79476-73-6Relevant academic research and scientific papers
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.
Cobalt(II), nickel(II), copper(II), zinc(II) and hafnium(IV) complexes of N′-(furan-3-ylmethylene)-2-(4-methoxyphenylamino)acetohydrazide
Emam, Sanaa M.,El-Saied, Fathy A.,Abou El-Enein, Saeyda A.,El-Shater, Heba A.
experimental part, p. 291 - 297 (2009/04/13)
Cobalt(II), nickel(II), copper(II), zinc(II) and hafnium(IV) complexes of furan-2-carbaldehyde 4-methoxy-N-anilinoacetohydrazone were synthesized and characterized by elemental and thermal (TG and DTA) analyses, IR, UV-vis and 1H NMR spectra as well as magnetic moment and molar conductivity. Mononuclear complexes are obtained with 1:1 molar ratio except complexes 3 and 9 which are obtained with 1:2 molar ratios. The IR spectra of ligand and metal complexes reveal various modes of chelation. The ligand behaves as a neutral bidentate one and coordination occurs via the carbonyl oxygen atom and azomethine nitrogen atom. The ligand behaves also as a monobasic tridentate one and coordination occurs through the enolic oxygen atom, azomethine nitrogen atom and the oxygen atom of furan ring. Moreover, the ligand behaves as a neutral tridentate and coordination occurs via the carbonyl oxygen, azomethine nitrogen and furan oxygen atoms as well as a monobasic bidentate and coordination occurs via the enolic oxygen atom and azomethine nitrogen atom. The electronic spectra and magnetic moment measurements reveal that all complexes possess octahedral geometry except the copper complex 10 possesses a square planar geometry. The thermal studies showed the type of water molecules involved in metal complexes as well as the thermal decomposition of some metal complexes.
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
