Parallel solution-phase synthesis and general biological activity of a uridine antibiotic analog library.
Parallel solution-phase synthesis and general biological activity of a uridine antibiotic analog library.
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尿苷抗生素模拟文库的平行溶液相合成和一般生物学活性。
DOI：
10.1021/co4001452
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发表时间：
2014-05-12
影响因子：
--
通讯作者：
Reynolds, Robert C.
中科院分区：
文献类型：
--
作者：
Moukha-Chafiq, Omar;Reynolds, Robert C.
在NIH路线图倡议的中试规模文库（PSL）计划下，以溶液相方式从胺2和羧酸33和77合成94个尿苷抗生素类似物的小文库。将不同的醛、磺酰氯和羧酸反应物组缩合成2，在酸介导的水解后，以良好的产率和高纯度得到目标化合物3-32。同样，用不同的胺和磺酰胺处理33得到34-75。将d-苯丙氨酸甲酯的氨基末端与33的游离5′-羧酸部分偶联，然后用氢氧化钠处理，得到羧酸类似物77。该材料的水解得到类似物78。中间体77用作通过与不同胺反应物的肽偶联反应制备新型二肽基尿苷类似物79-99的前体。所述化合物均未显示出显著的抗癌或抗疟疾活性。在NIH MLPCN计划提供和报告的初步筛选中，许多样品显示出各种有希望的酶和受体抑制、激动剂、拮抗剂或激活剂特性。
A small library of ninety four uridine antibiotic analogs was synthesized, under the Pilot Scale Library (PSL) Program of the NIH Roadmap initiative, from amine 2 and carboxylic acids 33 and 77 in solution-phase fashion. Diverse aldehyde, sulfonyl chloride, and carboxylic acid reactant sets were condensed to 2, leading after acid-mediated hydrolysis, to the targeted compounds 3–32 in good yields and high purity. Similarly, treatment of 33 with diverse amines and sulfonamides gave 34–75. The coupling of the amino terminus of d-phenylalanine methyl ester to the free 5′-carboxylic acid moiety of 33 followed by sodium hydroxide treatment led to carboxylic acid analog 77. Hydrolysis of this material gave analog 78. The intermediate 77 served as the precursor for the preparation of novel dipeptidyl uridine analogs 79–99 through peptide coupling reactions to diverse amine reactants. None of the described compounds show significant anticancer or antimalarial acivity. A number of samples exhibited a variety of promising inhibitory, agonist, antagonist, or activator properties with enzymes and receptors in primary screens supplied and reported through the NIH MLPCN program.
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影响因子：
15
作者：
ISONO, K;ASAHI, K;SUZUKI, S
通讯作者：
SUZUKI, S
影响因子：
2.1
作者：
Sawa, Nobuya;Wada, Takehiko;Inoue, Yoshihisa
通讯作者：
Inoue, Yoshihisa
影响因子：
1.3
作者：
Timoshchuk, Victor A.;Hogrefe, Richard I.
通讯作者：
Hogrefe, Richard I.
影响因子：
3.2
作者：
Valade, Anne;Urban, Dominique;Beau, Jean-Marie
通讯作者：
Beau, Jean-Marie
影响因子：
3.5
作者：
Vembaiyan, Kannan;Pearcey, Jean A.;Zou, Wei
通讯作者：
Zou, Wei