Development of sulfonamide compounds as potent methionine aminopeptidase type II inhibitors with antiproliferative properties

作者：Kawai M^*; BaMaung NY; Fidanze SD; Erickson SA; Tedrow JS; Sanders WJ; Vasudevan A; Park C; Hutchins C; Comess KM; Kalvin D; Wang J; Zhang Q; Lou P; Tucker Garcia L; Bouska J; Bell RL; Lesniewski R; Henkin J; Sheppard GS

来源：Bioorganic & Medicinal Chemistry Letters, 2006, 16(13): 3574-3577.

DOI：10.1016/j.bmcl.2006.03.085

• MetAP2
• sulfonamide
• antiproliferative

We have screened molecules for inhibition of MetAP2 as a novel approach toward antiangiogenesis and anticancer therapy using affinity selection/mass spectrometry (ASMS) employing MetAP2 loaded with Mn2+ as the active site metal. After a series of anthranilic acid sulfonamides with micromolar affinities was identified, chemistry efforts were initiated. The micromolar hits were quickly improved to potent nanomolar inhibitors by chemical modifications guided by insights from X-ray crystallography.

• 出版日期2006-7-1