2-(4-fluorophenyl)-3-oxo-3-(2-methylsulfanyl-pyrimidin-4-yl)-propionic acid methyl ester | 503071-67-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(4-fluorophenyl)-3-oxo-3-(2-methylsulfanyl-pyrimidin-4-yl)-propionic acid methyl ester
• 英文别名: 2-(4-fluorophenyl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-3-oxo-propionic acid methyl ester；methyl 2-(4-fluorophenyl)-3-(2-methylsulfanylpyrimidin-4-yl)-3-oxopropanoate
• CAS: 503071-67-8
• 化学式: C₁₅H₁₃FN₂O₃S
• 分子量: 320.344
• InChiKey: NWEKLKAEZPSPGG-UHFFFAOYSA-N

物化性质

• 沸点：
  451.7±35.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  94.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(4-fluorophenyl)-3-oxo-3-(2-methylsulfanyl-pyrimidin-4-yl)-propionic acid methyl ester 在 Oxone 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 生成 4-(4-fluorophenyl)-1,2-dimethyl-5-(2-methanesulfonyl-pyrimidin-4-yl)-1,2-dihydropyrazol-3-one
  参考文献：
  名称：

  The development of monocyclic pyrazolone based cytokine synthesis inhibitors

  摘要：

  4-Aryl-5-pyrimidyl based cytokine synthesis inhibitors that contain a novel monocyclic, pyrazolone heterocyclic core are described. Many of these inhibitors showed low nanomolar activity against LPS-induced TNF-alpha production. One of the compounds (6e) was found to be efficacious in the rat iodoacetate (RIA) in vivo model of osteoarthritis. The X-ray crystal structure of a pyrazolone inhibitor cocrystallized with mutated p38 (mp38) is presented.

  DOI：

  10.1016/j.bmcl.2005.03.007
• 作为产物：
  描述：

  2-甲硫基-嘧啶-4-甲醛 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-(2-methylsulfanyl-pyrimidin-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

• 1,2-dihydropyrazol-3-ones which controls inflammatory cytokines
  申请人：——

  公开号：US20030225082A1

  公开（公告）日：2003-12-04

  The present invention relates to compounds which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, or enantiomeric and diasteriomeric forms or pharmaceutically acceptable salts thereof, have the formula: 1 wherein R is an ether or amino unit, R 1 is substituted phenyl, each R 2 and R 3 unit is independently selected from the group consisting of: a) hydrogen; and b) substituted or unsubstituted C 1 -C 10 hydrocarbyl selected from the group consisting of: i) C 1 -C 10 linear, branched or cyclic alkyl; ii) C 1 -C 10 aryl; iii) C 1 -C 10 heterocyclic; iv) C 1 -C 10 heteroaryl.

  本发明涉及一种能够预防炎症细胞因子的细胞外释放的化合物，所述化合物，或其对映体和二对映体形式或其药用可接受的盐，具有以下结构式：1其中R为醚或氨基单元，R1为取代的苯基，每个R2和R3单元独立地选自以下组成的群体：a) 氢；和b) 从以下组成的群体中选择的取代或未取代的C1-C10烃基：i) C1-C10线性、支链或环烷基；ii) C1-C10芳基；iii) C1-C10杂环烃基；iv) C1-C10杂芳基。
• 6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which control inflammatory cytokines
  申请人：The Procter & Gamble Company

  公开号：US20040038971A1

  公开（公告）日：2004-02-26

  The present invention relates to compounds which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula: 1 wherein R 1 is substituted aryl; R 4 is substituted or unsubstituted aryl or heteroaryl.

  本发明涉及能够预防炎症细胞因子的细胞外释放的化合物，这些化合物包括所有对映异构体和二面体异构体形式以及其药学上可接受的盐，其化学式为：1其中R1为取代芳基；R4为取代或未取代的芳基或杂环芳基。
• 6,7-Dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which control inflammatory cytokines
  申请人：Clark Philip Michael

  公开号：US20050148610A1

  公开（公告）日：2005-07-07

  The present invention relates to methods for treating diseases or disease states which are mediated or otherwise affected by the extracellular release of cytokines, said method comprising the step of administering to a human or higher mammal in need of treatment, one or more of the 6,7-dihydro-5H-pyrazolo[1,2a]pyrazol-1-ones of the present invention.

  本发明涉及用于治疗由细胞因子的细胞外释放介导或影响的疾病或疾病状态的方法，所述方法包括向需要治疗的人类或高等哺乳动物中的一个或多个，给予本发明的6,7-二氢-5H-吡唑并[1,2a]吡唑-1-酮之一。
• 6,7-Dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which provide analgesia
  申请人：The Procter & Gamble Company

  公开号：US20040087639A1

  公开（公告）日：2004-05-06

  The present invention relates to compound which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula: 1 wherein R comprises ethers or amines; R 1 is: a) substituted or unsubstituted aryl; or b) substituted or unsubstituted heteroaryl; each R 2 unit is independently selected from the group consisting of: a) hydrogen; b) —(CH 2 ) j O(CH 2 ) n R 8 ; c) —(CH 2 ) j NR 9a R 9b ; d) —(CH 2 ) j CO 2 R 10 ; e) —(CH 2 ) j OCO 2 R 10 f) —(CH 2 ) j CON(R 10 ) 2 ; g) —(CH 2 ) j OCON(R 10 ) 2 ; h) two R 2 units can be taken together to form a carbonyl unit; i) and mixtures thereof; R 8 , R 9a , R 9b , and R 10 are each independently hydrogen, C 1 -C 4 alkyl, and mixtures thereof; R 9a and R 9b can be taken together to form a carbocyclic or heterocyclic ring comprising from 3 to 7 atoms; two R 10 units can be take together to form a carbocyclic or heterocyclic ring comprising from 3 to 7 atoms; j is an index from 0 to 5, n is an index from 0 to 5; Z is O, S, NR 11 , or NOR 11 ; R 11 is hydrogen or C 1 -C 4 alkyl.

  本发明涉及一种化合物，其能够预防炎性细胞因子的细胞外释放。该化合物包括所有对映异构体和二对映异构体形式以及其药学上可接受的盐，其化学式如下：1其中R包括醚或胺；R1是：a）取代或未取代的芳基；或b）取代或未取代的杂环芳基；每个R2单元独立地选自以下组：a）氢；b）—（CH2）jO（CH2）nR8；c）—（CH2）jNR9aR9b；d）—（CH2）jCO2R10；e）—（CH2）jOCO2R10f）—（CH2）jCON（R10）2；g）—（CH2）jOCON（R10）2；h）两个R2单元可以结合成一个羰基单元；i）以及其混合物；R8、R9a、R9b和R10各自独立地是氢、C1-C4烷基或其混合物；R9a和R9b可以结合成由3到7个原子组成的环状或杂环状环；两个R10单元可以结合成由3到7个原子组成的环状或杂环状环；j是从0到5的指数，n是从0到5的指数；Z为O、S、NR11或NOR11；R11为氢或C1-C4烷基。
• 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。