Synthesis and antineoplastic activity of 5-aryl-2,3-dihydropyrrolo[2,1-b]thiazole-6,7-dimethanol 6,7-bis(isopropylcarbamates)

Iraj Lalezari, Edward L. Schwartz

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

A series of 1-thia analogues of the pyrrolizine bis(carbamate) 9 (NSC-278214), namely 5-aryl-2,3-dihydropyrrolo-[2,1-6]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 μM 9. Hence compounds 7a-d retain significant antineoplastic activity.

Original languageEnglish (US)
Pages (from-to)1427-1429
Number of pages3
JournalJournal of Medicinal Chemistry
Volume31
Issue number7
StatePublished - 1988

Fingerprint

Thiazoles
Antineoplastic Agents
Cells
Carbamates
Proline
Cell Survival
Colon
Leukemia
Carcinoma
Cell Line
Assays
Growth
Derivatives
thiazolidine-2-carboxylic acid

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

@article{2257d87a5c9f43398dbf2fd9b81aec47,
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-[2,1-6]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 μM 9. Hence compounds 7a-d retain significant antineoplastic activity.",
author = "Iraj Lalezari and Schwartz, {Edward L.}",
year = "1988",
language = "English (US)",
volume = "31",
pages = "1427--1429",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "7",

}

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

Y1 - 1988

N2 - A series of 1-thia analogues of the pyrrolizine bis(carbamate) 9 (NSC-278214), namely 5-aryl-2,3-dihydropyrrolo-[2,1-6]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 μM 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-[2,1-6]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 μM 9. Hence compounds 7a-d retain significant antineoplastic activity.

UR - http://www.scopus.com/inward/record.url?scp=0023785369&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023785369&partnerID=8YFLogxK

M3 - Article

VL - 31

SP - 1427

EP - 1429

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 7

ER -