ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Richard G. Wilde; Jeffrey T. Billheimer; Sandie J. Germain; Elizabeth A. Hausner; Paul C. Meunier; Deborah A. Munzer; Janet K. Stoltenborg; Peter J. Gillies; Deborah L. Burcham; Shiew Mai Huang; John D. Klaczkiewicz; Soo S. Ko; Ruth R. Wexler

doi:10.1016/0968-0896(96)00143-5

ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Richard G. Wilde, Jeffrey T. Billheimer, Sandie J. Germain, Elizabeth A. Hausner, Paul C. Meunier, Deborah A. Munzer, Janet K. Stoltenborg, Peter J. Gillies, Deborah L. Burcham, Shiew Mai Huang, John D. Klaczkiewicz, Soo S. Ko, Ruth R. Wexler

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesteror esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.

Original language	American English
Pages (from-to)	1493-1513
Number of pages	21
Journal	Bioorganic and Medicinal Chemistry
Volume	4
Issue number	9
DOIs	https://doi.org/10.1016/0968-0896(96)00143-5
State	Published - 1996
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Keywords

Acyl-CoA:cholesterol
Acyltransferase
Atherosclerosis
Cycloaddition
thioaldehyde

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10.1016/0968-0896(96)00143-5

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Wilde, R. G., Billheimer, J. T., Germain, S. J., Hausner, E. A., Meunier, P. C., Munzer, D. A., Stoltenborg, J. K., Gillies, P. J., Burcham, D. L., Huang, S. M., Klaczkiewicz, J. D., Ko, S. S., & Wexler, R. R. (1996). ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes. Bioorganic and Medicinal Chemistry, 4(9), 1493-1513. https://doi.org/10.1016/0968-0896(96)00143-5

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title = "ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes",

abstract = "Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesteror esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.",

keywords = "Acyl-CoA:cholesterol, Acyltransferase, Atherosclerosis, Cycloaddition, thioaldehyde",

author = "Wilde, {Richard G.} and Billheimer, {Jeffrey T.} and Germain, {Sandie J.} and Hausner, {Elizabeth A.} and Meunier, {Paul C.} and Munzer, {Deborah A.} and Stoltenborg, {Janet K.} and Gillies, {Peter J.} and Burcham, {Deborah L.} and Huang, {Shiew Mai} and Klaczkiewicz, {John D.} and Ko, {Soo S.} and Wexler, {Ruth R.}",

year = "1996",

doi = "10.1016/0968-0896(96)00143-5",

language = "American English",

volume = "4",

pages = "1493--1513",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

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TY - JOUR

T1 - ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

AU - Wilde, Richard G.

AU - Billheimer, Jeffrey T.

AU - Germain, Sandie J.

AU - Hausner, Elizabeth A.

AU - Meunier, Paul C.

AU - Munzer, Deborah A.

AU - Stoltenborg, Janet K.

AU - Gillies, Peter J.

AU - Burcham, Deborah L.

AU - Huang, Shiew Mai

AU - Klaczkiewicz, John D.

AU - Ko, Soo S.

AU - Wexler, Ruth R.

PY - 1996

Y1 - 1996

N2 - Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesteror esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.

AB - Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesteror esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.

KW - Acyl-CoA:cholesterol

KW - Acyltransferase

KW - Atherosclerosis

KW - Cycloaddition

KW - thioaldehyde

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U2 - 10.1016/0968-0896(96)00143-5

DO - 10.1016/0968-0896(96)00143-5

M3 - Article

C2 - 8894107

SN - 0968-0896

VL - 4

SP - 1493

EP - 1513

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 9

ER -

ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Abstract

ASJC Scopus subject areas

Keywords

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