PHENOTHIAZINE DERIVATIVES

Twenty-eight 2- and 10-substituted phenothiazine derivatives have been sythesized for testing their actions on the central nervous system. 2-Hydroxy-10-(3-dimethylaminopropyl)phenothiazine (Ⅳ) was prepared by the condensation of 2-benzyloxyphenothiazine with 3-dimethylaminopropyl chloride and subsequent hydrogenolysis of the benzyl radical. The 2-acetoxy (Ⅴ) and 2-carbamyloxy (Ⅵ) derivatives were also prepared. 10-Chloroalkylphenothiazines (Ⅸ, Ⅹ) was reacted with hydrazine or diethanolamine to give compounds (Ⅺ—ⅩⅢ, ⅩⅥ, ⅩⅦ). The amino acid (ⅩⅪ) when treated with ethylene oxide formed the diethanolamino acid (ⅩⅫ). The latter evolved carbon dioxide upon storage in aqueous solution to give 10-diethanolaminobutylphenothiazine (ⅩⅩⅢ). 10-Chloroformylphenothiazine was treated with appropriate reactants to give the hydrazides (ⅩⅩⅩⅥ, ⅩⅩⅩⅧ), amides (ⅩⅩⅪ, ⅩⅩⅩⅢ—ⅩⅩⅩⅤ) and esters (ⅩL, ⅩLⅡ). Compound (ⅩL) could be decarboxylated to give (ⅩLⅠ), while similar treatment of (ⅩLⅡ) proved abortive. 2-(10-Phenothiazinyl) oxazoline (ⅩⅩⅫ) was prepared by heating the tosylate of (ⅩⅩⅪ) in acetic acid. Reaction of β-(10-phenothiazinyl)propionic acid with tryptamine gave 3-(β-(10-phenothiazinyl)propionamido)ethyl indole (ⅩⅩⅦ), reduction of which gave the amino compound (ⅩⅩⅧ). Pharmacologic tests showed that compounds (Ⅻ, ⅩⅩⅩⅥ, ⅩⅩⅩⅧ) have some depressant effects on the central nervous system of mice. It is of interest to point out that these are all hydrazine derivatives.