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Literature DB >> 25150376

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

Thangaiah Subramanian¹, Hongmei Ren², Karunai Leela Subramanian², Manjula Sunkara², Fredrick O Onono¹, Andrew J Morris³, H Peter Spielmann⁴.

Abstract

An efficient, diversity oriented synthesis of homoisoprenoid α-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 α-monofluoromethylene moiety.

Entities: Chemical Disease Gene Species

Keywords: Farnesyl diphosphate; Isoprenol; Mevalonate pathway; Phosphatase inhibitor; Phosphonate

Mesh：

Substances：

Year: 2014 PMID： 25150376 PMCID： PMC4206410 DOI： 10.1016/j.bmcl.2014.08.013

Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823

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References

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

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Review 2. Regulation of the mevalonate pathway.

Review 3. Sterols and isoprenoids: signaling molecules derived from the cholesterol biosynthetic pathway.

Review 4. The contribution of the cholesterol biosynthetic pathway to intermediary metabolism and cell function.

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10. Lipid phosphate phosphatases regulate lysophosphatidic acid production and signaling in platelets: studies using chemical inhibitors of lipid phosphate phosphatase activity.