Design and synthesis of non-hydrolyzable homoisoprenoid α-monofluorophosphonate inhibitors of PPAPDC family integral membrane lipid phosphatases

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:24

Article

Subramanian, Thangaiah¹  Ren, Hongmei²  Subramanian, Karunai Leela²  Sunkara, Manjula²  Onono, Fredrick O.¹  Morris, Andrew J.^2,3  Spielmann, H. Peter^1,4,5,6 

[1] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA

[2] Univ Kentucky, Div Cardiovasc Med, UK COM, Lexington, KY 40536 USA

[3] Univ Kentucky, Lexington Vet Affairs Med Ctr, Lexington, KY 40536 USA

[4] Univ Kentucky, Lucille P Markey Canc Ctr, Lexington, KY 40536 USA

[5] Univ Kentucky, Kentucky Ctr Struct Biol, Lexington, KY 40536 USA

[6] Univ Kentucky, Dept Chem, Lexington, KY 40536 USA

关键词: Farnesyl diphosphate;    Phosphonate;    Phosphatase inhibitor;    Mevalonate pathway;    Isoprenol;   

DOI  :  10.1016/j.bmcl.2014.08.013

来源: Elsevier

【 摘 要 】

An efficient, diversity oriented synthesis of homoisoprenoid alpha-monofluorophosphonates utilizing electrophilic fluorination is presented along with their activity as inhibitors of PPAPDC2 family integral membrane lipid phosphatases. These novel phosphatase-resistant analogues of isoprenoid monophosphates are a platform for further structure-activity relationship studies and provide access to other isoprenoid family members where the phosphate ester oxygen is replaced by a alpha-monofluoromethylene moiety. (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

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