TY - JOUR
T1 - Synthesis and Antineoplastic Activity of 5-aryl-2,3-dihydropyrrolo[2,1-b]thiazole-6,7-dimethanol 6,7-Bis(isopropylcarbamates)
AU - Lalezari, Iraj
AU - Schwartz, Edward L.
PY - 1988/7/1
Y1 - 1988/7/1
N2 - 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 μM (2-h exposure), while a comparable inhibition was observed with 150 μ 9. Hence compounds 7a-d retain significant antineoplastic activity.
AB - 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 μM (2-h exposure), while a comparable inhibition was observed with 150 μ 9. Hence compounds 7a-d retain significant antineoplastic activity.
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U2 - 10.1021/jm00402a030
DO - 10.1021/jm00402a030
M3 - Article
C2 - 3164410
AN - SCOPUS:0023785369
SN - 0022-2623
VL - 31
SP - 1427
EP - 1429
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 7
ER -