A New Synthetic Method for the Synthesis of Hydroxylated Isoquinolines: Preparation of Methyl 6,7- and 7,8-Dihydroxyisoquinoline-3-carboxylates, Potential Protein-Tyrosine Kinase Inhibitors
Year: 1992
Type: article
Abstract: Synthesis of potential protein-tyrosine kinase inhibitors (6c) and (6e) is presented as a general procedure for the preparation of polyhydroxylated iscquinolines.Key features of the method include selective hydroxyl protection of tenahydroisoquinolines by 0-acylation followed by ammatization using Mn02.Quantitative deprotection of resulting 0-acylisoquinolines is achieved using methanolic HCI.lscquinoline heterocycles are ubiquitous to a wide specrmmof natural products.lIt has recently been shown that the hydroxylated isoquinoline3-carboxyamide (2) posvsses significant inhibitory activity against platelet-derived growth factor (PDGF) protein tyrosine kinase (PTK)?This is of particular note in that inappropriate or aberrant expression of PDGF3 or other FTKs has been associated with a number of proliferative disorders, making inhibitors of FTKs potential candidates as anticancer therapeutics.43The 5.6-dihydroxyisoquinolineca~boxamide(2) can be viewed as a conformationally constrained analogue2 of the more general class of styryl-based PTK inhibitors exemplified by a-cyanocinnamamide (1).6In a like manner, the 7.8-dihydroxyisoquinolinecarboxamide (3) represents a confomlationally consnained mimetic of cinnamamide (1) having the phenyl ring rotated 180".Evidence suggests that this second orientation may be preferred for FTK inhibition.'
Source: Heterocycles
DOI: 10.3987/com-91-5958
Institutions: National Institutes of Health, National Cancer Institute
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: diamond
Funder: James Cook University
OpenAlex ID: W2951674070