(±)-(1S,4R,9S)-3,3-dimethyl-9-(2-methylallyl)-1,2,3,4-tetrahydro-1,4-(epiminomethano)naphthalene

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (±)-(1S,4R,9S)-3,3-dimethyl-9-(2-methylallyl)-1,2,3,4-tetrahydro-1,4-(epiminomethano)naphthalene
• 英文别名: 11,11-dimethyl-10-methallyl-9-azatricyclo[6.2.2.0^2,7]dodeca-2,4,6-triene；CID3160422；(1R,8S,10S)-11,11-dimethyl-10-(2-methylprop-2-enyl)-9-azatricyclo[6.2.2.02,7]dodeca-2,4,6-triene
• 化学式: C₁₇H₂₃N
• 分子量: 241.376
• InChiKey: ZVZCYSQBQLWXCC-HRCADAONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  苦味酸 、 (±)-(1S,4R,9S)-3,3-dimethyl-9-(2-methylallyl)-1,2,3,4-tetrahydro-1,4-(epiminomethano)naphthalene 以 甲醇 为溶剂， 以82%的产率得到
  参考文献：
  名称：

  摘要：

  Allylmetallation of isoquinolines, quinoline, and quinoxaline with allylic derivatives of zinc was examined for the first time. A convenient procedure was discovered and developed for the synthesis of 1,4-ethano-2,3-dihydroisoquinolines based on the reactions of isoquinolines with allylic derivatives of zinc. This multistage process involves double allylmetallation of the heterocyclic ring followed by cyclization through intramolecular carbometallation of the C=C bond. The structures of three key derivatives of 1,4-ethano-2,3-dihydroisoquinoline were established by X-ray diffraction analysis. The reactions of quinoxaline with allyl- and methallylzinc bromide proceeded stereospecifically to form trans-2,3-diallylated 1,2,3,4-tetrahydroquinoxalines. Heating of quinoline with methallylzinc bromide in THF afforded 4-methallylquinoline in nearly quantitative yield. The initially formed 1,4-metallation product underwent aromatization through elimination of HZnBr.

  DOI：

  10.1023/a:1015065721466
• 作为产物：
  描述：

  异喹啉 、 bromozinc(1+),2-methanidylprop-1-ene 以 四氢呋喃 为溶剂， 反应 1.17h， 以27%的产率得到(±)-(1S,4R,9S)-3,3-dimethyl-9-(2-methylallyl)-1,2,3,4-tetrahydro-1,4-(epiminomethano)naphthalene
  参考文献：
  名称：

  Bridged tetrahydroisoquinolines as selective NADPH oxidase 2 (Nox2) inhibitors

  摘要：

  (1SR,4RS)-3,3-二甲基-1,2,3,4-四氢-1,4-(亚胺甲桥萘)类化合物通过2至3步从市售原料合成，并针对一系列Nox同工酶进行了特异性和有效性的评估。其中，N-戊基和N-甲基噻吩取代的类似物11g和11h表现出选择性的Nox2抑制活性，其细胞IC50值分别为20和32 μM。

  DOI：

  10.1039/c3md00061c

文献信息

• [EN] TETRAHYDROISOQUINOLINES AS SELECTIVE NADPH OXIDASE 2 INHIBITORS<br/>[FR] TÉTRAHYDROISOQUINOLINES UTILES COMME INHIBITEURS SÉLECTIFS DE NADPH OXIDASE 2
  申请人：UNIV PITTSBURGH

  公开号：WO2014179592A1

  公开（公告）日：2014-11-06

  Embodiments of bridged tetrahydroisoquinolines and methods for their use in selectively inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 are disclosed. The disclosed compounds have a structure according to general formula I or a pharmaceutically acceptable salt thereof: wherein "−−−−−−−" represents a single or double bond, R1 is hydrogen, halogen, lower aliphatic, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Ra is hydrogen, -CH2R2, R 3, or -SO2R 4; R 2 is lower aliphatic, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R3 is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R4 is lower aliphatic, or substituted or unsubstituted aryl; and R5 is hydrogen, halogen, or lower aliphatic.

  揭示了桥联四氢异喹啉的实施例及其在选择性抑制烟酰胺腺嘌呤二核苷酸磷酸酶（NADPH）氧化酶2中的用途的方法。所述化合物具有如下一般式I或其药学上可接受的盐的结构：其中"−−−−−−−"代表单键或双键，R1为氢、卤素、低脂肪基、取代或未取代芳基，或取代或未取代杂芳基；Ra为氢、-CH2R2、R3，或-SO2R4；R2为低脂肪基、取代或未取代芳基，或取代或未取代杂芳基；R3为取代或未取代芳基，或取代或未取代杂芳基；R4为低脂肪基，或取代或未取代芳基；R5为氢、卤素，或低脂肪基。
• Tetrahydroisoquinolines as selective NADPH oxidase 2 inhibitors
  申请人：University of Pittsburgh—Of the Commonwealth System of Higher Education

  公开号：US10906876B2

  公开（公告）日：2021-02-02

  Embodiments of bridged tetrahydroisoquinolines and methods for their use in selectively inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 are disclosed. The disclosed compounds have a structure according to general formula I or a pharmaceutically acceptable salt thereof: wherein “” represents a single or double bond, R1 is hydrogen, halogen, lower aliphatic, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Ra is hydrogen, —CH2R2, R3, or —SO2R4; R2 is lower aliphatic, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R3 is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R4 is lower aliphatic, or substituted or unsubstituted aryl; and R5 is hydrogen, halogen, or lower aliphatic.

  本发明公开了桥式四氢异喹啉的实施方案及其用于选择性抑制烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶2的方法。所公开的化合物具有通式 I 的结构或其药学上可接受的盐： 其中""代表单键或双键，R1是氢、卤素、低脂族、取代或未取代的芳基或取代或未取代的杂芳基；Ra是氢、-CH2R2、R3或-SO2R4；R2 是低级脂肪族、取代或未取代的芳基、取代或未取代的杂芳基； R3 是取代或未取代的芳基、取代或未取代的杂芳基； R4 是低级脂肪族、取代或未取代的芳基；以及 R5 是氢、卤素或低级脂肪族。
• TETRAHYDROISOQUINOLINES AS SELECTIVE NADPH OXIDASE 2 INHIBITORS
  申请人：PAGANO Patrick J.

  公开号：US20160083351A1

  公开（公告）日：2016-03-24

  Embodiments of bridged tetrahydroisoquinolines and methods for their use in selectively inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 are disclosed. The disclosed compounds have a structure according to general formula I or a pharmaceutically acceptable salt thereof: wherein “ ” represents a single or double bond, R 1 is hydrogen, halogen, lower aliphatic, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R a is hydrogen, —CH 2 R 2 , R 3 , or —SO 2 R 4 ; R 2 is lower aliphatic, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 3 is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 4 is lower aliphatic, or substituted or unsubstituted aryl; and R 5 is hydrogen, halogen, or lower aliphatic.
• US9796681B2
  申请人：——

  公开号：US9796681B2

  公开（公告）日：2017-10-24
• ——
  作者：Yu. N. Bubnov、F. V. Pastukhov、Z. A. Starikova、A. V. Ignatenko

  DOI：10.1023/a:1015065721466

  日期：——

  Allylmetallation of isoquinolines, quinoline, and quinoxaline with allylic derivatives of zinc was examined for the first time. A convenient procedure was discovered and developed for the synthesis of 1,4-ethano-2,3-dihydroisoquinolines based on the reactions of isoquinolines with allylic derivatives of zinc. This multistage process involves double allylmetallation of the heterocyclic ring followed by cyclization through intramolecular carbometallation of the C=C bond. The structures of three key derivatives of 1,4-ethano-2,3-dihydroisoquinoline were established by X-ray diffraction analysis. The reactions of quinoxaline with allyl- and methallylzinc bromide proceeded stereospecifically to form trans-2,3-diallylated 1,2,3,4-tetrahydroquinoxalines. Heating of quinoline with methallylzinc bromide in THF afforded 4-methallylquinoline in nearly quantitative yield. The initially formed 1,4-metallation product underwent aromatization through elimination of HZnBr.