2-(methylsulfanyl)pyrimidine-4-carbonyl chloride | 503177-82-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(methylsulfanyl)pyrimidine-4-carbonyl chloride
• 英文别名: 2-methylsulfanylpyrimidine-4-carbonyl chloride；2-methylsulfanyl-pyrimidine-4-carbonyl chloride
• CAS: 503177-82-0
• 化学式: C₆H₅ClN₂OS
• 分子量: 188.638
• InChiKey: VDQRBYVOEZALFC-UHFFFAOYSA-N

物化性质

• 沸点：
  306.3±15.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  68.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(methylsulfanyl)pyrimidine-4-carbonyl chloride 在 Oxone 、 sodium hydroxide 、 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 18.5h， 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
• 作为产物：
  描述：

  2-甲硫基-4-嘧啶甲酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-(methylsulfanyl)pyrimidine-4-carbonyl chloride
  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。
• [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。
• Compound which inhibit the release of inflammatory cytokines
  申请人：The Procter & Gamble Company

  公开号：US20030105084A1

  公开（公告）日：2003-06-05

  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; R 2a and R 2b units are each independently hydrogen, ethers, amines, amides, carboxylates, or said units can form a double bond, a carbonyl, or R 2a and R 2b can be taken together to form a substituted or unsubstituted ring comprising from 4 to 8 atoms, said ring selected from the group consisting of: i) carbocyclic; ii) heterocyclic; iii) aryl; iv) heteroaryl; v) bicyclic; and vi) heterobicyclic.

  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，该化合物包括所有对映异构体和二面角异构体形式以及其药学上可接受的盐，其化学式为：1其中R代表醚或胺；R1是：a）取代或未取代芳基；或b）取代或未取代的杂环芳基；R2a和R2b单元分别独立地是氢、醚、胺、酰胺、羧酸盐，或这些单元可以形成双键、羰基，或者R2a和R2b可以结合在一起形成由4到8个原子组成的取代或未取代的环，所述环选择自以下组中：i）碳环；ii）杂环；iii）芳基；iv）杂芳基；v）双环；和vi）杂双环。
• Fused pyrazolone compounds which inhibit the release of inflammatory cytokines
  申请人：The Procter & Gamble Company

  公开号：US06821971B2

  公开（公告）日：2004-11-23

  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: wherein R comprises ethers or amines; R1 is: a) substituted or unsubstituted aryl; or b) substituted or unsubstituted heteroaryl; R2a and R2b units are each independently hydrogen, ethers, amines, amides, carboxylates, or said units can form a double bond, a carbonyl, or R2a and R2b can be taken together to form a substituted or unsubstituted ring comprising from 4 to 8 atoms, said ring selected from the group consisting of: i) carbocyclic; ii) heterocyclic; iii) aryl; iv) heteroaryl; v) bicyclic; and vi) heterobicyclic.

  本发明涉及一种化合物，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面角异构体形式及其药学上可接受的盐，其化学式为：其中R代表醚或胺；R1为：a）取代或未取代的芳基；或b）取代或未取代的杂环芳基；R2a和R2b单元分别独立地为氢、醚、胺、酰胺、羧酸盐，或这些单元可以形成双键、羰基，或R2a和R2b可以结合形成由4至8个原子组成的取代或未取代的环，所述环选自以下组：i）碳环；ii）杂环；iii）芳基；iv）杂环芳基；v）双环；和vi）杂双环。
• The development of monocyclic pyrazolone based cytokine synthesis inhibitors
  作者：Adam Golebiowski、Jennifer A. Townes、Matthew J. Laufersweiler、Todd A. Brugel、Michael P. Clark、Cynthia M. Clark、Jane F. Djung、Steven K. Laughlin、Mark P. Sabat、Roger G. Bookland、John C. VanRens、Biswanath De、Lily C. Hsieh、Michael J. Janusz、Richard L. Walter、Mark E. Webster、Marlene J. Mekel

  DOI：10.1016/j.bmcl.2005.03.007

  日期：2005.5

  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.