4-[2-(piperidin-1-yl)ethoxy]benzoyl chloride hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[2-(piperidin-1-yl)ethoxy]benzoyl chloride hydrochloride
• 英文别名: 4-[2-(N-piperidine)-ethoxy]benzoyl chloride；4-(2-Piperidinoethoxy)benzoyl Chloride Hydrochloride；4-[2-(1-piperidinyl)ethoxy]benzoyl chloride hydrochloride；4-(2-piperidine-1-ylethoxy)benzoyl chloride hydrochloride；4-[2-(piperidinyl)ethoxy]benzoyl chloride hydrochloride；4-(2-Piperidin-1-ium-1-ylethoxy)benzoyl chloride;chloride；4-(2-piperidin-1-ium-1-ylethoxy)benzoyl chloride;chloride
• 化学式: C₁₄H₁₈ClNO₂*ClH
• 分子量: 304.216
• InChiKey: WHKJLXLFQNXNNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[2-(piperidin-1-yl)ethoxy]benzoyl chloride hydrochloride 以 四氢呋喃 、 氯苯 为溶剂， 反应 10.5h， 生成 [2-(2-methoxyphenyl)-6-methoxybenzo[b]thien-3-yl] [4-[2-(1-piperidinyl)ethoxy]phenyl]methanone
  参考文献：
  名称：

  Structure−Activity Relationships of Selective Estrogen Receptor Modulators:  Modifications to the 2-Arylbenzothiophene Core of Raloxifene

  摘要：

  The 8-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. A series of raloxifene analogs which contain modifications to the 2-arylbenzothiophene core have been prepared and evaluated for the ability to bind to the estrogen receptor and inhibit MCF-7 breast cancer cell proliferation in vitro. Their ability to function as tissue-selective estrogen agonists in vivo has been assayed in a short-term, ovariectomized (OVX) rat model with end points of serum cholesterol lowering, uterine weight gain, and uterine eosinophil peroxidase activity. These studies have demonstrated that (1) the 6-hydroxy and, to a lesser extent, the 4'-hydroxy substituents of raloxifene are important for receptor binding and in vitro activity, (2) small, highly electronegative 4'-substituents such as hydroxy, fluoro, and chloro are preferred both in vitro and in vivo, (3) increased steric bulk at the 4'-position leads to increased uterine stimulation in, vivo, and (4) additional substitution of the 2-aryl moiety is tolerated while additional substitution at the 4-, 5-, or 7-position of the benzothiophene results in reduced biological activity. In addition, compounds in which the 2-aryl group is replaced by alkyl, cycloalkyl, and naphthyl substituents maintain a profile of in vitro and in vivo biological activity qualitatively similar to that of raloxifene. Several novel structural variants including 2-cyclohexyl, 2-naphthyl, and 6-carbomethoxy analogs also demonstrated efficacy in preventing bone loss in a chronic OVX rat model of postmenopausal osteopenia, at doses of 0.1-10 mg/kg.

  DOI：

  10.1021/jm9606352
• 作为产物：
  描述：

  N-羟乙基哌啶 在 氯化亚砜 、 偶氮二甲酸二异丙酯 、 三苯基膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 4-[2-(piperidin-1-yl)ethoxy]benzoyl chloride hydrochloride
  参考文献：
  名称：

  一种萘酚类化合物的制备及其在癌症治疗方面的应用

  摘要：

  本发明属于医药生物领域，公开了一类全新萘酚类化合物的设计及制备方法，以及将此类化合物或其的生物学可接受的盐作为活性成分制备在细胞生长调控机制和癌症治疗方面的应用。通过生物活性测试表明，本发明涉及的化合物对肿瘤细胞内STAT3细胞信号传导有显著的抑制作用，并且对肺癌、乳腺癌、结肠癌和白血病等多种癌细胞的增殖有明显的拮抗效果。此类化合物对癌症的临床治疗及癌症机制研究有潜在的重要意义，极具开发潜力，具有很好的应用前景。

  公开号：

  CN109316479B

文献信息

• A New Series of Estrogen Receptor Modulators: Effect of Alkyl Substituents on Receptor-Binding Affinity
  作者：Atsushi Kamada、Atsushi Sasaki、Noritaka Kitazawa、Tadashi Okabe、Kazumasa Nara、Shinichi Hamaoka、Shin Araki、Hiroaki Hagiwara

  DOI：10.1248/cpb.52.79

  日期：——

  New types of selective estrogen receptor modulators (SERMs) were synthesized and evaluated for their binding affinity and biological effect on reproductive cells. A proposed lead structure (B) was derivatized to provide compounds 30 and 44, which showed good estrogen-receptor binding affinity (Ki values: 6.3 and 10 nM, respectively), as well as minimal impact on mammary and uterine carcinoma cells. Introduction of an alkyl group in the core structure considerably enhanced receptor-binding affinity of the compounds tested. Synthesis and structure–activity relationships of these compounds are described.

  新型选择性雌激素受体调节剂（SERMs）被合成并评估其与生殖细胞的结合亲和力和生物学效应。提议的先导结构（B）被衍生化以提供化合物30和44，这些化合物显示出良好的雌激素受体结合亲和力（Ki值：分别为6.3和10 nM），同时对乳腺癌和子宫癌细胞的影响较小。核心结构中引入烷基基团显著增强了测试化合物的受体结合亲和力。文中描述了这些化合物的合成及其结构–活性关系。
• Process for the synthesis of vinyl sulfoxides
  申请人：Eli Lilly and Company

  公开号：US06372945B1

  公开（公告）日：2002-04-16

  The present invention is directed to a new process for the synthesis of vinyl sulfoxides, in particular diarylvinyl sulfoxides

  本发明涉及一种用于合成乙烯亚砜的新工艺，特别是二芳基乙烯亚砜。
• [EN] PROCESS FOR PREPARING RALOXIFENE HYDROCHLORIDE<br/>[FR] PROCEDE POUR PREPARER DE L'HYDROCHLORURE DE RALOXIFENE
  申请人：ERREGIERRE SPA

  公开号：WO2005003116A1

  公开（公告）日：2005-01-13

  Process for preparing raloxifene hydrochloride with a purity greater than 98% and low aluminium content comprising the following stages a) demethylation of 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene in pyridine and hydrochloric acid to obtain 6-hydroxy­2-(4-hydroxyphenyl)benzo[b]thiophene in pyridine hydrochloride, b) acetylation of 6-hydroxy-2-(4­hydroxyphonyl)benzo[b]thiophene with an acetylating agent to obtain the corresponding 6-acetoxy-2-(4 acetoxyphenyl)benzo[b]thiophene, c) acylation of 6-acetoxy-2-(4-acetoxyphonyl)benzo[b]thlophene with 4-(2 piperidinoethoxy)benzoylchloride hydrochloride with aluminium trichloride in halogenated solvent to obtain 6-acetoxy-2-(4­acetoxyphenyl)-3-[4-(2 piperidinoethoxy)benzoyl]-benzo[b]thiophene, d) hydrolysis of 6-acetoxy-2-(4-acetoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyll benzo[b]thiophene according to the following operating conditions: dl) treatment of 6-acetoxy-2-(4-acetoxyphonyl)-3-[4-(2­piperidinoethoxy)benzoyl]benzo[b]thiophene with alkaline hydroxide in alcohol solvent, d2) acidification of the product obtained in the preceding stage (dl) with a strong acid, to obtain the corresponding raloxifene salt with the strong acid, characterised in that the strong acid used in stage (d2) is concentrated hydrochloric acid.

  制备纯度大于98％且铝含量低的盐酸拉洛昔芬的过程包括以下阶段：a）在吡啶和盐酸中去甲基化6-甲氧基-2-（4-甲氧基苯基）苯并[b]噻吩，以获得吡啶盐酸中的6-羟基-2-（4-羟基苯基）苯并[b]噻吩，b）用乙酰化试剂对6-羟基-2-（4-羟基苯基）苯并[b]噻吩进行乙酰化，以获得相应的6-乙酰氧基-2-（4-乙酰氧基苯基）苯并[b]噻吩，c）用卤代溶剂中的氯化铝三和4-（2-哌啶乙氧基）苯甲酰氯盐酸酰化6-乙酰氧基-2-（4-乙酰氧基苯基）苯并[b]噻吩，以获得6-乙酰氧基-2-（4-乙酰氧基苯基）-3- [4-（2-哌啶乙氧基）苯甲酰] -苯并[b]噻吩，d）根据以下操作条件水解6-乙酰氧基-2-（4-乙酰氧基苯基）-3- [4-（2-哌啶乙氧基）苯甲酰] -苯并[b]噻吩：dl）在醇溶剂中用碱性氢氧化物处理6-乙酰氧基-2-（4-乙酰氧基苯基）-3- [4-（2-哌啶乙氧基）苯甲酰] -苯并[b]噻吩，d2）用强酸酸化前一阶段（dl）中获得的产物，以获得强酸的相应拉洛昔芬盐，其特征在于阶段（d2）中使用的强酸为浓盐酸。
• Benzothiphene derivatives for treating resistant tumors
  申请人：ELI LILLY AND COMPANY

  公开号：EP0773217A1

  公开（公告）日：1997-05-14

  This invention provides a series of substituted benzo[b]thiophenes useful in reversing multidrug resistance in a resistant neoplasm. The present invention also provides methods for reversing the multidrug resistance in a resistant neoplasm by treating a mammal in need of said treatment with a substituted benzothiophene. This invention also provides methods for treating neoplasms in a mammal which comprises administering to a mammal in need of this treatment a substituted benzothiophene in combination with an oncolytic agent.

  这项发明提供了一系列取代苯并[b]噻吩，可用于逆转耐药肿瘤的多药耐药性。本发明还提供了通过给需要该治疗的哺乳动物使用取代苯并噻吩来逆转多药耐药性的方法。该发明还提供了一种治疗哺乳动物肿瘤的方法，包括给需要此治疗的哺乳动物同时使用取代苯并噻吩和肿瘤溶解剂。
• Selective Estrogen Receptor Modulator
  申请人：Hamaoka Shinichi

  公开号：US20120004315A1

  公开（公告）日：2012-01-05

  The present invention provides a compound represented by the following formula (I); [wherein T represents a single bond, a C1-C4 alkylene group which may have a substituent and the like; formula (I-1) represents a single bond or a double bond; A represents a single bond, a bivalent 5- to 14-membered heterocyclic group which may have a substituent and the like; Y represents a single bond and the like; Z represents a methylene group and the like; ring G represents a phenylene group and the like which may condense with a 5- to 6-membered ring and may have a heteroatom; R a and R b are the same as or different from each other and represent a hydrogen atom and the like; W represents a single bond and the like; R′ represents 1 to 4 independent hydrogen atoms and the like; and R″ represents 1 to 4 independent hydrogen atoms and the like] or a salt thereof, or a hydrate thereof.

  本发明提供一种由以下式（I）表示的化合物; [其中T表示单键，可能具有取代基的C1-C4烷基和类似物；式（I-1）表示单键或双键；A表示单键，可能具有取代基的双价5-至14-成员杂环基和类似物；Y表示单键和类似物；Z表示亚甲基基团和类似物；环G表示苯基团和类似物，可能与5-至6-成员环缩合并可能具有杂原子；Ra和Rb相同或不同，表示氢原子和类似物；W表示单键和类似物；R'表示1到4个独立的氢原子和类似物；R''表示1到4个独立的氢原子和类似物]或其盐或水合物。