16665-38-6Relevant articles and documents
Rational Design of 2-Chloroadenine Derivatives as Highly Selective Phosphodiesterase 8A Inhibitors
Huang, Yadan,Wu, Xu-Nian,Zhou, Qian,Wu, Yinuo,Zheng, Dongxiao,Li, Zhe,Guo, Lei,Luo, Hai-Bin
, p. 15852 - 15863 (2020)
To validate the hypothesis that Tyr748 is a crucial residue to aid the discovery of highly selective phosphodiesterase 8A (PDE8A) inhibitors, we identified a series of 2-chloroadenine derivatives based on the hit clofarabine. Structure-based design targeting Tyr748 in PDE8 resulted in the lead compound 3a (IC50 = 0.010 μM) with high selectivity with a reasonable druglike profile. In the X-ray crystal structure, 3a bound to PDE8A with a different mode from 3-isobutyl-1-methylxanthine (a pan-PDE inhibitor) and gave a H-bond of 2.7 ? with Tyr748, which possibly interprets the 220-fold selectivity of 3a against PDE2A. Additionally, oral administration of compound 3a achieved remarkable therapeutic effects against vascular dementia (VaD), indicating that PDE8 inhibitors could serve as potential anti-VaD agents.
Peptidomimetic Vinyl Heterocyclic Inhibitors of Cruzain Effect Antitrypanosomal Activity
Chenna, Bala C.,Li, Linfeng,Mellott, Drake M.,Zhai, Xiang,Siqueira-Neto, Jair L.,Calvet Alvarez, Claudia,Bernatchez, Jean A.,Desormeaux, Emily,Alvarez Hernandez, Elizabeth,Gomez, Jana,McKerrow, James H.,Cruz-Reyes, Jorge,Meek, Thomas D.
, p. 3298 - 3316 (2020/04/08)
Cruzain, an essential cysteine protease of the parasitic protozoan, Trypanosoma cruzi, is an important drug target for Chagas disease. We describe here a new series of reversible but time-dependent inhibitors of cruzain, composed of a dipeptide scaffold appended to vinyl heterocycles meant to provide replacements for the irreversible reactive "warheads" of vinyl sulfone inactivators of cruzain. Peptidomimetic vinyl heterocyclic inhibitors (PVHIs) containing Cbz-Phe-Phe/homoPhe scaffolds with vinyl-2-pyrimidine, vinyl-2-pyridine, and vinyl-2-(N-methyl)-pyridine groups conferred reversible, time-dependent inhibition of cruzain (Ki? = 0.1-0.4 μM). These cruzain inhibitors exhibited moderate to excellent selectivity versus human cathepsins B, L, and S and showed no apparent toxicity to human cells but were effective in cell cultures of Trypanosoma brucei brucei (EC50 = 1-15 μM) and eliminated T. cruzi in infected murine cardiomyoblasts (EC50 = 5-8 μM). PVHIs represent a new class of cruzain inhibitors that could progress to viable candidate compounds to treat Chagas disease and human sleeping sickness.
IRIDIUM-BASED CATALYSTS FOR HIGHLY EFFICIENT DEHYDROGENATION AND HYDROGENATION REACTIONS IN AQUEOUS SOLUTION AND APPLICATIONS THEREOF
-
Page/Page column 13; 17, (2018/11/22)
A series of iridium-based catalysts for dehydrogenation of formic acid, and hydrogenation using formic acid as the hydrogen source, and the process using the catalyst(s) to produce hydrogen gas from formic acid solution, or to reduce aldehydes using formic acid, are disclosed and claimed. More specifically, the present invention relates to a group of pentamethylcyclopentadienyl (Cp*) iridium complexes with different Ν,Ν-bidentate ligands that catalyze dehydrogenation from formic acid, and chemo-selective hydrogenation of aldehydes, in the aqueous solution system in a highly efficient, and long life-time manner.