4-(4-(4-甲酰基-2,6-二甲基苯基氨基)嘧啶-2-基氨基)苯甲腈 | 500293-29-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(4-(4-甲酰基-2,6-二甲基苯基氨基)嘧啶-2-基氨基)苯甲腈
• 英文名称: 4-[4-(4-formyl-2,6-dimethylphenylamino)pyrimidin-2-ylamino]benzonitrile
• 英文别名: 4-((4-((4-Formyl-2,6-dimethylphenyl)amino)pyrimidin-2-yl)amino)benzonitrile；4-[[4-(4-formyl-2,6-dimethylanilino)pyrimidin-2-yl]amino]benzonitrile
• CAS: 500293-29-8
• 化学式: C₂₀H₁₇N₅O
• 分子量: 343.388
• InChiKey: JVBGOWLILCYEFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  90.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(4-(4-甲酰基-2,6-二甲基苯基氨基)嘧啶-2-基氨基)苯甲腈 在 Jones reagent 、 正丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 4-{4-[4-(2-cyanoacetyl)-2,6-dimethylphenylamino]pyrimidin-2-ylamino}benzonitrile
  参考文献：
  名称：

  Pharmaceutical compositions comprising a basic drug compound, a surfactant, and a physiologically tolerable water soluble acid

  摘要：

  这项发明提供了一种新型的药物组合物，包括一种碱性或酸性药物化合物、表面活性剂和一种生理耐受的水溶性酸或碱，其特点在于酸或碱与药物化合物的比例至少为1:1（按重量计）。

  公开号：

  US09192577B2
• 作为产物：
  描述：

  4-(4-(4-(羟基甲基)-2,6-二甲基苯基氨基)嘧啶-2-基氨基)苯甲腈 以69的产率得到4-(4-(4-甲酰基-2,6-二甲基苯基氨基)嘧啶-2-基氨基)苯甲腈
  参考文献：
  名称：

  Hiv inhibiting pyrimidines derivatives

  摘要：

  本发明涉及公式（I）的HIV复制抑制剂，其N-氧化物，药学上可接受的加成盐，季铵盐及其立体化学异构体，其中包含-a1＝a2-a3＝a4-和-b1＝b2-b3＝b4-的环表示苯基，吡啶基，嘧啶基，吡嗪基，吡咯嗪基；n为0至5；m为1至4；R1为氢；芳基；甲酰基；C1-6烷基羰基；C1-6烷基；C1-6烷氧羰基，取代的C1-6烷基，C1-6烷基羰基；R2为羟基，卤素，可选取代的C1-6烷基，C3-7环烷基，可选取代的C2-6烯基，可选取代的C2-6炔基，C1-6烷氧基，C1-6烷氧羰基，羧基，氰基，硝基，氨基，单烷基或双（C1-6烷基）氨基，多卤甲基，多卤甲氧基，多卤甲硫基，-S(═O)pR6，-NH-S(═O)pR6，-C(═O)R6，-NHC(═O)H，-C(═O)NHNH?2?，-NHC(═O)R6，-C(═NH)R6或5-成员杂环；X1为-NR5-，-NH-NH-，-N═N-，-O-，-C(═O)-，C1-4烷二基，-CHOH-，-S-，-S(═O)p-，-X2-C1-4烷二基-或-C1-4烷二基-X2-；R3为NHR13，NR13R14；-C(═O)-NHR13；-C(═O)-NR13R14；-C(═O)-R15；-CH═N-NH-C(═O)-R16；取代的C1-6烷基；可选取代的C1-6烷氧基C1-6烷基；取代的C2-6烯基；取代的C2-6炔基；取代的C2-6烷基；C1-6烷基取代羟基和第二取代基；-C(═N-O-R8)-C1-4烷基；R7；或-X3-R7；R4为卤素，羟基，C1-6烷基，C3-7环烷基，C1-6烷氧基，氰基，硝基，多卤C1-6烷基，多卤C1-6烷氧基，氨基羰基，C1-6烷氧羰基，C1-6烷基羰基，甲酰基，氨基，单烷基或双（C1-4烷基）氨基；它们作为药物的用途，它们的制备方法和包含它们的制药组合物。

  公开号：

  US20040198739A1

文献信息

• [EN] HIV INHIBITING PYRIMIDINES DERIVATIVES<br/>[FR] DERIVES DE PYRIMIDINES INHIBITEURS DE VIH
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2003016306A1

  公开（公告）日：2003-02-27

  This invention concerns HIV replication inhibitors of formula (I) the N-oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, wherein the ring containing -a?1=a2-a3=a4¿- and -b?1=b2-b3=b4¿- represents phenyl, pyridyl, pyrimidinyl, pirazinyl, pyridazinyl;n is 0 to 5; m is 1 to 4; R1 is hydrogen; aryl; formyl; C¿1-6?alkylcarbonyl; C?1-6¿alkyl; C¿1-6?alkyloxycarbonyl, substituted C1-6alkyl, C1-6alkylcarbonyl; R?2¿ is hydroxy, halo, optionally substituted C¿1-6?alkyl, C3-7cycloalkyl, optionally substituted C2-6alkenyl, optionally substituted C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, -S(=O)pR?6¿, -NH-S(=O)¿pR?6, -C(=O)R6, -NHC(=O)H, -C(=O)NHNH?2?, -NHC(=O)R?6¿, -C(=NH)R6 or a 5-membered heterocycle; X¿1? is -NR?5¿-, -NH-NH-, -N=N-, -O-, -C(=O)-, C¿1-4?alkanediyl, -CHOH-, -S-, -S(=O)p-, -X2-C1-4alkanediyl- or -C1-4alkanediyl-X2-; R?3 is NHR13; NR13R14¿; -C(=O)-NHR13; -C(=O)-NR13R14; -C(=O)-R15; -CH=N-NH-C(=O)-R16; substituted C¿1-6?alkyl; optionally substituted C1-6alkyloxyC1-6alkyl; substituted C2-6alkenyl; substituted C2-6alkynyl; C1-6alkyl substituted with hydroxy and a second substituent; -C(=N-O-R?8)-C¿1-4alkyl; R7; or -X¿3?-R?7; R4¿ is halo, hydroxy, C¿1-6?alkyl, C3-7cycloalkyl, C1-6alkyloxy, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, aminocarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyl, formyl, amino, mono- or di(C1-4alkyl)amino; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

  本发明涉及公式（I）的HIV复制抑制剂，其N-氧化物，药学上可接受的加成盐，季铵盐和立体化学异构体形式，其中含有-a?1=a2-a3=a4¿-和-b?1=b2-b3=b4¿-的环表示苯基，吡啶基，嘧啶基，吡嗪基，吡啶嗪基; n为0至5; m为1至4; R1为氢; 芳基; 甲酰基; C¿1-6?烷基酰基; C?1-6¿烷基; C¿1-6?烷氧羰基，取代的C1-6烷基，C1-6烷基酰基; R?2¿为羟基，卤素，可选取代的C¿1-6?烷基，C3-7环烷基，可选取代的C2-6烯基，可选取代的C2-6炔基，C1-6烷氧基，C1-6烷氧羰基，羧基，氰基，硝基，氨基，单烷基或二（C1-6烷基）氨基，多卤代甲基，多卤代甲氧基，多卤代甲硫基，-S（= O）pR?6¿，-NH-S（= O）¿pR?6，-C（= O）R6，-NHC（= O）H，-C（= O）NHNH?2？，-NHC（= O）R?6¿，-C（= NH）R6或5-成员杂环; X¿1？为-NR?5¿-，-NH-NH-，-N=N-，-O-，-C（= O）-，C¿1-4?烷二基，-CHOH-，-S-，-S（= O）p-，-X2-C1-4烷二基-或-C1-4烷二基-X2-; R?3为NHR13; NR13R14¿; -C（= O）-NHR13; -C（= O）-NR13R14; -C（= O）-R15; -CH=N-NH-C（= O）-R16; 取代的C¿1-6?烷基; 可选取代的C1-6烷氧C1-6烷基; 取代的C2-6烯基; 取代的C2-6炔基; C1-6烷基取代羟基和第二取代基; -C（= N-O-R?8）-C¿1-4烷基; R7; 或-X¿3？-R?7; R4¿为卤素，羟基，C¿1-6?烷基，C3-7环烷基，C1-6烷氧基，氰基，硝基，多卤代C1-6烷基，多卤代C1-6烷氧基，氨基羰基，C1-6烷氧羰基，C1-6烷基羰基，甲酰基，氨基，单烷基或二（C1-4烷基）氨基; 它们作为药物的用途，其制备过程和包含它们的制药组合物。
• HIV INHIBITING PYRIMIDINES DERIVATIVES
  申请人：Guillemont Jérôme Emile Georges

  公开号：US20120076835A1

  公开（公告）日：2012-03-29

  This invention concerns HIV replication inhibitors of formula the N-oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

  这项发明涉及公式为N-氧化物、药学上可接受的加合物、季铵盐及其立体化学异构体的HIV复制抑制剂；它们作为药物的使用、它们的制备过程以及包含它们的制药组合物。
• HIV REPLICATION INHIBITING PYRIMIDINES
  申请人：Janssen Pharmaceutica NV

  公开号：EP3808743A1

  公开（公告）日：2021-04-21

  This invention concerns HIV replication inhibitors of formula the N-oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, wherein the ring containing -a1=a2-a3=a4- and -b1=b2-b3=b4- represents phenyl, pyridyl, pyrimidinyl, pirazinyl, pyridazinyl;n is 0 to 5; m is 1 to 4; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; C1-6alkyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyloxy; substituted Cl-6alkyloxyCl-6alkylcarbonyl; R2 is hydroxy, halo, optionally substituted C1-6alkyl, C3-7cycloalkyl, optionally substituted C2-6alkenyl, optionally substituted C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, -S(=O)pR6, -NH-S(=O)pR6, -C(=O)R6, -NHC(=O)H, -C(=O)NHNH2, -NHC(=O)R6, -C(=NH)R6 or a 5-membered heterocycle; X1 is -NR5-, -NH-NH-, -N=N-, -O-, -C(=O)-, C1-4alkanediyl, -CHOH-, -S-, -S(=O)p-, -X2-C1-4alkanediyl- or -C1-4alkanediyl-X2-; R3 is NHR13; NR13R14; -C(=O)-NER13; -C(=O)-NR13R14; -C(=O)-R15; -CH=N-NH-C(=O)-R16; substituted C1-6alkyl; optionally substituted C1-6alkyloxyC1-6alkyl; substituted C2-6alkenyl; substituted C2-6alkynyl; C1-6alkyl substituted with hydroxy and a second substituent; -C(=N-O-R8)-C1-4alkyl; R7; or -X3-R7; R4 is halo, hydroxy, C1-6alkyl, C3-7cycloalkyl, C1-6alkyloxy, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, aminocarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyl, formyl, amino, mono- or di(C1-4alkyl)amino; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

  本发明涉及式中的艾滋病毒复制抑制剂 的N-氧化物、药学上可接受的加成盐、季胺及其立体异构体形式，其中含有-a1=a2-a3=a4-和-b1=b2-b3=b4-的环代表苯基、吡啶基、嘧啶基、吡嗪基、哒嗪基；取代的C1-6烷氧基Cl-6烷基羰基；R2 是羟基、卤代、任选取代的 C1-6 烷基、C3-7 环烷基、任选取代的 C2-6 烯基、任选取代的 C2-6 烷炔基、C1-6烷氧基、C1-6烷氧基羰基、羧基、氰基、硝基、氨基、单或双（C1-6烷氧基羰基）、C1-6烷氧基羰基、C1-6烷基羧基、C1-6烷基羰基氨基、单-或二(C1-6烷基)氨基、多卤甲基、多卤甲基氧基、多卤甲基硫代、-S(＝O)pR6、-NH-S(＝O)pR6、-C(＝O)R6、-NHC(＝O)H、-C(＝O)NHNH2、-NHC(＝O)R6、-C(＝NH)R6 或 5 元杂环；X1 是-NR5-、-NH-NH-、-N=N-、-O-、-C(=O)-、C1-4烷二基、-CHOH-、-S-、-S(=O)p-、-X2-C1-4烷二基-或-C1-4烷二基-X2-； R3 是 NHR13；NR13R14；-C(=O)-NER13；-C(=O)-NR13R14；-C(=O)-R15；-CH=N-NH-C(=O)-R16；取代的 C1-6 烷基；任选取代的 C1-6 烷氧基 C1-6 烷基；取代的 C2-6 烯基；取代的 C2-6 烷炔基；被羟基和第二个取代基取代的 C1-6 烷基；-R4为卤代、羟基、C1-6烷基、C3-7环烷基、C1-6烷氧基、氰基、硝基、多卤代C1-6烷基、多卤代C1-6烷氧基、氨基羰基、C1-6烷氧基羰基、C1-6烷基羰基、甲酰基、氨基、单-或二(C1-4烷基)氨基；它们的医药用途、制备工艺和包含它们的药物组合物。
• HIV replication inhibiting pyrimidines
  申请人：Janssen Pharmaceutica NV

  公开号：US10370340B2

  公开（公告）日：2019-08-06

  This invention concerns HIV replication inhibitors of formula the N-oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, wherein the ring containing -a1=a2-a3=a4- and -b1=b2-b3=b4- represents phenyl, pyridyl, pyrimidinyl, pirazinyl, pyridazinyl; n is 0 to 5; m is 1 to 4; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; C1-6alkyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyloxy; substituted C1-6alkyloxyC1-6alkylcarbonyl; R2 is hydroxy, halo, optionally substituted C1-6alkyl, C3-7cycloalkyl, optionally substituted C2-6alkenyl, optionally substituted C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, —NHC(═O)R6, —C(═NH)R6 or a 5-membered heterocycle; X1 is —NR5—, —NH—NH—, —N═N—, —O—, —C(═O)—, C1-4alkanediyl, —CHOH—, —S—, —S(═O)p—, —X2—C1-4alkanediyl- or —C1-4alkanediyl-X2—; R3 is NHR13; NR13R14; —C(═O)—NHR13; —C(═O)—NR13R14; —C(═O)—R15; —CH═N—NH—C(═O)—R16; substituted C1-6alkyl; optionally substituted C1-6alkyloxyC1-6alkyl; substituted C2-6alkenyl; substituted C2-6alkynyl; C1-6alkyl substituted with hydroxy and a second substituent; —C(═N—O—R8)—C1-4alkyl; R7; or —X3—R7; R4 is halo, hydroxy, C1-6alkyl, C3-7cycloalkyl, C1-6alkyloxy, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, aminocarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyl, formyl, amino, mono- or di(C1-4alkyl)amino; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

  本发明涉及式中的艾滋病毒复制抑制剂 的N-氧化物、药学上可接受的加成盐、季胺及其立体异构体形式，其中含有-a1=a2-a3=a4-和-b1=b2-b3=b4-的环代表苯基、吡啶基、嘧啶基、吡嗪基、哒嗪基；n 为 0 至 5；m 为 1 至 4；R1 为氢；芳基；甲酰基；C1-6烷基羰基；C1-6烷基；C1-6烷氧基羰基；取代的 C1-6烷基、C1-6烷基羰基、C1-6烷氧基羰基、C1-6烷基羰基氧基、C1-6烷基羧基取代的 C1-6 烷氧基 C1-6 烷基羰基；R2 是羟基、卤代、任选取代的 C1-6 烷基、C3-7 环烷基、任选取代的 C2-6 烯基、任选取代的 C2-6 烷炔基、C1-6 烷氧基、C1-6 烷氧羰基、羧基、氰基、硝基、氨基、单或二(C1-6烷基)氨基、多卤代甲基、多卤代甲基氧基、多卤代甲硫基、-S(═O)pR6、-NH-S(═O)pR6、-C(═O)R6、-NHC(═O)H、-C(═O)NHNH2、-NHC(═O)R6、-C(═NH)R6 或 5 元杂环；X1 是-NR5-、-NH-NH-、-N═N-、-O-、-C(═O)-、C1-4烷二基、-CHOH-、-S-、-S(═O)p-、-X2-C1-4烷二基-或-C1-4烷二基-X2-； R3 是 NHR13； NR13R14；-C(═O)-NHR13；-C(═O)-NR13R14；-C(═O)-R15；-CH═N-NH-C(═O)-R16；取代的 C1-6 烷基；任选取代的 C1-6 烷氧基 C1-6 烷基；取代的 C2-6 烯基；取代的 C2-6 烷炔基；被羟基和第二个取代基取代的 C1-6 烷基；-C(═N-O-R8)-C1-4烷基；R7；或-X3-R7；R4是卤代、羟基、C1-6烷基、C3-7环烷基、C1-6烷氧基、氰基、硝基、多卤代C1-6烷基、多卤代C1-6烷氧基、氨基羰基、C1-6烷氧基羰基、C1-6烷基羰基、甲酰基、氨基、单-或二(C1-4烷基)氨基；它们作为药物的用途、制备工艺和由它们组成的药物组合物。
• Synthesis of Novel Diarylpyrimidine Analogues and Their Antiviral Activity against Human Immunodeficiency Virus Type 1
  作者：Jerome Guillemont、Elisabeth Pasquier、Patrice Palandjian、Daniel Vernier、Sandrine Gaurrand、Paul J. Lewi、Jan Heeres、Marc R. de Jonge、Lucien M. H. Koymans、Frits F. D. Daeyaert、Maarten H. Vinkers、Eddy Arnold、Kalyan Das、Rudi Pauwels、Koen Andries、Marie-Pierre de Béthune、Eva Bettens、Kurt Hertogs、Piet Wigerinck、Philip Timmerman、Paul A. J. Janssen

  DOI：10.1021/jm040838n

  日期：2005.3.1

  This paper reports the synthesis and the antiviral properties of new diarylpyrimidine (DAPY) compounds as nonnucleoside reverse transcriptase inhibitors (NNRTIs). The synthesis program around this new DAPY series was further optimized to produce compounds displaying improved activity against a panel of eight clinically relevant single and double mutant strains of human immunodeficiency virus type 1 (HIV-1).