(4,5-dibromothiophen-2-yl)methanol | 773868-55-6

• 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: (4,5-dibromothiophen-2-yl)methanol
• CAS: 773868-55-6
• 化学式: C₅H₄Br₂OS
• 分子量: 271.96
• InChiKey: PEJZUWKPHCZNOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  48.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4,5-dibromothiophen-2-yl)methanol 在 三溴化磷 、 二异丁基氢化铝 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 生成
  参考文献：
  名称：

  Dual neurokinin NK1/NK2 antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N′-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N′-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides

  摘要：

  Based on the structure of N-[(R,R)-(E)-1-(4-chlorobenzyl)- 3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (1), attempts to improve the NK2 affinity have resulted in the discovery of N-[(R,R)-(E)-1-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3- yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (9, DNK333) exhibiting a 5-fold improved affinity to the NK2 receptor in comparison to 1. Simplification of the structure via elimination of a chiral centre led to 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-(3,4-dichlorobenzyl)-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamide (22), a potent and fairly balanced NK1/NK2 antagonist. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00631-x
• 作为产物：
  描述：

  4,5-二溴噻吩-2-羧酸甲酯 在 二异丁基氢化铝 作用下， 以 甲苯 为溶剂， 生成 (4,5-dibromothiophen-2-yl)methanol
  参考文献：
  名称：

  Dual neurokinin NK1/NK2 antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N′-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N′-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides

  摘要：

  Based on the structure of N-[(R,R)-(E)-1-(4-chlorobenzyl)- 3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (1), attempts to improve the NK2 affinity have resulted in the discovery of N-[(R,R)-(E)-1-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3- yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (9, DNK333) exhibiting a 5-fold improved affinity to the NK2 receptor in comparison to 1. Simplification of the structure via elimination of a chiral centre led to 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-(3,4-dichlorobenzyl)-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamide (22), a potent and fairly balanced NK1/NK2 antagonist. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00631-x

文献信息

• Discovery, Structure–Activity Relationship, and Biological Activity of Histone-Competitive Inhibitors of Histone Acetyltransferases P300/CBP
  作者：Fangrui Wu、Yuanda Hua、Salma Kaochar、Shenyou Nie、Yi-Lun Lin、Yuan Yao、Jingyu Wu、Xiaowei Wu、Xiaoyong Fu、Rachel Schiff、Christel M. Davis、Matthew Robertson、Erik A. Ehli、Cristian Coarfa、Nicholas Mitsiades、Yongcheng Song

  DOI：10.1021/acs.jmedchem.9b02164

  日期：2020.5.14

  Histone acetyltransferase (HAT) p300 and its paralog CBP acetylate histone lysine side chains and play critical roles in regulating gene transcription. The HAT domain of p300/CBP is a potential drug target for cancer. Through compound screening and medicinal chemistry, novel inhibitors of p300/CBP HAT with their IC50 values as low as 620 nM were discovered. The most potent inhibitor is competitive

  组蛋白乙酰转移酶（HAT）p300及其旁系同源CBP乙酰化组蛋白赖氨酸侧链，在调节基因转录中起关键作用。p300 / CBP的HAT结构域是潜在的癌症药物靶标。通过化合物筛选和药物化学，发现了新的p300 / CBP HAT抑制剂，其IC50值低至620 nM。最有效的抑制剂与组蛋白底物竞争，对p300 / CBP表现出高选择性。它抑制细胞乙酰化，并具有1-3μM的EC50对几种肿瘤细胞系增殖的强活性。雌激素受体（ER）阳性乳腺癌MCF-7细胞中的基因表达谱表明，抑制剂治疗可概括siRNA介导的p300基因敲低，抑制ER介导的基因转录，并抑制了许多与癌症相关的基因签名的表达。这些结果表明，该抑制剂不仅是用于p300 / CBP HAT生物学研究的有用探针，而且还是用于进一步开发针对癌症的药物的药理学线索。
• [EN] NOVEL INHIBITORS OF HISTONE ACETYLTRANSFERASE P300/CBP FOR CANCER THERAPY<br/>[FR] NOUVEAUX INHIBITEURS DE L'HISTONE ACÉTYLTRANSFÉRASE P300/CBP POUR LA THÉRAPIE DU CANCER
  申请人：BAYLOR COLLEGE MEDICINE

  公开号：WO2021207469A1

  公开（公告）日：2021-10-14

  Embodiments of the present disclosure pertain to compositions that include a compound that inhibits the histone acetyl transferase activity of a protein, such as p300 and/or CBP. Further embodiments of the present disclosure pertain to methods of inhibiting the histone acetyl transferase activity of a protein by exposing the protein to a composition that contains one or more of the compounds of the present disclosure. The compositions of the present disclosure may be exposed to a protein in vitro or in vivo. Additional embodiments of the present disclosure pertain to methods of treating a cancer in a subject by administering a composition of the present disclosure to the subject in order to treat the cancer.

  本公开的实施例涉及包含抑制蛋白质的组蛋白乙酰转移酶活性的化合物的组合物。这些蛋白质可以是p300和/或CBP。本公开的其他实施例涉及通过将蛋白质暴露在包含本公开的化合物之一或多个的组合物中来抑制蛋白质的组蛋白乙酰转移酶活性的方法。本公开的组合物可以在体外或体内暴露给蛋白质。本公开的其他实施例涉及通过向受试者投药本公开的组合物来治疗受试者的癌症的方法。
• Synthesis, Structure–Activity Relationships, and Antiviral Activity of Allosteric Inhibitors of Flavivirus NS2B–NS3 Protease
  作者：Shenyou Nie、Yuan Yao、Fangrui Wu、Xiaowei Wu、Jidong Zhao、Yuanda Hua、Jingyu Wu、Tong Huo、Yi-Lun Lin、Alexander R. Kneubehl、Megan B. Vogt、Josephine Ferreon、Rebecca Rico-Hesse、Yongcheng Song

  DOI：10.1021/acs.jmedchem.0c02070

  日期：2021.3.11

  structure–activity relationships are discussed. The ZVpro inhibitors also inhibit homologous proteases of dengue and West Nile viruses, and their inhibitory activities are correlated. The most potent compounds 47 and 103 potently inhibited Zika virus replication in cells with EC68 values of 300–600 nM and in a mouse model of Zika infection. These compounds represent novel pharmacological leads for drug

  黄病毒，包括寨卡病毒、登革热病毒和西尼罗河病毒，是重要的人类病原体。黄病毒的高度保守的 NS2B-NS3 蛋白酶对于病毒复制是必不可少的，因此是一个有前途的药物靶点。通过化合物筛选和药物化学研究，发现一系列新型 2,5,6-三取代吡嗪化合物是有效的寨卡病毒蛋白酶 (ZVpro) 变构抑制剂，IC 50值低至 130 nM。讨论了它们的结构-活性关系。ZVpro 抑制剂还抑制登革热病毒和西尼罗河病毒的同源蛋白酶，并且它们的抑制活性是相关的。最有效的化合物47和103有效抑制寨卡病毒在 EC 68细胞中的复制值 300-600 nM 和在寨卡病毒感染的小鼠模型中。这些化合物代表了针对黄病毒感染的药物开发的新药理学线索。
• Hydrosilylation of Carbonyl Compounds Catalyzed by Iridium(I) Complexes with (‐)‐Menthol‐Based Phosphorus(III) Ligands
  作者：Konrad Stęsik、Adrian Franczyk、Agnieszka Czapik、Ireneusz Kownacki、Jedrzej Walkowiak

  DOI：10.1002/cctc.202201510

  日期：——

  New iridium(I) complexes with phosphorus(III) ligands based on naturally occurring (−)-menthol were synthesized and tested in the hydrosilylation of carbonyl compounds (ketones, aldehydes, esters). Catalytic systems provided great activity and chemoselectivity in the reduction of the carbonyl group showing high tolerance to many functional groups, also the unsaturated C−C double and triple bonds.

  基于天然存在的 (−)-薄荷醇，合成了带有磷 (III) 配体的新型铱 (I) 配合物，并在羰基化合物（酮、醛、酯）的氢化硅烷化反应中进行了测试。催化系统在还原羰基方面提供了极大的活性和化学选择性，对许多官能团以及不饱和 C-C 双键和三键显示出高耐受性。
• Dual neurokinin NK1/NK2 antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N′-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N′-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides
  作者：Marc Gerspacher、Luigi La Vecchia、Robert Mah、Andreas von Sprecher、Gary P. Anderson、Natarajan Subramanian、Kathleen Hauser、Heinrich Bammerlin、Sabine Kimmel、Viviane Pawelzik、Karin Ryffel、Howard A. Ball

  DOI：10.1016/s0960-894x(01)00631-x

  日期：2001.12

  Based on the structure of N-[(R,R)-(E)-1-(4-chlorobenzyl)- 3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (1), attempts to improve the NK2 affinity have resulted in the discovery of N-[(R,R)-(E)-1-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3- yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (9, DNK333) exhibiting a 5-fold improved affinity to the NK2 receptor in comparison to 1. Simplification of the structure via elimination of a chiral centre led to 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-(3,4-dichlorobenzyl)-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamide (22), a potent and fairly balanced NK1/NK2 antagonist. (C) 2001 Elsevier Science Ltd. All rights reserved.