4-[2-(4-fluorophenyl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrol-3-yl]pyridine | 321344-76-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-[2-(4-fluorophenyl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrol-3-yl]pyridine
• 英文别名: 2-(4-fluorophenyl)-3-(pyridin-4-yl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrole
• CAS: 321344-76-7
• 化学式: C₂₀H₁₈FN₃
• 分子量: 319.381
• InChiKey: KBSNHBCOFHIUOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  40.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[2-(4-fluorophenyl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrol-3-yl]pyridine 在 palladium 10% on activated carbon 、 potassium carbonate 作用下， 以 甲醇 、 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 4.0h， 以53%的产率得到2-(4-fluorophenyl)-3,4-bis(pyridin-4-yl)-1H-pyrrole
  参考文献：
  名称：

  Tetrahydropyridine derivatives with inhibitory activity on the production of proinflammatory cytokines: Part 1

  摘要：

  We investigated proinflammatory cytokine TNF alpha production inhibitors in order to develop novel anti-inflammatory agents. According to the results, we found that 17, a pyrrole derivative possessing a tetrahydropyridine group at the beta-position, showed potent inhibitory activity in vitro (inhibition of lipopolysaccharide (LPS) induced TNF alpha production in human whole blood, IC(50) = 1.86 mu M) and in vivo (inhibition of LPS induced TNF alpha production in mice, ID(50) = 5.98 mg/kg). Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.094
• 作为产物：
  描述：

  2-(4-fluorophenyl)-4-(4-hydroxypiperidin-4-yl)-3-(pyridin-4-yl)-1-triisopropylsilyl-1H-pyrrole 在 三氟乙酸 、 四丁基氟化铵 作用下， 以 二氯甲烷 、 四氢呋喃 为溶剂， 反应 6.0h， 以93%的产率得到4-[2-(4-fluorophenyl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrol-3-yl]pyridine
  参考文献：
  名称：

  Tetrahydropyridine derivatives with inhibitory activity on the production of proinflammatory cytokines: Part 1

  摘要：

  We investigated proinflammatory cytokine TNF alpha production inhibitors in order to develop novel anti-inflammatory agents. According to the results, we found that 17, a pyrrole derivative possessing a tetrahydropyridine group at the beta-position, showed potent inhibitory activity in vitro (inhibition of lipopolysaccharide (LPS) induced TNF alpha production in human whole blood, IC(50) = 1.86 mu M) and in vivo (inhibition of LPS induced TNF alpha production in mice, ID(50) = 5.98 mg/kg). Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.094

文献信息

• Heteroaryl-substituted pyrrole derivatives, their preparation and their therapeutic uses
  申请人：SANKYO COMPANY, LIMITED

  公开号：US20040054173A1

  公开（公告）日：2004-03-18

  Compounds having activity against production of an inflammatory cytokine of formula (I)′: 1 A′ is pyrrole; R 1′ is phenyl or naphthyl; R 2′ is pyridyl or pyrimidinyl; R 3′ is (IIa)′, (IIb)′ or (IIc)′: 2 m′ is 1; E′ is nitrogen; D′ is >C(R 5′ )—, R 5′ is hydrogen, Substituent &agr;′ or Substituent &bgr;′; B′ is nitrogen-containing 5-membered heterocyclic; R 4′ is 1 to 3 substituents from Substituent &agr;′, Substituent &bgr;′ and Substituent &ggr;′; R 1′ and R 3′ are bonded to two atoms of the pyrrole adjacent to the pyrrole atom bonded to R 2′ ; Substituent &agr;′ is hydroxyl, nitro, cyano, halogen, alkoxy, halogeno alkoxy, alkylthio, halogeno alkylthio or —NR a′ R b′ ; R a′ and R b′ are hydrogen, alkyl, alkenyl, alkynyl, aralkyl or alkylsulfonyl, or R a′ and R b′ with the nitrogen atom form a heterocyclyl; Substituent &bgr;′ is alkyl, alkenyl, alkynyl, aralkyl or cycloalkyl; Substituent &ggr;′ is oxo, hydroxyimino, alkoxyimino, alkylene, alkylenedioxy, alkylsulfinyl, alkylsulfonyl, aryl, aryloxy, alkylidenyl or aralkylidenyl.

  具有对抗公式(I)′炎症细胞因子生成活性的化合物： 1 A′是吡咯；R 1′ 是苯基或萘基；R 2′ 是吡啶基或嘧啶基；R 3′ 是(IIa)′，(IIb)′或(IIc)′： 2 m′是1；E′是氮；D′是>C(R 5′ )—, R 5′ 是氢，取代基α′或取代基β′；B′是含氮的5-成员杂环；R 4′ 是来自取代基α′，取代基β′和取代基γ′的1至3个取代基；R 1′ 和R 3′ 分别与吡咯环上与R 2′ 相连的吡咯原子的两个相邻原子成键；取代基α′是羟基，硝基，氰基，卤素，烷氧基，卤代烷氧基，烷基亚砜，卤代烷基亚砜或—NR a′ R b′ ；R a′ 和R b′ 是氢，烷基，烯基，炔基，芳烷基或烷基亚磺酰基，或者R a′ 和R b′ 与氮原子形成杂环；取代基β′是烷基，烯基，炔基，芳烷基或环烷基；取代基γ′是氧代，羟基亚胺，烷氧基亚胺，亚烷基，亚烷基二氧，烷基亚磺酰基，烷基亚磺酰基，芳基，芳氧基，亚烷基或芳亚烷基。
• Heteroaryl-substituted pyrrole derivates, their preparation and their therapeutic uses
  申请人：Sankyo Company Limited

  公开号：EP1243589A1

  公开（公告）日：2002-09-25

  Compounds of formula (I): [wherein: A is a pyrrole ring; R1 is an optionally substituted phenyl or naphthyl group; R2 is an optionally substituted pyridyl or pyrimidinyl group; R3 represents a group of the formula -X-R4, wherein X is a single bond or an alkenylene group, and R4 is an optionally substituted nitrogen-containing heterocyclyl group; selected from the group consisting of 8-azabicyclo[3.2.1]octenyl, 9-azabicyclo[3.3.1]nonenyl and quinuclidinenyl groups, PROVIDED THAT said substituents R1 and R3 are bonded to the two atoms of said pyrrole ring which are adjacent to the atom of the pyrrole ring to which said substituent R2 is bonded] have excellent inhibitory activity against the production of inflammatory cytokines.

  化合物的结构式（I）：[其中：A为吡咯环；R1为可选取代的苯或萘基团；R2为可选取代的吡啶或嘧啶基团；R3代表具有下述结构的基团-X-R4，其中X为单键或烯基链，R4为可选取代的含氮杂环基团；所选取自8-氮杂双环[3.2.1]辛烯基、9-氮杂双环[3.3.1]壬烯基和喹啉环基团，前提是所述取代基R1和R3连接到所述吡咯环的两个相邻原子，这两个原子与所述取代基R2连接的吡咯环原子相邻]具有出色的抑制炎症细胞因子产生活性。
• CYCLIC TERTIARY AMINE COMPOUND
  申请人：Sankyo Company, Limited

  公开号：EP1632488A1

  公开（公告）日：2006-03-08

  The present invention provides a cyclic tertiary amine compound which is capable of inhibiting the production of inflammatory cytokines. It is either a compound having a structure represented by the following general formula (I): (wherein A represents an optionally substituted trivalent group derived from pyrimidine, pyrrole, or the like; R1 represents an aryl or a heteroaryl group which may optionally be substituted; R2 represents a heteroaryl group which may optionally be substituted; and R3 represents a cyclic tertiary amino group) or a pharmacologically acceptable salt of the compound.

  本发明提供了一种能够抑制炎症细胞因子产生的环状三级胺化合物。它是具有以下一般式(I)所表示结构的化合物：（其中A表示从嘧啶、吡咯等衍生的可选择取代的三价基团；R1表示可能被取代的芳基或杂环芳基团；R2表示可能被取代的杂环芳基团；R3表示环状三级胺基团），或该化合物的药理学可接受的盐。
• Cyclic tertiary amine compound
  申请人：Kimura Tomio

  公开号：US20070049620A1

  公开（公告）日：2007-03-01

  A cyclic tertiary amine compound which is capable of inhibiting the production of inflammatory cytoines. The compound having a structure represented by the following formula (I): wherein A represents an optionally substituted trivalent group which is benzene, pyrimidine, pyrrole, pyridine, pyridazine, furan, thiopene, pyrazole, imidazole, isoxazole or isothiazole; R 1 represents an aryl or a heteroaryl group, which is unsubstituted or substituted; R 2 represents a heteroaryl group which is unsubtituted or substituted; and R 3 represents a cyclic tertiary amino group, or a pharmacologically acceptable salt of the compound.

  一种环状三级胺化合物，能够抑制炎症细胞因子的产生。该化合物具有以下式子（I）所表示的结构：其中A代表苯、嘧啶、吡咯、吡啶、吡嗪、呋喃、噻吩、吡唑、咪唑、异恶唑或异硫唑的可选取代三价基团；R1代表非取代或取代的芳基或杂环基团；R2代表非取代或取代的杂环基团；R3代表环状三级胺基团，或该化合物的药理学上可接受的盐。
• COMPOSITIONS FOR PREVENTION OR TREATMENT OF HEPATOPATHY
  申请人：Sankyo Company, Limited

  公开号：EP1352906A1

  公开（公告）日：2003-10-15

  [Object] The object of the present invention is to provide a composition for the prophylaxis or treatment of hepatopathy. [Solution] A composition containing as an active ingredient a compound of formula (I), or a pharmacologically acceptable salt, ester or other derivative thereof for the prophylaxis or treatment of hepatopathy: [wherein: A is a pyrrole ring; R1 is an optionally substituted aryl or heteroaryl group; R2 is an optionally substituted heteroaryl group; R3 represents a group of the formula -X-R4, wherein X is a single bond or an optionally substituted alkylene, alkenylene or alkynylene group, and R4 is a substituted cycloalkyl group, a substituted aryl group, an optionally substituted heterocyclyl group, an optionally substituted heteroaryl group, or -NRaRb, wherein each of Ra and Rb is a hydrogen atom or an alkyl, alkenyl, alkynyl, aralkyl or alkylsulfonyl group; PROVIDED THAT said substituents R1 and R3 are bonded to the two atoms of said pyrrole ring which are adjacent to the atom of the pyrrole ring to which said substituent R2 is bonded].

  目的 本发明的目的是提供一种用于预防或治疗肝病的组合物。 [解决方案］ 一种含有式(I)化合物或其药理学上可接受的盐、酯或其他衍生物作为活性成分的组合物，用于预防或治疗肝病： 其中A 是吡咯环； R1 是任选取代的芳基或杂芳基； R2 是任选取代的杂芳基；R3代表式-X-R4的基团，其中X是单键或任选取代的亚烷基、亚烯基或亚炔基，R4是取代的环烷基、取代的芳基、任选取代的杂环烷基、任选取代的杂芳基，或-NRaRb，其中Ra和Rb各自是氢原子或烷基、烯基、炔基、芳基或烷基磺酰基；前提是所述取代基 R1 和 R3 与所述吡咯环的两个原子键合，这两个原子与所述取代基 R2 键合的吡咯环原子相邻]。