4,6-dichloro-N-(2,6-dibromo-4-methylphenyl)-1,3,5-triazin-2-amine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4,6-dichloro-N-(2,6-dibromo-4-methylphenyl)-1,3,5-triazin-2-amine
• 化学式: C₁₀H₆Br₂Cl₂N₄
• 分子量: 412.898
• InChiKey: DXOUGTMZHSSSLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  50.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,6-dichloro-N-(2,6-dibromo-4-methylphenyl)-1,3,5-triazin-2-amine 在 氨 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 139.0h， 生成 N²-(2,6-dibromo-4-methylphenyl)-N⁴-(4-fluorophenyl)-1,3,5-triazine-2,4,6-triamine
  参考文献：
  名称：

  Optimization of the pharmacokinetic properties of potent anti-trypanosomal triazine derivatives

  摘要：

  Human African trypanosomiasis is causing thousands of deaths every year in the rural areas of subsaharan Africa. There is a high unmet medical need since the approved drugs are poorly efficacious, show considerable toxicity and are not easy to administer. This work describes the optimization of the pharmacokinetic properties of a previously published family of triazine lead compounds. One compound (35 (UAMC-03011)) with potent anti-trypanosomal activity and no cytotoxicity was selected for further study because of its good microsomal stability and high selectivity for Trypanosoma brucei over a panel including Trypanosoma cruzi, Leishmania infantum, and Plasmodium falciparum. In vivo pharmacokinetic parameters were determined and the compound was studied in an acute in vivo mouse disease model. One of the important leamings of this study was that the rate of trypanocidal activity is an important parameter during the lead optimization process. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.03.048
• 作为产物：
  描述：

  三聚氯氰 、 2,6-二溴-4-甲基苯胺 生成 4,6-dichloro-N-(2,6-dibromo-4-methylphenyl)-1,3,5-triazin-2-amine
  参考文献：
  名称：

  DISUBSTITUTED TRIAZINE DIMERS FOR TREATMENT AND/OR PREVENTION OF INFECTIOUS DISEASES

  摘要：

  本发明涉及新型化合物（I），其中包含两个二取代三嗪环通过有机连接剂共价连接形成二聚体。这些化合物对非洲锥虫病、恙虫病、利什曼病、疟疾和艾滋病等感染性疾病的致病微生物具有活性。本发明还涉及这些疾病的预防和/或治疗。

  公开号：

  US20140323488A1

文献信息

• Trisubstituted 1,3,5-Triazine Derivatives
  申请人：Janssen Pharmaceutica N.V.

  公开号：US06150360A1

  公开（公告）日：2000-11-21

  This invention concerns the use of the compounds of formula ##STR1## the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein A is CH, CR.sup.4 or N; n is 0, 1, 2, 3 or 4; R.sup.1 and R.sup.2 are each independently selected from hydrogen, hydroxy, C.sub.1-12 alkyl, C.sub.1-12 alkyloxy, C.sub.1-12 alkylcarbonyl, C.sub.1-12 -alkyloxycarbonyl, aryl, amino, mono- or di(C.sub.1-12 alkyl)amino, mono- or di(C.sub.1-12 alkyl)aminocarbonyl wherein each of the aforementioned C.sub.1-12 alkyl groups may optionally and each individually be substituted; or R.sup.1 and R.sup.2 taken together may form pyrrolidinyl, piperidinyl, morpholinyl, azido or mono- or di(C.sub.1-12 alkyl)aminoC.sub.1-4 alkylidene; R.sup.3 is hydrogen, aryl, C.sub.1-6 alkylcarbonyl, optionally substituted C.sub.1-6 alkyl; and each R.sup.4 independently is hydroxy, halo, C.sub.1-6 alkyl, C.sub.1-6 -alkyloxy, cyano, aminocarbonyl, nitro, amino, trihalomethyl or trihalomethyloxy; L is --X--R.sup.5 or --X--Alk--R.sup.6 ; wherein R.sup.5 and R.sup.6 each independently are indanyl, indolyl or phenyl; each of said indanyl, indolyl or phenyl may be substituted; and X is --NR.sup.3 --, --NH--NH--, --N.dbd.N--, --O--, --S--, --S(.dbd.O)-- or --S(.dbd.O).sub.2 --; aryl is optionally substituted phenyl; Het is an optionally substituted aliphatic or aromatic heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection. It further relates to new compounds being a subgroup of the compounds of formula (I), their preparation and pharmaceutical compositions comprising them.

  本发明涉及使用下式化合物，其中A为CH、CR^4或N；n为0、1、2、3或4；R^1和R^2分别独立选择自氢、羟基、C_1-12烷基、C_1-12烷氧基、C_1-12烷基羰基、C_1-12烷氧羰基、芳基、氨基、单或双(C_1-12烷基)氨基、单或双(C_1-12烷基)氨基羰基，其中上述C_1-12烷基组分可以选择性地且各自独立地被取代；或者R^1和R^2一起可以形成吡咯烷基、哌啶基、吗啉基、偶氮基或单或双(C_1-12烷基)氨基C_1-4烷基亚甲基；R^3为氢、芳基、C_1-6烷基羰基、可选择取代的C_1-6烷基；每个R^4独立地为羟基、卤素、C_1-6烷基、C_1-6烷氧基、氰基、氨基羰基、硝基、氨基、三卤甲基或三卤甲氧基；L为--X--R^5或--X--Alk--R^6；其中R^5和R^6各自独立为茚基、吲哚基或苯基；每个所述的茚基、吲哚基或苯基可以被取代；X为--NR^3--、--NH--NH--、--N=dbd.N--、--O--、--S--、--S(.dbd.O)--或--S(.dbd.O)_2--；芳基为可选择取代的苯基；Het为可选择取代的脂环或芳环杂环基团；用于制造治疗感染HIV（人类免疫缺陷病毒）的患者的药物。还涉及新化合物，它们是式(I)化合物的一个亚组，它们的制备以及包含它们的药物组合物。
• Trisubstituted 1,3,5,-triazine derivatives
  申请人：Janssen Pharmaceutica N.V.

  公开号：US06372729B1

  公开（公告）日：2002-04-16

  This invention concerns the use of the compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein A is CH, CR4 or N; n is 0, 1, 2, 3 or 4; R1 and R2 are each independently selected from hydrogen, hydroxy, C1-12alkyl, C1-12alkyloxy, C1-12alkylcarbonyl, C1-12alkyloxycarbonyl, aryl, amino, mono- or di(C1-12alkyl)amino, mono- or di(C1-12alkyl)aminocarbonyl wherein each of the aforementioned C1-12alkyl groups may optionally and each individually be substituted; or R1 and R2 taken together may form pyrrolidinyl, piperidinyl, morpholinyl, azido or mono- or di(C1-12alkyl)aminoC1-4alkylidene; R3 is hydrogen, aryl, C1-6alkylcarbonyl, optionally substituted C1-6alkyl; and each R4 independently is hydroxy, halo, C1-6alkyl, C1-6alkyloxy, cyano, aminocarbonyl, nitro, amino, trihalomethyl or trihalomethyloxy; L is —X—R5 or —X-Alk-R6; wherein R5 and R6 each independently are indanyl, indolyl or phenyl; each of said indanyl, indolyl or phenyl may be substituted; and X is —NR3—, —NH—NH—, —N═N—, —O—, —S—, —S(═O)— or —S(═O)2—; aryl is optionally substituted phenyl; Het is an optionally substituted aliphatic or aromatic heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection. It further relates to new compounds being a subgroup of the compounds of formula (I), their preparation and pharmaceutical compositions comprising them.

  这项发明涉及使用公式中的化合物N-氧化物、药用可接受的加合盐和立体化学异构体，其中A为CH、CR4或N；n为0、1、2、3或4；R1和R2分别独立地选自氢、羟基、C1-12烷基、C1-12烷氧基、C1-12烷基羰基、C1-12烷氧羰基、芳基、氨基、单烷基或双烷基氨基、单烷基或双烷基氨基羰基，其中上述每个C1-12烷基基团可能选择性地且各自被取代；或者R1和R2联合形成吡咯烷基、哌啶基、吗啉基、叠氮基或单烷基或双烷基氨基C1-4烷基亚甲基；R3为氢、芳基、C1-6烷基羰基、可选择地取代的C1-6烷基；且每个R4独立地为羟基、卤素、C1-6烷基、C1-6烷氧基、氰基、氨基羰基、硝基、氨基、三卤甲基或三卤甲氧基；L为—X—R5或—X-烷基-R6；其中R5和R6各自独立地为茚基、吲哚基或苯基；每个所述的茚基、吲哚基或苯基可能被取代；X为—NR3—、—NH—NH—、—N=N—、—O—、—S—、—S(O)—或—S(O)2—；芳基为可选择取代的苯基；Het为可选择取代的脂肪族或芳香族杂环基；用于制造用于治疗患有HIV（人类免疫缺陷病毒）感染的受试者的药物。它还涉及新化合物，它们是公式（I）化合物的一个子组，其制备和包含它们的药物组合物。
• [EN] DISUBSTITUTED TRIAZINE DIMERS FOR TREATMENT AND/OR PREVENTION OF INFECTIOUS DISEASES<br/>[FR] DIMÈRES DE TRIAZINE DISUBSTITUÉE POUR LE TRAITEMENT E/OU LA PRÉVENTION DE MALADIES INFECTIEUSES
  申请人：UNIV ANTWERPEN

  公开号：WO2013068551A1

  公开（公告）日：2013-05-16

  The present invention relates to novel compounds (I) containing two disubstituted triazine rings covalently linked by an organic linker, thereby creating dimers. These compounds show activity against the causative infective agents of infectious diseases such as African trypanosomiasis, Chagas disease, Leishmaniasis, Malaria and HIV. The invention further relates to the prevention and/or treatment of these diseases.

  本发明涉及一种新型化合物（I），其中包含通过有机连接剂共价连接的两个二取代三嗪环，从而形成二聚体。这些化合物对致病的传染病如非洲锥虫病、克氏病、利什曼病、疟疾和艾滋病的感染性病原体表现出活性。该发明还涉及预防和/或治疗这些疾病。
• DISUBSTITUTED TRIAZINE DIMERS FOR TREATMENT AND/OR PREVENTION OF INFECTIOUS DISEASES
  申请人：LEWI Wim

  公开号：US20140323488A1

  公开（公告）日：2014-10-30

  The present invention relates to novel compounds (I) containing two disubstituted triazine rings covalently linked by an organic linker, thereby creating dimers. These compounds show activity against the causative infective agents of infectious diseases such as African trypanosomiasis, Chagas disease, Leishmaniasis, Malaria and HIV. The invention further relates to the prevention and/or treatment of these diseases.

  本发明涉及包含两个二取代三嗪环的新化合物（I），通过有机连接物共价连接，从而形成二聚体。这些化合物对引起传染病如非洲锥虫病、克氏病、利什曼病、疟疾和艾滋病的致病性感染剂表现出活性。该发明还涉及这些疾病的预防和/或治疗。
• Antiviral compositions
  申请人：Verreck Geert

  公开号：US20060127487A1

  公开（公告）日：2006-06-15

  The present invention is concerned with pharmaceutical compositions of antiviral compounds which can be administered to a mammal, in particular a human, suffering from a viral infection. These compositions comprise particles obtainable by melt-extruding a mixture comprising one or more antiviral compounds and one or more appropriate water-soluble polymers and subsequently milling said melt-extruded mixture.

  本发明涉及药物组合物，包括抗病毒化合物，可用于治疗哺乳动物，尤其是人类，患有病毒感染。这些组合物包括通过熔融挤出混合物制备的颗粒，该混合物包括一种或多种抗病毒化合物和一种或多种适当的水溶性聚合物，并随后对该熔融挤出的混合物进行磨碎。