(2E)-7-methoxy-2-(pyridin-4-ylmethylidene)-3,4-dihydronaphthalen-1(2H)-one | 135075-25-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (2E)-7-methoxy-2-(pyridin-4-ylmethylidene)-3,4-dihydronaphthalen-1(2H)-one
• 英文别名: 7-Methoxy-2-pyridin-4-ylmethylene-3,4-dihydro-2H-naphthalen-1-one；(2E)-7-methoxy-2-(pyridin-4-ylmethylidene)-3,4-dihydronaphthalen-1-one
• CAS: 135075-25-1
• 化学式: C₁₇H₁₅NO₂
• 分子量: 265.312
• InChiKey: SHPPSFGJYGIXDS-GXDHUFHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2E)-7-methoxy-2-(pyridin-4-ylmethylidene)-3,4-dihydronaphthalen-1(2H)-one 在 氢氧化钾 、 三溴化硼 、 一水合肼 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (1R,1aR,7bR)-1-pyridin-4-yl-1a,2,3,7b-tetrahydro-1H-cyclopropa[a]naphthalen-6-ol
  参考文献：
  名称：

  吡啶基取代的四氢环丙烷[a]萘：P450芳烃的高活性和选择性抑制剂。

  摘要：

  取代的exo-1-（4-吡啶基）-1a，2,3,7b-四氢-1H-环丙烷[a]萘作为雌激素生物合成抑制剂的合成和生物学评价[H（1）; 4-OCH3（2）；5-OCH 3（3）；6-OCH3（4）；1-CH3、6-OCH3（5）；4-OCH3，7-Br（6）; 6-OCH3，5-溴（7）; 4-羟基（8）；5-羟基（9）; 6-OH（10）]。合成关键步骤-形成环丙基环-是使用改良的Wolff-Kishner还原条件（N2H5OH / KOH; delta T）完成的，并且仅生成外构型的非对映异构体。外消旋化合物1-10显示出对人胎盘芳香酶（P450 arom）的抑制，其相对效力（rp）为3.7至303（化合物8和4；氨基戊二酰亚胺（AG）rp等同于1，fadrozole = 359）。通过在三苯甲酰基纤维素上的LPLC和非对映体酒石酸盐（4）的结晶分离4和7的对映体。（1aS，2S，7b

  DOI：

  10.1021/jm00012a009
• 作为产物：
  描述：

  4-吡啶甲醛 、 7-甲氧基-1-萘满酮 在 哌啶 、 溶剂黄146 作用下， 反应 1.5h， 以57%的产率得到(2E)-7-methoxy-2-(pyridin-4-ylmethylidene)-3,4-dihydronaphthalen-1(2H)-one
  参考文献：
  名称：

  吡啶基取代的四氢环丙烷[a]萘：P450芳烃的高活性和选择性抑制剂。

  摘要：

  取代的exo-1-（4-吡啶基）-1a，2,3,7b-四氢-1H-环丙烷[a]萘作为雌激素生物合成抑制剂的合成和生物学评价[H（1）; 4-OCH3（2）；5-OCH 3（3）；6-OCH3（4）；1-CH3、6-OCH3（5）；4-OCH3，7-Br（6）; 6-OCH3，5-溴（7）; 4-羟基（8）；5-羟基（9）; 6-OH（10）]。合成关键步骤-形成环丙基环-是使用改良的Wolff-Kishner还原条件（N2H5OH / KOH; delta T）完成的，并且仅生成外构型的非对映异构体。外消旋化合物1-10显示出对人胎盘芳香酶（P450 arom）的抑制，其相对效力（rp）为3.7至303（化合物8和4；氨基戊二酰亚胺（AG）rp等同于1，fadrozole = 359）。通过在三苯甲酰基纤维素上的LPLC和非对映体酒石酸盐（4）的结晶分离4和7的对映体。（1aS，2S，7b

  DOI：

  10.1021/jm00012a009

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。
• 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。
• New aromatase inhibitors. Synthesis and biological activity of pyridyl-substituted tetralone derivatives
  作者：Herbert Bayer、Christine Batzl、Rolf W. Hartman、Albrecht Mannschreck

  DOI：10.1021/jm00113a004

  日期：1991.9

  The (E)-2-(4-pyridylmethylene)-1-tetralones 1-7 (1, H; 2, 5-OCH3; 3, 6-OCH3; 4, 7-OCH3; 5, 5-OH; 6, 6-OH; 7, 7-OH) were obtained by aldol condensation of the corresponding 1-tetralones with 4-pyridinecarboxaldehyde, and in the case of the OH compounds 5 and 7 subsequent ether cleavage of the OCH3-substituted 2-(4-pyridylmethylene)-1-tetralones. Catalytic hydrogenation of 1-4 gave the 2-(4-pyridylmethyl)-1-tetralones 8-11 (8, H; 9, 5-OCH3; 10, 6-OCH3; 11, 7-OCH3). Subsequent ether cleavage of 9-11 led to the corresponding OH compounds 12-14 (12, 5-OH; 13, 6-OH; 14, 7-OH). The enantiomers of 11 and 12 were separated semipreparatively by HPLC on triacetylcellulose. All compounds (1-14) showed an inhibition of human placental aromatase exhibiting relative potencies from 2.2 to 213 [compounds 6 and (+)-12, respectively; aromatase inhibitory potency of aminoglutethimide (AG) = 1]. The compounds exhibited no or only a weak inhibition of desmolase [cholesterol side chain cleavage enzyme; maximum activity shown by 12, 23 % inhibition (25-mu-M); AG, 53 % inhibition (25-mu-M)]. In vivo, however, the compounds were not superior to AG as far as the reduction of the plasma estradiol concentration and the mammary carcinoma (MC) inhibiting properties are concerned (PMSG-primed SD rats as well as DMBA-induced MC of the SD rat, pre- and postmenopausal experiments, and the transplantable MXT-MC of the BD2F1 mouse). This is due to a fast decrease of the plasma E2 concentration inhibiting effect as could be shown by a kinetic experiment. In addition, select compounds inhibited rat ovarian aromatase much less than human placental aromatase (12, factor of 10). Estrogenic effects as a cause for the poor in vivo activity of the test compounds could be excluded, since they did not show affinity for the estrogen receptor.
• N-Oxide formation causes loss of aromatase inhibitory activity of pyridyl-substituted tetrahydronaphthalenes
  作者：M Mitrenga、RW Hartmann

  DOI：10.1016/0223-5234(96)88231-6

  日期：1995.1

  N-Oxidation plays a role in the metabolism of numerous pyridine-substituted drugs. In order to examine the effect of a possible N-oxidation on the activity of nonsteroidal aromatase inhibitors, three potent pyridine-substituted tetrahydronaphthalenes were converted to their corresponding N-oxides. Using human placental aromatase, it was shown that N-oxidation causes a nearly complete loss of aromatase inhibitory activity.
• 4H-naphtho 1,2-b pyran derivatives as antiproliferative agents
  申请人：ELI LILLY AND COMPANY LIMITED

  公开号：EP0557075B1

  公开（公告）日：1998-06-24