Thalidomide metabolites and analogues. 3. Synthesis and antiangiogenic activity of the teratogenic and TNFα-modulatory thalidomide analogue 2-(2,6-dioxopiperidine-3-yl)phthalimidine

Frederick A. Luzzio; Alexander V. Mayorov; Sylvia S.W. Ng; Erwin A. Kruger; William D. Figg

doi:10.1021/jm020079d

Thalidomide metabolites and analogues. 3. Synthesis and antiangiogenic activity of the teratogenic and TNFα-modulatory thalidomide analogue 2-(2,6-dioxopiperidine-3-yl)phthalimidine

Frederick A. Luzzio^*, Alexander V. Mayorov, Sylvia S.W. Ng, Erwin A. Kruger, William D. Figg

^*Corresponding author for this work

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

61 Scopus citations

Abstract

Versatile synthesis of the teratogenic, TNFα-modulatory, and antiangiogenic thalidomide analogue 2-(2,6-dioxopiperidine-3-yl)phthalimidine (1) and its direct antiangiogenic properties are described. With thalidomide or thalidomide derivatives as precursors, the synthesis involved either carbonyl reduction/thiation-desulfurization or carbonyl reduction/acyliminium ion reduction protocols. Compared to earlier studies with thalidomide, which was only active with microsomal treatment, 1 exhibited marginal inhibitory activity in the rat aortic ring assay, thereby demonstrating the requirement for metabolic activation.

Original language	English
Pages (from-to)	3793-3799
Number of pages	7
Journal	Journal of Medicinal Chemistry
Volume	46
Issue number	18
DOIs	https://doi.org/10.1021/jm020079d
State	Published - Aug 2003
Externally published	Yes

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title = "Thalidomide metabolites and analogues. 3. Synthesis and antiangiogenic activity of the teratogenic and TNFα-modulatory thalidomide analogue 2-(2,6-dioxopiperidine-3-yl)phthalimidine",

abstract = "Versatile synthesis of the teratogenic, TNFα-modulatory, and antiangiogenic thalidomide analogue 2-(2,6-dioxopiperidine-3-yl)phthalimidine (1) and its direct antiangiogenic properties are described. With thalidomide or thalidomide derivatives as precursors, the synthesis involved either carbonyl reduction/thiation-desulfurization or carbonyl reduction/acyliminium ion reduction protocols. Compared to earlier studies with thalidomide, which was only active with microsomal treatment, 1 exhibited marginal inhibitory activity in the rat aortic ring assay, thereby demonstrating the requirement for metabolic activation.",

author = "Luzzio, {Frederick A.} and Mayorov, {Alexander V.} and Ng, {Sylvia S.W.} and Kruger, {Erwin A.} and Figg, {William D.}",

year = "2003",

month = aug,

doi = "10.1021/jm020079d",

language = "English",

volume = "46",

pages = "3793--3799",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "18",

}

Thalidomide metabolites and analogues. 3. Synthesis and antiangiogenic activity of the teratogenic and TNFα-modulatory thalidomide analogue 2-(2,6-dioxopiperidine-3-yl)phthalimidine. / Luzzio, Frederick A.; Mayorov, Alexander V.; Ng, Sylvia S.W. et al.
In: Journal of Medicinal Chemistry, Vol. 46, No. 18, 08.2003, p. 3793-3799.

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

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T1 - Thalidomide metabolites and analogues. 3. Synthesis and antiangiogenic activity of the teratogenic and TNFα-modulatory thalidomide analogue 2-(2,6-dioxopiperidine-3-yl)phthalimidine

AU - Luzzio, Frederick A.

AU - Mayorov, Alexander V.

AU - Ng, Sylvia S.W.

AU - Kruger, Erwin A.

AU - Figg, William D.

PY - 2003/8

Y1 - 2003/8

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AB - Versatile synthesis of the teratogenic, TNFα-modulatory, and antiangiogenic thalidomide analogue 2-(2,6-dioxopiperidine-3-yl)phthalimidine (1) and its direct antiangiogenic properties are described. With thalidomide or thalidomide derivatives as precursors, the synthesis involved either carbonyl reduction/thiation-desulfurization or carbonyl reduction/acyliminium ion reduction protocols. Compared to earlier studies with thalidomide, which was only active with microsomal treatment, 1 exhibited marginal inhibitory activity in the rat aortic ring assay, thereby demonstrating the requirement for metabolic activation.

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Thalidomide metabolites and analogues. 3. Synthesis and antiangiogenic activity of the teratogenic and TNFα-modulatory thalidomide analogue 2-(2,6-dioxopiperidine-3-yl)phthalimidine

Abstract

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