79476-73-6Relevant articles and documents
Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure
Okawa, Tomohiro,Aramaki, Yoshio,Yamamoto, Mitsuo,Kobayashi, Toshitake,Fukumoto, Shoji,Toyoda, Yukio,Henta, Tsutomu,Hata, Akito,Ikeda, Shota,Kaneko, Manami,Hoffman, Isaac D.,Sang, Bi-Ching,Zou, Hua,Kawamoto, Tetsuji
, p. 6942 - 6990 (2017/09/07)
A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates β-adrenergic receptor (βAR)-mediated cAMP accumulation and prevents internalization of βARs in β2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.
Synthesis and characterization of Cu(II), Ni(II), Co(II), Mn(II), Zn(II), Ru(III), Hf(IV) and ZrO(II) complexes of 2-thiophenylidene-N-4-methoxy anilinoacetohydrazone
El-Saied,Abou El-Enein,Emam,El-Shater
experimental part, p. 1871 - 1883 (2010/07/04)
A new hydrazone ligand (HL), [2-(4-methoxyphenylamino)-N'-(thiophen-2-yl- methylene)acetohydrazide], was prepared and characterized. The ligand reacted with Cu(II), Ni(II), Co(II), Mn(II), Zn(II), Hf(IV), Ru(III) and ZrO(II) ions to yield mononuclear comp
