期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 58, 期 17, 页码 6747-6752出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.5b00902
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Herein we describe the optimization of a series of PDE4 inhibitors, with special focus on solubility and pharamcokinetics, to clinical compound 2, 4-(8-(3-fluorophenyl)-1,7-naphthyridin-6-yl)transcyclohexanecarboxylic acid. Although compound 2 produces emesis in humans when given as a single dose, its exemplary pharmacokinetic properties enabled a novel dosing regime comprising multiple escalating doses and the resultant achievement of high plasma drug levels without associated nausea or emesis.
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