title: Synthesis and antineoplastic activity of 5-aryl-2,3-dihydropyrrolo[2,1-b]thiazole-6,7-dimethanol 6,7-bis(isopropylcarbamates).
abstract: A series of 1-thia analogues of the pyrrolizine bis(carbamate) 9 (NSC-278214), namely 5-aryl-2,3-dihydropyrrolo-[2,1-b]thiazole-6,7-dimethanol 6,7-bis(isopropylcarbamates) (7a-d), were prepared by multistep syntheses from the proline analogue thiazolidine-2-carboxylic acid. The compounds were tested for growth inhibitory activity with the HL-60 human promyelocytic leukemia cell line. Three of the compounds had antileukemic activity equal to that of 9, while a 4-chlorophenyl analogue was approximately 75% more potent. A simple aromatic derivative, 1,2-benzenedimethanol 1,2-bis(isopropylcarbamate) (8), had no activity in this system. Antitumor activity was also tested in a colony formation assay with HT-29 human colon carcinoma cells. Compounds 7a-d reduced relative cell survival by over 3 logs at a concentration of 300 microM (2-h exposure), while a comparable inhibition was observed with 150 microM 9. Hence compounds 7a-d retain significant antineoplastic activity.
authors.affiliation: Department of Anesthesiology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York 10467.
authors.forename: I
authors.initials: I
authors.lastname: Lalezari
authors.forename: E L
authors.initials: EL
authors.lastname: Schwartz
mesh_terms: D002219:Carbamates / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
chemical_list: D002219:Carbamates; D011758:Pyrroles; D013844:Thiazoles