222713-07-7Relevant articles and documents
A synthesis of racemic thalidomide
Chang, Meng-Yang,Chen, Shui-Tein,Chang, Nein-Chen
, p. 1375 - 1382 (2003)
A synthesis of racemic thalidomide is described using formal [3+3] cycloaddition strategy as the key step. The total yield of thalidomide was 30% in three steps from ester 2.
Synthesis and biological evaluation of thalidomide derivatives as potential anti-psoriasis agents
Tang, Kai-Wei,Tseng, Chih-Hua,Lin, Zih-Chan,Fang, Jia-You,Chen, Yeh-Long,Tzeng, Cherng-Chyi
, (2018/12/02)
Several thalidomide derivatives were synthesized and evaluated for their anti-inflammatory activity. Introduction of the benzyl group to the parent thalidomide is unfavorable in which 2-(1-benzyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (4a) was inactivated. However, the inhibitory activities on TNF-α and IL-6 expression in HaCaT cells were improved by the substitution of a chloro-or methoxy-group at the phenyl position of 4a. The IL-6 inhibitory activity decreased in an order of 5c (69.44%) > 4c (48.73%) > 6c (3.19%) indicating the 3-substituted derivative is more active than the 4-substituted counterpart, which in turn is more active than the 2-substituted counterpart. Among them, 2-[1-(3-chlorobenzyl)-2,6-dioxopiperidin-3-yl]isoindoline-1,3-dione (5c) was found to inhibit TNF-α and IL-6 expression in HaCaT cells with a higher potency than thalidomide and no significant cell cytotoxicity was detected at 10 μM. In psoriasis, Compound 5c reduced IL-6, IL-8, IL-1β and IL-24 in imiquimod-stimulated models. Our results indicated that compound 5c is a potential lead of novel anti-psoriasis agents. Structural optimization of compound 5c and its in vivo assay are ongoing.
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.,Kruger, Erwin A.,Figg, William D.
, p. 3793 - 3799 (2007/10/03)
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.
A synthesis of thalidomide
Chang, Meng-Yang,Chang, Chung-Ho,Chen, Shui-Tein,Chang, Nein-Chen
, p. 383 - 385 (2007/10/03)
A synthesis of racemic thalidomide (1) was described and the important formal [3+3] cycloaddition strategy was a key step. The total yield of thalidomide (1) was 18% in five steps from known 3.
