methyl 4-bromo-2-fluorocinnamate | 862651-19-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: methyl 4-bromo-2-fluorocinnamate
• 英文别名: methyl 3-(4-bromo-2-fluorophenyl)acrylate；methyl 3-(4-bromo-2-fluorophenyl)-2-propenoate；methyl (E)-3-(4-bromo-2-fluorophenyl)prop-2-enoate
• CAS: 862651-19-2
• 化学式: C₁₀H₈BrFO₂
• 分子量: 259.075
• InChiKey: XRTIKCDGWXFCNF-HWKANZROSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-bromo-2-fluorocinnamate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 lithium hydroxide 、 potassium acetate 、 联硼酸频那醇酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 (E)-3-[4-[3-(1-adamantyl)-4-hydroxyphenyl]-2-fluorophenyl]prop-2-enoic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of a New Series of Retinoid-Related Biphenyl-4-ylacrylic Acids Endowed with Antiproliferative and Proapoptotic Activity

  摘要：

  Atypical retinoids (AR) represent a class of proapoptotic agents with promising potential in the treatment of neoplastic diseases. In the present work 4'-hydroxybiphenyl-4-ylacrylic acids were studied as a novel series of AR. The synthesized compounds were evaluated for their antiproliferative activity in a human promyelocytic leukemia cell line (NB4) and in an ovarian carcinoma cell system including IGROV-1, carrying a functional wild-type p53, and a cisplatin-resistant subline, IGROV-1/Pt-1. The presence of a bulky lipophilic group at position 3' (adamantan-1-yl being the best) and the E configuration of the acrylic moiety appear essential for activity below 1 mu M. No substitution on the rings or on the double bond improved the activity. A qualitative correlation between the log P and molecular volume of the 3'-substituent and the antiproliferative activity was found. From the study of a few selected compounds, it appears that the presence of the carboxylic group is an essential requirement for apoptogenic properties but not for antiproliferative activity, this being maintained in amide derivatives. On the other hand, compounds able to induce apoptosis produced a detectable level of genotoxic damage. This observation supports the hypothesis that the genotoxic stress is a critical event mediating apoptosis induction by compounds of this class. Among the compounds investigated, E-3-(3'-adamantan-1-yl-4'-hydroxybiphenyl-4-yl)acrylic acid (2) was chosen for further investigation.

  DOI：

  10.1021/jm049440h
• 作为产物：
  描述：

  甲氧羰基亚甲基三苯基正膦 、 4-溴-2-氟苯甲醛 以 甲苯 为溶剂， 反应 1.0h， 以78%的产率得到methyl 4-bromo-2-fluorocinnamate
  参考文献：
  名称：

  [EN] NOVEL BIAROMATIC COMPOUNDS WHICH ACTIVATE RECEPTORS OF PPAR TYPE AND THEIR USE IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS
  [FR] NOUVEAUX COMPOSES BIOAROMATIQUES ACTIVANT LES RECEPTEURS DE TYPE PPAR ET LEUR UTILISATION DANS DES COMPOSITIONS COSMETIQUES OU PHARMACEUTIQUES

  摘要：

  该发明涉及与以下一般式（I）相对应的新型双芳香族化合物，以及它们的制备方法和它们在人类或兽医药物（在皮肤病学、心血管疾病、免疫疾病和/或与脂质代谢相关的疾病领域）中的使用，或者在化妆品组合物中的使用。

  公开号：

  WO2006018325A1

文献信息

• [EN] NOVEL BIAROMATIC COMPOUNDS THAT ACTIVATE PPAR TYPE RECEPTORS, AND USE THEREOF IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS<br/>[FR] NOUVEAUX COMPOSES BIOAROMATIQUES ACTIVANT DES RECEPTEURS DE TYPE PPAR, ET LEUR UTILISATION DANS DES COMPOSITIONS PHARMACEUTIQUES OU COSMETIQUES
  申请人：GALDERMA RES & DEV

  公开号：WO2006018326A1

  公开（公告）日：2006-02-23

  The invention relates to novel biaromatic compounds that correspond to the general formula (I) and also to the method for preparing them, and to their use in pharmaceutical compositions for use in human or veterinary medicine (in dermatology, and also in the field of cardiovascular diseases, immune diseases and/or lipid metabolism-related diseases), or alternatively in cosmetic compositions.

  该发明涉及与一般式(I) 相对应的新型双芳香化合物，以及其制备方法，以及它们在制药组合物中的应用，用于人类或兽医药物（在皮肤科、心血管疾病、免疫疾病和/或脂质代谢相关疾病领域），或者用于化妆品组合物。
• 3,4-dihydro-4-oxo-3-(2-propenyl)-1-phthalazineacetic acids and
  申请人：Lipha, Lyonnaise Industrielle Pharmaceutique

  公开号：US05489592A1

  公开（公告）日：1996-02-06

  Novel 3,4-dihydro-4-oxo-3(prop-2-enyl)-1-phtalazineacetic acids and derivatives of formula (I) ##STR1## in which R.sub.1 R.sub.2 and R.sub.3 are the same or different and stand for H, a halogen or a linear or branched aliphatic, saturated or unsaturated radical, substituted or not by at least one halogen or R.sub.4 residue such as defined below, except when R.sub.4 is H; R.sub.4 and R.sub.5 are the same or different and stand for H, a linear or branched aliphatic radical, saturated or unsaturated, an aryl or heteroaryl radical, said radicals being substituted or not by at least one grouping such as fluorine, chlorine, bromine, methyl or trifluoromethyl, where R.sub.4 and R.sub.5 do not simultaneously denote H; R.sub.6 stands for hydroxy or alkoxy radical; R.sub.7 stands for H, a halogen, a linear or branched aliphatic saturated or unsaturated radical, an alkoxy radical, said radicals being substituted or not by analiphatic or halogenated radical, a nitro group, a substituted or unsubstituted amino group, S(O)n R.sub.8 or a cyano group; n is equal to 0,1 or 2; R.sub.8 is an aliphatic, linear or branched radical, an aryl or heteroaryl radical, an amino radical, said radicals being substituted or not by an aliphatic or halogenated radical. This invention also relates to the optional tautomeric forms of said acids and their pharmaceutically acceptable base addition salts. Also described is a process for preparing said compounds and the drugs containing same.

  新颖的3,4-二氢-4-氧基-3(丙-2-烯基)-1-邻苯二甲酸和式(I)的衍生物##STR1##其中R.sub.1、R.sub.2和R.sub.3相同或不同，代表H、卤素或线性或支链脂肪饱和或不饱和基团，该基团至少被一个卤素或R.sub.4残基取代，R.sub.4不为H时，除非R.sub.4为H；R.sub.4和R.sub.5相同或不同，代表H、线性或支链脂肪基团、饱和或不饱和基团、芳基或杂环芳基，这些基团至少被氟、氯、溴、甲基或三氟甲基等基团取代或不取代，其中R.sub.4和R.sub.5不同时代表H；R.sub.6代表羟基或烷氧基基团；R.sub.7代表H、卤素、线性或支链脂肪饱和或不饱和基团、烷氧基基团，该基团被脂肪基或卤素基团取代或不取代、硝基基团、取代或未取代的氨基基团、S(O)nR.sub.8或氰基团；n等于0、1或2；R.sub.8是线性或支链脂肪基团、芳基或杂环芳基、氨基基团，这些基团被脂肪基或卤素基团取代或不取代。本发明还涉及所述酸的可选互变异构体形式及其药学上可接受的碱盐。还描述了制备所述化合物和含有相同化合物的药物的方法。
• Biaromatic compound activators of ppargamma receptors and cosmetic/pharmaceutical compositions comprised thereof
  申请人：Clary Laurence

  公开号：US20070213336A1

  公开（公告）日：2007-09-13

  Novel biaromatic compounds having the general formula (I): and cosmetic/pharmaceutical compositions comprised thereof are useful in human or veterinary medicine (in dermatology and also in the fields of cardiovascular diseases, of immune diseases and/or of diseases related to the metabolism of lipids) or, alternatively, in cosmetic compositions.

  具有一般公式（I）的新型双芳香族化合物及其所组成的化妆品/药物组合物在人类或兽医医学（在皮肤科以及心血管疾病、免疫疾病和/或与脂质代谢有关的疾病领域）中非常有用，或者在化妆品组合物中使用。
• Biaromatic compound activators of PPARgamma receptors and cosmetic/pharmaceutical compositions comprised thereof
  申请人：Clary Laurence

  公开号：US20070207175A1

  公开（公告）日：2007-09-06

  Novel biaromatic compounds having the general formula (I): and cosmetic/pharmaceutical compositions comprised thereof are useful in human or veterinary medicine (in dermatology and also in the fields of cardiovascular diseases, of immune diseases and/or of diseases related to the metabolism of lipids) or, alternatively, in cosmetic compositions.

  具有下列一般式（I）的新型双芳香族化合物及其组成的化妆品/药物组合物在人类或兽医学（在皮肤科以及心血管疾病、免疫疾病和/或与脂类代谢相关的疾病领域）中是有用的，或者在化妆品组合物中也是有用的。
• Synthesis and SAR of potent and orally bioavailable tert-butylpyrrolidine archetype derived melanocortin subtype-4 receptor modulators
  作者：Liangqin Guo、Zhixiong Ye、Feroze Ujjainwalla、Heather L. Sings、Iyassu K. Sebhat、John Huber、David H. Weinberg、Rui Tang、Tanya MacNeil、Constantin Tamvakopoulos、Qianping Peng、Euan MacIntyre、Lex H.T. van der Ploeg、Mark T. Goulet、Matthew J. Wyvratt、Ravi P. Nargund

  DOI：10.1016/j.bmcl.2008.04.049

  日期：2008.6

  Discovery of a series of tert-butyl pyrrolidine derived, potent and orally bioavailable melanocortin receptor subtype-4 (MC4R) selective modulators is disclosed. (C) 2008 Elsevier Ltd. All rights reserved.