1-(2-{4-[(Z)-1-(4-iodophenyl)-2-phenyl-but-1-enyl]phenoxy}ethyl)pyrrolidine

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1-(2-{4-[(Z)-1-(4-iodophenyl)-2-phenyl-but-1-enyl]phenoxy}ethyl)pyrrolidine
• 英文别名: Pyrrolidine, 1-[2-[4-[(1E)-1-(4-iodophenyl)-2-phenyl-1-buten-1-yl]phenoxy]ethyl]-；1-[2-[4-[(Z)-1-(4-iodophenyl)-2-phenylbut-1-enyl]phenoxy]ethyl]pyrrolidine
• 化学式: C₂₈H₃₀INO
• 分子量: 523.457
• InChiKey: JJKOTMDDZAJTGQ-BYYHNAKLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.3
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2,2-dimethylpropionic acid (1RS,2SR)-1-(4-iodophenyl)-2-phenyl-1-[4-(2-pyrrolidin-1-ylethoxy)phenyl]butyl ester 在 六甲基二硅氮烷 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 12.0h， 以76%的产率得到
  参考文献：
  名称：

  开发高效和立体选择性的碘昔芬制造路线

  摘要：

  对 1-(2-{4-[(E)-1-(4-iodophenyl)-2-phenyl-but-1-enyl]phenoxy}ethyl)pyrrolidine (idoxifene) 的文献途径进行了修改，以应对各种规模-up 问题并提供初始供应。详细描述了一种新的高效、稳健和立体选择性的制造路线。该路线涉及通过非对映选择性合成叔醇 (1RS,2SR)-1-(4-iodophenyl)-2-phenyl-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]butan-1-ol对酮 1-(4-碘苯基)-2-苯基-1-丁酮进行格氏加成，然后进行衍生化和立体选择性顺式消除，从而以优异的收率和几何纯度提供碘昔芬。还描述了使用 McMurry 低价钛偶联反应对碘多昔芬的更直接途径的评估。

  DOI：

  10.1021/op0100394

文献信息

• TREATMENT OF MALE ANDROGEN DEFICIENCY SYMPTOMS OR DISEASES WITH SEX STEROID PRECURSOR COMBINED WITH SERM
  申请人：Labrie Fernand

  公开号：US20150250802A1

  公开（公告）日：2015-09-10

  Novel methods for prevention, reduction or elimination of the incidence of male androgen deficiency symptoms or diseases including male hypogonadism-associated symptoms and diseases associated with low serum testosterone and/or low DHEA or low total androgens in susceptible warm-blooded animals including humans involving administration of an amount of a sex steroid precursor, particularly dehydroepiandrosterone (DHEA) and a selective estrogen receptor modulator (SERM) (particularly acolbifene), an antiestrogen or a prodrug of the two. The symptoms or diseases are loss of libido, erectile dysfunction, tiredness, loss of energy, depression, bone loss, muscle loss, muscle weakness, fat accumulation, memory loss, cognition loss, Alzheimer's disease, dementia, loss of body hair, fertility problems, insomnia, gynecomastia, anemia, hot flushes, sweats, decreased sense of well-being, obesity, osteoporosis, hypercholesterolemia, hyperlipidemia, atherosclerosis, hypertension, insulin resistance, cardiovascular disease and type 2 diabetes. Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.

  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。
• 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-Amino Substituted-2-Substituted-1,2,3,4-tetrahydroquinoline Compounds
  申请人：Ruggeri B. Roger

  公开号：US20060247272A1

  公开（公告）日：2006-11-02

  4-Amino substituted-2-substituted-1,2,3,4-tetrahydroquinoline compounds, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in some mammals, including humans.

  4-氨基取代的2-取代的1,2,3,4-四氢喹啉化合物，含有此类化合物的制药组合物以及使用此类化合物以提高某些血浆脂质水平，包括高密度脂蛋白胆固醇，并降低某些其他血浆脂质水平，如低密度脂蛋白胆固醇和三酰甘油，因此治疗由低水平的高密度脂蛋白胆固醇和/或高水平的低密度脂蛋白胆固醇和三酰甘油加重的疾病，如动脉粥样硬化和心血管疾病在某些哺乳动物中，包括人类。
• Prevention and treatment of cardiovascular pathologies with tamoxifen analogues
  申请人：Poniard Pharmaceuticals, Inc.

  公开号：EP1980246A1

  公开（公告）日：2008-10-15

  Use is provided of a compound of formula (I): wherein Z is C=O or a covalent bond; Y is H or O(C1-C4)alkyl, R1 and R2 are individually (C1-C4)alkyl or together with N are a saturated heterocyclic group, R3 is ethyl or chloroethyl, R4 is H or together with R3 is -CH2-CH2- or -S-, R5 is O(C1-C4)alkyl or H and R6 is O(C1-C4)alkyl or H with the proviso that when R4, R5, and R6 are H, R3 is not ethyl; or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for use in: the treatment or prevention of cardiovascular pathologies e.g. atherosclerosis, thrombosis, myocardial infarction or stroke, inhibiting smooth muscle cell (SMC) proliferation associated with procedural vascular trauma, preventing or treating a cardiovascular or vascular indication in a mammal characterised by a decreased lumen diameter, or increasing the level of TGF-beta in a mammal, effective to elevate the level of TGF-beta to treat and/or prevent conditions such as atherosclerosis, thrombosis, myocardial infarction, and stroke. Useful compounds include idoxifene, toremifene or salts thereof. Further provided is a method for identifying an agent that elevates the level of TGF beta. Another embodiment of the invention is an assay or kit to determine TGF-beta in vitro. Also provided is a therapeutic method comprising inhibiting smooth muscle cell proliferation associated with procedural vascular trauma employing the administration of tamoxifen or structural analogs thereof, including compounds of formula (1).

  提供了式 (I) 化合物的用途： 其中 Z 是 C=O 或共价键； Y 是 H 或 O（C1-C4）烷基、 R1 和 R2 单独为 (C1-C4) 烷基或与 N 一起为饱和杂环基团、 R3 是乙基或氯乙基、 R4 是 H 或与 R3 一起是-CH2-CH2-或-S-，R5 是 O（C1-C4）烷基或 H，R6 是 O（C1-C4）烷基或 H，但当 R4、R5 和 R6 是 H 时，R3 不是乙基； 或其药学上可接受的盐，用于制造以下用途的药物治疗或预防心血管病变，如动脉粥样硬化、血栓形成、心肌梗塞或中风；抑制与程序性血管创伤相关的平滑肌细胞（SMC）增殖；预防或治疗哺乳动物以管腔直径减小为特征的心血管或血管适应症；或提高哺乳动物体内 TGF-beta 的水平，有效提高 TGF-beta 的水平以治疗和/或预防动脉粥样硬化、血栓形成、心肌梗塞和中风等疾病。有用的化合物包括依多昔芬、托瑞米芬或其盐类。本发明还提供了一种鉴定可提高 TGF beta 水平的制剂的方法。本发明的另一个实施方案是一种测定体外 TGF-beta 的检测方法或试剂盒。本发明还提供了一种治疗方法，包括通过施用他莫昔芬或其结构类似物（包括式（1）化合物）来抑制与程序性血管创伤相关的平滑肌细胞增殖。
• 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。