16675-59-5Relevant articles and documents
Synthesis and pharmacological evaluation of novel isoquinoline N-sulphonylhydrazones designed as ROCK inhibitors
Oliveira, Ramon Guerra de,Guerra, Fabiana Sélos,Mermelstein, Cláudia dos Santos,Fernandes, Patrícia Dias,Bastos, Isadora Tairinne de Sena,Costa, Fanny Nascimento,Barroso, Regina Cely Rodrigues,Ferreira, Fabio Furlan,Fraga, Carlos Alberto Manssour
, p. 1181 - 1193 (2018)
In this study, we synthesized a new congener series of N-sulphonylhydrazones designed as candidate ROCK inhibitors using the molecular hybridization of the clinically approved drug fasudil (1) and the IKK-β inhibitor LASSBio-1524 (2). Among the synthesized compounds, the N-methylated derivative 11 (LASSBio-2065) showed the best inhibitory profile for both ROCK isoforms, with IC50 values of 3.1 and 3.8 μM for ROCK1 and ROCK2, respectively. Moreover, these compounds were also active in the scratch assay performed in human breast cancer MDA-MB 231 cells and did not display toxicity in MTT and LDH assays. Molecular modelling studies provided insights into the possible binding modes of these N-sulphonylhydrazones, which present a new molecular architecture capable of being optimized and developed as therapeutically useful ROCK inhibitors.
Ruthenium-catalyzed chemo-and enantioselective hydrogenation of isoquinoline carbocycles
Jin, Yushu,Makida, Yusuke,Uchida, Tatsuya,Kuwano, Ryoichi
, p. 3829 - 3839 (2018/04/14)
A chemoselective hydrogenation of isoquinoline carbocycles was achieved by using the catalyst prepared from Ru(methallyl)2(cod) and trans-chelate chiral ligand PhTRAP. The unique chemoselectivity achieved in this hydrogenation could be ascribed to the trans-chelation of the chiral ligand. The procedure for preparing the catalyst strongly affects the reproducibility of the carbocycle hydrogenation. Various 5-, 6-, 7-, and 8-substituted isoquinolines were selectively hydrogenated at their carbocycles to afford 5,6,7,8-tetrahydroisoquinolines as major products in high yields with moderate or good enantioselectivities. Some mechanistic studies suggested that the stereogenic center was created during the initial addition of H2 to the aromatic ring in the hydrogenation of 5-substituted isoquinolines. In other words, the stereochemical control was accompanied by the dearomatization.
ISOQUINOLINE-5-CARBOXAMIDE DERIVATIVE HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASE
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Paragraph 0129-0131, (2015/07/15)
A compound selected from the group consisting of an isoquinoline-5-carboxamide derivative of formula (I), a pharmaceutically acceptable salt, an isomer, a hydrate and a solvate thereof is effective for the prevention or treatment of diseases associated with abnormal cell growth, which are caused by abnormal activation of a protein kinases.
