2-(4-Chloro-phenyl)-isonicotinic acid | 500586-44-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-(4-Chloro-phenyl)-isonicotinic acid
• 英文别名: 2-(4-Chlorophenyl)isonicotinic acid；2-(4-chlorophenyl)pyridine-4-carboxylic acid
• CAS: 500586-44-7
• 化学式: C₁₂H₈ClNO₂
• mdl: MFCD16317509
• 分子量: 233.654
• InChiKey: BRBHDPCWBZWZTP-UHFFFAOYSA-N

物化性质

• 熔点：
  263-264 °C
• 沸点：
  500.1±40.0 °C(Predicted)
• 密度：
  1.355±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-Chloro-phenyl)-isonicotinic acid 在 氯化亚砜 作用下， 生成 2-(4-chlorophenyl)pyridine-4-carbonyl chloride
  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-氯-4-氰基吡啶 在 四(三苯基膦)钯 、 水 、 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 生成 2-(4-Chloro-phenyl)-isonicotinic acid
  参考文献：
  名称：

  选择性靶向艰难梭菌的吡啶酰胺类抗菌药物的构效关系

  摘要：

  艰难梭菌是主要的健康威胁。这种病原体在由口服抗生素引起的肠道微生物群失调期间引发肠道感染。艰难梭菌难以根除，因为它能够形成对抗生素不敏感的孢子。为了解决治疗复发性艰难梭菌感染的迫切需求，需要选择性靶向艰难梭菌而不是常见肠道微生物群的抗生素。我们在本文中描述了对艰难梭菌表现出强效和选择性活性的吡啶酰胺类抗菌剂。108种异烟酰胺4类似物的构效关系研究了一种对耐甲氧西林金黄色葡萄球菌和艰难梭菌具有同等活性的化合物。引入以类似物87为例的吡啶酰胺核心导致对艰难梭菌的极好的效力和选择性。吡啶酰胺类选择性靶向艰难梭菌和预防肠道菌群失调的能力有望用于治疗复发性艰难梭菌感染。

  DOI：

  10.1021/acsmedchemlett.1c00135

文献信息

• Copper‐Catalyzed C4‐selective Carboxylation of Pyridines with CO2 via Pyridylphosphonium Salts
  作者：Shibiao Tang、Zezhao Liu、Jiakai Zhang、Bin Li、Baiquan Wang

  DOI：10.1002/anie.202318572

  日期：2024.3.22

  A practical copper-catalyzed C4-selective carboxylation of pyridines with CO2 via pyridylphosphonium salts has been developed. The C−P bond carboxylation with CO2 was achieved for the first time. This work represents a novel mode of site-selective carboxylation of pyridines, which may be a useful approach in new drug design and discovery in the future.

  已经开发出一种实用的铜催化吡啶与CO 2通过吡啶基鏻盐的C4选择性羧化反应。首次实现了CO 2的CP键羧化。这项工作代表了吡啶位点选择性羧化的一种新模式，这可能是未来新药设计和发现的一种有用方法。
• Discovery of Dap-3 Polymyxin Analogues for the Treatment of Multidrug-Resistant Gram-Negative Nosocomial Infections
  作者：Thomas V. Magee、Matthew F. Brown、Jeremy T. Starr、David C. Ackley、Joseph A. Abramite、Jiri Aubrecht、Andrew Butler、Jared L. Crandon、Fadia Dib-Hajj、Mark E. Flanagan、Karl Granskog、Joel R. Hardink、Michael D. Huband、Rebecca Irvine、Michael Kuhn、Karen L. Leach、Bryan Li、Jian Lin、David R. Luke、Shawn H. MacVane、Alita A. Miller、Sandra McCurdy、James M. McKim、David P. Nicolau、Thuy-Trinh Nguyen、Mark C. Noe、John P. O’Donnell、Scott B. Seibel、Yue Shen、Antonia F. Stepan、Andrew P. Tomaras、Paul C. Wilga、Li Zhang、Jinfeng Xu、Jinshan Michael Chen

  DOI：10.1021/jm400416u

  日期：2013.6.27

  We report novel polymyxin analogues with improved antibacterial in vitro potency against polymprin resistant recent clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa. In addition, a human renal cell in vitro assay (hRPTEC) was used to inform structure-toxicity relationships and further differentiate analogues. Replacement of the Dab-3 residue with a Dap-3 in combination with a relatively polar 6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl side chain as a fatty acyl replacement yielded analogue 5x, which demonstrated an improved in vitro antimicrobial and renal cytotoxicity profiles relative to polymyxin B (PMB). However, in vivo PK/PD comparison of 5x and PMB in a murine neutropenic thigh model against P. aeruginosa strains with matched MICs showed that 5x was inferior to PMB in vivo, suggesting a lack of improved therapeutic index in spite of apparent in vitro advantages.