Pyridines, 1,4-dihydro-, binding

Ferry DR, Russell MA, Cullen MH (1992) P-glycoprotein possesses a 1,4-dihydro-pyridine-selective drug acceptor site which is alloserically coupled to a vinca-alkaloid-selective binding site. Biochem Biophys Res Commun 188 440-445... 

T. Niwa. V. Tokuma, K. Nakagawa, H. Noguchi. Y. Yamazoe, and R. Kato, Stereoselective oxidation and plasma binding of nilvadipine, a new dihydro-pyridine calcium antagonist, in man, Res. Commun. Chem. Biihol. Pharmacol, 60 161 (1988). 

Fig. 13. Chemical structures for allosteric and ATP-competitive Eg5 inhibitors, (a) Monastrol ((S)-ethyl 1,2,3,4-tetrahydro-4-(3-hydroxyphenyl)-6-methyl-2-thioxopyrimidine-5-carboxylate), the first compound discovered which bound to the allosteric pocket the compound has an IC50 of 22 uM. (b) CK-f 06023 (N-((R)-f-(3-benzyl-7-chloro-3,4-dihydro-4-oxoquinazolin-2-yl)propyl)-4-bromo-N-(3-(dimethylamino)propyl) benzamide), which binds to the same allosteric pocket as Monastrol and has a Ki of f 2 nM. (c) CK-238273 N-(3-aminopropyl)-N-((R)-f -(3-benzyl-7-chloro-3,4-dihydro-4-oxoquinazolin-2-yl)-2-methylpropyl)-4-methylbenzamide), an optimized analog of CK-f 06023 which is in phase II and has a Ki of f. 7 nM. (d) 4-(2-(f -phenylethyl)thiazol-4-yl)pyridine, an ATP-competitive thiazole compound which was an initial hit from the Merck compound collection the compound has an IC50 of f f uM. (e) 4-(2-(f -(4-chlorophenyl)cyclo-propyl)thiazol-4-yl)pyridine, an optimized ATP-competitive thiazole compound with an IC50 of 290 nM.

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