1393534-89-8Relevant articles and documents
Discovery of Clinical Candidate (5-(3-(4-Chlorophenoxy)prop-1-yn-1-yl)-3-hydroxypicolinoyl)glycine, an Orally Bioavailable Prolyl Hydroxylase Inhibitor for the Treatment of Anemia
Zhang, Xiaojin,Lei, Yonghua,Hu, Tianhan,Wu, Yue,Li, Zhihong,Jiang, Zhensheng,Yang, Changyong,Zhang, Lianshan,You, Qidong
, p. 10045 - 10060 (2020/10/18)
The design and discovery of a new series of (5-alkynyl-3-hydroxypicolinoyl)glycine inhibitors of prolyl hydroxylase (PHD) are described. These compounds showed potent in vitro inhibitory activity toward PHD2 in a fluorescence polarization-based assay. Remarkably, oral administration of 17, with an IC50 of 64.2 nM toward PHD2, was found to stabilize HIF-α, elevate erythropoietin (EPO), and alleviate anemia in a cisplatin-induced anemia mouse model with an oral dose of 25 mg/kg. Rat and dog studies showed that 17 has good pharmacokinetic properties, with oral bioavailabilities of 55.7 and 54.0%, respectively, and shows excellent safety profiles even at a high dose of 200 mg/kg in these animals. Based on these results, 17 is currently being evaluated in a phase I clinical trial for anemia.
BORON-CONTAINING SMALL MOLECULES
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Paragraph 0562; 0563, (2017/09/19)
Compounds, pharmaceutical formulations, and methods of treating bacterial infections are disclosed.
Dynamic combinatorial chemistry employing boronic acids/boronate esters leads to potent oxygenase inhibitors
Demetriades, Marina,Leung, Ivanhoe K. H.,Chowdhury, Rasheduzzaman,Chan, Mun Chiang,McDonough, Michael A.,Yeoh, Kar Kheng,Tian, Ya-Min,Claridge, Timothy D. W.,Ratcliffe, Peter J.,Woon, Esther C. Y.,Schofield, Christopher J.
, p. 6672 - 6675 (2012/09/22)
Dynamic duo: The reversible reaction of boronic acids with alcohols to form boronate esters, coupled to protein mass spectrometry analyses, was used to discover potent oxygenase inhibitors. This dynamic combinatorial mass spectrometry technique could potentially be applied to the identification of other protein inhibitors. Copyright
