2-(4''-[2'''-piperidinoethoxy]phenyl)-3-(4'-tetrahydropyranyloxyphenyl)-7-tetrahydropyranyloxy-2,3-dihydro-4H-1-benzopyran-4-one | 151533-32-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 2-(4''-[2'''-piperidinoethoxy]phenyl)-3-(4'-tetrahydropyranyloxyphenyl)-7-tetrahydropyranyloxy-2,3-dihydro-4H-1-benzopyran-4-one
• 英文别名: 2-[4-(2-piperidin-1-ylethoxy)-phenyl]-7-(tetrahydropyran-2-yloxy)-3-[4-(tetrahydropyran-2-yloxy)-phenyl]-2,3-dihydro-4H-1-benzopyran-4-one；chromanone；2,3-Dihydro-2-[4-[2-(1-piperidinyl)ethoxy]phenyl]-7-[(tetrahydro-2H-pyran-2-yl)oxy]-3-[4-[(tetrahydro-2H-pyran-2-yl)oxy]phenyl]-4H-1-benzopyran-4-one；7-(oxan-2-yloxy)-3-[4-(oxan-2-yloxy)phenyl]-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2,3-dihydrochromen-4-one
• CAS: 151533-32-3
• 化学式: C₃₈H₄₅NO₇
• 分子量: 627.778
• InChiKey: LETVKJYWENEASE-UHFFFAOYSA-N

物化性质

• 沸点：
  785.7±60.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  46
• 可旋转键数：
  10
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(4''-[2'''-piperidinoethoxy]phenyl)-3-(4'-tetrahydropyranyloxyphenyl)-7-tetrahydropyranyloxy-2,3-dihydro-4H-1-benzopyran-4-one 在 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 EM-651
  参考文献：
  名称：

  （S）-（+）-4- [7-（2,2-二甲基-1-氧丙氧基）-4-甲基-2- [4- [2-（1-哌啶基）-乙氧基]苯基] -2H- 1,2-苯并吡喃-3-基]-苯基2,2-二甲基丙酸酯（EM-800）：一种高效，特异性和口服活性的非甾体抗雌激素药。

  摘要：

  DOI：

  10.1021/jm970095o
• 作为产物：
  描述：

  1-(2,4-二羟基苯基)-2-(4-羟基苯基)-乙酮 在 哌啶 、 对甲苯磺酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 24.0h， 生成 2-(4''-[2'''-piperidinoethoxy]phenyl)-3-(4'-tetrahydropyranyloxyphenyl)-7-tetrahydropyranyloxy-2,3-dihydro-4H-1-benzopyran-4-one
  参考文献：
  名称：

  TREATMENT OF MALE ANDROGEN DEFICIENCY SYMPTOMS OR DISEASES WITH SEX STEROID PRECURSOR COMBINED WITH SERM

  摘要：

  预防、减少或消除男性雄激素缺乏症状或疾病的新方法，包括男性睾丸功能减退相关症状和与低血清睾酮和/或低DHEA或低总雄激素有关的疾病，涉及给予一定量的性激素前体，特别是去氢表雄酮（DHEA）和选择性雌激素受体调节剂（SERM）（特别是阿科比芬），一种抗雌激素或两者的前药。这些症状或疾病包括性欲减退、勃起功能障碍、疲劳、精力下降、抑郁、骨质流失、肌肉流失、肌肉无力、脂肪积累、记忆力减退、认知能力减退、阿尔茨海默病、痴呆、体毛减少、生育问题、失眠、男性乳房发育、贫血、潮热、出汗、幸福感降低、肥胖、骨质疏松症、高胆固醇血症、高脂血症、动脉粥样硬化、高血压、胰岛素抵抗、心血管疾病和2型糖尿病。还公开了用于给药活性成分的药物组合物和有用于该发明的工具包。

  公开号：

  US20150250802A1

文献信息

• Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors
  申请人：Endorecherche, Inc.

  公开号：US06670346B1

  公开（公告）日：2003-12-30

  Novel methods for the medical treatment and/or inhibition of the development of osteoporosis, breast cancer, hypercholesterolemia, hyperlipidemia or atherosclerosis in susceptible warm-blooded animals including humans involving administration of selective estrogen receptor modulator particularly compounds having the general structure: and an amount of a sex steroid precursor selected from the group consisting of dehydroepiandrosterone, dehydroepiandrosterone sulfate, androst-5-ene-3&bgr;,17&bgr;-diol and compounds converted in vivo to one of the foregoing presursor. Further administration of bisphosphonates in combination with selective estrogen receptor modulators and/or sex steroid precursor is disclosed for the medical treatment and/or inhibition of the development of osteoporosis. Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.

  针对易感温血动物，包括人类，治疗和/或抑制骨质疏松症、乳腺癌、高胆固醇血症、高脂血症或动脉粥样硬化的新方法涉及给予选择性雌激素受体调节剂，特别是具有以下一般结构的化合物：以及来自去氢表雄酮、去氢表雄酮硫酸酯、雄甾-5-烯-3β,17β-二醇和体内转化为上述前体之一的化合物之一的性激素前体的数量。此外，揭示了联合给予双膦酸盐与选择性雌激素受体调节剂和/或性激素前体用于治疗和/或抑制骨质疏松症的方法。还公开了用于传递活性成分的药物组合物和有益于该发明的工具包。
• TREATMENT OF HOT FLUSHES, VASOMOTOR SYMPTOMS, AND NIGHT SWEATS WITH SEX STEROID PRECURSORS IN COMBINATION WITH SELECTIVE ESTROGEN RECEPTOR MODULATORS
  申请人：Endorecherche, Inc.

  公开号：EP3178480A1

  公开（公告）日：2017-06-14

  Novel methods for reduction or elimination of the incidence of hot flushes, vasomotor symptoms, and night sweats while decreasing the risk of acquiring breast, uterine or endometrial cancer and furthermore having beneficial effect by inhibiting the development of osteoporosis, hypercholesterolemia, hyperlipidemia, atherosclerosis, hypertension, insulin resistance, diabetes type 2, loss of muscle mass, adiposity, Alzheimer's disease, loss of cognition, loss of memory, or vaginal dryness in susceptible warm-blooded animals including humans involving administration of an amount of a sex steroid precursor, particularly dehydroepiandrosterone (DHEA) and an antiestrogen or a selective estrogen receptor modulator, particularly benzopyran compounds. Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.

  用于减少或消除潮热、血管运动症状和夜间盗汗的新方法，同时降低乳腺、子宫或子宫内膜癌症的发病风险，并通过抑制骨质疏松症、高胆固醇血症、高脂血症、动脉粥样硬化、高血压、胰岛素抵抗、2型糖尿病、肌肉流失、脂肪堆积、阿尔茨海默病、认知能力丧失、记忆力丧失或阴道干燥等疾病的发展具有益处的影响的方法，涉及给予一定量的性激素前体，特别是去氢表雄酮（DHEA）和抗雌激素或选择性雌激素受体调节剂，特别是苯并吡喃化合物。还公开了用于传递活性成分的药物组合物和有益于该发明的工具。
• 4-fluoroalkyl-2h-benzopyrans anti-estogenic activity
  申请人：——

  公开号：US20040034017A1

  公开（公告）日：2004-02-19

  This invention describes the new 4-fluoroalkyl-2H-benzopyrans of general formula I, 1 in which Z is a straight-chain or branched-chain alkyl group with up to 5 carbon atoms that is fluorinated in at least one place, preferably a trifluoromethyl group, and R 1 , R 2 , X, Y and n have the meanings that are indicated in the description. The new compounds have at their disposal strong antiestrogenic action. In addition, they can have at their disposal estrogenic action that occurs in a tissue-selective manner. They can be used for the production of pharmaceutical agents, especially for the treatment of estrogen-dependent diseases and tumors and pharmaceutical agents for hormone replacement therapy (HRT) as well as for the prevention and treatment of osteoporosis.

  该发明描述了一种新的4-氟烷基-2H-苯并吡喃的一般化学式I，其中Z是一种直链或支链烷基，含有多达5个碳原子，在至少一个位置上被氟化，最好是三氟甲基基团，而R1、R2、X、Y和n具有描述中指示的含义。这些新化合物具有强烈的抗雌激素作用。此外，它们可以具有以组织选择性方式发生的雌激素作用。它们可用于生产药物，特别是用于治疗依赖雌激素的疾病和肿瘤的药物，以及用于激素替代疗法（HRT）的药物和用于骨质疏松症的预防和治疗。
• [EN] ENANTIOSELECTIVE SYNTHESIS<br/>[FR] SYNTHESE ENANTIOSELECTIVE
  申请人：SCHERING CORP

  公开号：WO2000009493A1

  公开（公告）日：2000-02-24

  A short practical commercial process for the efficient enantioselective synthesis of the non-steroidal antiestrogen of formula (I) or (XIV) or a pharmaceutically acceptable salt thereof.

  一种简短实用的商业化进程，用于高效对映选择性合成公式（I）或（XIV）的非甾体抗雌激素或其药用可接受盐。
• Treatment of Alzheimer's disease, loss of cognition, memory loss and dementia with sex steroid precursors in combination with selective estrogen receptor modulators
  申请人：Labrie Fernand

  公开号：US10342805B2

  公开（公告）日：2019-07-09

  Novel methods for reduction or elimination the incidence of hot flushes, vasomotor symptoms, and night sweats while decreasing the risk of acquiring breast, uterine or endometrial cancer and furthermore having beneficial effect by inhibiting the development of osteoporosis, hypercholesterolemia, hyperlipidemia, atherosclerosis, hypertension, insulin resistance, diabetes type 2, loss of muscle mass, adiposity, Alzheimer's disease, loss of cognition, loss of memory, or vaginal dryness in susceptible warm-blooded animals including humans involving administration of an amount of a sex steroid precursor, particularly dehydroepiandrosterone (DHEA) and an antiestrogen or a selective estrogen receptor modulator, particularly compounds having the general structure: Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.

  减少或消除潮热、血管运动症状和盗汗发生率的新方法，同时降低罹患乳腺癌、子宫癌或子宫内膜癌的风险，并通过抑制骨质疏松症、高胆固醇血症、高脂血症、动脉粥样硬化、高血压、胰岛素抵抗、2 型糖尿病、肌肉质量下降、肥胖症、老年痴呆症、认知能力下降、记忆力减退或阴道干涩等疾病的发展而产生益处、对包括人类在内的易感温血动物的肌肉质量下降、肥胖、老年痴呆症、认知能力下降、记忆力减退或阴道干涩等症状有抑制作用，其中涉及给药一定量的性类固醇前体，特别是脱氢表雄酮（DHEA）和抗雌激素或选择性雌激素受体调节剂，特别是具有一般结构的化合物： 此外，还公开了用于输送活性成分的药物组合物和对本发明有用的试剂盒。