(E)-2-(3-Pyridyl)methylene-1-tetralone | 13640-51-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (E)-2-(3-Pyridyl)methylene-1-tetralone
• 英文别名: (2E)-2-(pyridin-3-ylmethylidene)-3,4-dihydronaphthalen-1(2H)-one；2-(3-Pyridylmethylene)-3,4-dihydro-1(2H)-naphthalenone；(2E)-2-(pyridin-3-ylmethylidene)-3,4-dihydronaphthalen-1-one
• CAS: 13640-51-2
• 化学式: C₁₆H₁₃NO
• 分子量: 235.285
• InChiKey: FQGOMCZTOHRVAC-GXDHUFHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-2-(3-Pyridyl)methylene-1-tetralone 在 氢氧化钾 、 一水合肼 作用下， 以 二乙二醇 为溶剂， 反应 1.5h， 以68%的产率得到3-(1a,2,3,7b-Tetrahydro-1H-cyclopropa[a]naphthalen-1-yl)-pyridine
  参考文献：
  名称：

  四氢萘：杂环取代基对类固醇酶P450 arom和P450 17抑制的影响。

  摘要：

  （E）-4-咪唑基化合物16（rp = 71）显示出竞争性抑制类型。另一方面，这些化合物中的某些抑制大鼠睾丸P45017。3-吡啶基化合物20显示最大活性（rp = 10，keconconazole的ro = 1）。20是唯一对TXA（2）合酶具有显着抑制作用的化合物（IC（50）= 14.5 microM；达唑昔本的IC（50）= 1.1 microM）。关于对类固醇生成酶的选择性，化合物16对P450 arom相对选择性，而化合物20对P450 17相对选择性。（P450 arom：K（m）睾丸激素= 42 nM，K（i）16 = 33 nM，K（ i）20 = 3microM。P45017：K（m）孕酮= 7 microM，K（i）16 = 9 microM，K（i）20 = 80 nM）。17和24不是选择性的，因为它们显示出对P450 arom（K（i）17 = 26 nM，K（i）24

  DOI：

  10.1021/jm950377t
• 作为产物：
  描述：

  3-吡啶甲醛 、 3,4-二氢-1(2H)-萘酮 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 以29.7%的产率得到(E)-2-(3-Pyridyl)methylene-1-tetralone
  参考文献：
  名称：

  2-杂亚芳基-1-四氢萘酮衍生物作为单胺氧化酶抑制剂的合成及体外评价

  摘要：

  本研究调查了一系列十二种2-亚杂亚烷基-1-四氢萘酮衍生物对人单胺氧化酶（MAO）的抑制特性。还包括相关的环己基亚甲基，环戊基亚甲基和亚苄基取代的1-四氢萘酮。这些化合物与2-苄叉基-1-茚满酮类化合物有关，该类化合物先前已显示出对MAO-B同工型具有特异性，可抑制MAO。在酸（盐酸）或碱（氢氧化钾）催化下，通过7-甲氧基-1-四氢萘酮或1-四氢萘酮与各种醛之间的Claisen-Schmidt缩合反应合成目标化合物。MAO抑制研究的结果表明，与MAO-A相比，2-杂亚芳基-1-四氢萘酮和相关衍生物在大多数情况下是MAO-B同工型的更具选择性的抑制剂。发现（2E）-2-苄叉基-7-甲氧基-3,4-二氢萘-1（2 H）-一（IC50 = 0.707μM）是最有效的MAO-B抑制剂，而最有效的MAO-A抑制剂抑制剂为（2E）-2-[（（2-氯吡啶基-3-基）亚甲基] -7-甲氧基-3,4-二氢萘-1（2

  DOI：

  10.1055/a-0620-8309

文献信息

• Novel dihydronaphthalene compounds and processes of producing the same
  申请人：——

  公开号：US20020032211A1

  公开（公告）日：2002-03-14

  Dihydronaphthalene compounds have excellent 17&agr;-hydroxylase/C 17-20 -lyase inhibiting activity, thromboxan A 2 synthesis inhibiting activity, and aromatase inhibiting activity and are thereby are useful as preventive and/or therapeutic agents for various male sex hormone- and female sex hormone-dependent diseases such as prostate cancer, prostatomegaly, masculinization, breast cancer, mastopathy, uterine cancer, endometriosis, and ovarian cancer, as well as myocardial infarction, angina pectoris, and bronchial asthma.

  二氢萘化合物具有优秀的17α-羟化酶/C17-20-裂解酶抑制活性，血栓素A2合成抑制活性和芳香化酶抑制活性，因此可用作预防和/或治疗各种男性激素和女性激素依赖性疾病的药物，如前列腺癌、前列腺增生、阳痿、乳腺癌、乳腺增生、子宫癌、子宫内膜异位症和卵巢癌，以及心肌梗死、心绞痛和支气管哮喘。
• Pharmaceutical compounds
  申请人：LILLY INDUSTRIES LIMITED

  公开号：EP0618206A1

  公开（公告）日：1994-10-05

  The invention provides pharmaceutical compounds of the formula: in which A --- B is CH₂-CH₂ or CH=CH; X is a pyridine or benzene ring; when X is pyridine n is 0; when X is benzene n is 0, 1 or 2 and when A --- B is CH₂-CH₂, R¹ is attached at any of the positions 7 to 10, and when A --- B is CH=CH, R¹ is attached at any of the positions 5 to 10; each R¹ is halo, carboxy, trifluoromethyl, hydroxy, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkylthio, hydroxy-C₁₋₄ alkyl, hydroxy-C₁₋₄ alkoxy, nitrogen-containing heterocyclyl, nitro, trifluoromethoxy, -COOR⁵ where R⁵ is an ester group, -COR⁶, -CONR⁶R⁷ or -NR⁶R⁷ where R⁶ and R⁷ are each hydrogen or C₁₋₄ alkyl; R² is phenyl, naphthyl or heteroaryl selected from thienyl, pyridyl, benzothienyl, quinolinyl, benzofuranyl or benzimidazolyl, said phenyl, naphthyl and heteroaryl groups being optionally substituted, or R² is furanyl optionally substituted with C₁₋₄ alkyl; R³ is nitrile, carboxy, -COOR⁸ where R⁸ is an ester group, -CONR⁹R¹⁰ where R⁹ and R¹⁰ are each hydrogen or C₁₋₄ alkyl, or -SO₂R¹¹ where R¹¹ is C₁₋₄ alkyl, optionally substituted phenyl or optionally substituted phenyl-C₁₋₄ alkyl; and R⁴ is 1-pyrrolyl, 1-imidazolyl or 1-pyrazolyl, said 1-pyrrolyl, 1-imidazolyl and 1-pyrazolyl being optionally substituted by one or two C₁₋₄ alkyl, carboxyl, hydroxy-C₁₋₄ alkyl or -CHO groups, or 1-(1,2,4-triazolyl), 1-(1,3,4-triazolyl) or 2-(1,2,3-triazolyl), said triazolyl groups being optionally substituted by a C₁₋₄ alkyl or C₁₋₄ perfluoroalkyl group, or 1-tetrazolyl optionally substituted by C₁₋₄ alkyl; and salts thereof.

  本发明提供了式中的药物化合物： 其中 A --- B 是 CH₂-CH₂ 或 CH=CH； X 是吡啶或苯环； 当 X 为吡啶时 n 为 0； 当X为苯时，n为0、1或2；当A--B为CH₂-CH₂时，R¹连接在7至10的任一位置；当A--B为CH＝CH时，R¹连接在5至10的任一位置； 每个 R¹ 是卤代、羧基、三氟甲基、羟基、C₁₋₄ 烷基、C₁₋₄ 烷氧基、C₁₋₄ 烷硫基、羟基-C₁₋₄ 烷基、羟基-C₁₋₄ 烷氧基、含氮杂环基、硝基、三氟甲氧基、-COOR⁵（其中 R⁵ 是酯基）、-COR⁶、-CONR⁶R⁷ 或-NR⁶R⁷（其中 R⁶ 和 R⁷ 各为氢或 C₁₋₄ 烷基）； R² 是苯基、萘基或选自噻吩基、吡啶基、苯并噻吩基、喹啉基、苯并呋喃基或苯并腙唑基的杂芳基，所述苯基、萘基和杂芳基被任选取代，或 R² 是被 C₁₋₄ 烷基任选取代的呋喃基； R³ 是腈、羧基、-COOR⁸（其中 R⁸ 是酯基）、-CONR⁹R¹⁰（其中 R⁹ 和 R¹⁰ 分别是氢或 C₁₋₄ 烷基）或-SO₂₋₄烷基、或-SO₂R¹¹，其中 R¹¹ 是 C₁₋₄烷基、任选取代的苯基或任选取代的苯基-C₁₋₄烷基；和 R⁴ 是 1-吡咯基、1-咪唑基或 1-吡唑基，所述 1-吡咯基、1-咪唑基和 1-吡唑基可任选被一个或两个 C₁₋₄烷基、羧基、羟基-C₁₋₄烷基或 -CHO 基团取代，或 1-(1,2、1-(1,2,3,4-三唑基)、1-(1,3,4-三唑基)或 2-(1,2,3-三唑基)，所述三唑基可选择被 C₁₋₄烷基或 C₁₋₄全氟烷基取代，或可选择被 C₁₋₄烷基取代的 1-四唑基； 及其盐类。
• NOVEL DIHYDRONAPHTHALENE COMPOUNDS AND PROCESS FOR PRODUCING THE SAME
  申请人：Yukijirushi Nyugyo Kabushiki Kaisha

  公开号：EP1028110A1

  公开（公告）日：2000-08-16

  Dihydronaphthalene compounds have excellent 17α-hydroxylase/C17-20-lyase inhibiting activity, thromboxan A2 synthesis inhibiting activity, and aromatase inhibiting activity and are thereby are useful as preventive and/or therapeutic agents for various male sex hormone- and female sex hormone-dependent diseases such as prostate cancer, prostatomegaly, masculinization, breast cancer, mastopathy, uterine cancer, endometriosis, and ovarian cancer, as well as myocardial infarction, angina pectoris, and bronchial asthma.

  二氢萘化合物具有优异的 17α- 羟化酶/C17-20-赖氨酸酶抑制活性、血栓素 A2 合成抑制活性和芳香化酶抑制活性，因此可用作各种男性性激素和女性性激素依赖性疾病（如前列腺癌）的预防和/或治疗药物、前列腺肥大、男性化、乳腺癌、乳腺增生症、子宫癌、子宫内膜异位症和卵巢癌，以及心肌梗塞、心绞痛和支气管哮喘。
• El-Rayyes, N. R.; Al-Saleh, B.; Al-Omran, F., Journal of Heterocyclic Chemistry, 1986, vol. 23, p. 1789 - 1793
  作者：El-Rayyes, N. R.、Al-Saleh, B.、Al-Omran, F.、Edun, M.

  DOI：——

  日期：——
• Tetralone derivatives are MIF tautomerase inhibitors and attenuate macrophage activation and amplify the hypothermic response in endotoxemic mice
  作者：János Garai、Marcell Krekó、László Őrfi、Péter Balázs Jakus、Zoltán Rumbus、Patrik Kéringer、András Garami、Eszter Vámos、Dominika Kovács、Viola Bagóné Vántus、Balázs Radnai、Tamás Lóránd

  DOI：10.1080/14756366.2021.1916010

  日期：2021.1.1

  Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine playing crucial role in immunity. MIF exerts a unique tautomerase enzymatic activity that has relevance concerning its multiple functions and its small molecule inhibitors have been proven to block its pro-inflammatory effects. Here we demonstrate that some of the E-2-arylmethylene-1-tetralones and their heteroanalogues efficiently bind to MIF's active site and inhibit MIF tautomeric (enolase, ketolase activity) functions. A small set of the synthesised derivatives, namely compounds (4), (23), (24), (26) and (32), reduced inflammatory macrophage activation. Two of the selected compounds (24) and (26), however, markedly inhibited ROS and nitrite production, NF-κB activation, TNF-α, IL-6 and CCL-2 cytokine expression. Pre-treatment of mice with compound (24) exaggerated the hypothermic response to high dose of bacterial endotoxin. Our experiments suggest that tetralones and their derivatives inhibit MIF's tautomeric functions and regulate macrophage activation and thermal changes in severe forms of systemic inflammation.