23195-63-3Relevant academic research and scientific papers
Ibrexafungerp: An orally active β-1,3-glucan synthesis inhibitor
Apgar, James M.,Wilkening, Robert R.,Parker, Dann L.,Meng, Dongfang,Wildonger, Kenneth J.,Sperbeck, Donald,Greenlee, Mark L.,Balkovec, James M.,Flattery, Amy M.,Abruzzo, George K.,Galgoci, Andrew M.,Giacobbe, Robert A.,Gill, Charles J.,Hsu, Ming-Jo,Liberator, Paul,Misura, Andrew S.,Motyl, Mary,Nielsen Kahn, Jennifer,Powles, Maryann,Racine, Fred,Dragovic, Jasminka,Fan, Weiming,Kirwan, Robin,Lee, Shu,Liu, Hao,Mamai, Ahmed,Nelson, Kingsley,Peel, Michael
, (2020/12/14)
We previously reported medicinal chemistry efforts that identified MK-5204, an orally efficacious β-1,3-glucan synthesis inhibitor derived from the natural product enfumafungin. Further extensive optimization of the C2 triazole substituent identified 4-pyridyl as the preferred replacement for the carboxamide of MK-5204, leading to improvements in antifungal activity in the presence of serum, and increased oral exposure. Reoptimizing the aminoether at C3 in the presence of this newly discovered C2 substituent, confirmed that the (R) t-butyl, methyl aminoether of MK-5204 provided the best balance of these two key parameters, culminating in the discovery of ibrexafungerp, which is currently in phase III clinical trials. Ibrexafungerp displayed significantly improved oral efficacy in murine infection models, making it a superior candidate for clinical development as an oral treatment for Candida and Aspergillus infections.
Design, synthesis, and biological activity of novel tetrahydropyrazolopyridone derivatives as FXa inhibitors with potent anticoagulant activity
Sun, Xiaoqing,Hong, Zexin,Liu, Moyi,Guo, Su,Yang, Di,Wang, Yong,Lan, Tian,Gao, Linyu,Qi, Hongxia,Gong, Ping,Liu, Yajing
, p. 2800 - 2810 (2017/04/18)
A series of novel tetrahydropyrazolopyridone derivatives containing 1,3,4-triazole, triazolylmethyl, and partially saturated heterocyclic moieties as P2 binding element was designed, synthesized, and evaluated in vitro for anticoagulant activity in human and rabbit plasma. All compounds showed moderate to significant potency, and compounds 15b, 15c, 20b, 20c, and 22b were further examined for their inhibitory activity against human FXa in vitro. While compounds 15c and 22b were tested for rat venous thrombosis in vivo. The most promising compound 15c, with an IC50 (FXa) value of 0.14?μM and 98% inhibition rate, warranted further investigation as an FXa inhibitor.
Synthesis of 1-methyl-5-(pyrazol-3- and -5-yl- and 1,2,4-triazol-3- and 5-yl)-1,2,3,6-tetrahydropyridine derivatives and their evaluation as muscarinic receptor ligands
Del Giudice, Maria Rosaria,Mustazza, Carlo,Borioni, Anna,Gatta, Franco,Tayebati, Khosrow,Amenta, Francesco,Tucci, Paolo,Pieretti, Stefano
, p. 143 - 154 (2007/10/03)
A series of 1-methyl-5-(pyrazol-3- and -5-yl- and 1,2,4-triazol-3- and 5-yl)-1,2,3,6-tetrahydropyridine derivatives structurally related to arecoline were synthesized and evaluated on M1, M2, and M3 muscarinic receptors using [3H]pirenzepine and [3H]NMS as ligands. The binding affinity depended on the position and size of the substituents. The most interesting compounds were further evaluated in functional studies on isolated organs and in vivo for cholinergic side effects. Compounds 51 and 6 i displayed good M1 and M3 antagonistic properties in vitro and were devoid of cholinergic side effects in vivo.
Substituted 1H-1,2,4-triazoles
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, (2008/06/13)
This disclosure describes new compounds and compositions of matter useful as anti-inflammatory agents and as inhibitors of the progressive joint deterioration characteristic of arthritic disease and the methods of meliorating inflammation and of inhibitin
