ethyl 2-amino-4-cyclopentylthiophene-3-carboxylate | 1248980-12-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: ethyl 2-amino-4-cyclopentylthiophene-3-carboxylate
• CAS: 1248980-12-2
• 化学式: C₁₂H₁₇NO₂S
• 分子量: 239.338
• InChiKey: QPNUFNCRXZXKBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-amino-4-cyclopentylthiophene-3-carboxylate 在 lithium hydroxide monohydrate 、 chloro(2-dicyclohexylphosphino-2’,6’-diisopropoxy-1,1’-biphenyl)[2-(2’-amino-1,1‘-biphenyl)]palladium(II) 2nd generation 、 水 、 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 4-cyclopentyl-2-[(4-morpholinobenzoyl)amino]thiophene-3-carboxylic acid
  参考文献：
  名称：

  [EN] NON-FUSED THIOPHENE DERIVATIVES AND THEIR USES
  [FR] DÉRIVÉS DE THIOPHÈNE NON FUSIONNÉS ET LEURS UTILISATIONS

  摘要：

  本发明涉及一类新型非融合噻吩衍生物及其用于治疗感染、癌症、代谢性疾病、心血管疾病、铁贮存紊乱和炎症性疾病等疾病的用途。

  公开号：

  WO2019154953A1
• 作为产物：
  描述：

  环戊基乙酮 、 氰乙酸乙酯 在 sulfur 、 二乙胺 作用下， 以 乙醇 为溶剂， 反应 18.0h， 生成 ethyl 2-amino-4-cyclopentylthiophene-3-carboxylate
  参考文献：
  名称：

  Selective Inhibitors of Bacterial t-RNA-(N¹G37) Methyltransferase (TrmD) That Demonstrate Novel Ordering of the Lid Domain

  摘要：

  The tRNA-(N(1)G37) methyltransferase (TrmD) is essential for growth and highly conserved in both Gram-positive and Gram-negative bacterial pathogens. Additionally, TrmD is very distinct from its human orthologue TRM5 and thus is a suitable target for the design of novel antibacterials. Screening of a collection of compound fragments using Haemophilus influenzae TrmD identified inhibitory, fused thieno-pyrimidones that were competitive with S-adenosylmethionine (SAM), the physiological methyl donor substrate. Guided by X-ray cocrystal structures, fragment 1 was elaborated into a nanomolar inhibitor of a broad range of Gram-negative TrmD isozymes. These compounds demonstrated no activity against representative human SAM utilizing enzymes, PRMT1 and SET7/9. This is the first report of selective, nanomolar inhibitors of TrmD with demonstrated ability to order the TrmD lid in the absence of tRNA.

  DOI：

  10.1021/jm400718n

文献信息

• Selective Inhibitors of Bacterial t-RNA-(N¹G37) Methyltransferase (TrmD) That Demonstrate Novel Ordering of the Lid Domain
  作者：Pamela J. Hill、Ayome Abibi、Robert Albert、Beth Andrews、Moriah M. Gagnon、Ning Gao、Tyler Grebe、Laurel I. Hajec、Jian Huang、Stephania Livchak、Sushmita D. Lahiri、David C. McKinney、Jason Thresher、Hongming Wang、Nelson Olivier、Ed T. Buurman

  DOI：10.1021/jm400718n

  日期：2013.9.26

  The tRNA-(N(1)G37) methyltransferase (TrmD) is essential for growth and highly conserved in both Gram-positive and Gram-negative bacterial pathogens. Additionally, TrmD is very distinct from its human orthologue TRM5 and thus is a suitable target for the design of novel antibacterials. Screening of a collection of compound fragments using Haemophilus influenzae TrmD identified inhibitory, fused thieno-pyrimidones that were competitive with S-adenosylmethionine (SAM), the physiological methyl donor substrate. Guided by X-ray cocrystal structures, fragment 1 was elaborated into a nanomolar inhibitor of a broad range of Gram-negative TrmD isozymes. These compounds demonstrated no activity against representative human SAM utilizing enzymes, PRMT1 and SET7/9. This is the first report of selective, nanomolar inhibitors of TrmD with demonstrated ability to order the TrmD lid in the absence of tRNA.
• Identification of the first small-molecule inhibitor of the REV7 DNA repair protein interaction
  作者：Marcelo L. Actis、Nigus D. Ambaye、Benjamin J. Evison、Youming Shao、Murugendra Vanarotti、Akira Inoue、Ezelle T. McDonald、Sotaro Kikuchi、Richard Heath、Kodai Hara、Hiroshi Hashimoto、Naoaki Fujii

  DOI：10.1016/j.bmc.2016.07.026

  日期：2016.9

  DNA interstrand crosslink (ICL) repair (ICLR) has been implicated in the resistance of cancer cells to ICL-inducing chemotherapeutic agents. Despite the clinical significance of ICL-inducing chemotherapy, few studies have focused on developing small-molecule inhibitors for ICLR. The mammalian DNA polymerase zeta, which comprises the catalytic subunit REV3L and the non-catalytic subunit REV7, is essential for ICLR. To identify small-molecule compounds that are mechanistically capable of inhibiting ICLR by targeting REV7, high-throughput screening and structure-activity relationship (SAR) analysis were performed. Compound 1 was identified as an inhibitor of the interaction of REV7 with the REV7-binding sequence of REV3L. Compound 7 (an optimized analog of compound 1) bound directly to REV7 in nuclear magnetic resonance analyses, and inhibited the reactivation of a reporter plasmid containing an ICL in between the promoter and reporter regions. The normalized clonogenic survival of HeLa cells treated with cisplatin and compound 7 was lower than that for cells treated with cisplatin only. These findings indicate that a small-molecule inhibitor of the REV7/REV3L interaction can chemosensitize cells by inhibiting ICLR. (C) 2016 Elsevier Ltd. All rights reserved.
• [EN] NON-FUSED THIOPHENE DERIVATIVES AND THEIR USES<br/>[FR] DÉRIVÉS DE THIOPHÈNE NON FUSIONNÉS ET LEURS UTILISATIONS
  申请人：ENYO PHARMA

  公开号：WO2019154953A1

  公开（公告）日：2019-08-15

  The present invention relates to a new class of non-fused thiophene derivatives and their uses for treating diseases such as infection, cancer, metabolic diseases, cardiovascular diseases, iron storage disorders and inflammatory disorders.

  本发明涉及一类新型非融合噻吩衍生物及其用于治疗感染、癌症、代谢性疾病、心血管疾病、铁贮存紊乱和炎症性疾病等疾病的用途。