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MedChemexpress LLC
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Product Name:SB-649868
CAS:380899-24-1
Purity:200RMB/10mg Package:>98%
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| | SB-649868 Basic information |
| Product Name: | SB-649868 | | Synonyms: | SB-649868;N-[[(2S)-1-[[5-(4-Fluorophenyl)-2-methyl-4-thiazolyl]carbonyl]-2-piperidinyl]methyl]-4-benzofurancarboxamide;N-[[(2S)-1-[5-(4-FLUOROPHENYL)-2-METHYL-1,3-THIAZOLE-4-CARBONYL]PIPERIDIN-2-YL]METHYL]-1-BENZOFURAN-4-CARBOXAMIDE;SB-649868, CID25195495;SB649868; SB 649868;CS-2650;4-Benzofurancarboxamide, N-[[(2S)-1-[[5-(4-fluorophenyl)-2-methyl-4-thiazolyl]carbonyl]-2-piperidinyl]methyl]-;(S)-N-((1-(5-(4-Fluorophenyl)-2-methylthiazole-4-carbonyl)piperidin-2-yl)methyl)benzofuran-4-carboxamide | | CAS: | 380899-24-1 | | MF: | C26H24FN3O3S | | MW: | 477.55 | | EINECS: | | | Product Categories: | | | Mol File: | 380899-24-1.mol |  |
| | SB-649868 Chemical Properties |
| Boiling point | 725.1±55.0 °C(Predicted) | | density | 1.305±0.06 g/cm3(Predicted) | | storage temp. | Store at -20°C | | solubility | DMF: 15mg/mL; DMF:PBS (pH 7.2) (1:20): 0.04mg/mL; DMSO: 10mg/mL; Ethanol: 0.3mg/mL | | form | A crystalline solid | | pka | 14.54±0.46(Predicted) | | color | White to off-white |
| | SB-649868 Usage And Synthesis |
| Biological Activity | SB-649868 is an orally active and selective orexin OX1 and OX2 receptor antagonist (at OX1 and OX2 receptors, pKi 9.4 and 9.5, respectively). | | in vitro | SB-649868 is identified as one the most in vitro potent dual OX 1 and OX 2 receptor antagonist known at that time (pK i =9.4 and 9.5 at the OX 1 and OX 2 receptor, respectively) . SB-649868 antagonizes orexin-A-induced inositol 1 phosphate (IP1) accumulation with the following pK B value (OX 1 =9.67; OX 2 =9.64). It displaces the [ 3 < /sup> H]ACT-078573 receptor binding with the following pKi values: OX 1 =9.27; OX 2 =8.91. Increasing concentrations of SB-649868 (0.3 nM- 30 nM) induces a rightward shift of the orexin-A CRCs with a depression of the agonist efficacy suggesting a clear non-surmountable behavior. The calculated apparent pK b values are 9.67±0.03 and 9.64±0.07 for OX 1 and OX 2 . | | in vivo | Pharmacokinetic studies in the male CD rat, performed at 1 mg/kg, iv and 3 mg/kg, po, demonstrate an excellent pharmacokinetic profile for a hypnotic agent featuring moderate clearance in plasma (Cl p =24 mL/min/kg), short half-life of (<0.6 h) and a low volume of distribution (V ss =1.1 l/kg), coupled with excellent oral bioavailability (F=85%) and good exposure in plasma (C max =333 ng/mL). A brain to blood ratio (B/B) of 0.1:1 is observed 1 h after iv administration, a value in line with the expected partition between the two compartments based on the lower tissue binding observed in vitro in brain tissues (fraction unbound/brain=5.28%) with respect to plasma proteins (fraction unbound/plasma=1.34%). SB-649868, administered orally 3 h before OX-A injection at doses of 1, 3 and 10 mg/kg, causes a dose-dependent reduction of OX-A induced grooming as measured by total time spent grooming and number of grooming bouts ( p <0.01 at 3 a nd 10 mg/kg po) . From dissociation kinetic studies using [ 3 H]ACT-078573, the calculated long half-life, (t 1/2 ) supports the non-surmountability profile of SB-649868 (t 1/2 =35.91 min) at OX 1 orexin receptor. The long or moderately long t 1/2 < /sub> values for SB-649868 at OX 2 orexin receptor (t 1/2 =8.09 min). | | target | pKi: 9.4 (OX 1 ), 9.5 (OX 2 ) |
| | SB-649868 Preparation Products And Raw materials |
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