8-(2,4-dichlorophenyl)-2-methyl-4-hydroxyquinoline | 215115-07-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 8-(2,4-dichlorophenyl)-2-methyl-4-hydroxyquinoline
• 英文别名: 2-methyl-4-hydroxy-8-(2',4'-dichlorophenyl)quinoline；8-(2,4-Dichloro-phenyl)-2-methyl-quinolin-4-ol；8-(2,4-dichlorophenyl)-2-methyl-1H-quinolin-4-one
• CAS: 215115-07-4
• 化学式: C₁₆H₁₁Cl₂NO
• 分子量: 304.175
• InChiKey: VYPXHRUYISNLQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-(2,4-dichlorophenyl)-2-methyl-4-hydroxyquinoline 在 sodium hydroxide 、 三氯氧磷 作用下， 生成 4-chloro-8-(2,4-dichlorophenyl)-2-methylquinoline
  参考文献：
  名称：

  CRF antagonistic quino- and quinazolines

  摘要：

  本发明涉及公式化合物，包括其立体异构体和药学上可接受的酸加成盐形式，其中R1是C1-6烷基、NR6R7、OR6或SR7；R2是氢、C1-6烷基、C1-6烷氧基或C1-6烷基硫基；R3是Ar1或Het1；R4和R5各自独立地选自氢、卤素、C1-6烷基、C1-6烷氧基、三氟甲基、氰基、硝基、氨基和单或双(C1-6烷基)氨基；R6是氢、C1-6烷基、C1-6烷基磺酰基、C1-6烷基磺酸氧基或C1-6烷基硫基；R7是氢、C1-8烷基、单或双(C3-6环烷基)甲基、C3-6环烷基、C3-6烯基、羟基C1-6烷基、C1-6烷基羧酸酯-C1-6烷基或C1-6烷氧基C1-6烷基；R6是C1-8烷基、单或双(C3-6环烷基)-甲基、Ar2CH2、C1-6烷氧基C1-6烷基、羟基C1-6烷基、C3-6烯基、噻吩基甲基、呋喃基甲基、C1-6烷基硫基C1-6烷基、单或双(C1-6烷基)氨基C1-6烷基、双(C1-6烷基)氨基、C1-6烷基羧酰基C1-6烷基；或R6和R7与它们连接的氮原子一起可以形成吡咯烷基、哌嗪基、同型哌嗪基或吗啉基，可选择地取代C1-6烷基或C1-6烷氧基C1-6烷基；Ar1和Ar2各自可选地取代苯基；Het1是可选地取代的吡啶基；具有CRF受体拮抗性质的制剂；将此类化合物作为活性成分的制药组合物；通过给予公式(I)化合物的有效量来治疗与CRF过度分泌相关的疾病，如抑郁症、焦虑症、物质滥用等。

  公开号：

  US06482836B1
• 作为产物：
  描述：

  2-(2,4-dichlorophenyl)aniline 在 对甲苯磺酸 作用下， 以 二苯醚 、 苯 为溶剂， 反应 0.58h， 生成 8-(2,4-dichlorophenyl)-2-methyl-4-hydroxyquinoline
  参考文献：
  名称：

  Synthesis and SAR of 8-Arylquinolines as potent corticotropin-Releasing factor1 (CRF1) receptor antagonists

  摘要：

  A series of 4-substituted 8-aryl-2-methylquinolines 4 was designed and synthesized as highly potent antagonists for the human CRF1 receptor. This series of compounds displayed parallel SAR to other bicyclic systems such as pyrazolo[l,5-a]pyrimidines, with several compounds possessing low nanomolar binding affinity. In addition to the high potency, the basicity of this 4-aminoquinoline core may offer CRF1 antagonists with lower lipophilicity. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00684-x

文献信息

• Tetrahydropyridino or piperidino heterocylic derivatives
  申请人：——

  公开号：US20040034061A1

  公开（公告）日：2004-02-19

  A tetrahydropyridino or piperidino heterocyclic derivative represented by the formula [I]: A-Het  [I] has a high affinity for CRF receptors and is effective against diseases in which CRF is considered to be involved.

  一种由公式[I]表示的四氢吡啶或哌啶杂环衍生物：A-Het，[I]具有高亲和力对抗CRF受体，并对CRF被认为参与的疾病有效。
• CRF antagonistic quino- and quinazolines
  申请人：——

  公开号：US06482836B1

  公开（公告）日：2002-11-19

  This invention concerns compounds of formula including the stereoisomers and the pharmaceutically acceptable acid addition salt forms thereof, wherein R1 is C1-6alkyl, NR6R7, OR6 or SR7; R2 is hydrogen, C1-6alkyl, C1-6alkyloxy or C1-6alkylthio; R3 is Ar1 or Het1; R4 and R5 are each independently selected from hydrogen, halo, C1-6alkyl, C1-6alkyloxy, trifluoromethyl, cyano, nitro, amino, and mono- or di(C1-6alkyl)amino; R6 is hydrogen, C1-6alkyl, C1-6alkylsulfonyl, C1-6alkylsulfoxy or C1-6alkylthio; R7 is hydrogen, C1-8alkyl, mono- or di(C3-6cycloalkyl)methyl, C3-6cycloalkyl, C3-6alkenyl, hydroxyC1-6alkyl, C1-6alkylcarbonyloxy-C1-6alkyl or C1-6alkyloxyC1-6alkyl; R6 is C1-8alkyl, mono- or di(C3-6cycloalkyl)-methyl, Ar2CH2, C1-6alkyloxyC1-6alkyl, hydroxyC1-6alkyl, C3-6alkenyl, thienylmethyl, furanylmethyl, C1-6alkylthioC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, di(C1-6alkyl)amino, C1-6alkylcarbonylC1-6alkyl; or R6 and R7 taken together with the nitrogen atom to which they are attached may form a pyrrolidinyl, piperidinyl, homopiperidinyl or morpholinyl group, optionally substituted with C1-6alkyl or C1-6alkyloxyC1-6alkyl; and Ar1 and Ar2 are each optionally substituted phenyl; and Het1 is optionally substituted pyridinyl; having CRF receptor antagonistic properties; pharmaceutical compositions containing such compounds as active ingredients; methods of treating disorders related to hypersecretion of CRF such as depression, anxiety, substance abuse, by administering an effective amount of a compound of formula (I).

  本发明涉及公式化合物，包括其立体异构体和药学上可接受的酸加成盐形式，其中R1是C1-6烷基、NR6R7、OR6或SR7；R2是氢、C1-6烷基、C1-6烷氧基或C1-6烷基硫基；R3是Ar1或Het1；R4和R5各自独立地选自氢、卤素、C1-6烷基、C1-6烷氧基、三氟甲基、氰基、硝基、氨基和单或双(C1-6烷基)氨基；R6是氢、C1-6烷基、C1-6烷基磺酰基、C1-6烷基磺酸氧基或C1-6烷基硫基；R7是氢、C1-8烷基、单或双(C3-6环烷基)甲基、C3-6环烷基、C3-6烯基、羟基C1-6烷基、C1-6烷基羧酸酯-C1-6烷基或C1-6烷氧基C1-6烷基；R6是C1-8烷基、单或双(C3-6环烷基)-甲基、Ar2CH2、C1-6烷氧基C1-6烷基、羟基C1-6烷基、C3-6烯基、噻吩基甲基、呋喃基甲基、C1-6烷基硫基C1-6烷基、单或双(C1-6烷基)氨基C1-6烷基、双(C1-6烷基)氨基、C1-6烷基羧酰基C1-6烷基；或R6和R7与它们连接的氮原子一起可以形成吡咯烷基、哌嗪基、同型哌嗪基或吗啉基，可选择地取代C1-6烷基或C1-6烷氧基C1-6烷基；Ar1和Ar2各自可选地取代苯基；Het1是可选地取代的吡啶基；具有CRF受体拮抗性质的制剂；将此类化合物作为活性成分的制药组合物；通过给予公式(I)化合物的有效量来治疗与CRF过度分泌相关的疾病，如抑郁症、焦虑症、物质滥用等。
• [EN] CRF ANTAGONISTIC QUINO- AND QUINAZOLINES<br/>[FR] QUINO- ET QUINAZOLINES ANTAGONISTES CRF
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1998047874A1

  公开（公告）日：1998-10-29

  (EN) This invention concerns compounds of formula (I), including the stereoisomers and the pharmaceutically acceptable acid addition salt forms thereof, wherein R1 is C1-6alkyl, NR6R7, OR6 or SR7; R2 is hydrogen, C1-6alkyl, C1-6alkyloxy or C1-6alkylthio; R3 is Ar1 or Het1; R4 and R5 are each independently selected from hydrogen, halo, C1-6alkyl, C1-6alkyloxy, trifluoromethyl, cyano, nitro, amino, and mono- or di(C1-6alkyl)amino; R6 is hydrogen, C1-6alkyl, C1-6alkylsulfonyl, C1-6alkylsulfoxy or C1-6alkylthio; R7 is hydrogen, C1-8alkyl, mono- or di(C3-6cycloalkyl)methyl, C3-6cycloalkyl, C3-6alkenyl, hydroxyC1-6alkyl, C1-6alkylcarbonyloxy-C1-6alkyl or C1-6alkyloxyC1-6alkyl; R6 is C1-8alkyl, mono- or di(C3-6cycloalkyl)-methyl, Ar2CH2, C1-6alkyloxyC1-6alkyl, hydroxyC1-6alkyl, C3-6alkenyl, thienylmethyl, furanylmethyl, C1-6alkylthioC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, di(C1-6alkyl)amino, C1-6alkylcarbonylC1-6alkyl; or R6 and R7 taken together with the nitrogen atom to which they are attached may form a pyrrolidinyl, piperidinyl, homopiperidinyl or morpholinyl group, optionally substituted with C1-6alkyl or C1-6alkyloxyC1-6alkyl; and Ar1 and Ar2 are each optionally substituted phenyl; and Het1 is optionally substituted pyridinyl; having CRF receptor antagonistic properties; pharmaceutical compositions containing such compounds as active ingredients; methods of treating disorders related to hypersecretion of CRF such as depression, anxiety, substance abuse, by administering an effective amount of a compound of formula (I).(FR) La présente invention concerne des composés représentés par la formule (I) comprenant des stéréoisomères et les formes de sels d'addition acides pharmaceutiquement acceptables de ceux-ci, dans laquelle R1 représente C1-6alkyle, NR6R7, OR6 ou SR7; R2 représente hydrogène, C1-6alkyle, C1-6alkyloxy ou C1-6alkylthio; R3 représente Ar1 or Het1; R4 et R5 sont chacun sélectionnés indépendamment dans le groupe hydrogène, halo, C1-6alkyle, C1-6alkyloxy, trifluorométhyl, cyano, nitro, amino, et mono- ou di(C1-6alkyle)amino; R6 représente hydrogène, C1-6alkyle, C1-6alkylsulfonyl, C1-6alkylsulfoxy ou C1-6alkylthio; R7 représente hydrogène, C1-8alkyle, mono- ou di(C3-6cyclo-alkyle)méthyl, C3-6cycloalkyl, C3-6alcényl, hydroxyC1-6alkyle, C1-6alkylcarbonyloxyC1-6alkyle ou C1-6alkyloxyC1-6alkyle; R6 représente C1-8alkyle, mono- ou di(C3-6cycloalkyl)-méthyl, Ar2CH2, C1-6alkyloxyC1-6alkyle, hydroxyC1-6alkyle, C3-6alcényle, thiénylméthyl, furanylméthyl, C1-6alkylthioC1-6alkyle, mono ou di(C1-6alkyle)aminoC1-6alkyle, di(C1-6alkyle)amino, C1-6alkylcarbonylC1-6alkyle; ou R6 et R7 pris ensemble avec l'atome d'azote auquel ils sont liés peuvent former un pyrrolidinyl, un pipéridinyl, un homopipéridinyl ou un groupe morpholinyl, éventuellement substitué avec C1-6alkyle ou C1-6alkyloxyC1-6alkyle; et Ar1 et Ar2 représentent chacun un phényl éventuellement substitué; Het1 représente un pyridinyl éventuellement substitué; présentant des propriétés antagonistes de récepteur CFR. La présente invention concerne également des compositions pharmaceutiques contenant lesdits composés comme ingrédients actifs ainsi que des procédés de traitement d'affections liées à l'hypersécrétion de CRF telles que la dépression, l'anxiété, l'abus de substance, en administrant une quantité efficace d'un composé représenté par la formule (I).

  本发明涉及化合物(I)的公式，包括其立体异构体和药学上可接受的酸加成盐形式，其中R1为C1-6烷基，NR6R7，OR6或SR7; R2为氢，C1-6烷基，C1-6烷氧基或C1-6烷硫基; R3为Ar1或Het1; R4和R5各自独立地选择自氢，卤素，C1-6烷基，C1-6烷氧基，三氟甲基，氰基，硝基，氨基和单个或双(C1-6烷基)氨基; R6为氢，C1-6烷基，C1-6烷基磺酰基，C1-6烷氧基或C1-6烷硫基; R7为氢，C1-8烷基，单个或双(C3-6环烷基)甲基，C3-6环烷基，C3-6烯基，羟基C1-6烷基，C1-6烷基羧酸酯-C1-6烷基或C1-6烷氧基C1-6烷基; R6为C1-8烷基，单个或双(C3-6环烷基)-甲基，Ar2CH2，C1-6烷氧基C1-6烷基，羟基C1-6烷基，C3-6烯基，噻吩基甲基，呋喃基甲基，C1-6烷硫基C1-6烷基，单个或双(C1-6烷基)氨基C1-6烷基，双(C1-6烷基)氨基，C1-6烷基羰基C1-6烷基; 或R6和R7与它们连接的氮原子一起可以形成一个吡咯烷基，哌嗪基，同源哌嗪基或吗啡啉基，可选地取代C1-6烷基或C1-6烷氧基C1-6烷基; Ar1和Ar2各自为可选取代的苯基; Het1为可选取代的吡啶基; 具有CRF受体拮抗作用; 包含这样的化合物作为活性成分的药物组合物; 通过给予公式(I)化合物的有效量来治疗与CRF过度分泌相关的疾病，如抑郁症、焦虑症、物质滥用的方法。
• [EN] TETRAHYDROPYRIDINO OR PIPERIDINO HETEROCYCLIC DERIVATIVES<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES DE TÉTRAHDYROPYRIDINO OU DE PIPÉRIDINO
  申请人：TAISHO PHARMA CO LTD

  公开号：WO2002002549A1

  公开（公告）日：2002-01-10

  A tetrahydropyridino or piperidino heterocyclic derivative represented by the formula [I]: A-Het [I]has a high affinity for CRF receptors and is effective against diseases in which CRF is considered to be involved.

  一种由公式[I]表示的四氢吡啶或哌啶杂环衍生物，其中A-Het [I]具有高亲和力的CRF受体，并且对于CRF被认为参与的疾病是有效的。
• Tetrahydropyridin or piperidino heterocyclic derivatives
  申请人：Nakazato Atsuro

  公开号：US20050009874A1

  公开（公告）日：2005-01-13

  A tetrahydropyridino or piperidino heterocyclic derivative represented by the formula [I]: A-Het   [I] has a high affinity for CRF receptors and is effective against diseases in which CRF is considered to be involved.

  一种由公式[I]表示的四氢吡啶或哌啶杂环衍生物，其中A-Het，具有高亲和力CRF受体，并且对于CRF被认为参与的疾病是有效的。