2-cyclohexyl-6-(piperazin-1-yl)-2,3-dihydro-1H-isoindol-1-one | 217493-04-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-cyclohexyl-6-(piperazin-1-yl)-2,3-dihydro-1H-isoindol-1-one
• 英文别名: 2-cyclohexyl-2,3-dihydro-6-(piperazin-1-yl)-1H-isoindol-1-one；2-cyclohexyl-6-piperazin-1-yl-3H-isoindol-1-one
• CAS: 217493-04-4
• 化学式: C₁₈H₂₅N₃O
• 分子量: 299.416
• InChiKey: PKIOSMWDHUFYEW-UHFFFAOYSA-N

物化性质

• 沸点：
  521.6±50.0 °C(Predicted)
• 密度：
  1.176±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-cyclohexyl-6-(piperazin-1-yl)-2,3-dihydro-1H-isoindol-1-one 在 三乙胺 作用下， 以 甲苯 为溶剂， 生成 4-(2-cyclohexyl-1-oxo-2,3-dihydro-1H-isoindol-6-yl)piperazine-1-carboxylic acid benzhydrylamide
  参考文献：
  名称：

  Nitrogenous heterocyclic compounds and hyperlipemia remedy containing the same

  摘要：

  化合物的化学式（I）及其药学上可接受的盐和溶剂的披露。这些化合物可以抑制肝脏中三酸甘油酯的生物合成，并可以抑制肝脏中含载脂蛋白B的脂蛋白的分泌。因此，它们对于预防或治疗高脂血症（特别是高超低密度脂蛋白血症）和由高脂血症引起的心肌梗死或胰腺炎等动脉粥样硬化疾病是有用的。其中A代表基团—CR1R2—（CH2）i—，其中R1和R2分别代表氢原子或烷基，—CH═CH—，—O—CH2—或—S(O)j—CH2—；B代表氢或卤原子；X代表—CR3R4R5，—NR6R7，—（CH2—CH═C(CH3)—CH2）p—CH2CH═C(CH3)2，烷基，环烷基，苯基，肉桂基或杂环芳香环；Y代表—（CH2）q—，—CH═CH—，—NR8—，氧原子或键；Z代表酰基或键；K代表烷基或键；L代表—CH═CH—或键；M代表氢原子，烷基，环烷基，苯基，杂环环，联苯基或二苯基甲基。

  公开号：

  US06417362B1

文献信息

• Nitrogen-containing heterocyclic compounds and benzamide compounds and drugs containing the same
  申请人：——

  公开号：US20040224959A1

  公开（公告）日：2004-11-11

  Disclosed are compounds represented by formula (I) which have triglyceride biosynthesis inhibitory activity in the liver and inhibitory activity against the secretion of apolipoprotein B-containing lipoprotein from the liver and particularly have excellent inhibitory activity against the secretion of apolipoprotein B-containing lipoprotein, are free from side effect of accumulation of lipids in the liver, and are useful for the treatment and prevention of hyperlipidemia and arteriosclerotic diseases. In formula (I), R 1 and R 2 represent alkyl, alkoxy, cycloalkyl, phenyl, alkenyl, alkynyl, or a five- or six-membered saturated or unsaturated heterocyclic ring, or R 1 and R 2 , together with a nitrogen atom to which R 1 and R 2 are attached, may form a ring; R 3 and R 4 represent a hydrogen atom, alkyl, a halogen atom, hydroxyl, nitrile, alkoxycarbonyl, alkoxy, or carboxyl; or R 2 and R 3 may be attached to each other to form —(CH 2 ) m —, —N═CH—, —CH═N—, or —(C 1-6 alkyl)C═N—; A, D, E, and G each represent a carbon atom, or any one of A, D, E, and G represents a nitrogen atom with the other three each representing a carbon atom; Q represents a nitrogen atom or a carbon atom; Y represents a group represented by formula (II) wherein X represents a hydrogen atom, group —C(═O)N(R 5 )R 6 or group —C(═O)OR 7 , R 8 is absent or represents a bond, an oxygen atom, a sulfur atom, —SO 2 —, —SO—, —CH 2 —CH 2 —, or —CH═CH—, and R 9 and R 10 represent a hydrogen atom, alkyl, alkoxy, a halogen atom, or hydroxyl; and Z represents —(CH 2 ) n —, —O—(CH 2 ) i —, or —C(═O)NH—(CH 2 ) i —. 1

  本发明涉及一种由公式（I）表示的化合物，其在肝脏中具有三酰甘油生物合成抑制活性和抑制含载脂蛋白B的脂蛋白从肝脏分泌的活性，特别是对含载脂蛋白B的脂蛋白的分泌具有出色的抑制活性，且不会出现在肝脏中积累脂质的副作用，对于治疗和预防高脂血症和动脉粥样硬化疾病非常有用。在公式（I）中，R1和R2代表烷基、烷氧基、环烷基、苯基、烯基、炔基或五元或六元饱和或不饱和杂环环，或R1和R2与R1和R2附着的氮原子一起形成环; R3和R4代表氢原子、烷基、卤素原子、羟基、腈、烷氧羰基、烷氧基或羧基; 或R2和R3可以相互附着以形成-（CH2）m-、-N═CH-、-CH═N-或-（C1-6烷基）C═N-; A、D、E和G每个代表一个碳原子，或任何一个A、D、E和G代表一个氮原子，其他三个代表一个碳原子; Q代表一个氮原子或一个碳原子; Y代表由公式（II）表示的基团，其中X代表氢原子、基团-C(═O)N(R5)R6或基团-C(═O)OR7，R8不存在或代表一个键，一个氧原子，一个硫原子，-SO2-，-SO-，-CH2-CH2-或-CH═CH-，R9和R10代表氢原子、烷基、烷氧基、卤素原子或羟基; Z代表-（CH2）n-、-O-（CH2）i-或-C(═O)NH-（CH2）i-。
• Nitrogen-containing heterocyclic compounds and therapeutic agents for hyperlipidemia comprising the same
  申请人：——

  公开号：US20020156276A1

  公开（公告）日：2002-10-24

  Disclosed are compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof. The compounds can inhibit the biosynthesis of triglycerides in the liver and can inhibit the secretion of lipoprotein containing apolipoprotein B from the liver. Therefore, they are useful for the prevention or treatment of hyperlipidemia (particularly hyper-very-low-density-lipoproteinemia) and arteriosclerotic diseases, such as cardiac infarction, or pancreatitis induced by hyperlipidemia. 1 wherein A represents group —CR 1 R 2 —( CH 2 ) 1 — where R 1 and R 2 each represent a hydrogen atom or alkyl, —CH═CH—, —O—CH 2 —, or —S(O) j —CH 2 —; B represents a hydrogen or halogen atom; X represents —CR 3 R 4 R 5 , —NR 6 R 7 , —(CH 2 —CH═C(CH 3 )—CH 2 ) p —CH 2 CH═C(CH 3 ) 2 , alkyl, cycloalkyl, phenyl, cinnamyl, or heteroaromatic ring; Y represents —(CH 2 ) q —, —CH═CH—, —NR 8 —, an oxygen atom, or a bond; z represents carbonyl or a bond; K represents alkylene or a bond; L represents —CH═CH— or a bond; and M represents a hydrogen atom, alkyl, cycloalkyl, phenyl, heterocyclic ring, biphenyl, or diphenylmethyl.

  本发明涉及一种由公式（I）表示的化合物及其药学上可接受的盐和溶剂化物。该化合物可以抑制肝脏中三酰甘油的生物合成，并可以抑制含载载脂蛋白B的脂蛋白从肝脏分泌。因此，它们可用于预防或治疗高脂血症（特别是高极低密度脂蛋白血症）和动脉硬化性疾病，如心肌梗死或由高脂血症引起的胰腺炎。 其中，A代表基团—CR1R2—（ CH2）1—，其中R1和R2分别代表氢原子或烷基，—CH═CH—，—O—CH2—或—S（O）j—CH2—；B代表氢或卤素原子；X代表—CR3R4R5，—NR6R7，—（CH2—CH═C（CH3）—CH2）p—CH2CH═C（CH3）2，烷基，环烷基，苯基，肉桂基或杂环芳香环；Y代表—（CH2）q—，—CH═CH—，—NR8—，氧原子或键；z代表羰基或键；K代表烷基或键；L代表—CH═CH—或键；M代表氢原子，烷基，环烷基，苯基，杂环环，联苯或二苯甲基。
• NITROGENOUS HETEROCYCLIC COMPOUNDS AND HYPERLIPEMIA REMEDY CONTAINING THE SAME
  申请人：Meiji Seika Kaisha, Ltd.

  公开号：EP0999208A1

  公开（公告）日：2000-05-10

  Disclosed are compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof. The compounds can inhibit the biosynthesis of triglycerides in the liver and can inhibit the secretion of lipoprotein containing apolipoprotein B from the liver. Therefore, they are useful for the prevention or treatment of hyperlipidemia (particularly hyper-very-low-density-lipoproteinemia) and arteriosclerotic diseases, such as cardiac infarction, or pancreatitis induced by hyperlipidemia.    wherein A represents group -CR1R2-(CH2)i- where R1 and R2 each represent a hydrogen atom or alkyl, -CH=CH-, -O-CH2-, or -S(O)j-CH2-; B represents a hydrogen or halogen atom; X represents -CR3R4R5, -NR6R7, -(CH2-CH=C(CH3)-CH2)p-CH2CH=C(CH3)2, alkyl, cycloalkyl, phenyl, cinnamyl, or heteroaromatic ring; Y represents -(CH2)q-, -CH=CH-, -NR8-, an oxygen atom, or a bond; Z represents carbonyl or a bond; K represents alkylene or a bond; L represents -CH=CH- or a bond; and M represents a hydrogen atom, alkyl, cycloalkyl, phenyl, heterocyclic ring, biphenyl, or diphenylmethyl.

  公开了式 (I) 所代表的化合物及其药学上可接受的盐和溶液。这些化合物可抑制肝脏中甘油三酯的生物合成，并可抑制肝脏分泌含有载脂蛋白 B 的脂蛋白。因此，它们可用于预防或治疗高脂血症（尤其是高极低密度脂蛋白血症）和动脉硬化性疾病，如心肌梗塞或由高脂血症诱发的胰腺炎。 其中 A 代表基团-CR1R2-(CH2)- 其中 R1 和 R2 各自代表氢原子或烷基、-CH=CH-、-O-CH2-或-S(O)j-CH2-；B 代表氢原子或卤素原子；X 代表-CR3R4R5、-NR6R7、-(CH2-CH=C(CH3)-CH2)p-CH2CH=C(CH3)2、烷基、环烷基、苯基、肉桂基或杂芳环；Y 代表-(CH2)q-、-CH=CH-、-NR8-、氧原子或键； Z 代表羰基或键； K 代表亚烷基或键； L 代表-CH=CH-或键； M 代表氢原子、烷基、环烷基、苯基、杂环、联苯或二苯基甲基。
• NITROGEN-CONTAINING HETEROCYCLIC COMPOUNDS AND BENAMIDE COMPOUNDS AND DRUGS CONTAINING THE SAME
  申请人：Meiji Seika Kaisha, Ltd.

  公开号：EP1180514A1

  公开（公告）日：2002-02-20

  Disclosed are compounds represented by formula (I) which have triglyceride biosynthesis inhibitory activity in the liver and inhibitory activity against the secretion of apolipoprotein B-containing lipoprotein from the liver and particularly have excellent inhibitory activity against the secretion of apolipoprotein B-containing lipoprotein, are free from side effect of accumulation of lipids in the liver, and are useful for the treatment and prevention of hyperlipidemia and arteriosclerotic diseases. In formula (I), R1 and R2 represent alkyl, alkoxy, cycloalkyl, phenyl, alkenyl, alkynyl, or a five- or six-membered saturated or unsaturated heterocyclic ring, or R1 and R2, together with a nitrogen atom to which R1 and R2 are attached, may form a ring; R3 and R4 represent a hydrogen atom, alkyl, a halogen atom, hydroxyl, nitrile, alkoxycarbonyl, alkoxy, or carboxyl; or R2 and R3 may be attached to each other to form -(CH2)m-, -N=CH-, -CH=N-, or -(C1-6 alkyl)C=N-; A, D, E, and G each represent a carbon atom, or any one of A, D, E, and G represents a nitrogen atom with the other three each representing a carbon atom; Q represents a nitrogen atom or a carbon atom; Y represents a group represented by formula (II) wherein X represents a hydrogen atom, group -C(=O)N(R5)R6 or group -C(=O)OR7, R8 is absent or represents a bond, an oxygen atom, a sulfur atom, -SO2-, -SO-, -CH2-CH2-, or - CH=CH-, and R9 and R10 represent a hydrogen atom, alkyl, alkoxy, a halogen atom, or hydroxyl; and Z represents - (CH2)n-, -O-(CH2)i-, or -C(=O)NH-(CH2)i-.

  本发明公开了式(I)代表的化合物，该化合物具有抑制肝脏中甘油三酯生物合成的活性和抑制肝脏分泌含脂蛋白B的脂蛋白的活性，特别是对肝脏分泌含脂蛋白B的脂蛋白具有极好的抑制活性，无肝脏中脂类蓄积的副作用，可用于治疗和预防高脂血症和动脉硬化性疾病。在式（I）中，R1 和 R2 代表烷基、烷氧基、环烷基、苯基、烯基、炔基或五元或六元饱和或不饱和杂环，或 R1 和 R2 与 R1 和 R2 所连接的氮原子一起可形成一个环；R3 和 R4 代表氢原子、烷基、卤素原子、羟基、腈基、烷氧羰基、烷氧基或羧基；或 R2 和 R3 可相互连接形成-(CH2)m-、-N=CH-、-CH=N-或-(C1-6 烷基)C=N-；A、D、E 和 G 各代表一个碳原子，或 A、D、E 和 G 中的任何一个代表一个氮原子，其他三个各代表一个碳原子； Q 代表一个氮原子或一个碳原子；Y 代表由式 (II) 所代表的基团，其中 X 代表氢原子、基团-C(=O)N(R5)R6 或基团-C(=O)OR7，R8 不存在或代表键、氧原子、硫原子、-SO2-、-SO-、-CH2-CH2- 或-CH=CH-，R9 和 R10 代表氢原子、烷基、烷氧基、卤素原子或羟基；Z 代表-(CH2)n-、-O-(CH2)-i 或-C(=O)NH-(CH2)-i。
• EP1180514
  申请人：——

  公开号：——

  公开（公告）日：——