Methyl 3-[(4-methylsulfonylphenyl)methyl]-4-oxo-1-phenyl-7-(trifluoromethyl)-1,8-naphthyridine-2-carboxylate | 1080674-72-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: Methyl 3-[(4-methylsulfonylphenyl)methyl]-4-oxo-1-phenyl-7-(trifluoromethyl)-1,8-naphthyridine-2-carboxylate
• CAS: 1080674-72-1
• 化学式: C₂₅H₁₉F₃N₂O₅S
• 分子量: 516.497
• InChiKey: CGUOXTCHDHXWRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  1-(2-chloro-6-(trifluoromethyl)pyridin-3-yl)ethanone 在 10% Pd/C 、 氢气 、 palladium diacetate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 Methyl 3-[(4-methylsulfonylphenyl)methyl]-4-oxo-1-phenyl-7-(trifluoromethyl)-1,8-naphthyridine-2-carboxylate
  参考文献：
  名称：

  Discovery of a novel series of 4-quinolone JNK inhibitors

  摘要：

  A novel series of highly selective JNK inhibitors based on the 4-quinolone scaffold was designed and synthesized. Structure based drug design was utilized to guide the compound design as well as improvements in the physicochemical properties of the series. Compound (13c) has an IC50 of 62/170 nM for JNK1/2, excellent kinase selectivity and impressive efficacy in a rodent asthma model. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.10.066

文献信息

• Dihydroquinone and dihydronaphthridine inhibitors of JNK
  申请人：Abbot Sarah C.

  公开号：US20080287458A1

  公开（公告）日：2008-11-20

  Compounds of formula I are effective modulators of JNK: wherein X is CR 11 or N; Y is —C(O)R 3 , 5-membered heteroaryl, or 5-membered heterocyclyl; Z is phenyl, cycloalkyl, heterocyclyl or heteroaryl, and is substituted with R 1 and R 2 ; R 1 and R 2 are each independently H, halo, CN, lower alkyl, or —Y 1 —Y 2 —Y 3 —R 8 , or R 1 and R 2 together form —O(CH 2 ) n O—, where n is 1 or 2; Y 1 is —O—, —C(O)—, —C(O)O—, —C(O)NR 9 —, —NR 9 C(O)—, —S—, —SO 2 —, or a bond; Y 2 is cycloalkylene, heterocycloalkylene, lower alkylene or a bond; Y 3 is —O—, —C(O)—, —C(O)O—, —C(O)NR 9 —, —NR 9 C(O)—, —SO 2 —, or a bond; R 8 is H, lower alkyl, lower alkoxy, cycloalkyl, heterocycloalkyl, or —NR 9 R 10 , wherein R 8 other than H is optionally substituted with lower alkyl, halo, —CF 3 , or —OH; R 9 and R 10 are each independently H or lower alkyl; R 3 is OH, lower alkyl, lower alkoxy, (lower alkoxy)-lower alkoxy, or —NR 9 R 10 ; R 4 is lower alkyl, phenyl, heterocyclyl, cycloalkyl, heterocycloalkyl, or heteroaryl, and is optionally substituted with lower alkyl, hydroxy, lower alkoxy, halo, nitro, amino, cyano, or halo-lower alkyl; R 5 and R 6 are each independently H, halo, cyano, lower alkyl, —CF 3 , lower alkoxy, —OCHF 2 , —NO 2 , or —NR 9 R 10 ; R 7 is H, F, Cl, methyl, or OH; R 11 is H, lower alkyl, lower cycloalkyl, or phenyl; or a pharmaceutically acceptable salt thereof.

  式I的化合物是JNK的有效调节剂： 其中 X为CR11或N； Y为—C(O)R3，5-成员杂芳基，或5-成员杂环烷基； Z为苯基，环烷基，杂环烷基或杂芳基，并且被R1和R2取代； R1和R2各自独立地为H，卤素，CN，较低烷基，或—Y1—Y2—Y3—R8，或R1和R2一起形成—O(CH2)nO—，其中n为1或2； Y1为—O—，—C(O)—，—C(O)O—，—C(O)NR9—，—NR9C(O)—，—S—，—SO2—，或键； Y2为环烷亚烷基，杂环烷亚烷基，较低烷基亚烷基或键； Y3为—O—，—C(O)—，—C(O)O—，—C(O)NR9—，—NR9C(O)—，—SO2—，或键； R8为H，较低烷基，较低烷氧基，环烷基，杂环烷基，或—NR9R10，其中R8除H外可选择地被较低烷基，卤素，—CF3，或—OH取代； R9和R10各自独立地为H或较低烷基； R3为OH，较低烷基，较低烷氧基，(较低烷氧基)-较低烷氧基，或—NR9R10； R4为较低烷基，苯基，杂环烷基，环烷基，杂环烷基，或杂芳基，并且可选择地被较低烷基，羟基，较低烷氧基，卤素，硝基，氨基，氰基，或卤素较低烷基取代； R5和R6各自独立地为H，卤素，氰基，较低烷基，—CF3，较低烷氧基，—OCHF2，—NO2，或—NR9R10； R7为H，F，Cl，甲基，或OH； R11为H，较低烷基，较低环烷基，或苯基； 或其药用可接受盐。
• DIHYDROQUINONE AND DIHYDRONAPHTHRIDINE INHIBITORS OF JNK
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2148862B1

  公开（公告）日：2012-03-28
• US8163906B2
  申请人：——

  公开号：US8163906B2

  公开（公告）日：2012-04-24
• [EN] DIHYDROQUINONE AND DIHYDRONAPHTHRIDINE INHIBITORS OF JNK<br/>[FR] INHIBITEURS DE JNK À BASE DE DIHYDROQUINONE ET DE DIHYDRONAPHTRIDINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2008138920A1

  公开（公告）日：2008-11-20

  [EN] Compounds of formula I or a pharmaceutically acceptable salt thereof are effective modulators of JNK: (formula) wherein X, Y, Z, R⁴, R⁵, R⁶ and R⁷ are as defined herein.
  [FR] L'invention concerne des composés représentés par la formule I ou un sel pharmaceutiquement acceptable de ceux-ci, qui constituent des modulateurs efficaces de JNK: X, Y, Z, R⁴, R⁵, R⁶ et R⁷ étant définis dans le descriptif.
• Discovery of a novel series of 4-quinolone JNK inhibitors
  作者：Leyi Gong、Yun-Chou Tan、Genevieve Boice、Sarah Abbot、Kristen McCaleb、Pravin Iyer、Fengrong Zuo、Joseph Dal Porto、Brian Wong、Sue Jin、Alice Chang、Patricia Tran、Gary Hsieh、Linghao Niu、Ada Shao、Deborah Reuter、Christine M. Lukacs、R. Ursula Kammlott、Andreas Kuglstatter、David Goldstein

  DOI：10.1016/j.bmcl.2012.10.066

  日期：2012.12

  A novel series of highly selective JNK inhibitors based on the 4-quinolone scaffold was designed and synthesized. Structure based drug design was utilized to guide the compound design as well as improvements in the physicochemical properties of the series. Compound (13c) has an IC50 of 62/170 nM for JNK1/2, excellent kinase selectivity and impressive efficacy in a rodent asthma model. Published by Elsevier Ltd.