Synthesis and photobiological activity of N,N-disubstituted 4-amino-3-chloro-2H-thieno[2,3-h]-1-benzopyran-2-ones, 7-thioisosteres of 4-amino-3-chloroangelicins.
A convenient synthesis of a series of N,N-disubstituted 4-amino-3-chloro-2H-thieno[2,3-h]-1-benzopyran-2-ones (IV), which are 7-thioisosteres of 4-amino-3-chloroangelicins, was accomplished via dehydrochlorination and dehydrogenation of the 1,4-cycloadducts obtained by reaction of dichloroketene with N,N-disubstituted (E)-5-aminomethylene-6,7-dihydrobenzo-[b]thiophen-4(5H)-ones . Some aspects of the photobiological activity of these thioangelicins were studied; three of them (IV a, e, f) appeared to inhibit DNA synthesis in Ehrlich ascites tumor cells. The most active compound, namely 3-chloro-4-morpholino-7-thioangelicin (IV e), afforded 70% of the antiproliferative effect of 8-MOP, but unlike this reference compound was unable to induce erythema on guinea pig skin. However, compounds (IV a, f) produced a slight erythema, thus suggesting that a relationship between antiproliferative and phototoxic effects does not exist.
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D004273:DNA, Neoplasm / Q000096:biosynthesis; D011564:Furocoumarins; D006801:Humans; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010787:Photosensitivity Disorders / Q000139:chemically induced; D012867:Skin / Q000187:drug effects; D013055:Spectrophotometry, Infrared; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
D004273:DNA, Neoplasm; D011564:Furocoumarins; D013876:Thiophenes