并行固相合成阿糖腺苷抗生素类似物文库。
Parallel solution-phase synthesis of an adenosine antibiotic analog library.
机构信息
Southern Research Institute, Drug Discovery Division, Birmingham, AL 35205, USA.
出版信息
ACS Comb Sci. 2013 Mar 11;15(3):147-52. doi: 10.1021/co300127z. Epub 2013 Feb 11.
Abstract
A library of eighty one adenosine antibiotic analogs was prepared under the Pilot Scale Library Program of the NIH Roadmap initiative from 5'-amino-5'-deoxy-2',3'-O-isopropylidene-adenosine 3. Diverse aldehyde, sulfonyl chloride and carboxylic acid reactant sets were condensed to 3, in solution-phase fashion, leading after acid-mediated hydrolysis to the targeted compounds in good yields and high purity. No marked antituberculosis or anticancer activity was noted on preliminary cellular testing, but these nucleoside analogs should be useful candidates for other types of biological activity.
摘要
在 NIH 路线图计划的试点规模文库计划下，从 5'-氨基-5'-脱氧-2',3'-O-亚异丙基腺苷 3 制备了 81 种腺苷抗生素类似物文库。将各种醛、磺酰氯和羧酸反应物在溶液相中与 3 缩合，然后经酸介导水解得到目标化合物，产率高，纯度高。在初步的细胞试验中，没有观察到明显的抗结核或抗癌活性，但这些核苷类似物应该是其他类型生物活性的有用候选物。
相似文献
1
Parallel solution-phase synthesis of an adenosine antibiotic analog library.并行固相合成阿糖腺苷抗生素类似物文库。
ACS Comb Sci. 2013 Mar 11;15(3):147-52. doi: 10.1021/co300127z. Epub 2013 Feb 11.
2
Synthesis of novel peptidyl adenosine antibiotic analogs.新型肽基腺苷抗生素类似物的合成
Nucleosides Nucleotides Nucleic Acids. 2014;33(2):53-63. doi: 10.1080/15257770.2013.866243.
3
Synthesis and general biological activity of a small adenosine-5'-(carboxamide and sulfanilamide) library.一个小型腺苷 - 5'-（羧酰胺和磺胺）文库的合成及一般生物学活性
Nucleosides Nucleotides Nucleic Acids. 2014;33(11):709-29. doi: 10.1080/15257770.2014.931588.
4
Parallel solution-phase synthesis and general biological activity of a uridine antibiotic analog library.尿苷抗生素类似物文库的平行溶液相合成及一般生物学活性
ACS Comb Sci. 2014 May 12;16(5):232-7. doi: 10.1021/co4001452. Epub 2014 Apr 3.
5
Design, diversity-oriented synthesis and structure activity relationship studies of quinolinyl heterocycles as antimycobacterial agents.设计、多样性导向合成和喹啉杂环类化合物的结构活性关系研究作为抗结核药物。
Eur J Med Chem. 2013;70:536-47. doi: 10.1016/j.ejmech.2013.10.034. Epub 2013 Oct 22.
6
Discovery of novel anti-tuberculosis agents with pyrrolo[1,2-a]quinoxaline-based scaffold.基于吡咯并[1,2-a]喹喔啉骨架的新型抗结核药物的发现
Bioorg Med Chem Lett. 2018 Jun 15;28(11):2084-2090. doi: 10.1016/j.bmcl.2018.04.043. Epub 2018 May 2.
7
Inhibition of siderophore biosynthesis by 2-triazole substituted analogues of 5'-O-[N-(salicyl)sulfamoyl]adenosine: antibacterial nucleosides effective against Mycobacterium tuberculosis.5'-O-[N-(水杨酰基)氨磺酰基]腺苷的2-三唑取代类似物对铁载体生物合成的抑制作用：对结核分枝杆菌有效的抗菌核苷。
J Med Chem. 2008 Dec 11;51(23):7495-507. doi: 10.1021/jm8008037.
8
Synthesis, antitubercular and anticancer activities of substituted furyl-quinazolin-3(4H)-ones.取代呋喃基喹唑啉-3(4H)-酮的合成、抗结核及抗癌活性
Arch Pharm (Weinheim). 2007 Dec;340(12):635-41. doi: 10.1002/ardp.200700096.
9
1-Substituted-5-[(3,5-dinitrobenzyl)sulfanyl]-1H-tetrazoles and their isosteric analogs: A new class of selective antitubercular agents active against drug-susceptible and multidrug-resistant mycobacteria.1-取代-5-[(3,5-二硝基苄基)硫烷基]-1H-四唑及其等排类似物：一类新型的对药物敏感和耐多药分枝杆菌具有活性的选择性抗结核药物。
Eur J Med Chem. 2014 Jul 23;82:324-40. doi: 10.1016/j.ejmech.2014.05.069. Epub 2014 Jun 2.
10
Synthesis of some novel 2-substituted-5-[isopropylthiazole] clubbed 1,2,4-triazole and 1,3,4-oxadiazoles as potential antimicrobial and antitubercular agents.合成了一些新型的 2-取代-5-[异丙基噻唑]连接的 1,2,4-三唑和 1,3,4-恶二唑类化合物，作为潜在的抗菌和抗结核药物。
Eur J Med Chem. 2010 May;45(5):2063-74. doi: 10.1016/j.ejmech.2010.01.045. Epub 2010 Jan 28.
引用本文的文献
1
Parallel synthesis of 5'-amino-5'-deoxy-adenosine derivatives for focused chemical space exploration and their application as methyltransferase inhibitors.用于聚焦化学空间探索的5'-氨基-5'-脱氧腺苷衍生物的平行合成及其作为甲基转移酶抑制剂的应用。
RSC Med Chem. 2025 Aug 12. doi: 10.1039/d5md00376h.
2
Identification of DOT1L inhibitors by structure-based virtual screening adapted from a nucleoside-focused library.基于核苷为重点的文库的结构为基础的虚拟筛选鉴定 DOT1L 抑制剂。
Eur J Med Chem. 2020 Mar 1;189:112023. doi: 10.1016/j.ejmech.2019.112023. Epub 2020 Jan 2.
3
Solution-phase parallel synthesis of acyclic nucleoside libraries of purine, pyrimidine, and triazole acetamides.嘌呤、嘧啶和三唑乙酰胺的无环核苷文库的溶液相平行合成。
ACS Comb Sci. 2014 Sep 8;16(9):485-93. doi: 10.1021/co500067c. Epub 2014 Jun 24.
4
Parallel solution-phase synthesis and general biological activity of a uridine antibiotic analog library.尿苷抗生素类似物文库的平行溶液相合成及一般生物学活性
ACS Comb Sci. 2014 May 12;16(5):232-7. doi: 10.1021/co4001452. Epub 2014 Apr 3.
本文引用的文献
1
Small molecule inhibitors that discriminate between protein arginine N-methyltransferases PRMT1 and CARM1.区分蛋白精氨酸 N-甲基转移酶 PRMT1 和 CARM1 的小分子抑制剂。
Org Biomol Chem. 2011 Oct 26;9(22):7814-21. doi: 10.1039/c1ob06100c. Epub 2011 Sep 27.
2
Selective inhibitors of histone methyltransferase DOT1L: design, synthesis, and crystallographic studies.组蛋白甲基转移酶 DOT1L 的选择性抑制剂：设计、合成与晶体学研究。
J Am Chem Soc. 2011 Oct 26;133(42):16746-9. doi: 10.1021/ja206312b. Epub 2011 Oct 4.
3
Cofactor-type inhibitors of inosine monophosphate dehydrogenase via modular approach: targeting the pyrophosphate binding sub-domain.通过模块化方法设计肌苷单磷酸脱氢酶的辅助因子型抑制剂：靶向焦磷酸结合亚结构域。
Bioorg Med Chem. 2011 Mar 1;19(5):1594-605. doi: 10.1016/j.bmc.2011.01.042. Epub 2011 Jan 27.
4
Development of novel bisubstrate-type inhibitors of histone methyltransferase SET7/9.新型组蛋白甲基转移酶 SET7/9 的双底物型抑制剂的开发。
Bioorg Med Chem. 2010 Dec 1;18(23):8158-66. doi: 10.1016/j.bmc.2010.10.022. Epub 2010 Oct 14.
5
Toward the development of potent and selective bisubstrate inhibitors of protein arginine methyltransferases.针对开发强效和选择性的双底物蛋白精氨酸甲基转移酶抑制剂。
Bioorg Med Chem Lett. 2010 Apr 1;20(7):2103-5. doi: 10.1016/j.bmcl.2010.02.069. Epub 2010 Feb 20.
6
High-throughput screening for inhibitors of Mycobacterium tuberculosis H37Rv.结核分枝杆菌 H37Rv 抑制剂的高通量筛选。
Tuberculosis (Edinb). 2009 Sep;89(5):334-53. doi: 10.1016/j.tube.2009.05.008. Epub 2009 Sep 15.
7
New S-adenosyl-L-methionine analogues: synthesis and reactivity studies.新型S-腺苷-L-甲硫氨酸类似物：合成与反应性研究
Org Lett. 2009 Jul 16;11(14):2976-9. doi: 10.1021/ol9009859.
8
Pyrimidine as constituent of natural biologically active compounds.嘧啶作为天然生物活性化合物的组成成分。
Chem Biodivers. 2005 Jan;2(1):1-50. doi: 10.1002/cbdv.200490173.
9
The chemodiversity of purine as a constituent of natural products.作为天然产物成分的嘌呤的化学多样性。
Chem Biodivers. 2004 Mar;1(3):361-401. doi: 10.1002/cbdv.200490033.
10
Conjugation of adenosine and hexa-(D-arginine) leads to a nanomolar bisubstrate-analog inhibitor of basophilic protein kinases.腺苷与六聚（D - 精氨酸）的缀合产生了一种纳摩尔级的嗜碱性蛋白激酶双底物类似物抑制剂。
J Med Chem. 2006 Nov 30;49(24):7150-9. doi: 10.1021/jm0605942.
Zotero 插件