm060873p

Reference yield:

4-hydroxy-3-nitropyridine (5435-54-1) → GSK269962A (850664-21-0,925213-63-4)

Guidance literature:

Multi-step reaction with 13 steps

1: 99 percent / POCl₃ / toluene / 16 h / 110 °C

2: 80 percent / potassium t-butoxide; t-BuOOH / tetrahydrofuran; decane; liquid ammonia / 2 h / -35 °C

3: 74 percent / POCl₃ / toluene / 6 h / Heating

4: 83 percent / tetrahydrofuran; H₂O / 1 h

5: 96 percent / K₂CO₃ / dimethylformamide / 24 h / 100 °C

6: H₂ / Pd/C / methanol; tetrahydrofuran / 6 h / 3750.3 Torr

7: Et₃N; EDCl / D₂O / 15 - 20 °C

8: acetic acid / 5 h / Heating

9: aq. HCl; sodium nitrite / methanol / 28 h / 15 - 20 °C

10: 88 percent / hydroxylamine / tetrahydrofuran / 10 h / Heating

11: 42 percent / Et₃N / dioxane / 9 h / Heating

12: 100 percent / H₂SO₄ / 2 h / 50 °C

13: 83 percent / pyridine / CH₂Cl₂ / 70 °C

With pyridine; hydrogenchloride; tert.-butylhydroperoxide; sulfuric acid; potassium tert-butylate; hydrogen; hydroxylamine; potassium carbonate; acetic acid; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; sodium nitrite; trichlorophosphate; palladium on activated charcoal; In tetrahydrofuran; 1,4-dioxane; methanol; decane; dichloromethane; ammonia; water; water-d2; N,N-dimethyl-formamide; toluene;

DOI:10.1021/jm060873p

Reference yield:

2-chloro-N-ethyl-5-nitro-4-pyridinamine (607373-89-7) → GSK269962A (850664-21-0,925213-63-4)

Guidance literature:

Multi-step reaction with 9 steps

1: 96 percent / K₂CO₃ / dimethylformamide / 24 h / 100 °C

2: H₂ / Pd/C / methanol; tetrahydrofuran / 6 h / 3750.3 Torr

3: Et₃N; EDCl / D₂O / 15 - 20 °C

4: acetic acid / 5 h / Heating

5: aq. HCl; sodium nitrite / methanol / 28 h / 15 - 20 °C

6: 88 percent / hydroxylamine / tetrahydrofuran / 10 h / Heating

7: 42 percent / Et₃N / dioxane / 9 h / Heating

8: 100 percent / H₂SO₄ / 2 h / 50 °C

9: 83 percent / pyridine / CH₂Cl₂ / 70 °C

With pyridine; hydrogenchloride; sulfuric acid; hydrogen; hydroxylamine; potassium carbonate; acetic acid; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; sodium nitrite; palladium on activated charcoal; In tetrahydrofuran; 1,4-dioxane; methanol; dichloromethane; water-d2; N,N-dimethyl-formamide;

DOI:10.1021/jm060873p

upstream raw materials:

4-{6-[(3-aminophenyl)oxy]-1-ethyl-1H-imidazo[4,5-c]pyridin-2-yl}-furazan-3-amine

4-chloro-2-hydroxy-5-nitropyridine

2-chloro-N-ethyl-5-nitro-4-pyridinamine

N-(3-{[5-amino-4-(ethylamino)-2-pyridinyl]oxy}phenyl)-4-methylbenzenesulfonamide