左美洛昔芬 | 78994-23-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 中文名称: 左美洛昔芬
• 英文名称: ormeloxifene
• 英文别名: centchroman；Choice-7；Saheli；(+/-)-3,4-trans-7-methoxy-2,2-dimethyl-3-phenyl-4-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}chromane；Levormeloxifene；1-[2-[4-[(3R,4R)-7-methoxy-2,2-dimethyl-3-phenyl-3,4-dihydrochromen-4-yl]phenoxy]ethyl]pyrrolidine
• CAS: 78994-23-7
• 化学式: C₃₀H₃₅NO₃
• 分子量: 457.613
• InChiKey: XZEUAXYWNKYKPL-WDYNHAJCSA-N

物化性质

• 熔点：
  197°
• 比旋光度：
  D20 -192.9° (c = 1.0 in CHCl3)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

活体研究表明，.ormeloxifene可被肝脏迅速代谢。在大鼠中，这种药物的主要活性代谢物是7-去甲基.ormeloxifene。

_In vivo_ studies suggest that ormeloxifene is quickly metabolized by the liver. In rats, the active metabolite of this drug is 7-desmethylated ormeloxifene.

来源:DrugBank

毒理性

• 蛋白质结合

大约90%的奥尔默洛昔芬与白蛋白结合。

Approximately 90% of ormeloxifene is bound to albumin.

来源:DrugBank

吸收、分配和排泄

• 吸收

在给予30毫克.ormeloxifene( n = 11)的健康非哺乳志愿者中，Cmax、tmax和AUC0-分别为55.5纳克/毫升、5.2小时和5199纳克·小时/毫升。

In healthy, non-lactating volunteers given 30 mg of ormeloxifene (n=11), the Cmax, tmax and AUC0-∞ were 55.5 ng/mL, 5.2 h, and 5199 ng⋅h/mL, respectively.

来源:DrugBank

吸收、分配和排泄

• 消除途径

体内研究表明，ormeloxifene主要通过粪便从体内排出。

_In vivo_ studies suggest that ormeloxifene is excreted from the body primarily via feces.

来源:DrugBank

吸收、分配和排泄

• 分布容积

在健康的女性中，表观分布容积（Vd/F）高于总体液，而且哺乳状态对此参数没有影响。

In healthy women, the apparent volume of distribution (Vd/F) was higher than the total body fluid, and the nursing state does not have an effect on this parameter.

来源:DrugBank

吸收、分配和排泄

• 清除

在健康的非哺乳期志愿者中给予30毫克欧米洛昔芬（n=11）后，其清除率为0.14升/小时。

In healthy, non-lactating volunteers given 30 mg of ormeloxifene (n=11), the clearance is 0.14 L/h.

来源:DrugBank

安全信息

• 储存条件：
  -20°C，密闭保存，并保持干燥。

制备方法与用途

L-Centchroman是一种选择性雌激素受体调节剂。

反应信息

• 作为反应物：
  描述：

  左美洛昔芬 在 氢氧化钾 、 一水合肼 作用下， 以 二乙二醇 为溶剂， 反应 0.5h， 以25%的产率得到trans-2,2-dimethyl-3-phenyl-4-[p-(β-pyrrolidinoethoxy)phenyl]-7-hydroxychroman
  参考文献：
  名称：

  Antifertility agents. 38. Effect of the side chain and its position on the activity of 3,4-diarylchromans

  摘要：

  In a study of the effect of the substituent on the receptor binding affinity (RBA), estrogenicity, and antiimplantation (AI) activity in trans-3,4-diarylchromans, it has been found that demethylation of trans-2, 2-dimethyl-3-phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl]-7-methoxychroman (centchroman, 1) to the corresponding 7-hydroxy compound (7) results in a 20-fold increase in RBA (112%) without any appreciable change in AI activity. On the other hand, absence of the pyrrolidinoethyl group from the 4-phenyl residue (6) leads to a drop in both RBA and AI activity. A chain length of two to three carbon atoms and a pyrrolidino ring appear to be necessary for activity in these compounds. It has been found that while the trans isomers with the tertiary aminoalkoxy side chain in the para position of the 4-phenyl radical were the most active, in the corresponding cis-chromans and chromenes, analogues with this chain in the meta position were most active; the ortho substituted compounds of all these series were inactive. In 3-phenyl-substituted compounds, the trans isomer carrying the p-hydroxy substituent (33) was found to be the most active; the corresponding pyrrolidinoethyl ether (13) showed a lower order of activity. The implication of these observations on the mapping of the different subsites on the receptor has been discussed.

  DOI：

  10.1021/jm00358a026
• 作为产物：
  描述：

  cis-7-Methoxy-2,2-dimethyl-3-phenyl-4-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}chromane 以97.4的产率得到左美洛昔芬
  参考文献：
  名称：

  J. Med. Chem. 1976, 19, 276-279

  摘要：

  DOI：

文献信息

• Dibenzyl Amine Compounds and Derivatives
  申请人：Chang George

  公开号：US20070213371A1

  公开（公告）日：2007-09-13

  Dibenzyl amine compounds and derivatives, 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.

  二苯基胺化合物及其衍生物，含有这种化合物的药物组合物以及使用这种化合物提高某些血浆脂质水平，包括高密度脂蛋白胆固醇，并降低其他一些血浆脂质水平，如低密度脂蛋白胆固醇和甘油三酯，并据此治疗由高密度脂蛋白胆固醇水平低和/或低密度脂蛋白胆固醇和甘油三酯水平高加重的疾病，如动脉粥样硬化和心血管疾病在某些哺乳动物，包括人类。
• [EN] AMINE-LINKED C3-GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN DEGRADATION<br/>[FR] DÉGRONIMÈRES DE C3-GLUTARIMIDE LIÉS À UNE AMINE POUR LA DÉGRADATION DE PROTÉINES CIBLES
  申请人：C4 THERAPEUTICS INC

  公开号：WO2017197051A1

  公开（公告）日：2017-11-16

  This invention provides amine-linked C3-glutarimide Degronimers and Degrons for therapeutic applications as described further herein, and methods of use and compositions thereof as well as methods for their preparation.

  这项发明提供了胺连接的C3-戊二酰亚胺Degronimers和Degrons，用于治疗应用，如本文进一步描述的，以及它们的使用方法、组合物以及它们的制备方法。
• [EN] SYNTHETIC OLIGOGLUCOSAMINES FOR IMPROVEMENT OF PLANT GROWTH AND YIELD<br/>[FR] OLIGOGLUCOSAMINES SYNTHÉTIQUES POUR L'AMÉLIORATION DE LA CROISSANCE ET DU RENDEMENT DE VÉGÉTAUX
  申请人：DU PONT

  公开号：WO2015130893A1

  公开（公告）日：2015-09-03

  The disclosure provides formulations comprising synthetic oligoglucosamines and methods for improving plant growth and crop yield therewith. These formulations may be applied to propagating materials, including seeds and other regenerable plant parts, including cuttings, bulbs, rhizomes and tubers. They may also be applied to foliage, or soil either prior to or following planting of propagating materials. Such applications may be made alone or in combination with fungicides, insecticides, nematicides and other agricultural agents used to improve plant growth and crop yield.

  该披露提供了包含合成寡聚葡聚糖胺的配方，以及利用这些配方改善植物生长和作物产量的方法。这些配方可以应用于繁殖材料，包括种子和其他可再生植物部分，如插条、球茎、根茎和块茎。它们也可以应用于叶片或土壤，无论是在种植繁殖材料之前还是之后。这些应用可以单独进行，也可以与杀菌剂、杀虫剂、线虫杀灭剂和其他用于改善植物生长和作物产量的农业药剂结合使用。
• [EN] GLUCOCORTICOID RECEPTOR MODULATORS<br/>[FR] MODULATEURS DE RÉCEPTEURS DES GLUCOCORTICOÏDES
  申请人：ORIC PHARMACEUTICALS INC

  公开号：WO2018191283A1

  公开（公告）日：2018-10-18

  Described herein are glucocorticoid receptor modulators and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for the treatment of cancer and hypercortisolism.

  本文描述了糖皮质激素受体调节剂和包含该类化合物的药物组合物。这些化合物和组合物对于治疗癌症和高皮质醇症是有用的。
• HETEROARYL/ARYL PYRIMIDINE ANALOGS AND THEIR USE AS AGONISTS OF THE WNT-BETA-CATENIN CELLULAR MESSAGING SYSTEM
  申请人：BURSAVICH Matthew Gregory

  公开号：US20080287452A1

  公开（公告）日：2008-11-20

  The present invention relates to heteroaryl/aryl pyrimidine analogs, methods of making aryl/heteroaryl pyrimidine analogs, compositions comprising a aryl/heteroaryl pyrimidine analog, and methods for treating canonical Wnt-β-catenin cellular messaging system-related disorders comprising administering to a subject in need thereof an effective amount of a heteroaryl/aryl pyrimidine analog.

  本发明涉及杂环芳基/芳基嘧啶类似物，制备芳基/杂环芳基嘧啶类似物的方法，包含芳基/杂环芳基嘧啶类似物的组合物，以及治疗与经典Wnt-β-连环蛋白细胞信息传递系统相关疾病的方法，包括向需要的受试者施用有效量的杂环芳基/芳基嘧啶类似物。