Phenothiazine photosensitizers: part 2. 3,7-Bis(arylamino)phenothiazines

The synthesis and characterisation of a series of phenothiazines for possib le use in photochemotherapy is reported. Oxidative amination of 10H-phenoth iazine using anilines and iodine in tetrahydrofuran led to a series of 3,7- bis(arylamino)phenothiazin-5-ium salts. 4-Substituted primary anilines gave rise to a secondary amino functionality at positions 3- and 7- of the phen othiazine chromophores. The relative ease of deprotonation of these compoun ds to the corresponding quinoneimines correlated well with the electronic p roperties of the 4-substituent in the original aniline. In vitro singlet ox ygen yields for these derivatives were much lower than for the standard pho tosensitizer, methylene blue. The use of N-methylaniline did not lead to in creased photosensitizing efficacy. However, the phenothiazines resulting fr om the use of benzylamines in place of anilines were more akin to new methy lene blue N. Ail of the derivatives exhibited much greater lipophilicities than methylene blue. (C) 1999 Elsevier Science Ltd. All rights reserved.