Common mechanisms of inhibition for the Na+/glucose (hSGLT1) and Na+/Cl–/GABA (hGAT1) cotransporters was written by Hirayama, Bruce A.;Diez-Sampedro, Ana;Wright, Ernest M.. And the article was included in British Journal of Pharmacology in 2001.Synthetic Route of C22H26ClNO2 This article mentions the following:
1 Electrophysiol. methods were used to investigate the interaction of inhibitors with the human Na+/glucose (hSGLT1) and Na+/Cl–/GABA (hGAT1) cotransporters. Inhibitor constants were estimated from both inhibition of substrate-dependent current and inhibitor-induced changes in cotransporter conformation. 2 The competitive, non-transported inhibitors are substrate derivatives with inhibition constants from 200 nM (phlorizin) to 17 mM (esculin) for hSGLT1, and 300 nM (SKF89976A) to 10 mM (baclofen) for hGAT1. At least for hSGLT1, values determined using either method were proportional over 5-orders of magnitude. 3 Correlation of inhibition to structure of the inhibitors resulted in a pharmacophore for glycoside binding to hSGLT1: the aglycon is coplanar with the pyranose ring, and binds to a hydrophobic/aromatic surface of at least 7脳12脜. Important hydrogen bond interactions occur at five positions bordering this surface. 4 In both hSGLT1 and hGAT1 the data suggests that there is a large, hydrophobic inhibitor binding site 鈭?脜 from the substrate binding site. This suggests an architectural similarity between hSGLT1 and hGAT1. There is also structural similarity between non-competitive and competitive inhibitors, e.g., phloretin is the aglycon of phlorizin (hSGLT1) and nortriptyline resembles SKF89976A without nipecotic acid (hGAT1). 5 Our studies establish that measurement of the effect of inhibitors on presteady state currents is a valid non-radioactive method for the determination of inhibitor binding constants Furthermore, anal. of the presteady state currents provide novel insights into partial reactions of the transport cycle and mode of action of the inhibitors. In the experiment, the researchers used many compounds, for example, SKF-89976A Hydrochloride (cas: 85375-15-1Synthetic Route of C22H26ClNO2).
SKF-89976A Hydrochloride (cas: 85375-15-1) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Synthetic Route of C22H26ClNO2
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem