4-[[5-chloro-4-(2,4,6-trimethylphenoxy)-2-pyrimidinyl]amino]benzonitrile

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[[5-chloro-4-(2,4,6-trimethylphenoxy)-2-pyrimidinyl]amino]benzonitrile
• 英文别名: 4-[[5-Chloro-4-(2,4,6-trimethylphenoxy)pyrimidin-2-yl]amino]benzonitrile
• 化学式: C₂₀H₁₇ClN₄O
• 分子量: 364.834
• InChiKey: KVBBXKYHZZJUGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  70.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,4,6-三甲酚 、 4-[(4,5-dichloro-2-pyrimidinyl)amino]benzonitrile 在 sodium hydride 作用下， 以 1,4-二氧六环 、 正己烷 、 mineral oil 为溶剂， 反应 15.25h， 以80.2%的产率得到4-[[5-chloro-4-(2,4,6-trimethylphenoxy)-2-pyrimidinyl]amino]benzonitrile
  参考文献：
  名称：

  PRODRUGS OF HIV REPLICATION INHIBITING PYRIMIDINES

  摘要：

  公开号：

  EP1282607B1

文献信息

• Prodrugs of hiv replication inhibiting pyrimidines
  申请人：——

  公开号：US20030186990A1

  公开（公告）日：2003-10-02

  The present invention concerns compounds of formula (A 1 )(A 2 )N—R 1 (I),the N-oxide forms, the pharmaceutically acceptable addition salts, the quaternary amines and stereochemically isomeric forms thereof, wherein R 1 is substituted C 1-6 alkyl; —S(═O)—R 8 ; —S(═O) 2 —R 8 ; C 7-12 alkylcarbonyl; optionally substituted C 1-6 alkyloxycarbonylC 1-6 alkylcarbonyl; with R 8 being C 1-6 alkyl, aryl 1 or Het 1 ; (A 1 )(A 2 )N— is the covalently bonded form of the corresponding intermediate of formula (A 1 )(A 2 )N—H, which is a HIV replication inhibiting pyrimidine of formula 1

  该发明涉及化合物的公式(A1)(A2)N—R1(I)，其N-氧化物形式、药用可接受的附加盐、季铵盐和立体化学异构体形式，其中R1为取代的C1-6烷基；—S(═O)—R8；—S(═O)2—R8；C7-12烷基羰基；可选择地取代的C1-6烷氧羰基C1-6烷基羰基；其中R8为C1-6烷基、芳基或Het1；(A1)(A2)N—为公式(A1)(A2)N—H对应中间体的共价结合形式，该中间体为公式1的HIV复制抑制嘧啶。
• HIV REPLICATION INHIBITING PYRIMIDINES
  申请人：——

  公开号：US20030114472A1

  公开（公告）日：2003-06-19

  This invention concerns the use of compounds of formula 1 the N-oxides, the pharmaceutically acceptable addition salts, quaternary amines and the stereochemically isomeric forms thereof, wherein -a 1 =-a 2 -a 3 =a 4 - forms a phenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the attached vinyl group; n is 0 to 4; and where possible 5; R 1 is hydrogen, aryl, formyl, C 1-6 alkylcarbonyl, C 1-6 alkyl, C 1-6 alkyloxy-carbonyl, substituted C 1-6 alkyl, or substituted C 1-6 alkyloxyC 1-6 alkylcarbonyl; each R 2 independently is hydroxy, halo, optionally substituted C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, C 3-7 cycloalkyl, C 1-6 alkyloxy, C 1-6 alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C 1-6 alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalo-methylthio, —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 heterocyclic ring; p is 1 or 2; L is optionally substituted C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl or C 3-7 cycloalkyl; or L is —X—R 3 wherein R 3 is optionally substituted phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl; X is —NR 1 —, —NH—NH—, —N═N—, —O—, —C(═O)—, —CHOH—, —S—, —S(═O)— or —S(═O) 2 —; Q is hydrogen, C 1-6 alkyl, halo, polyhalo-C 1-6 alkyl or an optionally substituted amino group; Y represents hydroxy, halo, C 3-7 cycloalkyl, optionally substituted C 1-6 alkyl, C 2-6 alkenyl or 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 aryl; aryl is optionally substituted phenyl; Het is an optionally substituted heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection.

  这项发明涉及使用式1化合物，其N-氧化物，药用可接受的加成盐，季铵盐和其立体化学异构体，其中-a1=-a2-a3=a4-形成苯基，吡啶基，嘧啶基，吡啉基或吡嗪基与附加的乙烯基；n为0至4；如可能为5；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，或取代的C1-6烷氧基烷基羰基；每个R2独立地为羟基，卤素，可选地取代的C1-6烷基，C2-6烯基或C2-6炔基，C3-7环烷基，C1-6烷氧基，C1-6烷氧羰基，羧基，氰基，硝基，氨基，单或双(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)NHNH2，—NHC(═O)R6，—C(═NH)R6或5-成员杂环环；p为1或2；L为可选地取代的C1-10烷基，C2-10烯基，C2-10炔基或C3-7环烷基；或L为—X—R3，其中R3为可选地取代的苯基，吡啶基，嘧啶基，吡嗪基或吡啉基；X为—NR1—，—NH—NH—，—N═N—，—O—，—C(═O)—，—CHOH—，—S—，—S(═O)—或—S(═O)2—；Q为氢，C1-6烷基，卤素，多卤C1-6烷基或可选地取代的氨基；Y代表羟基，卤素，C3-7环烷基，可选地取代的C1-6烷基，C2-6烯基或C2-6炔基，C1-6烷氧基，C1-6烷氧羰基，羧基，氰基，硝基，氨基，单或双(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)NHNH2，—NHC(═O)R6，—C(═NH)R6或芳基；芳基为可选地取代的苯基；Het为可选地取代的杂环基团；用于制造治疗感染艾滋病毒（Human Immunodeficiency Virus）的患者的药物。
• [EN] HIV REPLICATION INHIBITING PYRIMIDINES<br/>[FR] PYRIMIDINES INHIBANT LA REPLICATION DU VIH
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2000027825A1

  公开（公告）日：2000-05-18

  This invention concerns the use of compounds of formula (I), the N-oxides, the pharmaceutically acceptable addition salts, quaternary amines and the stereochemically isomeric forms thereof, wherein -a?1=a2=a3=a4¿- forms a phenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the attached vinyl group; n is 0 to 4; and where possible 5; R1 is hydrogen, aryl, formyl, C¿1-6?alkylcarbonyl, C1-6alkyl, C1-6alkyloxycarbonyl, substituted C1-6alkyl, or substituted C1-6alkyloxyC1-6alkylcarbonyl; each R?2¿ independently is hydroxy, halo, optionally substituted C¿1-6?alkyl, C2-6alkenyl or C2-6alkynyl, C3-7cycloalkyl, 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 heterocyclic ring; p is 1 or 2; L is optionally substituted C¿1-10?alkyl, C2-10alkenyl, C2-10alkynyl or C3-7cycloalkyl; or L is -X-R?3¿ wherein R3 is optionally substituted phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl; X is -NR1-, -NH-NH-, -N=N-, -O-, -C(=O)-, -CHOH-, -S-, -S(=O)- or -S(=O)¿2?-; Q is hydrogen, C1-6alkyl, halo, polyhalo-C1-6alkyl or an optionally substituted amino group; Y represents hydroxy, halo, C3-7cycloalkyl, optionally substituted C1-6alkyl, C2-6alkenyl or 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 aryl; aryl is optionally substituted phenyl; Het is an optionally substituted heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection.

  本发明涉及使用式(I)化合物，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-a?1=a2=a3=a4¿-形成一个苯基、吡啶基、嘧啶基、吡嗪基或吡唑基，并与附加的乙烯基结合；n为0至4，如可能为5；R1为氢、芳基、甲酰基、C¿1-6?烷基羰基、C1-6烷基、C1-6烷氧羰基、取代C1-6烷基或取代C1-6烷氧基C1-6烷基羰基；每个R?2¿独立地为羟基、卤素、可选取代的C¿1-6?烷基、C2-6烯基或C2-6炔基、C3-7环烷基、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)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-成员杂环环；p为1或2；L为可选取代的C¿1-10?烷基、C2-10烯基、C2-10炔基或C3-7环烷基；或L为-X-R?3¿，其中R3为可选取代的苯基、吡啶基、嘧啶基、吡嗪基或吡唑基；X为-NR1-、-NH-NH-、-N=N-、-O-、-C(=O)-、-CHOH-、-S-、-S(=O)-或-S(=O)¿2?-；Q为氢、C1-6烷基、卤素、多卤代C1-6烷基或可选取代的氨基；Y代表羟基、卤素、C3-7环烷基、可选取代的C1-6烷基、C2-6烯基或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)pR?6¿、-NH-S(=O)¿pR?6、-C(=O)R6、-NHC(=O)H、-C(=O)NHNH¿2?、-NHC(=O)R?6¿、-C(=NH)R6或芳基；芳基为可选取代的苯基；Het为可选取代的杂环基团；用于制造治疗HIV（人类免疫缺陷病毒）感染患者的药物。
• HIV replication inhibiting pyrimidines
  申请人：De Corte Bart

  公开号：US20050288278A1

  公开（公告）日：2005-12-29

  This invention concerns the use of compounds of formula the N-oxides, the pharmaceutically acceptable addition salts, quaternary amines and the stereochemically isomeric forms thereof, wherein -a 1 =a 2 -a 3 =a 4 - forms a phenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the attached vinyl group; n is 0 to 4; and where possible 5; R 1 is hydrogen, aryl, formyl, C 1-6 alkylcarbonyl, C 1-6 alkyl, C 1-6 alkyloxy-carbonyl, substituted C 1-6 alkyl, or substituted C 1-6 alkyloxyC 1-6 alkylcarbonyl; each R 2 independently is hydroxy, halo, optionally substituted C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, C 3-7 cycloalkyl, C 1-6 alkyloxy, C 1-6 alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C 1-6 alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalo-methylthio, —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 heterocyclic ring; p is 1 or 2; L is optionally substituted C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl or C 3-7 cycloalkyl; or L is —X—R 3 wherein R 3 is optionally substituted phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl; X is —NR 1 —, —NH—NH—, —N═N—, —O—, —C(═O)—, —CHOH—, —S—, —S(═O)— or —S(═O)2—; Q is hydrogen, C 1-6 alkyl, halo, polyhalo-C 1-6 alkyl or an optionally substituted amino group; Y represents hydroxy, halo, C 3-7 cycloalkyl, optionally substituted C 1-6 alkyl, C 2-6 alkenyl or 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 aryl; aryl is optionally substituted phenyl. Het is an optionally substituted heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection.

  本发明涉及使用式N-氧化物化合物，其药学上可接受的加合物盐、季铵盐及其立体化学异构体，其中-a1=a2-a3=a4-形成带有附加乙烯基的苯基、吡啶基、嘧啶基、吡嗪基或吡唑基；n为0至4，如有可能为5；R1是氢、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烷基或取代的C1-6烷氧基C1-6烷基羰基；每个R2独立地是羟基、卤素、可选取代的C1-6烷基、C2-6烯基或C2-6炔基、C3-7环烷基、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)NHNH2、-NHC(═O)R6、-C(═NH)R6或5-成员杂环环；p为1或2；L是可选取代的C1-10烷基、C2-10烯基、C2-10炔基或C3-7环烷基；或L是-X-R3，其中R3是可选取代的苯基、吡啶基、嘧啶基、吡嗪基或吡唑基；X是-NR1-、-NH-NH-、-N═N-、-O-、-C(═O)-、-CHOH-、-S-、-S(═O)-或-S(═O)2-；Q是氢、C1-6烷基、卤素、多卤基C1-6烷基或可选取代的氨基基团；Y代表羟基、卤素、C3-7环烷基、可选取代的C1-6烷基、C2-6烯基或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)NHNH2、-NHC(═O)R6、-C(═NH)R6或芳基；芳基是可选取代的苯基。Het是可选取代的杂环基；用于制造治疗HIV（人类免疫缺陷病毒）感染患者的药物。
• Prodrugs of HIV replication inhibiting pyrimidines
  申请人：Kukla Joseph Michael

  公开号：US20060009474A1

  公开（公告）日：2006-01-12

  The present invention concerns compounds of formula (A 1 )(A 2 )N—R 1 (I), the N-oxide forms, the pharmaceutically acceptable addition salts, the quaternary amines and stereochemically isomeric forms thereof, wherein R 1 is substituted C 1-6 alkyl; —S(═O)—R 8 ; —S(═O) 2 —R 8 ; C 7-12 alkylcarbonyl; optionally substituted C 1-6 alkyloxycarbonylC 1-6 alkylcarbonyl; with R 8 being C 1-6 alkyl, aryl 1 or Het 1 ; (A 1 )(A 2 )N— is the covalently bonded form of the corresponding intermediate of formula (A 1 )(A 2 )N—H, which is a HIV replication inhibiting pyrimidine of formula

  （A1）（A2）N—R1（I）的化合物是本发明的重点，其中包括N-氧化物形式、药学上可接受的加合盐、季铵盐和立体化学异构体形式，其中R1是取代的C1-6烷基；—S（═O）—R8；—S（═O）2—R8；C7-12烷基羰基；可选取代的C1-6烷氧羰基C1-6烷基羰基，其中R8是C1-6烷基、芳基1或Het1；（A1）（A2）N—是相应中间体（A1）（A2）N—H的共价结合形式，该中间体是式的HIV复制抑制嘧啶：