methyl (E)-3-(4'-fluoro[1,1'-biphenyl]-4-yl)acrylate | 1008744-48-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl (E)-3-(4'-fluoro[1,1'-biphenyl]-4-yl)acrylate
• 英文别名: methyl (2E)-3-(4'-fluoro[1,1'-biphenyl]-4-yl)-2-propenoate；methyl (2E)-3-(4'-fluorobiphenyl-4-yl)prop-2-enoate；methyl (E)-3-[4-(4-fluorophenyl)phenyl]prop-2-enoate
• CAS: 1008744-48-6
• 化学式: C₁₆H₁₃FO₂
• 分子量: 256.276
• InChiKey: IZVFLSMDXWELFY-NYYWCZLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (E)-3-(4'-fluoro[1,1'-biphenyl]-4-yl)acrylate 在 palladium 10% on activated carbon 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 2.5h， 生成 3-(4-(4-氟苯基)苯基)丙酸甲酯
  参考文献：
  名称：

  WO2008/23336

  摘要：

  公开号：
• 作为产物：
  描述：

  3-(4-溴苯基)-2-丙酸甲酯 、 4-氟苯硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以87%的产率得到methyl (E)-3-(4'-fluoro[1,1'-biphenyl]-4-yl)acrylate
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of Varied Ether Linker Analogues of the Antitubercular Drug (6S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)

  摘要：

  New analogues of antitubercular drug PA-824 were synthesized, featuring alternative side chain ether linkers of varying size and flexibility, seeking drug candidates with enhanced metabolic stability and high efficacy. Both alpha-methyl substitution and removal of the benzylic methylene were broadly tolerated in vitro, with a biaryl example of the latter class exhibiting an 8-fold better efficacy than the parent drug in a mouse model of acute Mycobacterium tuberculosis infection and negligible fragmentation to an alcohol metabolite in liver microsomes. Extended linkers (notably propenyloxy, propynyloxy, and pentynyloxy) provided greater potencies against replicating M. tb (monoaryl analogues), with propynyl ethers being most effective under anaerobic (nonreplicating) conditions (mono/biaryl analogues). For benzyloxybenzyl and biaryl derivatives, aerobic activity was maximal with the original (OCH2) linker. One propynyloxy-linked compound displayed an 89-fold higher efficacy than the parent drug in the acute model, and it was slightly superior to antitubercular drug OPC-67683 in a chronic infection model.

  DOI：

  10.1021/jm200377r

文献信息

• Auto-Tandem Copper-Catalyzed Carboxylation of Undirected Alkenyl C–H Bonds with CO₂ by Harnessing β-Hydride Elimination
  作者：Harekrishna Sahoo、Liang Zhang、Jianhua Cheng、Masayoshi Nishiura、Zhaomin Hou

  DOI：10.1021/jacs.2c10754

  日期：2022.12.28

  The exploration into challenging scenarios of the application of elementary reactions offers excellent opportunities for the development of unique transformations under organometallic catalysis. As a ubiquitous reaction of metal alkyl complexes, β-hydride elimination plays a crucial role in a number of important catalytic transformations. However, its functions in these catalytic cycles are limited

  对基本反应应用的挑战性场景的探索为在有机金属催化下发展独特的转化提供了极好的机会。作为金属烷基配合物的普遍反应，β-氢化物消除在许多重要的催化转化中起着至关重要的作用。然而，它在这些催化循环中的功能仅限于释放烯烃产物或通过进一步迁移插入产生异构化中间体。在此，我们报道了 β-氢化物消除的精确操作能够实现自动串联铜催化，用于无向烯基 C-H 键与 CO 2的羧化。在这种转化中，促进了烷基铜中间体的 β-氢化物消除，同时它与 CO 反应2被压制。生成的氢化铜反过来与 CO 2反应，提供多任务催化剂的途径，这使得 C-H 键在两个机械上不同的催化循环中串联硼化/羧化。
• Matrix metalloproteinase inhibitors
  申请人：Ranbaxy Laboratories Limited

  公开号：EP2322507A1

  公开（公告）日：2011-05-18

  The present invention relates to β-hydroxy and amino substituted carboxylic acids, which act as matrix metalloprotease inhibitors, particularly diastereomerically pure β-hydroxy carboxylic acids, corresponding processes for the synthesis of and pharmaceutical compositions containing the compounds of the present invention. Compounds of the present invention are useful in the treatment of various inflammatory, autoimmune and allergic diseases, such as methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, wound healing disorders, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by the over-expression and over-activation of a matrix metalloproteinase using the compounds.

  本发明涉及作为基质金属蛋白酶抑制剂的β-羟基和氨基取代的羧酸，特别是非对映异构纯的β-羟基羧酸，以及合成本发明化合物的相应工艺和含有本发明化合物的药物组合物。本发明的化合物可用于治疗各种炎症、自身免疫性和过敏性疾病，如治疗哮喘、类风湿性关节炎、慢性阻塞性肺病、鼻炎、骨关节炎、银屑病关节炎、牛皮癣、肺纤维化、伤口愈合障碍、肺部炎症、急性呼吸窘迫综合征、牙周炎、多发性硬化症、多发性骨髓瘤、多发性硬化症、多发性硬化症的方法、牙周炎、多发性硬化症、牙龈炎、动脉粥样硬化、导致再狭窄和缺血性心力衰竭的新内膜增生、中风、肾脏疾病、肿瘤转移，以及其他以基质金属蛋白酶过度表达和过度激活为特征的炎症性疾病。
• WO2008/23336
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and Structure–Activity Relationships of Varied Ether Linker Analogues of the Antitubercular Drug (6<i>S</i>)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5<i>H</i>-imidazo[2,1-<i>b</i>][1,3]oxazine (PA-824)
  作者：Andrew M. Thompson、Hamish S. Sutherland、Brian D. Palmer、Iveta Kmentova、Adrian Blaser、Scott G. Franzblau、Baojie Wan、Yuehong Wang、Zhenkun Ma、William A. Denny

  DOI：10.1021/jm200377r

  日期：2011.10.13

  New analogues of antitubercular drug PA-824 were synthesized, featuring alternative side chain ether linkers of varying size and flexibility, seeking drug candidates with enhanced metabolic stability and high efficacy. Both alpha-methyl substitution and removal of the benzylic methylene were broadly tolerated in vitro, with a biaryl example of the latter class exhibiting an 8-fold better efficacy than the parent drug in a mouse model of acute Mycobacterium tuberculosis infection and negligible fragmentation to an alcohol metabolite in liver microsomes. Extended linkers (notably propenyloxy, propynyloxy, and pentynyloxy) provided greater potencies against replicating M. tb (monoaryl analogues), with propynyl ethers being most effective under anaerobic (nonreplicating) conditions (mono/biaryl analogues). For benzyloxybenzyl and biaryl derivatives, aerobic activity was maximal with the original (OCH2) linker. One propynyloxy-linked compound displayed an 89-fold higher efficacy than the parent drug in the acute model, and it was slightly superior to antitubercular drug OPC-67683 in a chronic infection model.