100644-00-6Relevant articles and documents
Synthesis of a tritium-labeled indolidan analogue and its use as a radioligand for phosphodiesterase-inhibitor cardiotonic binding sites
Robertson,Krushinski,Utterback,Kauffman
, p. 1476 - 1480 (1989)
We have radiolabeled a structural analogue of indolidan, a potent phosphodiesterase-inhibitor cardiotonic, to permit biochemical studies regarding the interaction of this class of drugs with their pharmacological receptor. [3H]-LY186126 (1,3-dihydro-3,3-dimethyl-1-[3H3]methyl-5-(1,4,5,6-tetrahydro-4-metht yl-6-oxo-3-pyridazinyl)-2H-indol-2-one; [3H]-3) was selected as a synthetic target because of its potency as a cardiotonic and the ability to readily incorporate three tritia via the indolone N-CH3 substituent. Alkylation of a desmethyl precursor with tritium-labeled iodomethane resulted in [3H]-3 with a radiochemical purity of 98% and a specific activity of 79.2 Ci/mmol. This radioligand binds with high affinity to myocardial membrane vesicles. The binding was saturable, and K(d) and B(max) values of 4.1 nM and 383 fmol/mg protein were obtained. A series of indolidan congeners displaced [3H]-3 bound to myocardial vesicles, and K(i) values for inhibition of binding were highly correlated with canine inotropic ED50 values, suggesting the specific binding of [3H]-3 to cardiac vesicles is pharmacologically relevant.
Dihydropyridazinone cardiotonics: The discovery and inotropic activity of 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyrid azinyl)-2H-indol-2-one
Robertson,Krushinski,Beedle,Wyss,Pollock,Wilson,Kauffman,Hayes
, p. 1832 - 1840 (2007/10/02)
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