| Identification | Back Directory | [Name]
SB 239063 | [CAS]
193551-21-2 | [Synonyms]
CS-402
SB 239063
SB-239063; SB239063
SB 239063 - CAS 798558-40-4 - Calbiochem
rans-4-[4-(4-Fluorophenyl)-5-(2-methoxy-4-pyrimidinyl)-1H-imidazol-1-yl]cyclohexano
TRANS-1-(4-HYDROXYCYCLOHEXYL)-4-(FLUOROPHENYL)-5-(2-METHOXYPYRIMIDIN-4-YL) IMIDAZOLE
TRANS-4-[4-(4-FLUOROPHENYL)-5-(2-METHOXY-4-PYRIMIDINYL)-1H-IMIDAZOL-1-YL]CYCLOHEXANOL
TRANS-1-(4-HYDROXYCYCLOHEXYL)-4-(4-FLUOROPHENYL)-5-(2-METHOXYPYRIMIDIN-4-YL) IMIDAZOLE
TRANS-1-(4-HYDROXYCYCLOHEXYL)-4-(4-FLUOROPHENYL)-5-(2-METHOXYPYRIDIMIDIN-4-YL)IMIDAZOLE
Cyclohexanol, 4-[4-(4-fluorophenyl)-5-(2-methoxy-4-pyrimidinyl)-1H-imidazol-1-yl]-, trans-
Rel-(1r,4r)-4-(4-(4-fluorophenyl)-5-(2-methoxypyrimidin-4-yl)-1H-imidazol-1-yl)cyclohexan-1-ol | [Molecular Formula]
C20H21FN4O2 | [MDL Number]
MFCD03792786 | [MOL File]
193551-21-2.mol | [Molecular Weight]
368.4 |
| Chemical Properties | Back Directory | [Melting point ]
206-207.2 °C
| [storage temp. ]
2-8°C
| [solubility ]
DMSO: 11 mg/mL
| [form ]
White solid | [color ]
white
| [InChI]
InChI=1S/C20H21FN4O2/c1-27-20-22-11-10-17(24-20)19-18(13-2-4-14(21)5-3-13)23-12-25(19)15-6-8-16(26)9-7-15/h2-5,10-12,15-16,26H,6-9H2,1H3/t15-,16- | [InChIKey]
ZQUSFAUAYSEREK-WKILWMFISA-N | [SMILES]
[C@@H]1(O)CC[C@@H](N2C=NC(C3=CC=C(F)C=C3)=C2C2C=CN=C(OC)N=2)CC1 |
| Hazard Information | Back Directory | [Uses]
SB239063 is neuroprotective, decreases the number of activated microglia and facilitates neurogenesis in oxygen-glucose-deprived hippocampal slice cultures. A protein kinase inhibitor | [Definition]
ChEBI: A member of the class of imidazoles carrying 4-hydroxycyclohexyl, 4-fluorophenyl and 2-methoxypyrimidin-4-yl substituents at positions 1, 4 and 5 respectively. | [Hazard]
A poison by ingestion. | [Biological Activity]
Potent and selective p38 MAP kinase inhibitor (IC 50 = 44 nM for p38a). Displays > 220-fold selectivity over ERK, JNK1 and other kinases; ~ 3-fold more selective than SB 203580 (4-[5-(4-Fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-1H-i midazol-4-yl]pyridine and 4-[5-(4-Fluorophenyl)-2-[4-(methylsulphonyl)phenyl]-1H- imidazol-4-yl]pyridine hydrochloride
). Reduces inflammatory cytokine production and is neuroprotective following oral administration in vivo . | [General Description]
SB 239063 helps to decrease neutrophilia, inflammatory cytokines, matrix metallopeptidase 9 (MMP-9) and fibrosis in the lung. | [Biochem/physiol Actions]
Potent p38 MAP kinase inhibitor. Selective for α and β. No activity against γ and δ isoforms. | [Synthesis]
The general procedure for the synthesis of (1r,4r)-rel-4-(4-(4-fluorophenyl)-5-(2-methoxypyrimidin-4-yl)-1H-imidazol-1-yl)cyclohexanol, using the compound (CAS: 193551-20-1) as a starting material was as follows:
Example 2: Synthesis of trans-1-(4-hydroxycyclohexyl)-4-(4-fluorophenyl)-5-(2-methoxypyrimidin-4-yl)imidazole
To a solution of the compound prepared in Example 1 (j) (0.099 g, dissolved in MeOH/THF (1 mL, 1:1 volume ratio), corresponding to 0.27 mmol) was added a NaBH4 solution (1 mL, 1 M solution. This NaBH4 solution was prepared by mixing 0.10 g NaBH4, MeOH (2.5 mL) and 25% NaOMe in MeOH solution (0.2 mL)). The reaction mixture was stirred for 10 min and then the reaction was quenched with saturated Na2CO3 solution, followed by evaporation to remove the solvent. The residue was purified by recrystallization from the mixed MeOH/H2O solvent to afford the target product (1r,4r)-rel-4-(4-(4-fluorophenyl)-5-(2-methoxypyrimidin-4-yl)-1H-imidazol-1-yl)cyclohexanol as white acicular crystals (0.063 g, 63% yield). The melting point of the product was 188-190 °C. | [in vitro]
in oxygen-glucose-deprived hippocampal slice cultures, treatment with 20 μm and 100 μm sb239063 significantly reduced the levels of the pro-inflammatory cytokine il-1β and reduced cell death after oxygen-glucose deprivation and strikingly diminished microglia activation[2]. | [in vivo]
oral administration of 3–30 mg/kg sb 239063 given twice a day dose-dependently inhibited airway neutrophil infiltration and interleukin (il)-6 levels 48 h after lipopolysaccharide (lps) inhalation [1]. in a bleomycin-induced pulmonary fibrosis model rats, sb 239063 treatment (2.4 or 4.8 mg/day via osmotic pump) significantly inhibited bleomycin-induced right ventricular hypertrophy (indicative of secondary pulmonary hypertension) and increased in lung hydroxyproline synthesis (indicative of collagen synthesis and fibrosis) (1). in conscious guinea pigs, administration of sb 239063 (10 or 30 mg/kg p.o.) showed approximately 50% inhibition of oa-induced pulmonary eosinophil influx, measured by bal 24 h after antigen(1). orally administration of sb 239063 (30 mg/kg) attenuated il-6 bronchoalveolar lavage fluid concentrations (> 90% inhibition) and mmp-9 activity (64% inhibition) measured 6 h after lps exposure. in guinea pig cultured alveolar macrophages, sb 239063 inhibited lps-induced il-6 production with ic50 of 362 nm. in lipopolysaccharide-stimulated human peripheral blood monocytes, sb 239063 inhibited il-1 and tnf-α production with an ic50 of 0.12 and 0.35 μm, respectively(1). | [storage]
Desiccate at +4°C | [References]
[1] underwood d c, osborn r r, bochnowicz s, et al. sb 239063, a p38 mapk inhibitor, reduces neutrophilia, inflammatory cytokines, mmp-9, and fibrosis in lung[j]. american journal of physiology-lung cellular and molecular physiology, 2000, 279(5): l895-l902.
[2] strassburger m, braun h, reymann k g. anti-inflammatory treatment with the p38 mitogen-activated protein kinase inhibitor sb239063 is neuroprotective, decreases the number of activated microglia and facilitates neurogenesis in oxygen–glucose-deprived hippocampal slice cultures[j]. european journal of pharmacology, 2008, 592(1): 55-61. |
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| Company Name: |
J & K SCIENTIFIC LTD.
|
| Telephone: |
18210857532 18210857532 |
| Website: |
https://www.jkchemical.com |
| Company Name: |
LETOPHARM LIMITED
|
| Telephone: |
+86-21-5821 5861 |
| Website: |
www.letopharm.com |
| Company Name: |
Sigma-Aldrich
|
| Telephone: |
021-61415566 800-8193336 |
| Website: |
https://www.sigmaaldrich.cn |
| Company Name: |
SPIRO PHARMA
|
| Telephone: |
|
| Website: |
www.spiropharma.com.cn |
|