2-(4-fluorophenyl)-3-oxo-3-pyridin-4-yl-propionic acid methyl ester | 433217-05-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(4-fluorophenyl)-3-oxo-3-pyridin-4-yl-propionic acid methyl ester
• 英文别名: methyl 2-(4-fluorophenyl)-3-oxo-3-pyridin-4-ylpropanoate
• CAS: 433217-05-1
• 化学式: C₁₅H₁₂FNO₃
• 分子量: 273.264
• InChiKey: QBYVCFMDICKWSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  56.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-fluorophenyl)-3-oxo-3-pyridin-4-yl-propionic acid methyl ester 在 sodium chloride 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以21%的产率得到2-(4-氟-苯基)-1-吡啶-4-乙酮
  参考文献：
  名称：

  3-Heteroaryl-2-pyridones:  Benzodiazepine Site Ligands with Functional Selectivity for α2/α3-Subtypes of Human GABA_A Receptor-Ion Channels

  摘要：

  A novel series of 3-heteroaryl-5,6-bis(aryl)-1-methyl-2-pyridones were developed with high affinity for the benzodiazepine (BZ) binding site of human gamma-aminobutyric acid (GABA(A)) receptor ion channels, low binding selectivity for alpha2- and/or alpha3- over alpha1-containing GABA(A) receptor subtypes and high binding selectivity over alpha5 subtypes. High affinity appeared to be associated with a coplanar conformation of the pyridone and sulfur-containing 3-heteroaryl rings resulting from an attractive S...O intramolecular interaction. Functional selectivity (i.e., selective efficacy) for alpha2 and/or alpha3 GABA(A) receptor subtypes over alpha1 was observed in several of these compounds in electrophysiological assays. Furthermore, an alpha3 subtype selective inverse agonist was proconvulsant and anxiogenic in rodents while an alpha2/alpha3 subtype selective partial agonist was anticonvulsant and anxiolytic, supporting the hypothesis that subtype selective BZ site agonists may provide new anxiolytic therapies.

  DOI：

  10.1021/jm0110789
• 作为产物：
  描述：

  4-氟苯基乙酸甲酯 在 吡啶 、 chromium(VI) oxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 2-(4-fluorophenyl)-3-oxo-3-pyridin-4-yl-propionic acid methyl ester
  参考文献：
  名称：

  新的基于双环吡唑的细胞因子合成抑制剂的开发。

  摘要：

  描述了包含新的双环吡唑杂环核心的TNF-α生产的基于4-芳基-5-嘧啶基的细胞因子合成抑制剂。这些抑制剂中的许多在基于THP-1细胞的测定中显示出对LPS诱导的TNF-α产生的纳摩尔活性较低，在分离的酶测定中显示出对人p38αMAP激酶的较低纳摩尔活性。呈现了与突变的p38（mp38）共结晶的双环吡唑抑制剂的X射线晶体结构。

  DOI：

  10.1016/j.bmcl.2004.07.024

文献信息

• Isoxazolone compounds useful in treating diseases associated with unwanted cytokine activity
  申请人：——

  公开号：US20030096814A1

  公开（公告）日：2003-05-22

  Isoxazolone compounds having the generic structure: 1 are used to treat disease associated with unwanted cytokine activity, including rheumatoid arthritis, osteoarthritis, diabetes, HIV/AIDS, inflammatory bowel disease, Crohn's disease, ulcerative colitis, congestive heart, hypertension, chronic obstructive pulmonary disease, septic shock syndrome, tuberculosis, adult respiratory distress, asthma, atherosclerosis, muscle degeneration, periodontal disease, cachexia, Reiter's syndrome, gout, acute synovitis, anorexia and bulimia nervosa fever, malaise, myalgia and headaches.

  具有通用结构的异唑酮类化合物1被用于治疗与不必要的细胞因子活性相关的疾病，包括类风湿性关节炎、骨关节炎、糖尿病、HIV/AIDS、炎症性肠病、克罗恩病、溃疡性结肠炎、充血性心脏病、高血压、慢性阻塞性肺疾病、败血症休克综合症、结核病、成人呼吸窘迫综合症、哮喘、动脉硬化、肌肉退化、牙周病、消瘦症、Reiter综合症、痛风、急性滑膜炎、厌食症和贪食症、发热、不适、肌肉痛和头痛。
• The development of new bicyclic pyrazole-based cytokine synthesis inhibitors
  作者：Jennifer A. Townes、Adam Golebiowski、Michael P. Clark、Matthew J. Laufersweiler、Todd A. Brugel、Mark Sabat、Roger G. Bookland、Steve K. Laughlin、John C. VanRens、Biswanath De、Lily C. Hsieh、Susan C. Xu、Michael J. Janusz、Richard L. Walter

  DOI：10.1016/j.bmcl.2004.07.024

  日期：2004.10

  4-Aryl-5-pyrimidyl-based cytokine synthesis inhibitors of TNF-alpha production, which contain a novel bicyclic pyrazole heterocyclic core, are described. Many of these inhibitors showed low nanomolar activity against LPS-induced TNF-alpha production in a THP-1 cell-based assay and against human p38 alpha MAP kinase in an isolated enzyme assay. The X-ray crystal structure of a bicyclic pyrazole inhibitor co-crystallized

  描述了包含新的双环吡唑杂环核心的TNF-α生产的基于4-芳基-5-嘧啶基的细胞因子合成抑制剂。这些抑制剂中的许多在基于THP-1细胞的测定中显示出对LPS诱导的TNF-α产生的纳摩尔活性较低，在分离的酶测定中显示出对人p38αMAP激酶的较低纳摩尔活性。呈现了与突变的p38（mp38）共结晶的双环吡唑抑制剂的X射线晶体结构。
• [EN] ISOXAZOLONE COMPOUNDS USEFUL IN TREATING DISEASES ASSOCIATED WITH UNWANTED CYTOKINE ACTIVITY<br/>[FR] COMPOSES D'ISOXAZOLONE UTILES POUR TRAITER DES MALADIES ASSOCIEES A UN ACTIVITE NON DESIREE DES CYTOKINES
  申请人：PROCTER & GAMBLE

  公开号：WO2002094266A1

  公开（公告）日：2002-11-28

  Isoxazolone compounds having the generic structure: are used to treat disease associated with unwanted cytokine activity, including rheumatoid arthritis, osteoarthritis, diabetes, HIV/AIDS, inflammatory bowel disease, Crohn's disease, ulcerative colitis, congestive heart, hypertension, chronic obstructive pulmonary disease, septic shock syndrome, tuberculosis, adult respiratory distress, asthma, atherosclerosis, muscle degeneration, periodontal disease, cachexia, Reiter's syndrome, gout, acute synovitis, anorexia and bulimia nervosa fever, malaise, myalgia and headaches.

  具有通用结构的异唑酮类化合物被用于治疗与不需要的细胞因子活性有关的疾病，包括风湿性关节炎、骨关节炎、糖尿病、HIV/AIDS、炎症性肠病、克罗恩病、溃疡性结肠炎、充血性心脏病、高血压、慢性阻塞性肺病、感染性休克综合征、结核、成人呼吸窘迫综合征、哮喘、动脉硬化、肌肉退化、牙周病、消瘦症、Reiter综合征、痛风、急性滑膜炎、厌食症和贪食症、发热、不适、肌痛和头痛。
• ISOXAZOLONE COMPOUNDS USEFUL IN TREATING DISEASES ASSOCIATED WITH UNWANTED CYTOKINE ACTIVITY
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：EP1392299A1

  公开（公告）日：2004-03-03
• US6790846B2
  申请人：——

  公开号：US6790846B2

  公开（公告）日：2004-09-14