Enantioselective synthesis and biological evaluation of 5-o-carboranyl pyrimidine nucleosides.
Enantioselective synthesis and biological evaluation of 5-o-carboranyl pyrimidine nucleosides.
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5-o-碳硼烷基嘧啶核苷的对映选择性合成和生物学评价。
DOI：
10.1016/s0968-0896(99)00222-9
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发表时间：
1999
影响因子：
3.5
通讯作者：
Schinazi,RF
中科院分区：
文献类型：
--
作者：
Mourier,NS;Eleuteri,A;Hurwitz,SJ;Tharnish,PM;Schinazi,RF
碱基修饰的含碳硼烷的核苷如5-O-碳硼烷基-2 ′-脱氧尿苷（CDU）与中子结合时具有治疗某些恶性肿瘤的潜力。在各种细胞中缺乏毒性、在癌细胞中高积累和细胞内磷酸化是用于脑肿瘤和其他恶性肿瘤的硼中子捕获疗法（BNCT）的修饰核苷的期望特征。本工作的目的是合成几种5-O-碳硼烷核苷的两种β-对映体。这些衍生物可能具有有利的性质，如高亲脂性、高转运性、磷酸化能力和对catalysts的抗性。还合成了2′，3 ′-二羟基核苷的β-异构体和糖基中含有杂原子的类似物。碳硼烷基嘧啶核苷由母体β-d-核苷、β-l-核苷或通过偶联反应制备。二氧戊环衍生物7是通过保护的5-O-碳硼烷基尿嘧啶（8，CU）与相应的保护杂环之间的偶联反应制备的。在N-糖基化过程中使用特定催化剂以促进β-异构体的形成。这些新的手性5-O-碳硼烷基嘧啶衍生物的生物学评价表明，这些化合物中的大多数在各种正常和恶性细胞中具有低毒性，并在淋巴母细胞系中达到高细胞水平。增加糖基上羟基的数量，不同程度地降低了细胞蓄积和血清结合。确定了五种化合物作为BNCT的潜在药物进行进一步的生物学评价。
Base-modified carborane-containing nucleosides such as 5-o-carboranyl-2′-deoxyuridine (CDU) when combined with neutrons have potential for the treatment of certain malignancies. Lack of toxicity in various cells, high accumulation in cancer cells and intracellular phosphorylation are desirable characteristics for modified nucleosides used in boron neutron capture therapy (BNCT) for brain tumors and other malignancies. The aim of this work was to synthesize the two β-enantiomers of several 5-o-carboranyl-containing nucleosides. These derivatives may possess favorable properties such as high lipophilicity, high transportability, the ability to be phosphorylated, and resistance to catabolism. β-Isomers of 2′,3′-dihydroxynucleosides and analogues containing a heteroatom in the sugar moiety were also synthesized. Carboranyl pyrimidine nucleosides were prepared either from the parent β-d-nucleoside, β-l-nucleoside, or by a coupling reaction. The dioxolane derivative 7 was prepared by a coupling reaction between protected 5-o-carboranyluracil (8, CU) and the corresponding protected heterocycle. Specific catalysts were used during the N-glycosylation process to favor the formation of the β-isomer. Biological evaluation of these new chiral 5-o-carboranyl pyrimidine derivatives indicated that most of these compounds have low toxicity in a variety of normal and malignant cells and achieved high cellular levels in a lymphoblastoid cell line. Increasing the number of hydroxyl groups on the sugar moiety decreased the cellular accumulation and serum binding to different extents. Five compounds were identified for further biological evaluation as potential agents for BNCT.
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2,3-二脱氢-2,3-双脱氧-5-氟胞苷 (D4FC) 类似物的合成和生物学评价：发现对 HIV-1 逆转录酶具有有效抑制活性的碳环核苷三磷酸。
影响因子：
7.3
作者：
Shi,J;McAtee,JJ;SchlueterWirtz,S;Tharnish,P;Juodawlkis,A;Liotta,DC;Schinazi,RF
通讯作者：
Schinazi,RF
2-脱氧-L-尿苷的合成。
影响因子：
1.8
作者：
A. Holý
通讯作者：
A. Holý
DOI：
10.1016/0360-3016(91)90705-9
发表时间：
1991-08-01
影响因子：
7
作者：
HARARI, PM;HYNYNEN, KH;CASSADY, JR
通讯作者：
CASSADY, JR
5-邻碳硼基-2,3-二脱氢-2,3-二脱氧尿苷四种光学异构体的合成和生物学性质。
DOI：
10.1080/07328319808004670
发表时间：
1998
期刊：
Nucleosides & nucleotides.
影响因子：
--
作者：
Graciet,JC;Shi,J;Schinazi,RF
通讯作者：
Schinazi,RF
影响因子：
15
作者：
FULCRANDELKATTAN, G;LESNIKOWSKI, ZJ;SCHINAZI, RF
通讯作者：
SCHINAZI, RF