Structural-based design and synthesis of novel 9-deazaguanine derivatives having a phosphate mimic as multi-substrate analogue inhibitors for mammalian PNPs
Structural-based design and synthesis of novel 9-deazaguanine derivatives having a phosphate mimic as multi-substrate analogue inhibitors for mammalian PNPs
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DOI：
10.1016/j.bmc.2010.01.062
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发表时间：
2010-03-15
影响因子：
3.5
通讯作者：
Yokomatsu, Tsutomu
中科院分区：
文献类型：
--
作者：
Hikishima, Sadao;Hashimoto, Mariko;Yokomatsu, Tsutomu
根据9-（5′，5′-二氟-5′-磷戊基）鸟嘌呤（DFPP-G）与小牛脾脏PNP二元配合物的x射线晶体学数据，设计9-（5′，5′-二氟-5′-磷戊基）-9-去氮鸟嘌呤核苷磷酸化酶（PNP）的多底物类似抑制剂。以9-二氮杂-9-碘鸟嘌呤衍生物和ω -炔基二氟亚甲基膦酸盐为关键反应，通过Sonogashira偶联反应合成了dppp - dg及其类似化合物。实验细节集中在合成化学以及新合成的DFPP-DG衍生物的物理和生物特性的一些见解。(C) 2010 Elsevier Ltd.版权所有。
9-(5',5'-Difluoro-5'-phosphonopentyl)-9-deazaguanine (DFPP-DG) was designed as a multi-substrate analogue inhibitor against purine nucleoside phosphorylase (PNP) on the basis of X-ray crystallographic data obtained for a binary complex of 9-(5',5'-difluoro-5'-phosphonopentyl)guanine (DFPP-G) with calf-spleen PNP. DFPP-DG and its analogous compounds were synthesized by the Sonogashira coupling reaction between a 9-deaza-9-iodoguanine derivative and omega-alkynyldifluoromethylene phosphonates as a key reaction. The experimental details focused on the synthetic chemistry along with some insights into the physical and biological properties of newly synthesized DFPP-DG derivatives are disclosed. (C) 2010 Elsevier Ltd. All rights reserved.