222713-09-9Relevant articles and documents
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 facile scheme for phthalimide ? phthalimidine conversion
Luzzio, Frederick A.,Piatt Zacherl, DeAnna,Figg, William D.
, p. 2087 - 2090 (2007/10/03)
Desulfurization of phenylthiolactams using an ultrasound-promoted Raney nickel protocol yields the corresponding N-substituted phthalimidines. Benzylic oxidation of the N-substituted phthalimidines by treatment with 2,2'-bipyridinium chlorochromate/m-chloroperbenzoic acid (BPCC/MCPBA) affords the original phthalimides. The reduction-desulfurization is applied to the preparation of a deoxythalidomide derivative which is a TNF-α inhibitor.
