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 | 823786-21-6

• 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-(羟基甲基)-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-hydroxymethyl-2,6-dimethylphenylamino)pyrimidin-2-ylamino]benzonitrile
• 英文别名: 4-((4-((4-(Hydroxymethyl)-2,6-dimethylphenyl)amino)pyrimidin-2-yl)amino)benzonitrile；4-[[4-[4-(hydroxymethyl)-2,6-dimethylanilino]pyrimidin-2-yl]amino]benzonitrile
• CAS: 823786-21-6
• 化学式: C₂₀H₁₉N₅O
• 分子量: 345.404
• InChiKey: QYMDCCDRTJHJIB-UHFFFAOYSA-N

物化性质

• 熔点：
  246 °C(Solv: isopropyl ether (108-20-3))
• 沸点：
  601.8±65.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  93.9
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  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 在 manganese(IV) oxide 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 29.0h， 生成 利匹韦林
  参考文献：
  名称：

  Synthesis of Novel Diarylpyrimidine Analogues and Their Antiviral Activity against Human Immunodeficiency Virus Type 1

  摘要：

  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).

  DOI：

  10.1021/jm040838n
• 作为产物：
  描述：

  4-N[2(4-氯吡啶基)]-氨基苯腈 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 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
  参考文献：
  名称：

  Synthesis of Novel Diarylpyrimidine Analogues and Their Antiviral Activity against Human Immunodeficiency Virus Type 1

  摘要：

  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).

  DOI：

  10.1021/jm040838n

文献信息

• Pharmaceutical compositions comprising a basic drug compound, a surfactant, and a physiologically tolerable water soluble acid
  申请人：Vandecruys Roger Petrus Gerebern

  公开号：US09192577B2

  公开（公告）日：2015-11-24

  The invention provides a novel pharmaceutical composition comprising a basic respectively acidic drug compound, a surfactant and a physiologically tolerable water-soluble acid respectively base characterized in that the acid respectively base:drug compound ratio is at least 1:1 by weight.

  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）。
• [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：——

  公开号：US20040198739A1

  公开（公告）日：2004-10-07

  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 =a 2 -a 3 =a 4 - and -b 1 =b 2 -b 3 =b 4 - represents pheynl, pyridyl, pyrimidinyl, pirazinyl, pyridazinyl;n is 0 to 5; m is 1 to 4; R 1 is hydrogen; aryl; formyl; C 1-6 alkylcarbonyl; C 1-6 alkyl; C 1-6 alkyloxycarbonyl, substituted C 1-6 alkyl, C 1-6 alkylcarbonyl; R 2 is hydroxy, halo, optionally substituted C 1-6 alkyl, C 3-7 cycloalkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, C 1-6 alkyloxy, C 1-6 alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C 1-6 alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O) p R 6 , —NH—S(═O) p R 6 , —C(═O)R 6 , —NHC(═O)H, —C(═O)NHNH?2?, —NHC(═O)R 6 , —C(═NH)R 6 or a 5-membered hetrocycl; X 1 is —NR 5 —, —NH—NH—, —N═N—, —O—, —C(═O)—, C 1-4 alkanediyl, —CHOH—, —S—, —S(═O) p —, —X 2 —C 1-4 alkanediyl- or —C 1-4 alkanediyl-X 2 —; R 3 is NHR 13 , NR 13 R 14 ; —C(═O)—NHR 13 ; —C(═O)—NR 13 R 14 ; —C(═O)—R 15 ; —CH═N—NH—C(═O)—R 16 ; substituted C 1-6 alkyl; optionally substituted C 1-6 alkyloxyC 1-6 alkyl; substituted C 2-6 alkenyl; substituted C 2-6 alkynyl; substituted C 2-6 alkylenyl; C 1-6 alkyl substituted with hydroxy and a second substituent; —C(═N—O—R 8 )—C 1-4 alkyl; R 7 ; or —X 3 —R 7 ; R 4 is halo, hydroxy, C 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkyloxy, cyano, nitro, polyhaloC 1-6 alkyl, polyhaloC 1-6 alkyloxy, aminocarbonyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylcarbonyl, formyl, amino, mono- or di(C 1-4 alkyl) amino; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them. 1

  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。
• J. Med. Chem. 2005, 48, 2072-2079
  作者：

  DOI：——

  日期：——
• Drugs. Fut. 2007, 32, 1046-1052
  作者：

  DOI：——

  日期：——