3-fluoro-N,4-dimethoxy-N-methylbenzamide | 851958-47-9

• 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: 3-fluoro-N,4-dimethoxy-N-methylbenzamide
• 英文别名: 3-fluoro-4,N-dimethoxy-N-methyl-benzamide
• CAS: 851958-47-9
• 化学式: C₁₀H₁₂FNO₃
• mdl: MFCD18918966
• 分子量: 213.209
• InChiKey: HNLGLBKKILFOEU-UHFFFAOYSA-N

物化性质

• 沸点：
  359.5±32.0 °C(Predicted)
• 密度：
  1.189±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-fluoro-N,4-dimethoxy-N-methylbenzamide 、 2-萘甲醚 在 正丁基锂 、 四甲基乙二胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.0h， 生成 (3-Fluoro-4-methoxyphenyl)-(3-methoxynaphthalen-2-yl)methanone
  参考文献：
  名称：

  Novel Aldosterone Synthase Inhibitors with Extended Carbocyclic Skeleton by a Combined Ligand-Based and Structure-Based Drug Design Approach

  摘要：

  Pharmacophore modeling of a series of aldosterone synthase (CYP11B2) inhibitors triggered the design of compounds 11 and 12 by extending a previously established naphthalene molecular scaffold (e.g., present in molecules 1 and 2) via introduction of a phenyl or benzyl residue in 3-position. These additional aromatic moieties have been hypothesized to fit into the newly identified hydrophobic pharmacophore feature HY3. Subsequent docking studies in our refined CYP11B2 protein model have been performed prior to synthesis to estimate the inhibitory properties of the proposed molecules. While phenyl-substituted compound 11 (IC50 > 500 nM) did not dock under the given pharmacophore constraint (i.e., the Fe(heme)-N(ligand) interaction), benzyl-substituted compound 12 (IC50 = 154 nM) was found to exploit a previously unexplored subpocket of the inhibitor binding site. By structural optimization based on the pharmacophore hypothesis, 25 novel compounds were synthesized, among them highly potent CYP11B2 inhibitors (e.g., 17, IC50 = 2.7 nM) with pronounced selectivity toward the most important steroidogenic and hepatic CYP enzymes.

  DOI：

  10.1021/jm800683c
• 作为产物：
  描述：

  3-氟-4-甲氧基苯甲酰氯 、 二甲羟胺盐酸盐 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以88%的产率得到3-fluoro-N,4-dimethoxy-N-methylbenzamide
  参考文献：
  名称：

  Novel Aldosterone Synthase Inhibitors with Extended Carbocyclic Skeleton by a Combined Ligand-Based and Structure-Based Drug Design Approach

  摘要：

  Pharmacophore modeling of a series of aldosterone synthase (CYP11B2) inhibitors triggered the design of compounds 11 and 12 by extending a previously established naphthalene molecular scaffold (e.g., present in molecules 1 and 2) via introduction of a phenyl or benzyl residue in 3-position. These additional aromatic moieties have been hypothesized to fit into the newly identified hydrophobic pharmacophore feature HY3. Subsequent docking studies in our refined CYP11B2 protein model have been performed prior to synthesis to estimate the inhibitory properties of the proposed molecules. While phenyl-substituted compound 11 (IC50 > 500 nM) did not dock under the given pharmacophore constraint (i.e., the Fe(heme)-N(ligand) interaction), benzyl-substituted compound 12 (IC50 = 154 nM) was found to exploit a previously unexplored subpocket of the inhibitor binding site. By structural optimization based on the pharmacophore hypothesis, 25 novel compounds were synthesized, among them highly potent CYP11B2 inhibitors (e.g., 17, IC50 = 2.7 nM) with pronounced selectivity toward the most important steroidogenic and hepatic CYP enzymes.

  DOI：

  10.1021/jm800683c

文献信息

• Diphenylethylene compounds and uses thereof
  申请人：Muller W. George

  公开号：US20050107339A1

  公开（公告）日：2005-05-19

  The present invention relates to Diphenylethylene Compounds and compositions comprising a Diphenylethylene Compound. The present invention also relates to methods for preventing or treating various diseases and disorders by administering to a subject in need thereof one or more Diphenylethylene Compounds. In particular, the invention relates to methods for preventing or treating cancer or an inflammatory disorder by administering to a subject in need thereof one or more Diphenylethylene Compounds. The present invention further relates to articles of manufacture and kits comprising one or more Diphenylethylene Compounds.

  本发明涉及二苯乙烯化合物和包含二苯乙烯化合物的组合物。本发明还涉及通过向需要的受试者施用一种或多种二苯乙烯化合物来预防或治疗各种疾病和紊乱的方法。具体而言，该发明涉及通过向需要的受试者施用一种或多种二苯乙烯化合物来预防或治疗癌症或炎症性紊乱的方法。本发明还涉及包含一种或多种二苯乙烯化合物的制品和工具包。
• [EN] 3-SUBSTITUTED PROPIONIC ACIDS AS ALPHA V INTEGRIN INHIBITORS<br/>[FR] ACIDES PROPIONIQUES À SUBSTITUTION EN POSITION 3 EN TANT QU'INHIBITEURS D'INTÉGRINE ALPHA V
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2018089353A1

  公开（公告）日：2018-05-17

  The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αν- containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of ay- containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了化合物的公式(I)：或其立体异构体、互变异构体或药学上可接受的盐或溶剂，其中所有变量如本文所定义。这些化合物是αν-含有整合素的拮抗剂。本发明还涉及包含这些化合物的药物组合物和使用这些化合物和药物组合物来治疗与ay-含有整合素失调相关的疾病、疾病或症状的方法，例如病理纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。
• 3-substituted propionic acids as αV integrin inhibitors
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US10968219B2

  公开（公告）日：2021-04-06

  The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αv-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of ay-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了式（I）化合物：或其立体异构体、同系物或药学上可接受的盐或溶液，其中所有变量如本文所定义。这些化合物是含αv整合素的拮抗剂。本发明还涉及包含这些化合物的药物组合物，以及通过使用这些化合物和药物组合物治疗与含ay整合素失调相关的疾病、紊乱或病症的方法，如病理性纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。
• DIPHENYLETHYLENE COMPOUNDS AND USES THEREOF
  申请人：CELGENE CORPORATION

  公开号：EP1799634A2

  公开（公告）日：2007-06-27
• 3-SUBSTITUTED PROPIONIC ACIDS AS ALPHA V INTEGRIN INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP3538525A1

  公开（公告）日：2019-09-18