2-bromo-1-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone | 1314083-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 2-bromo-1-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone
• 英文别名: 3-bromoacetyl-1-methyl-7-azaindole；2-Bromo-1-(1-methylpyrrolo[2,3-b]pyridin-3-yl)ethanone；2-bromo-1-(1-methylpyrrolo[2,3-b]pyridin-3-yl)ethanone
• CAS: 1314083-42-5
• 化学式: C₁₀H₉BrN₂O
• 分子量: 253.098
• InChiKey: NJLZVPWXYAZLDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-甲氧基硫代苯甲胺 、 2-bromo-1-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone 以 乙醇 为溶剂， 反应 0.5h， 以82%的产率得到3-[2-(4-methoxyphenyl)-1,3-thiazol-4-yl]-1-methyl-1H-7-azaindole
  参考文献：
  名称：

  Synthesis and Antitumor Activity of 3-(2-Phenyl-1,3-thiazol-4-yl)-1H-indoles and 3-(2-Phenyl-1,3-thiazol-4-yl)-1H-7-azaindoles

  摘要：

  AbstractGiven the potent antimicrobial, antiviral, and antitumor activities of many natural products, there is an increasing interest in the synthesis of new molecules based on natural compound scaffolds. Based on a 2,4‐bis(3′‐indolyl)imidazole skeleton, two new series of phenylthiazolylindoles and phenylthiazolyl‐7‐azaindoles were obtained by Hantzsch reaction between substituted phenylthioamides and the α‐bromoacetyl derivatives. Some azaindole derivatives, tested at the National Cancer Institute against a panel of ∼60 tumor cell lines derived from nine human cancer cell types, showed inhibitory effects against all cell lines investigated at micromolar to nanomolar concentrations. Two of them exhibited a high affinity for CDK1, with IC50 values of 0.41 and 0.85 μM. These promising results will set the foundation for future investigations into the development of anticancer therapies.

  DOI：

  10.1002/cmdc.201100078
• 作为产物：
  描述：

  7-氮杂吲哚 在 aluminum (III) chloride 、 三(3,6-二氧杂庚基)胺 、 potassium tert-butylate 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 0.67h， 生成 2-bromo-1-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone
  参考文献：
  名称：

  新型1 H-吡咯并[2,3- b ]吡啶衍生物降冰片素类似物：腹膜间皮瘤实验模型的合成和抗肿瘤活性

  摘要：

  在这项研究中，我们描述了新的降钙素原类似物，1 H-吡咯并[2,3- b ]吡啶衍生物的合成及其在弥漫性恶性腹膜间皮瘤（DMPM）（一种罕见且快速致命的疾病）的实验模型中的生物学作用对常规疗法有反应。三种活性最高的化合物1f（3- [2-（5-氟-1-甲基-1 H-吲哚-3-基）-1,3-噻唑-4-基] -1 H-吡咯并[2， 3- b ]吡啶），3f（3- [2-（1 H-吲哚-3-基）-1,3-噻唑-4-基] -1-甲基-1 H-吡咯并[2,3- b ]吡啶）和1l（3- [2-（5-氟-1-甲基-1 H-indol-3-yl）-1,3-thiazol-4-yl] -1-methyl-1 H -pyrrolo [2,3- b ]吡啶），它们被证明是细胞周期蛋白依赖性激酶1抑制剂，持续降低DMPM细胞增殖并诱导caspase依赖性凋亡反应，并同时降低抗凋亡蛋白survivin的活跃Thr

  DOI：

  10.1021/jm400842x

文献信息

• New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation
  作者：Anna Carbone、Barbara Parrino、Maria Cusimano、Virginia Spanò、Alessandra Montalbano、Paola Barraja、Domenico Schillaci、Girolamo Cirrincione、Patrizia Diana、Stella Cascioferro

  DOI：10.3390/md16080274

  日期：——

  New thiazole nortopsentin analogues were conveniently synthesized and evaluated for their activity as inhibitors of biofilm formation of relevant Gram-positive and Gram-negative pathogens. All compounds were able to interfere with the first step of biofilm formation in a dose-dependent manner, showing a selectivity against the staphylococcal strains. The most active derivatives elicited IC50 values

  可方便地合成新的噻唑降钙素原类似物，并评估其作为相关革兰氏阳性和革兰氏阴性病原体生物膜形成抑制剂的活性。所有化合物均能够以剂量依赖性方式干扰生物膜形成的第一步，显示出对葡萄球菌菌株的选择性。活性最高的衍生物对金黄色葡萄球菌ATCC 25923的IC50值为0.40⁻2.03µM。新化合物表现出典型的抗毒力特性，能够抑制生物膜的形成而不会影响浮游生物形式的微生物生长。
• Synthesis and Antitumor Activity of New Thiazole Nortopsentin Analogs
  作者：Virginia Spanò、Alessandro Attanzio、Stella Cascioferro、Anna Carbone、Alessandra Montalbano、Paola Barraja、Luisa Tesoriere、Girolamo Cirrincione、Patrizia Diana、Barbara Parrino

  DOI：10.3390/md14120226

  日期：——

  New thiazole nortopsentin analogs in which one of the two indole units was replaced by a naphthyl and/or 7-azaindolyl portion, were conveniently synthesized. Among these, three derivatives showed good antiproliferative activity, in particular against MCF7 cell line, with GI50 values in the micromolar range. Their cytotoxic effect on MCF7 cells was further investigated in order to elucidate their mode

  方便地合成了新的噻唑降冰片素类似物，其中两个吲哚单元之一被萘基和/或7-氮杂吲哚基部分取代。其中，三种衍生物显示出良好的抗增殖活性，尤其是针对MCF7细胞系，其GI50值在微摩尔范围内。为了阐明它们的作用方式，进一步研究了它们对MCF7细胞的细胞毒性作用。结果表明，这三种化合物可作为促凋亡剂，诱导活细胞向早期凋亡的明显转移，而不会发挥坏死作用。它们还引起细胞周期扰动，G0 / G1和S期细胞百分比显着下降，同时G2 / M期细胞百分比增加，并出现subG1细胞群。
• Synthesis and Antiproliferative Activity of Thiazolyl-bis-pyrrolo[2,3-b]pyridines and Indolyl-thiazolyl-pyrrolo[2,3-c]pyridines, Nortopsentin Analogues
  作者：Anna Carbone、Barbara Parrino、Gloria Vita、Alessandro Attanzio、Virginia Spanò、Alessandra Montalbano、Paola Barraja、Luisa Tesoriere、Maria Livrea、Patrizia Diana、Girolamo Cirrincione

  DOI：10.3390/md13010460

  日期：——

  Two new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and indole units were both substituted by 7-azaindole moieties or one indole unit was replaced by a 6-azaindole portion, were efficiently synthesized. Compounds belonging to both series inhibited the growth of HCT-116 colorectal cancer cells at low micromolar concentrations, whereas they did not affect the viability of normal-like intestinal cells. A compound of the former series induced apoptosis, evident as externalization of plasma membrane phosphatidylserine (PS), and changes of mitochondrial trans-membrane potential, while blocking the cell cycle in G2/M phase. In contrast, a derivative of the latter series elicited distinct responses in accordance with the dose. Thus, low concentrations (GI30) induced morphological changes characteristic of autophagic death with massive formation of cytoplasmic acid vacuoles without apparent loss of nuclear material, and with arrest of cell cycle at the G1 phase, whereas higher concentrations (GI70) induced apoptosis with arrest of cell cycle at the G1 phase.

  两种新的nortopsentin类似物系列被高效合成，其中天然产物的咪唑环被噻唑取代，吲哚单元被7-氮杂吲哚部分替换，或者一个吲哚单元被6-氮杂吲哚部分替换。这两类化合物都能在低微摩尔浓度下抑制HCT-116结直肠癌细胞的生长，而对正常肠道细胞的生存力没有影响。前一系列中的一个化合物诱导细胞凋亡，表现为细胞膜磷脂酰丝氨酸（PS）的外翻和线粒体跨膜电位的改变，同时阻滞细胞周期在G2/M期。相反，后一系列的一个衍生物在不同剂量下引发不同的反应。因此，低浓度（GI30）引起细胞形态变化，表现出自噬性死亡的特征，伴随大量胞质酸性空泡的形成，而无明显的核物质损失，并阻滞细胞周期在G1期；而在更高浓度（GI70）下则诱导凋亡，同样阻滞细胞周期在G1期。
• Synthesis, antitumor activity and CDK1 inhibiton of new thiazole nortopsentin analogues
  作者：Barbara Parrino、Alessandro Attanzio、Virginia Spanò、Stella Cascioferro、Alessandra Montalbano、Paola Barraja、Luisa Tesoriere、Patrizia Diana、Girolamo Cirrincione、Anna Carbone

  DOI：10.1016/j.ejmech.2017.06.052

  日期：2017.9

  A new series of thiazole nortopsentin analogues was conveniently synthesized with fair overall yields. The antiproliferative activity of the new derivatives was tested against different human tumor cell lines of the NCI full panel. Four of them showed good antitumor activity with GI50 values from micro to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, was pro-apoptotic

  方便地合成了一系列新的噻唑降钙素原类似物，总收率很高。测试了新衍生物对NCI全图的不同人类肿瘤细胞系的抗增殖活性。其中四个显示出良好的抗肿瘤活性，GI 50值从微摩尔到纳摩尔水平。这些衍生物的抗增殖作用的机制是促凋亡的，与质膜磷脂酰丝氨酸的外在化和DNA片段化有关。新噻唑类化合物中最具活性和选择性的是将活细胞限制在G2 / M期，并显着抑制了体外CDK1活性。
• Metabolomics-assisted discovery of a new anticancer GLS-1 inhibitor chemotype from a nortopsentin-inspired library: From phenotype screening to target identification
  作者：Daniela Carbone、Vincenzo Vestuto、Maria Rosalia Ferraro、Tania Ciaglia、Camilla Pecoraro、Eduardo Sommella、Stella Cascioferro、Emanuela Salviati、Sara Novi、Mario Felice Tecce、Giuseppina Amodio、Nunzio Iraci、Girolamo Cirrincione、Pietro Campiglia、Patrizia Diana、Alessia Bertamino、Barbara Parrino、Carmine Ostacolo

  DOI：10.1016/j.ejmech.2022.114233

  日期：2022.4