Inhibitors of monoamine oxidase IV: 6(or 8)substituted tetrahydro-β-carbolines and their 9-methyl analogs

✍ Scribed by Beng T. Ho; William M. McIsaac; L. Wayne Tansey

• Publisher: John Wiley and Sons
• Year: 1969
• Tongue: English
• Weight: 498 KB
• Volume: 58
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600580821

✦ Synopsis

Several analogs of tetrahydro-p-carboline (I) and 9-methyltetrahydro-p-carboline (VII) with substituents on C-6 or C-8 were synthesized. Methylation of the N-9 position of a tetrahydro p-carboline is generally achieved in the presence of a base. However, the preparations of 8,9-dimethyltetrahydro-p-carboline and 8-chloro-9-rnethyltetrahydro-~-carboline from 8-methyltetrahydro-p-carboline and 8-chlorotetrahydro-p-carboline, respectively, required the blockage of the N-2 position, otherwise methylation would favor this position over the N-9 due to the steric interference caused by the C-8 substituent. Although C-6 substitution in general resulted in a decrease in inhibitory activity, introduction of a methyl group to C-8 of I and VII did not affect the activities of I and VII. When the 8-methyl groups of the two series were replaced by chlorine atoms, a fourfold increase in activity was observed. The inhibitory activity of the resulting 8-chloro-9-methyltetrahydrop-carboline was even greater than VII, the best inhibitor previously reported.