2-((1-benzylpiperidin-4-yl)methyl)-2-bromo-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-((1-benzylpiperidin-4-yl)methyl)-2-bromo-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one
• 英文别名: 1-benzyl-4-[(5,6-dimethoxy-2-bromo-1-indanon)-2-yl]methylpiperidine；2-[(1-benzylpiperidin-4-yl)methyl]-2-bromo-5,6-dimethoxy-3H-inden-1-one
• 化学式: C₂₄H₂₈BrNO₃
• 分子量: 458.395
• InChiKey: UHUMJMYZGOMQRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-((1-benzylpiperidin-4-yl)methyl)-2-bromo-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one 、 N-氰基-4-甲基-N-苯基苯磺酰胺 在 锌 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以75%的产率得到2-((1-benzylpiperidin-4-yl)methyl)-5,6-dimethoxy-1-oxo-2,3-dihydro-1H-indene-2-carbonitrile
  参考文献：
  名称：

  通过还原氰化法获得带有季碳中心的α-氰基羰基

  摘要：

  开发了使用亲电子氰化试剂和锌还原剂对叔烷基溴进行还原性氰化的反应，在温和的反应条件下，提供了多种含氰基全碳四元中心的α-氰基酮，酯和羧酰胺，收率良好。通过密度泛函理论计算，阐明了相应的反应机理，包括原位生成的有机锌试剂和反应性的区别。

  DOI：

  10.1021/acs.orglett.1c00465
• 作为产物：
  描述：

  多萘哌齐碱 在 氢溴酸 、 二甲基亚砜 作用下， 以 水 、 乙酸乙酯 为溶剂， 以78%的产率得到2-((1-benzylpiperidin-4-yl)methyl)-2-bromo-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one
  参考文献：
  名称：

  通过还原氰化法获得带有季碳中心的α-氰基羰基

  摘要：

  开发了使用亲电子氰化试剂和锌还原剂对叔烷基溴进行还原性氰化的反应，在温和的反应条件下，提供了多种含氰基全碳四元中心的α-氰基酮，酯和羧酰胺，收率良好。通过密度泛函理论计算，阐明了相应的反应机理，包括原位生成的有机锌试剂和反应性的区别。

  DOI：

  10.1021/acs.orglett.1c00465

文献信息

• [EN] NOVEL DERIVATIVES OF DONEPEZIL<br/>[FR] NOUVEAU DÉRIVÉS DU DONÉPÉZIL
  申请人：SUZHOU SHANGZHI BIOTECH LTD

  公开号：WO2014008629A1

  公开（公告）日：2014-01-16

  This invention relates to novel compounds and hydrochloric acid salts thereof. More specifically, this invention relates to novel compounds and hydrochloric acid salts thereof derived from donepezil. This invention also provides compositions comprising one or more compounds of this invention and a carrier and the use of the disclosed compounds and compositions in methods of treating diseases and conditions that are beneficially treated by administering an acetylcholinesterase (AChE) inhibitor, such as donepezil.

  这项发明涉及新颖化合物及其盐酸盐。更具体地说，这项发明涉及从多奈哌齐派生的新颖化合物和其盐酸盐。该发明还提供了包含本发明中一种或多种化合物和载体的组合物，以及利用所披露的化合物和组合物在治疗通过给予乙酰胆碱酯酶（AChE）抑制剂，如多奈哌齐，有益治疗的疾病和症状的方法。
• Sigma receptor binding agent containing indanone derivative
  申请人：Iimura Yoichi

  公开号：US20090137629A1

  公开（公告）日：2009-05-28

  A method for treatment of a mental disorder containing the step of administering a therapeutically effective amount of a sigma receptor binding agent containing an indanone compound represented by the following formula (I), a pharmacologically acceptable salt thereof or a hydrate of them. The variables of formula (I) are recited in the present specification.

  一种治疗精神障碍的方法，包括以下步骤：给予治疗有效量的sigma受体结合剂，该结合剂包含以下式子（I）所表示的indanone化合物，其药理学上可接受的盐或水合物。式子（I）的变量在本说明书中已列出。
• Photoinduced promiscuity of cyclohexanone monooxygenase for the enantioselective synthesis of α-deuterated carbonyl compounds
  作者：Yongzhen Peng、Kongchen Xia、Qi Wu

  DOI：10.1016/j.mcat.2023.113709

  日期：2024.1

  The direct asymmetric synthesis of deuterium compounds has gained increasing attention. Here we report the engineered cyclohexanone monooxygenase from Acinetobacter sp. NCIMB 9871 for the synthesis of chiral α-deuterated carbonyl compounds via enantioselective reductive dehalogenation. The engineered CHMO exhibited good chemoselectivity, stereoselectivity and d-incorporation (up to 92% yield, 98% e

  氘化合物的直接不对称合成越来越受到人们的关注。在这里，我们报道了来自不动杆菌属的工程环己酮单加氧酶。NCIMB 9871 用于通过对映选择性还原脱卤合成手性 α-氘代羰基化合物。工程化的 CHMO对一系列 α-卤代羰基化合物表现出良好的化学选择性、立体选择性和 d-掺入（高达 92% 产率、98% ee和 96% d-掺入）。该方法还用于合成氘代药物，这证明了其在合成化学中的广阔应用前景。
• SIGMA RECEPTOR BINDER CONTAINING INDANONE DERIVATIVE
  申请人：Eisai Co., Ltd.

  公开号：EP1468684A1

  公开（公告）日：2004-10-20

  The present invention provides an indanone derivative and an excellent sigma receptor binding agent comprising an indanone derivative. More specifically, it provides a sigma receptor binding agent comprising an indanone derivative represented by the following formula, a pharmacologically acceptable salt thereof or a hydrate of them. In the formula (I), R1, R2, R3 and R4 are the same as or different from each other and each represents hydrogen atom, a halogen atom, hydroxyl group, nitrile group, a C1-6 alkyl group which may be substituted, a cycloalkyl group having three to eight carbon atoms which may be substituted, a C1-6 alkoxy group which may be substituted, a cycloalkoxy group having three to eight carbon atoms which may be substituted, an acyl group having one to six carbon atoms which may be substituted, a C1-6 alkoxycarbonyl group which may be substituted, a C1-6 alkylaminocarbonyloxy group which may be substituted, a di(C1-6 alkyl)aminocarbonyloxy group which may be substituted, nitro group, an amino group which may be substituted, an amido group which may be substituted, mercapto group or a thio-C1-6 alkoxy group which may be substituted, and further R1 with R2, R2 with R3, or R3 with R4 may together form an aliphatic ring, an aromatic ring, a heterocyclic ring or an alkylenedioxy ring; the partial structure: represents a group represented by >CH-CH2-, >C=CH- or >C(-R7)-CH2-; m represents an integer of 0 or 1 to 5; and R5 represents hydrogen atom, a C1-6 alkyl group which may be substituted, a C2-6 alkenyl group which may be substituted, a C2-6 alkynyl group which may be substituted, a cycloalkyl group having three to eight carbon atoms which may be substituted, a 2,2-(alkylenedioxy)ethyl group or a group represented by the formula: (wherein the ring C represents benzene ring, an aliphatic ring or a heterocyclic ring; R6s are the same as or different from each other and each represents hydrogen atom, a halogen atom, hydroxyl group, nitrile group, a C1-6 alkyl group which may be substituted, a C2-6 alkenyl group which may be substituted, a C2-6 alkynyl group which may be substituted, a cycloalkyl group having three to eight carbon atoms which may be substituted, a C1-6 alkoxy group which may be substituted, a C1-6 alkoxyalkoxy group which may be substituted, an aryloxy group which may be substituted or an aralkyloxy group which may be substituted, and further two of R6s may together form an aliphatic ring, an aromatic ring, a heterocyclic ring or an alkylenedioxy ring; R7 represents a halogen atom, hydroxyl group, a C1-6 alkyl group which may be substituted, a C1-6 alkoxy group, nitrile group, a halogeno-C1-6 alkyl group, a hydroxyl-C1-6 alkyl group, a cyano-C1-6 alkyl group, an amino-C1-6 alkyl group, nitro group, azide group, an amino group which may be substituted, a carbamoyl group which may be substituted, a carboxyl group which may be substituted, mercapto group or a thio-C1-6 alkoxy group; and n represents an integer of 1 to 5), provided that 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine, a pharmacologically acceptable salt thereof or a hydrate of them are excluded.

  本发明提供了一种茚满酮衍生物和一种包含茚满酮衍生物的优良σ受体结合剂。更具体地说，本发明提供了一种σ受体结合剂，它由下式所代表的茚酮衍生物、其药理学上可接受的盐或它们的水合物组成。 在式 (I) 中，R1、R2、R3 和 R4 彼此相同或不同，各自代表氢原子、卤素原子、羟基、腈基、可被取代的 C1-6 烷基、具有三至八个碳原子且可被取代的环烷基、可被取代的 C1-6 烷氧基、具有三至八个碳原子且可被取代的环烷氧基、具有一至六个碳原子且可被取代的酰基、可被取代的 C1-6 烷氧基羰基、可被取代的 C1-6 烷基氨基羰氧基、可被取代的二（C1-6 烷基）氨基羰氧基、硝基、可被取代的氨基、可被取代的酰胺基、巯基或可被取代的硫代-C1-6 烷氧基，此外，R1 与 R2、R2 与 R3 或 R3 与 R4 可共同形成脂肪环、芳香环、杂环或烷基二氧基环；部分结构： 代表由 >CH-CH2-、>C=CH- 或 >C(-R7)-CH2-代表的基团；m 代表 0 或 1 至 5 的整数；R5 代表氢原子、可被取代的 C1-6 烷基、可被取代的 C2-6 烯基、可被取代的 C2-6 烷基、可被取代的具有 3 至 8 个碳原子的环烷基、2,2-(烷基二氧基)乙基或由式...代表的基团： (其中环 C 代表苯环、脂肪环或杂环；R6s 彼此相同或不同，各自代表氢原子、卤素原子、羟基、腈基、可被取代的 C1-6 烷基、可被取代的 C2-6 烯基、可被取代的 C2-6 烷基、具有三至八个碳原子的可被取代的环烷基、可被取代的 C1-6 烷氧基、可被取代的 C1-6 烷氧基、可被取代的芳氧基或可被取代的芳烷氧基，另外两个 R6 可共同形成脂肪环、芳香环、杂环或烷二氧基环；R7 代表卤素原子、羟基、可被取代的 C1-6 烷基、C1-6 烷氧基、腈基、卤素-C1-6 烷基、羟基-C1-6 烷基、氰基-C1-6 烷基、氨基-C1-6 烷基、硝基、叠氮基、可被取代的氨基、可被取代的氨基甲酰基、可被取代的羧基、巯基或硫代-C1-6 烷氧基；和 n 代表 1 至 5 的整数），但不包括 1-苄基-4-[(5,6-二甲氧基-1-茚酮)-2-基]甲基哌啶、其药理学上可接受的盐或它们的水合物。
• Sigma receptor binder containing indanone derivative
  申请人：Iimura Yoichi

  公开号：US20050107432A1

  公开（公告）日：2005-05-19

  The present invention provides an indanone derivative and an excellent sigma receptor binding agent comprising an indanone derivative. More specifically, it provides a sigma receptor binding agent comprising an indanone derivative represented by the following formula, a pharmacologically acceptable salt thereof or a hydrate of them. In the formula (I), R 1 , R 2 , R 3 and R 4 are the same as or different from each other and each represents hydrogen atom, a halogen atom, hydroxyl group, nitrile group, a C 1-6 alkyl group which may be substituted, a cycloalkyl group having three to eight carbon atoms which may be substituted, a C 1-6 alkoxy group which may be substituted, a cycloalkoxy group having three to eight carbon atoms which may be substituted, an acyl group having one to six carbon atoms which may be substituted, a C 1-6 alkoxycarbonyl group which may be substituted, a C 1-6 alkylaminocarbonyloxy group which may be substituted, a di(C 1-6 alkyl)aminocarbonyloxy group which may be substituted, nitro group, an amino group which may be substituted, an amido group which may be substituted, mercapto group or a thio-C 1-6 alkoxy group which may be substituted, and further R 1 with R 2 , R 2 with R 3 , or R 3 with R 4 may together form an aliphatic ring, an aromatic ring, a heterocyclic ring or an alkylenedioxy ring; the partial structure: represents a group represented by >CH—CH 2 —, >C═CH— or >C(—R 7 )—CH 2 —; m represents an integer of 0 or 1 to 5; and R 5 represents hydrogen atom, a C 1-6 alkyl group which may be substituted, a C 2-6 alkenyl group which may be substituted, a C 2-6 alkynyl group which may be substituted, a cycloalkyl group having three to eight carbon atoms which may be substituted, a 2,2-(alkylenedioxy)ethyl group or a group represented by the formula: (wherein the ring C represents benzene ring, an aliphatic ring or a heterocyclic ring; R 6 s are the same as or different from each other and each represents hydrogen atom, a halogen atom, hydroxyl group, nitrile group, a C 1-6 alkyl group which may be substituted, a C 2-6 alkenyl group which may be substituted, a C 2-6 alkynyl group which may be substituted, a cycloalkyl group having three to eight carbon atoms which may be substituted, a C 1-6 alkoxy group which may be substituted, a C 1-6 alkoxyalkoxy group which may be substituted, an aryloxy group which may be substituted or an aralkyloxy group which may be substituted, and further two of R 6 s may together form an aliphatic ring, an aromatic ring, a heterocyclic ring or an alkylenedioxy ring; R 7 represents a halogen atom, hydroxyl group, a C 1-6 alkyl group which may be substituted, a C 1-6 alkoxy group, nitrile group, a halogeno-C 1-6 alkyl group, a hydroxyl-C 1-6 alkyl group, a cyano-C 1-6 alkyl group, an amino-C 1-6 alkyl group, nitro group, azide group, an amino group which may be substituted, a carbamoyl group which may be substituted, a carboxyl group which may be substituted, mercapto group or a thio-C 1-6 alkoxy group; and n represents an integer of 1 to 5), provided that 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine, a pharmacologically acceptable salt thereof or a hydrate of them are excluded.

  本发明提供了一种茚满酮衍生物和一种包含茚满酮衍生物的优良σ受体结合剂。更具体地说，本发明提供了一种σ受体结合剂，它包含下式所代表的茚满酮衍生物、其药理学上可接受的盐或它们的水合物。 在式 (I) 中，R 1 , R 2 , R 3 和 R 4 相同或不同，且各自代表氢原子、卤素原子、羟基、腈基、C 1-6 烷基（可被取代）、具有三至八个碳原子的环烷基（可被取代）、C 1-6 1-6 可被取代的 C 1-6 烷氧基、具有三至八个碳原子且可被取代的环烷氧基、具有一至六个碳原子且可被取代的酰基、C 1-6 1-6 烷氧基羰基（可被取代）、C 1-6 烷基氨基羰氧基（可被取代）、二（C 1-6 1-6 烷基）氨基羰氧基（可被取代）、硝基、氨基（可被取代）、酰胺基（可被取代）、巯基或硫代-C 1-6 1-6 烷氧基（可被取代），以及进一步的 R 1 与 R 2 , R 2 与 R 3 或 R 3 与 R 4 可共同形成脂肪族环、芳香族环、杂环或烷基二氧基环； 部分结构： 代表一个由 >CH-CH 2 -、>C═CH- 或 >C(-R 7 ) -CH 2 -代表 0 或 1 至 5 的整数；以及 R 5 代表氢原子、C 1-6 烷基（可被取代）、C 2-6 可被取代的 C 2-6 烷基 2-6 可被取代的 C 2-6 烷基、可被取代的 C 2-6 烯基、可被取代的 C 2-6 炔基、具有 3 至 8 个碳原子的可被取代的环烷基、2,2-(亚烷基二氧基)乙基或由以下式子表示的基团： (其中环 C 代表苯环、脂肪族环或杂环； R 6 相同或不同，且各自代表氢原子、卤素原子、羟基、腈基、C 1-6 烷基（可被取代）、C 2-6 烯基（可被取代）、C 2-6 可被取代的 C 2-6 烷基、可被取代的 C 2-6 烯基、可被取代的 C 2-6 炔基、具有三至八个碳原子的环烷基、可被取代的 C 1-6 烷氧基（可被取代）、C 1-6 可被取代的 C 1-6 烷氧基、可被取代的 C 1-6 烷氧基、可被取代的芳氧基或可被取代的芳烷氧基，以及 R 6 中的两个可共同形成脂肪环、芳香环、杂环或烷基二氧基环； R 7 7 代表卤素原子、羟基、C 1-6 烷基（可被取代）、C 1-6 烷氧基、腈基、卤素-C 1-6 烷基、羟基-C 1-6 烷基、氰基-C 1-6 烷基、氨基-C 1-6 烷基、硝基、叠氮基、可被取代的氨基、可被取代的氨基甲酰基、可被取代的羧基、巯基或硫代-C 1-6 1-6 烷氧基；以及 n 代表 1 至 5 的整数），但不包括 1-苄基-4-[(5,6-二甲氧基-1-茚酮)-2-基]甲基哌啶、其药理学上可接受的盐或它们的水合物。