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生物活性核苷膦酸盐概述

Overview of Biologically Active Nucleoside Phosphonates.

作者信息

Groaz Elisabetta, De Jonghe Steven

机构信息

Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.

Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.

出版信息

Front Chem. 2021 Jan 8;8:616863. doi: 10.3389/fchem.2020.616863. eCollection 2020.

DOI:10.3389/fchem.2020.616863
PMID:33490040
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7821050/
Abstract

The use of the phosphonate motif featuring a carbon-phosphorous bond as bioisosteric replacement of the labile P-O bond is widely recognized as an attractive structural concept in different areas of medicinal chemistry, since it addresses the very fundamental principles of enzymatic stability and minimized metabolic activation. This review discusses the most influential successes in drug design with special emphasis on nucleoside phosphonates and their prodrugs as antiviral and cancer treatment agents. A description of structurally related analogs able to interfere with the transmission of other infectious diseases caused by pathogens like bacteria and parasites will then follow. Finally, molecules acting as agonists/antagonists of P2X and P2Y receptors along with nucleotidase inhibitors will also be covered. This review aims to guide readers through the fundamentals of nucleoside phosphonate therapeutics in order to inspire the future design of molecules to target infections that are refractory to currently available therapeutic options.

摘要

使用具有碳 - 磷键的膦酸酯基序作为不稳定的磷 - 氧键的生物电子等排体替代物，在药物化学的不同领域被广泛认为是一个有吸引力的结构概念，因为它涉及酶稳定性和最小化代谢活化的基本原理。本综述讨论了药物设计中最具影响力的成功案例，特别强调核苷膦酸酯及其前药作为抗病毒和癌症治疗药物。随后将描述能够干扰由细菌和寄生虫等病原体引起的其他传染病传播的结构相关类似物。最后，还将涵盖作为P2X和P2Y受体激动剂/拮抗剂的分子以及核苷酸酶抑制剂。本综述旨在引导读者了解核苷膦酸酯治疗的基本原理，以激发未来针对目前可用治疗方案难以治疗的感染设计分子。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0898/7821050/3d8e0dcb3366/fchem-08-616863-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0898/7821050/42c6740c0f8e/fchem-08-616863-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0898/7821050/875eabaa9e2a/fchem-08-616863-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0898/7821050/cc72d69dcfb9/fchem-08-616863-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0898/7821050/4eee5eeb744e/fchem-08-616863-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0898/7821050/c4235ec0e93b/fchem-08-616863-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0898/7821050/fbe37c3f6cf6/fchem-08-616863-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0898/7821050/7fbc80e364d0/fchem-08-616863-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0898/7821050/ae35752e57ea/fchem-08-616863-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0898/7821050/124d628fea38/fchem-08-616863-g0011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0898/7821050/da89d1e2785d/fchem-08-616863-g0013.jpg

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