New Route of Benzyne Cyclization for Synthesis of 2,3,4,5-Tetrahydro- 1H-pyrido[4,3-b]indole Derivatives Avoiding Highly Toxic Aryl Hydrazines

摘要

Substituted tetrahydropyridoindoles display a broad spectrum of biological and pharmacological activities. Of them, mebhydrolin, 5-benzyl-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, (I, Fig. 1) [1], dimebon, 2,8-dimethyl-5-[2-(6- methyl-3-pyridinyl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b] indole (II, Fig. 1) [2], and alosetron, 5-methyl-2-[(4- methyl-1H-imidazol-5-yl)methyl]-2,3,4,5-tetrahydro-1Hpyrido[4,3-b]indol-1-one (III, Fig. 1) [3] are clinically used as antihistamine agents and serotonin antagonists. Dimebon was clinically tested to treat Alzheimer and Huntington diseases, yet owing to negative side effects, the drug has remained unlicensed for any neurodegenerative diseases.