4-amino-2,6-dichloro-α,α-dimethylbenzeneacetonitrile | 261512-48-5

• 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-amino-2,6-dichloro-α,α-dimethylbenzeneacetonitrile
• 英文别名: 2-(4-amino-2,6-dichloro-phenyl)-2-methyl-propionitrile；4-amino-2,6-dichloro-a,a-dimethylbenzeneacetonitrile；2-(4-amino-2,6-dichlorophenyl)-2-methylpropanenitrile
• CAS: 261512-48-5
• 化学式: C₁₀H₁₀Cl₂N₂
• 分子量: 229.109
• InChiKey: WUVLDSPUVGYUOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-amino-2,6-dichloro-α,α-dimethylbenzeneacetonitrile 在 吡啶 、 盐酸 、 硫化氢 、 potassium acetate 、 碳酸氢钠 、 potassium carbonate 、 溶剂黄146 、 巯基乙酸 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium nitrite 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 47.5h， 生成 2-{1-[2,6-Dichloro-4-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-phenyl]-1-methyl-ethyl}-4-phenyl-thiazole-5-carboxylic acid pentyl ester
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 1,2,4-Triazinylphenylalkylthiazolecarboxylic Acid Esters as Cytokine-Inhibiting Antedrugs with Strong Bronchodilating Effects in an Animal Model of Asthma

  摘要：

  The influx of leukocytes (eosinophils, lymphocytes, and monocytes) into the airways and their production of proinflammatory cytokines contribute to the severity of allergic asthma. We describe here the synthesis and pharmacological evaluation of a series of triazinylphenylalkyl-thiazolecarboxylic acid esters that were designed to act as lung-specific antedrugs and inhibitors of the production of interleukin (IL)-5, a primary eosinophil-activating and proinflammatory cytokine. Closer examination of the hydroxypropyl ester, 15, indicated its high metabolic stability (t(1/2) > 240 min) in human lung S9 fraction but rapid conversion (t(1/2) = 15 min) into the pharmacologically inactive carboxylic acid by human liver preparations. In stimulated human whole blood cultures, 15 reduced not only the production of IL-5 (IC50 = 78 nM) but also the biosynthesis of the monocyte chemotactic proteins MCP-1 (IC50 = 220 nM), MCP-2 (IC50 = 580 nM), and MCP-3 (IC50 = 80 nM). In vivo, intratracheal administration of 15 (6 mg/animal) to allergic sheep, either before (-4 h) or after (+1.5 h) the pulmonary allergen challenge, completely abrogated the late-phase airway response and reduced the bronchial hyperreactivity to inhaled carbachol.

  DOI：

  10.1021/jm049479m
• 作为产物：
  描述：

  2,6-dichloro-α,α-dimethyl-4-nitrobenzeneacetonitrile 在 aluminum nickel 作用下， 以 甲醇 为溶剂， 生成 4-amino-2,6-dichloro-α,α-dimethylbenzeneacetonitrile
  参考文献：
  名称：

  Non-steroidal IL-5 inhibitors, processes and intermediates for their preparation and pharmaceutical compositions comprising said inhibitors

  摘要：

  本发明涉及用于治疗嗜酸性粒细胞依赖性炎症性疾病的IL-5抑制6-氨基尿嘧啶衍生物，以及用于它们的制备的过程和中间体，以及包含所述衍生物的药物组合物。还涉及将这些衍生物用作药物的用途，以及使用这些衍生物标记受体或成像器官的过程。

  公开号：

  US20030114453A1
• 作为试剂：
  描述：

  2-(2,6-Dichloro-4-nitro-phenyl)-2-methyl-propionitrile 在 镍 氢气 、 甲醇 、 4-amino-2,6-dichloro-α,α-dimethylbenzeneacetonitrile 作用下， 以 甲醇 为溶剂， 25.0 ℃ 、40.0 MPa 条件下， 反应 1.0h， 以yielding 17.1 g of 4-amino-2,6-dichloro-α,α-dimethylbenzeneacetonitrile (intermediate 3)的产率得到4-amino-2,6-dichloro-α,α-dimethylbenzeneacetonitrile
  参考文献：
  名称：

  Non-steroidal IL-5 inhibitors, processes and intermediates for their preparation and pharmaceutical compositions comprising said inhibitors

  摘要：

  本发明涉及抑制IL-5的6-氮杂尿嘧啶衍生物，用于治疗依赖嗜酸性粒细胞的炎症性疾病，以及其制备过程和中间体以及包含所述衍生物的制药组合物。它还涉及将这种衍生物用作药物的用途，以及使用所述衍生物标记受体或成像器官的过程。

  公开号：

  US20030114453A1

文献信息

• IL-5 inhibiting 6-azauracil derivatives
  申请人：——

  公开号：US20020010177A1

  公开（公告）日：2002-01-24

  The present invention is concerned with the compounds of formula 1 the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein p is 0 to 4; X is O, S, NR 5 or a direct bond; Y is O, S, NR 5 or S(O) 2 ; R 1 independently is C 1-6 alkyl, halo, polyhaloC 1-6 alkyl, hydroxy, mercapto, C 1-6 alkyloxy, C 1-6 alkylthio, C 1-6 alkylcarbonyloxy, aryl, cyano, nitro, Het 3 , R 6 , NR 7 R 8 or substituted C 1-4 alkyl; R 2 is Het 1 , C 3-7 cycloalkyl or optionally substituted C 1-6 alkyl and if X is O, S or NR 5 , then R 2 may also represent aminocarbonyl, aminothiocarbonyl, C 1-4 alkylcarbonyl, C 1-4 alkylthiocarbonyl, arylcarbonyl, arylthiocarbonyl, Het 1 carbonyl or Het 1 thiocarbonyl; R 3 and R 4 independently are hydrogen, C 1-6 alkyl or C 3-7 cycloalkyl; R 3 and R 4 form a C 2-6 alkanediyl; R 5 is hydrogen or C 1-4 alkyl; R 6 is a sulfonyl or sulfinyl derivative; R 7 and R 8 are independently hydrogen, optionally substituted C 1-4 alkyl, aryl, a carbonyl containing moiety, C 3-7 cycloalkyl, —Y—C 1-4 alkanediyl-C(=O)—O—R 14 , Het 3 , Het 4 and R 6 ; R 11 is hydroxy, mercapto, cyano, nitro, halo, trihalomethyl, C 1-4 alkyloxy, formyl, trihaloC 1-4 alkylsulfonyloxy, R 6 , RNR 7 R 8 , C(=O)NR 7 R 8 , C 1-4 alkanediyl-C(=O)—O—R 14 , —C(=O)—O—R 14 , —Y—C 1-4 alkanediyl-C(=O)—O—R 14 , aryl, aryloxy, arylcarbonyl, C 3-7 cycloalkyl, C 3-7 cycloalkyloxy, phthalimide-2-yl, Het 3 and C(=O)Het 3 ; R 14 is hydrogen, C 1-4 alkyl, C 3-7 cycloalkyl, aminocarbonylmethylene or mono-or di(C 1-4 alkyl)aminocarbonylmethylene; aryl is optionally substituted phenyl; Het 1 , Het 2 , Het 3 and Het 4 are optionally substituted heterocycles; to processes for their preparation and compositions comprising them. It further relates to their use as a medicine.

  本发明涉及公式1的化合物，包括N-氧化物、药学上可接受的加合盐及其立体化异构体，其中p为0至4；X为O、S、NR5或直接键；Y为O、S、NR5或S(O)2；R1独立地为C1-6烷基、卤素、多卤代C1-6烷基、羟基、巯基、C1-6烷氧基、C1-6烷硫基、C1-6烷基羰氧基、芳基、氰基、硝基、Het3、R6、NR7R8或取代的C1-4烷基；R2为Het1、C3-7环烷基或可选择取代的C1-6烷基，如果X为O、S或NR5，则R2也可以表示氨基羰基、氨基硫代羰基、C1-4烷基羰基、C1-4烷基硫代羰基、芳基羰基、芳基硫代羰基、Het1羰基或Het1硫代羰基；R3和R4独立地为氢、C1-6烷基或C3-7环烷基；R3和R4形成一个C2-6烷二基；R5为氢或C1-4烷基；R6为磺酰基或亚砜衍生物；R7和R8独立地为氢、可选择取代的C1-4烷基、芳基、含羰基的基团、C3-7环烷基、—Y—C1-4烷二基-C(=O)—O—R14、Het3、Het4和R6；R11为羟基、巯基、氰基、硝基、卤素、三卤甲基、C1-4烷氧基、甲酰基、三卤代C1-4烷基磺酰氧基、R6、RNR7R8、C(=O)NR7R8、C1-4烷二基-C(=O)—O—R14、—C(=O)—O—R14、—Y—C1-4烷二基-C(=O)—O—R14、芳基、芳氧基、芳基羰基、C3-7环烷基、C3-7环烷氧基、邻苯二酰亚胺-2-基、Het3和C(=O)Het3；R14为氢、C1-4烷基、C3-7环烷基、氨基羰基亚甲基或单烷基或双(C1-4烷基)氨基羰基亚甲基；芳基为可选择取代的苯基；Het1、Het2、Het3和Het4为可选择取代的杂环；以及其制备方法和含有它们的组合物。进一步涉及它们作为药物的用途。
• NOVEL BENZAMIDE DERIVATIVES AS MODULATORS OF THE FOLLICLE STIMULATING HORMONE
  申请人：Bonnet Beatrice

  公开号：US20100249123A1

  公开（公告）日：2010-09-30

  The present invention provides new compounds of formula I, wherein Q, R 1 , R 2 , R 4 , R 5 , R 6 , X i , R 7 , R 8 , M and G 1 n are defined as in formula I; invention compounds are modulators of follicle-stimulating hormone—(“FSH”) which are useful for male and female contraception as well as other disorders modulated by FSH receptor.

  本发明提供了新的I式化合物，其中Q、R1、R2、R4、R5、R6、Xi、R7、R8、M和G1n如I式中所定义；发明化合物是促卵泡素-（“FSH”）的调节剂，可用于男性和女性避孕以及其他受FSH受体调节的疾病。
• Interleukin-5 inhibiting 6-azauracil derivatives
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0987265A1

  公开（公告）日：2000-03-22

  The present invention is concerned with the compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein p is 0 to 4; X is O, S, NR5 or a direct bond; Y is O, S, NR5 or S(O)2; R1 independently is C1-6alkyl, halo, polyhaloC1-6alkyl, hydroxy, mercapto, C1-6alkyloxy, C1-6alkylthio, C1-6alkylcarbonyloxy, aryl, cyano, nitro, Het3, R6, NR7R8 or substituted C1-4alkyl; R2 is Het1, C3-7cycloalkyl or optionally substituted C1-6alkyl and if X is O, S or NR5, then R2 may also represent aminocarbonyl, aminothiocarbonyl, C1-4alkylcarbonyl, C1-4alkylthiocarbonyl, arylcarbonyl, arylthiocarbonyl, Het1carbonyl or Het1thiocarbonyl; R3 and R4 independently are hydrogen, C1-6alkyl or C3-7cycloalkyl; R3 and R4 form a C2-6alkanediyl; R5 is hydrogen or C1-4alkyl; R6 a sulfonyl or sulfinyl derivative; R7 and R8 are independently hydrogen, optionally substituted C1-4alkyl, aryl, a carbonyl containing moiety, C3-7cycloalkyl, -Y-C1-4alkanediyl-C(=O)-O-R14, Het3 and R6; R11 is hydroxy, mercapto, cyano, nitro, halo, trihalomethyl, C1-4alkyloxy, formyl, trihaloC1-4alkylsulfonyloxy, R6, NR7R8, C(=O)NR7R8, C1-4alkanediyl-C(=O)-O-R14, - C(=O)-O-R14, -Y-C1-4alkanediyl-C(=O)-O-R14, aryl, aryloxy, arylcarbonyl, C3-7cycloalkyl, C3-7cycloalkyloxy, phthalimide-2-yl, Het3, Het4 and C(=O)Het3; R14 is hydrogen, C1-4alkyl, C3-7cycloalkyl, aminocarbonylmethylene or mono-or di(C1-4alkyl)aminocarbonylmethylene; aryl is optionally substituted phenyl; Het1, Het2, Het3 and Het4 are optionally substituted heterocycles; to processes for their preparation and compositions comprising them. It further relates to their use as a medicine.

  本发明涉及式化合物 其中 p 为 0 至 4；X 为 O、S、NR5 或直接键；Y 为 O、S、NR5 或 S(O)2；R1 独立地为 C1-6 烷基、卤代、多卤代 C1-6 烷基、羟基、巯基、C1-6 烷氧基、C1-6 烷硫基、C1-6 烷基羰基氧基、芳基、氰基、硝基、Het3、R6、NR7R8 或取代的 C1-4 烷基；R2 是 Het1、C3-7 环烷基或任选取代的 C1-6 烷基，如果 X 是 O、S 或 NR5，则 R2 还可以代表氨基羰基、氨基硫代羰基、C1-4烷基羰基、C1-4烷基硫代羰基、芳基羰基、芳基硫代羰基、Het1羰基或 Het1硫代羰基；R3 和 R4 独立地为氢、C1-6烷基或 C3-7 环烷基；R3 和 R4 形成 C2-6 烷二基；R5 为氢或 C1-4 烷基；R6 为磺酰基或亚磺酰基衍生物；R7 和 R8 独立地是氢、任选取代的 C1-4 烷基、芳基、含羰基的分子、C3-7 环 烷基、-Y-C1-4 烷二基-C(=O)-O-R14、Het3 和 R6；R11 是羟基、巯基、氰基、硝基、卤代、三卤甲基、C1-4 烷氧基、甲酰基、三卤 C1-4 烷基磺酰氧基、R6、NR7R8、C(=O)NR7R8、C1-4烷二基-C(=O)-O-R14、- C(＝O)-O-R14、-Y-C1-4烷二基-C(＝O)-O-R14、芳基、芳氧基、芳羰基、C3-7 环烷基、C3-7 环烷氧基、邻苯二甲酰亚胺-2-基、Het3、Het4 和 C(＝O)Het3；R14是氢、C1-4烷基、C3-7环烷基、氨基羰基亚甲基或单或二(C1-4烷基)氨基羰基亚甲基；芳基是任选取代的苯基；Het1、Het2、Het3和Het4是任选取代的杂环；还涉及它们的制备工艺和包含它们的组合物。还涉及它们作为药物的用途。
• WO2008/117175
  申请人：——

  公开号：——

  公开（公告）日：——
• INTERLEUKIN-5 INHIBITING 6-AZAURACIL DERIVATIVES
  申请人：Janssen Pharmaceutica N.V.

  公开号：EP1114046B1

  公开（公告）日：2003-04-23