2-(2-thienyl)-4-quinoline carboxylic acid chloride | 148121-98-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-(2-thienyl)-4-quinoline carboxylic acid chloride
• 英文别名: 2-Thiophen-2-ylquinoline-4-carbonyl chloride
• CAS: 148121-98-6
• 化学式: C₁₄H₈ClNOS
• 分子量: 273.743
• InChiKey: BAKLRUBYYKAGAK-UHFFFAOYSA-N

物化性质

• 沸点：
  439.2±40.0 °C(Predicted)
• 密度：
  1.382±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  58.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  磺胺异噁唑 、 2-(2-thienyl)-4-quinoline carboxylic acid chloride 在 吡啶 作用下， 生成 N-[4-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-2-thiophen-2-ylquinoline-4-carboxamide
  参考文献：
  名称：

  Discovering novel chemical inhibitors of human cyclophilin A: Virtual screening, synthesis, and bioassay

  摘要：

  Cyclophilin A (CypA) is a member of cyclophilins, a family of the highly homologous peptidyl prolyl cis-trans isomerases (PPIases), which can bind to cyclosporin A (CsA). CypA plays critical roles in various biological processes, including protein folding, assembly, transportation, regulation of neuron growth, and HIV replication. The discovery of CypA inhibitor is now of a great special interest in the treatment of immunological disorders. In this study, a series of novel small molecular CypA inhibitors have been discovered by using structure-based virtual screening in conjunction with chemical synthesis and bioassay. The SPECS-1 database containing 85,000 small molecular compounds was searched by virtual screening against the crystal structure of human CypA. After SPR-based binding affinity assay, 15 compounds were found to show binding affinities to CypA at submicro-molar or micromolar level (compounds 1-15). Seven compounds were selected as the starting point for the further structure modification in considering binding activity, synthesis difficulty, and structure similarity. We thus synthesized 40 new small molecular compounds (1-6, 15, 16a-q, 17a-d, and 18a-I), and four of which (compounds 16b, 16h 16k,. and 18g) showed high CypA PPIase inhibition activities with IC50S of 2.5-6,2 mu M. Pharmacological assay indicated that these four Compounds demonstrated somewhat inhibition activities against the proliferation of spleen cells. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.11.006
• 作为产物：
  描述：

  2-(噻吩-2-基)喹啉-4-甲酸 生成 2-(2-thienyl)-4-quinoline carboxylic acid chloride
  参考文献：
  名称：

  强大的小分子SIRT6激活剂的发现：结构与活性的关系和抗胰腺导管腺癌的活性。

  摘要：

  SIRT6激活被认为是治疗许多疾病，特别是癌症的有希望的靶标。在此，我们报告发现了一系列新的小分子SIRT6激活剂。结构-活性关系分析导致鉴定出最有效的化合物2-（1-苯并呋喃-2-基）-N-（二苯甲基）喹啉-4-甲酰胺（12q），EC 1.5值为0.58±在FLUOR DE LYS分析中，对SIRT6依赖性肽脱乙酰作用的0.12μM和EC 50值为5.35±0.69μM。它对其他HDAC家族成员以及415种激酶显示弱或无活性，表明对SIRT6的选择性好。12q显著抑制增殖和胰腺导管腺癌（PDAC）细胞迁移的体外。它也显着抑制了PDAC肿瘤异种移植模型中的肿瘤生长。该化合物显示出有吸引力的药代动力学性质。总体而言，12q可能是治疗PDAC的良好先导化合物，值得进一步研究。

  DOI：

  10.1021/acs.jmedchem.0c01183

文献信息

• Discovery of a Novel Class of Selective Non-Peptide Antagonists for the Human Neurokinin-3 Receptor. 1. Identification of the 4-Quinolinecarboxamide Framework
  作者：Giuseppe A. M. Giardina、Henry M. Sarau、Carlo Farina、Andrew D. Medhurst、Mario Grugni、Luca F. Raveglia、Dulcie B. Schmidt、Roberto Rigolio、Mark Luttmann、Vittorio Vecchietti、Douglas W. P. Hay

  DOI：10.1021/jm960818o

  日期：1997.6.1

  A novel class of potent and selective non-peptide neurokinin-3 (NK-3) receptor antagonists, featuring the 4-quinolinecarboxamide framework, has been designed based upon chemically diverse NK-1 receptor antagonists. The novel compounds 33-76, prompted by chemical modifications of the prototype 4, have been characterized by binding analysis using a membrane preparation of chinese hamster ovary (CHO)

  基于化学上不同的NK-1受体拮抗剂，设计了一种新型的有效且选择性的非肽神经激肽3（NK-3）受体拮抗剂，其特征在于4-喹啉羧酰胺骨架。通过原型4的化学修饰促进了新型化合物33-76的表达，其特征在于使用表达人神经激肽3受体（hNK-3-CHO）的中国仓鼠卵巢（CHO）细胞膜制剂进行结合分析，并建立了明确的结构-活性关系（SAR）。从SARs（R）-N- [α-（甲氧基羰基）苄基] -2-苯基喹啉-4-羧酰胺（65，SB 218795，hNK-3-CHO结合Ki = 13 nM）出现，是最有效的化合物之一这个新颖的班级。对其他神经激肽受体（hNK-2-CHO和hNK-1-CHO）的选择性研究表明，对hNK-3的选择性是对hNK-2受体的65倍（hNK-2-CHO结合Ki = 1221 nM）。相对于hNK-1受体具有超过7000倍的选择性（hNK-1-CHO结合Ki => 100 micro
• Identification of a New Series of STAT3 Inhibitors by Virtual Screening
  作者：Kenji Matsuno、Yoshiaki Masuda、Yutaka Uehara、Hiroshi Sato、Ayumu Muroya、Osamu Takahashi、Takane Yokotagawa、Toshio Furuya、Tadashi Okawara、Masami Otsuka、Naohisa Ogo、Tadashi Ashizawa、Chie Oshita、Sachiko Tai、Hidee Ishii、Yasuto Akiyama、Akira Asai

  DOI：10.1021/ml1000273

  日期：2010.11.11

  The signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for oncology drug development. We identified a N-[2-(1,3,4-oxadiazolyl)]-4-quinolinecarboxamide derivative, STX-0119, as a novel STAT3 dimerization inhibitor by a virtual screen using a customized version of the DOCK4 program with the crystal structure of STAT3 In addition, we used in vitro cell-based assays such as the luciferase reporter gene assay and the fluorescence resonance energy transfer-based STAT3 dimerization assay STX-0119 selectively abrogated the DNA binding activity of STAT3 and suppressed the expression of STAT3-regulated oncoproteins such as c-myc and survivin in cancer cells. In contrast a truncated inactive analogue, STX-0872, did not exhibit those activites, Oral administration of STX-0119 effectively abrogated the growth of human lymphoma cells in a SCC-3 subcutaneous xenograft model without visible toxicity Structure-activity relationships of STX-0119 derivatives were investigated using the docking model of the STAT3-SH2 domain/STX-0119.
• Reactions of epoxides of the pyran series involving ring expansion. Reaction of 4-methyl-3,4-epoxytetrahydropyran with potassium thiocyanate
  作者：S. A. Vasil'eva、Yu. A. Kashina、M. V. Kulikova、M. N. Zemtsova、M. G. Safarov

  DOI：10.1007/bf00531316

  日期：1992.8
• 6-Acylamino-2-aminoquinolines as Potent Melanin-Concentrating Hormone 1 Receptor Antagonists. Identification, Structure−Activity Relationship, and Investigation of Binding Mode
  作者：Trond Ulven、Thomas M. Frimurer、Jean-Marie Receveur、Paul Brian Little、Øystein Rist、Pia K. Nørregaard、Thomas Högberg

  DOI：10.1021/jm050103y

  日期：2005.9.1

  Novel 6-acylamino-2-aminoquinoline melanin-concentrating hormone 1 receptor (MCHIR) antagonists were identified by sequential in silico screening with 3D pharmacophore models derived from a series of benzamide antagonists. The structure- activity relationship exploration by synthesis of analogues found structural demands around the western part of the compounds to be quite specific, whereas much structural freedom was found in the eastern part. Vvhile these compounds in general suffered from poor solubility properties, the 4-trifluoromethoxy-phenoxyacetamide western appendage provided a favorable combination of activity and solubility properties. The amine in the eastern appendage, originally required by the pharmacophore model and believed to interact with Asp123 in transmembrane 3 of MCH1R, could be removed without diminishing affinity or functional activity of the compounds. Docking studies suggested that the Asp123 interacts preferentially with the nitrogen of the central quinoline. Synthesis and testing of specific analogues supported our revised binding mode hypothesis.
• Discovery of Potent Small-Molecule SIRT6 Activators: Structure–Activity Relationship and Anti-Pancreatic Ductal Adenocarcinoma Activity
  作者：Xiuli Chen、Weining Sun、Shenzhen Huang、Hailin Zhang、Guifeng Lin、Hui Li、Jingxin Qiao、Linli Li、Shengyong Yang

  DOI：10.1021/acs.jmedchem.0c01183

  日期：2020.9.24

  other HDAC family members as well as 415 kinases, indicating good selectivity for SIRT6. 12q significantly inhibited the proliferation and migration of pancreatic ductal adenocarcinoma (PDAC) cells in vitro. It also markedly suppressed the tumor growth in a PDAC tumor xenograft model. This compound showed attractive pharmacokinetic properties. Overall, 12q could be a good lead compound for the treatment

  SIRT6激活被认为是治疗许多疾病，特别是癌症的有希望的靶标。在此，我们报告发现了一系列新的小分子SIRT6激活剂。结构-活性关系分析导致鉴定出最有效的化合物2-（1-苯并呋喃-2-基）-N-（二苯甲基）喹啉-4-甲酰胺（12q），EC 1.5值为0.58±在FLUOR DE LYS分析中，对SIRT6依赖性肽脱乙酰作用的0.12μM和EC 50值为5.35±0.69μM。它对其他HDAC家族成员以及415种激酶显示弱或无活性，表明对SIRT6的选择性好。12q显著抑制增殖和胰腺导管腺癌（PDAC）细胞迁移的体外。它也显着抑制了PDAC肿瘤异种移植模型中的肿瘤生长。该化合物显示出有吸引力的药代动力学性质。总体而言，12q可能是治疗PDAC的良好先导化合物，值得进一步研究。