TY - JOUR
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
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=0042921615&partnerID=8YFLogxK
U2 - 10.1021/jm020079d
DO - 10.1021/jm020079d
M3 - Article
C2 - 12930142
AN - SCOPUS:0042921615
SN - 0022-2623
VL - 46
SP - 3793
EP - 3799
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 18
ER -