Antiparasitic activities of novel, orally available fumagillin analogs

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:19

Article

Arico-Muendel, Christopher¹  Centrella, Paolo A.¹  Contonio, Brooke D.¹  Morgan, Barry A.¹  O'Donovan, Gary¹  Paradise, Christopher L.¹  Skinner, Steven R.¹  Sluboski, Barbara¹  Svendsen, Jennifer L.¹  White, Kerry F.¹  Debnath, Anjan²  Gut, Jiri²  Wilson, Nathan²  McKerrow, James H.²  DeRisi, Joseph L.²  Rosenthal, Philip J.²  Chiang, Peter K.³ 

[1] Praecis Pharmaceut, Waltham, MA 02451 USA

[2] Univ Calif San Francisco, San Francisco, CA 94158 USA

[3] Pharmadyn Inc, Sunnyvale, CA 94085 USA

关键词: MetAP2;    Fumagillin;    TNP-470;    Antiparasitic;    Malaria;    Trypanosomes;    Amoeba;    PPI-2458;   

DOI  :  10.1016/j.bmcl.2009.07.029

来源: Elsevier

【 摘 要 】

Fumagillin, an irreversible inhibitor of MetAP2, has been shown to potently inhibit growth of malaria parasites in vitro. Here, we demonstrate activity of fumagillin analogs with an improved pharmacokinetic profile against malaria parasites, trypanosomes, and amoebas. A subset of the compounds showed efficacy in a murine malaria model. The observed SAR forms a basis for further optimization of fumagillin based inhibitors against parasitic targets by inhibition of MetAP2. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

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