4-hydroxy-1H-indole-2-carbonitrile | 106469-57-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-hydroxy-1H-indole-2-carbonitrile
• CAS: 106469-57-2
• 化学式: C₉H₆N₂O
• 分子量: 158.159
• InChiKey: HKKCHULRVUXUBK-UHFFFAOYSA-N

物化性质

• 溶解度：
  <34.54mg/ml，溶于 DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  59.8
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-hydroxy-1H-indole-2-carbonitrile 在 吗啉 作用下， 反应 7.5h， 生成 4-{3-[4-(1-Amino-1-methyl-ethyl)-1-methyl-cyclohexylamino]-2-hydroxy-propoxy}-1H-indole-2-carbonitrile
  参考文献：
  名称：

  β-肾上腺素受体的亲和标记：衍生自吲哚的烷基化β-受体阻滞剂的制备和性质。

  摘要：

  合成了对β-肾上腺素受体具有高亲和力的新的吲哚衍生的烷基化配体，并对其性质进行了研究。制备了N8-（溴乙酰基）-N1- [3-（4-吲哚氧基）-2-羟丙基]-（Z）-1,8-二氨基对-庚烷（8）及其N1，N8异构体（9）。通过使溴乙酰溴与4-吲哚基缩水甘油醚与（Z）-1,8-二氨基-对-薄荷烷的缩合产物反应而得到。使用2-氰基-4-吲哚基缩水甘油醚的类似反应产生了各自的氰基衍生物10和11。β-肾上腺素受体在大鼠心脏和肺部膜制剂上的表观亲和力（Ki，M）为4.6 X 10（-10）和1.34 X 10（-9）适用于8，2.3 X 10（-8）和4.5 X 10（-9）适用于9，6.1 X 10（-10）和1.49 X 10（-9）适用于10，以及1.83 X 10 （-9）和2.78 X 10（-9）表示11。当膜与上述配体（1 X 10（-8）M 30分钟，30摄氏度），然后彻底洗涤，[

  DOI：

  10.1021/jm00387a005
• 作为产物：
  描述：

  4-苄氧基吲哚-2-羧酸 在 palladium on activated charcoal 吡啶 、 氯化亚砜 、 氨 、 ammonium formate 、 N,N-二甲基甲酰胺 、 三氟乙酸酐 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 4-hydroxy-1H-indole-2-carbonitrile
  参考文献：
  名称：

  β-肾上腺素受体的亲和标记：衍生自吲哚的烷基化β-受体阻滞剂的制备和性质。

  摘要：

  合成了对β-肾上腺素受体具有高亲和力的新的吲哚衍生的烷基化配体，并对其性质进行了研究。制备了N8-（溴乙酰基）-N1- [3-（4-吲哚氧基）-2-羟丙基]-（Z）-1,8-二氨基对-庚烷（8）及其N1，N8异构体（9）。通过使溴乙酰溴与4-吲哚基缩水甘油醚与（Z）-1,8-二氨基-对-薄荷烷的缩合产物反应而得到。使用2-氰基-4-吲哚基缩水甘油醚的类似反应产生了各自的氰基衍生物10和11。β-肾上腺素受体在大鼠心脏和肺部膜制剂上的表观亲和力（Ki，M）为4.6 X 10（-10）和1.34 X 10（-9）适用于8，2.3 X 10（-8）和4.5 X 10（-9）适用于9，6.1 X 10（-10）和1.49 X 10（-9）适用于10，以及1.83 X 10 （-9）和2.78 X 10（-9）表示11。当膜与上述配体（1 X 10（-8）M 30分钟，30摄氏度），然后彻底洗涤，[

  DOI：

  10.1021/jm00387a005

文献信息

• Anti-cancer agents and uses thereof
  申请人：Kelly Martha

  公开号：US20060270686A1

  公开（公告）日：2006-11-30

  The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I: and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A 1 is N or CR 1 ; A 3 is N or CR 3 ; A 5 is N or CR 5 ; R 1 , R 3 —R 6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, non-small cell lung and colon.

  本发明涉及新化合物及其盐，它们的合成以及它们作为抗癌剂的用途。这些化合物包括式I的化合物： 和其溶剂化物、水合物和药用可接受盐，其中A 1 为N或CR 1 ；A 3 为N或CR 3 ；A 5 为N或CR 5 ；R 1 ，R 3 —R 6 和L在说明书中有定义；n为0或1；X为在环部分具有6-10个碳的可选择取代芳基，在环部分具有1-3个氮原子的可选择取代的6元杂芳基，在环部分具有0-4个氮原子且可选择具有1个硫原子或1个氧原子的可选择取代的5元杂芳基，或者在其中6元环与5元环或6元环融合的可选择取代的杂芳基，其中在每种情况下1、2、3或4个环原子是从氮、氧和硫中独立选择的杂原子。它们对广泛范围的癌症，特别是白血病、非小细胞肺癌和结肠癌有效。
• Benzoxazinone derivatives, their preparation and use
  申请人：——

  公开号：US20040063704A1

  公开（公告）日：2004-04-01

  The present invention relates to novel compounds of formula (1) or a pharmaceutically acceptable salt thereof, wherein Ar is phenyl, naphthyl, a monocyclic heteroaromatic group or a bicyclic heteroaromatic group, said Ar group being optionally substituted by 1-4 substituents, which may be the same or different, and which are selected from the group consisting of: halogen, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, trifluoromethanesulfonyloxy, pentafluoroethyl, C 1-6 alkoxy, arylC 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkoxyC 1-6 -alkyl, C 3-7 cycloalkylC 1-6 alkoxy, C 1-6 alkanoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyloxy, C 1-6 alkylsulfonylC 1-6 alkyl, arylsulfonyl, arylsulfonyloxy, arylsulfonylC 1-6 alkyl, C 1-6 alkylsulfonamido, C 1-6 alkylamido, C 1-6 alkylsulfonamidoC 1-6 alkyl, C 1-6 alkylamidoC 1-6 alkyl, arylsulfonamido, arylcarboxamido, arylsullonamidoC 1-6 alkyl, arylcarboxamidoC 1-6 alkyl, aroyl, arylC 1-6 alkyl, arylC 1-6 alkanoyl, a group R 3 OCO(CH 2 ) s , R 3 CON(R 4 )(CH 2 ) s , R 3 R 4 NCO(C 2 ) s or R 3 R 4 NSO 2 (CH 2 ) where each of R 3 and R 4 independently represents a hydrogen atom or C 1-4 alkyl or R 3 and R 4 form part of a C 1-6 azacyloalkane or C 3- 6 (2-oxo)azacycloalkane ring and s represents zero or an integer from 1 to 4, and a group Ar 1 Z, wherein Z represents a single bond, O, S or CH 2 and Ar 1 represents a phenyl or a monocyclic heteroaromatic group, said Ar 1 group being optionally substituted by 1-3 substituents, which may be the same or different, and which are selected from the group consisting of a halogen, hydroxy, cyano, trifluoromethyl, C 1-6 alkyl, C 1-6 alkoxy or C 1-6 alkanoyl; when Ar is a phenyl or a monocyclic heteroaromatic group, substitutents positioned ortho to one another may be linked to form a 5- or 6-membered ring: R 1 is hydrogen, C 1-6 alkyl, C 3-6 alkenyl, C 3-6 alkynyl or arylC 1-6 alkyl; R 2 is halogen, C 1-6 alkyl, cyano, CF 3 , C 1-6 alkanoyl, C 1-6 alkoxy or hydroxy; X is CH or N; Y is a single bond, O, or C═O; p is 0, 1 or 2; r is 0, 1, 2 or 3; m is 2, 3 or 4; n and q are independently 1 or 2. Processes for preparing the compounds, pharmaceutical compositions containing them and their use as medicaments for various CNS disorders, including deression and/or anxiety, are also disclosed.

  本发明涉及公式（1）的新化合物或其药学上可接受的盐，其中Ar是苯基，萘基，单环杂芳基或双环杂芳基，所述Ar基可以选择性地被1-4个取代基取代，这些取代基可以相同或不同，选自以下群组：卤素，羟基，氰基，硝基，三氟甲基，三氟甲氧基，C1-6烷基，三氟甲磺酰氧基，五氟乙基，C1-6烷氧基，芳基C1-6烷氧基，C1-6烷硫基，C1-6烷氧基C1-6烷基，C3-7环烷基C1-6烷氧基，C1-6酰基，C1-6烷氧羰基，C1-6烷基磺酰基，C1-6烷基亚磺基，C1-6烷基磺酰氧基，C1-6烷基磺酰基C1-6烷基，芳基磺酰基，芳基磺酰氧基，芳基磺酰基C1-6烷基，C1-6烷基磺酰胺基，C1-6烷基酰胺基，C1-6烷基磺酰胺基C1-6烷基，C1-6烷基酰胺基C1-6烷基，芳基磺酰胺基，芳基羧酰胺，芳基磺酰胺基C1-6烷基，芳基羧酰胺基C1-6烷基，酰基，芳基C1-6烷基，芳基C1-6酰基，一个R3OCO（CH2）s，R3CON（R4）（CH2）s，R3R4NCO（C2）s或R3R4NSO2（CH2）组，其中R3和R4各自独立地表示氢原子或C1-4烷基，或R3和R4构成C1-6氮杂环烷或C3-6（2-氧代）氮杂环烷环，s表示零或1-4的整数，以及一个Ar1Z基，其中Z表示单键，O，S或CH2，Ar1表示苯基或单环杂芳基，所述Ar1基可以选择性地被1-3个取代基取代，这些取代基可以相同或不同，选自以下群组：卤素，羟基，氰基，三氟甲基，C1-6烷基，C1-6烷氧基或C1-6酰基；当Ar是苯基或单环杂芳基时，相对位于一个环上的取代基可以连接形成5-或6-成员环；R1是氢，C1-6烷基，C3-6烯基，C3-6炔基或芳基C1-6烷基；R2是卤素，C1-6烷基，氰基，CF3，C1-6酰基，C1-6烷氧基或羟基；X是CH或N；Y是单键，O或C═O；p是0，1或2；r是0，1，2或3；m是2，3或4；n和q独立地为1或2。还公开了制备这些化合物的方法，包含它们的制药组合物以及它们作为治疗各种中枢神经系统疾病，包括抑郁和/或焦虑的药物的用途。
• ANTI-CANCER AGENTS AND USES THEREOF
  申请人：KELLY Martha

  公开号：US20090093479A1

  公开（公告）日：2009-04-09

  The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I: and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A 1 is N or CR 1 ; A 3 is N or CR 3 ; A 5 is N or CR 5 ; R 1 , R 3 -R 6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, non-small cell lung and colon.

  本发明涉及新化合物及其盐，它们的合成方法以及它们作为抗癌剂的用途。这些化合物包括式I的化合物及其溶剂化物、水化物和药学上可接受的盐，其中A1为N或CR1；A3为N或CR3；A5为N或CR5；R1、R3-R6和L在规范中有定义；n为0或1；X是一个具有6-10个碳原子的环部分可选取代的芳基基团，一个具有1-3个氮原子的环部分可选取代的6元杂芳基基团，一个具有0-4个氮原子并可选地在环部分含有1个硫原子或1个氧原子的5元杂芳基基团，或者一个6元环与一个5元环或6元环融合的可选取代的杂芳基基团，在每种情况下，1、2、3或4个环原子是独立选择的氮、氧和硫杂原子。它们对广泛的癌症，尤其是白血病、非小细胞肺癌和结肠癌都有良好的治疗效果。
• 3-Aminopropoxyaryl derivatives, their preparation and pharmaceutical compositions containing them
  申请人：SANDOZ AG

  公开号：EP0013878A1

  公开（公告）日：1980-08-06

  The compounds of formula I where R1, R2 and R3 have various significances, are useful as antiarrhythmic, a-adrenoceptor blocking and, when a cyano or carbamoyl group is attached in the 2 position of the indole nucleus, additionally as β-adrenoceptor blocking agents. They are prepared by amination.

  式 I 的化合物 其中 R1、R2 和 R3 具有不同的意义，可用作抗心律失常、a 肾上腺素受体阻断剂，当吲哚核的 2 位上连接有氰基或氨基甲酰基时，还可用作 β 肾上腺素受体阻断剂。 它们是通过胺化反应制备的。
• Selective binding compounds for 5-hydroxytryptamine 1-A-receptors and pharmaceutical compositions containing them
  申请人：THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

  公开号：EP0338877A1

  公开（公告）日：1989-10-25

  Compounds that selectively bind 5-HT1A recep­tors in preference to other 5-HT receptors are provided along with methods for their use. Such compounds have the formula wherein A is an aromatic group selected to provide, with the glycidyl residue that forms the next portion of the molecule, a 5-HT-like portion of the molecule that represents the primary binding site of the mole­cule with a 5-HT receptor; X represents a quarternary carbon and its attached alkyl groups; Y represents a hydrocarbon linking group; Z represents hydrogen or an organic group containing up to 12 carbon and/or hetero­atoms in its skeletal structure; and R¹ and R² inde­pendently represent hydrogen or an alkyl group. The aromatic group is most preferably indole or an indole derivative.

  提供了选择性结合 5-HT1A 受体而非其他 5-HT 受体的化合物及其使用方法。此类化合物的化学式为 其中 A 是芳香基团，与构成分子下一部分的缩水甘油残基一起提供分子的 5-HT 样性部分，该部分代表分子与 5-HT 受体的主要结合位点；X 代表四元碳及其连接的烷基；Y 代表烃连接基团；Z 代表氢或在其骨架结构中含有多达 12 个碳和/或杂原子的有机基团；R¹ 和 R² 独立地代表氢或烷基。芳香基团最好是吲哚或吲哚衍生物。