2-(4-fluorophenyl)-3-(2-methanesulfonyl-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one | 503071-72-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-fluorophenyl)-3-(2-methanesulfonyl-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one
• 英文别名: 6-(4-fluorophenyl)-7-(2-methylsulfonylpyrimidin-4-yl)-2,3-dihydro-1H-pyrazolo[1,2-a]pyrazol-5-one
• CAS: 503071-72-5
• 化学式: C₁₇H₁₅FN₄O₃S
• 分子量: 374.396
• InChiKey: XGAKJVDFGWJLBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  91.8
• 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-(2-methanesulfonyl-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one 在 NaH 、 苯胺 作用下， 以 四氢呋喃 为溶剂， 以20%的产率得到2-(4-Fluorophenyl)-3-(2-phenylamino-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one
  参考文献：
  名称：

  6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which control inflammatory cytokines

  摘要：

  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。

  公开号：

  US20040038971A1
• 作为产物：
  描述：

  2-[2-(4-fluorophenyl)acetyl]pyrazolidine-1-carboxylic acid benzyl ester 在 palladium on activated charcoal Oxone 、 sodium hydroxide 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 41.5h， 生成 2-(4-fluorophenyl)-3-(2-methanesulfonyl-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one
  参考文献：
  名称：

  Development of Orally Bioavailable Bicyclic Pyrazolones as Inhibitors of Tumor Necrosis Factor-α Production

  摘要：

  2-Aryl-3-pyrimidinyl based tumor necrosis factor-alpha (TNF-alpha) inhibitors, which contain a novel bicyclic pyrazolope core, are described. Many showed low-nanomolar activity against lipopolysaccharide-induced TNF-alpha production in monocytic cells. Secondary screening data are presented for the pyrimidinyl bicyclic pyrazolones. Several of these analogues showed good oral bioavailability in rat and efficacy in the rat iodoacetate in vivo model.

  DOI：

  10.1021/jm049968m

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：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。
• [EN] 1,2-DIHYDROPYRAZOL-3-ONES AS CYTOKINE MEDIATORS<br/>[FR] 1,2-DIHYDROPYRAZOL-3-ONES CONTROLANT LES CYTOKINES INFLAMMATOIRES
  申请人：PROCTER & GAMBLE

  公开号：WO2003080184A1

  公开（公告）日：2003-10-02

  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: (A) wherein R is an ether or amino unit, R1 is substituted phenyl, each R2 and R3 unit is independently selected from the group consisting of: a) hydrogen; and b) substituted or unsubstituted C1-C10 hydrocarbyl selected from the group consisting of: i) C1-C10 linear, branched or cyclic alkyl; ii) C1-C10 aryl; iii) C1-C10 heterocyclic; iv) C1-C10 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，该化合物或其对映体和二对映异构体形式或其药学上可接受的盐具有以下式子：（A），其中R是醚或氨基单元，R1是取代的苯基，每个R2和R3单元独立地选择自以下组：a）氢；和b）取代或未取代的C1-C10烃基，所述C1-C10烃基选择自以下组：i）C1-C10线性、支链或环烷基；ii）C1-C10芳基；iii）C1-C10杂环基；iv）C1-C10杂芳基。
• [EN] 6,7-DIHYDRO-5H-PYRAZOLO[1,2-A]PYRAZOL-1-ONES WHICH CONTROL INFLAMMATORY CYTOKINES<br/>[FR] 6,7-DIHYDRO-5H-PYRAZOLO[1,2-A]PYRAZOL-1-ONES CONTROLANT LES CYTOKINES INFLAMMATOIRES
  申请人：PROCTER & GAMBLE

  公开号：WO2003024971A1

  公开（公告）日：2003-03-27

  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 (I): wherein R comprises ethers or amines; R1 is: a) substituted or unsubstituted aryl; or b) substituted or unsubstituted heteroaryl; each R2 unit is independently selected from the group consisting of: a) hydrogen; b) -(CH¿2?)jO(CH2)nR?8¿; c) -(CH¿2?)jNR?9aR9b¿; d) -(CH¿2?)jCO2R?10¿; e) -(CH¿2?)jOCO?2R10¿ f) -(CH¿2?)jCON(R?10)¿2 g) -(CH2)jOCON(R10)2; h) two R2 units can be taken together to form a carbonyl unit; i) and mixtures thereof; R?8, R9a, R9b, and R10¿ are each independently hydrogen, C¿1?-C4 alkyl, and mixtures thereof; R?9a and R9b¿ can be taken together to form a carbocyclic or heterocyclic ring comprising from 3 to 7 atoms; two R10 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, NR11, or NOR11; R11 is hydrogen or C¿1?-C4 alkyl.

  本发明涉及一种能够防止炎性细胞因子的细胞外释放的化合物，该化合物包括所有对映异构体和立体异构体以及其药学上可接受的盐，其化学式为（I）：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基；每个R2基团独立地选择自以下群组：a）氢；b）-(CH2)jO(CH2)nR8；c）-(CH2)jNR9aR9b；d）-(CH2)jCO2R10；e）-(CH2)jOCO2R10；f）-(CH2)jCON（R10）2；g）-(CH2)jOCON（R10）2；h）两个R2基团可以结合形成一个羰基基团；i）及其混合物；R8、R9a、R9b和R10各自独立地是氢、C1-C4烷基和其混合物；R9a和R9b可以结合形成由3至7个原子组成的环烷基或杂环基；两个R10基团可以结合形成由3至7个原子组成的环烷基或杂环基；j是从0至5的指数，n是从0至5的指数；Z是O、S、NR11或NOR11；R11是氢或C1-C4烷基。