N-methoxy-N-methyl-4-(4-dimethylaminophenyl)benzamide | 179055-23-3

• 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: N-methoxy-N-methyl-4-(4-dimethylaminophenyl)benzamide
• 英文别名: 4-[4-(dimethylamino)phenyl]-N-methoxy-N-methylbenzamide
• CAS: 179055-23-3
• 化学式: C₁₇H₂₀N₂O₂
• 分子量: 284.358
• InChiKey: IBBWGKBDJKBFFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-methoxy-N-methyl-4-(4-dimethylaminophenyl)benzamide 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以33%的产率得到4’-(dimethylamino)-[1,1’-biphenyl]-4-carbaldehyde
  参考文献：
  名称：

  Inhibitors of acyl-CoA: cholesterol O-acyltransferase (ACAT). Part 1: Identification and structure-activity relationships of a novel series of substituted N-alkyl-N-biphenylylmethyl-N′-arylureas

  摘要：

  A series of N-alkyl-N-biphenylylmethyl-N'-arylurea and related derivatives represented by 1 have been prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyltransferase in vitro and to lower plasma cholesterol levels in cholesterol-fed rats in vivo. Linking of two phenyl groups via oxygen and introduction of fluorine at appropriate positions on the biphenyl moiety improved in vitro and in vivo activity, From this series of analogs, compound 40 (FR179254), which had potent in vitro potency (rabbit intestinal microsomes IC50 = 25 nM), showed excellent plasma cholesterol-lowering activity when administered via the diet (ED50 = 0.045 mg/kg). However, the hypocholesterolemic effect of this compound was moderate when dosed by oral gavage in PEG400 as a vehicle (ED50 = 5.3 mg/kg). Modification of the N'-aryl moiety led to the identification of compound 50 (FR182980) which was efficacious in both dosing models (ED50 = 0.034 mg/kg and 0.11 mg/kg, respectively). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(97)10009-8
• 作为产物：
  描述：

  4-羧基苯硼酸 在 四(三苯基膦)钯 sodium carbonate 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 88.0h， 生成 N-methoxy-N-methyl-4-(4-dimethylaminophenyl)benzamide
  参考文献：
  名称：

  Inhibitors of acyl-CoA: cholesterol O-acyltransferase (ACAT). Part 1: Identification and structure-activity relationships of a novel series of substituted N-alkyl-N-biphenylylmethyl-N′-arylureas

  摘要：

  A series of N-alkyl-N-biphenylylmethyl-N'-arylurea and related derivatives represented by 1 have been prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyltransferase in vitro and to lower plasma cholesterol levels in cholesterol-fed rats in vivo. Linking of two phenyl groups via oxygen and introduction of fluorine at appropriate positions on the biphenyl moiety improved in vitro and in vivo activity, From this series of analogs, compound 40 (FR179254), which had potent in vitro potency (rabbit intestinal microsomes IC50 = 25 nM), showed excellent plasma cholesterol-lowering activity when administered via the diet (ED50 = 0.045 mg/kg). However, the hypocholesterolemic effect of this compound was moderate when dosed by oral gavage in PEG400 as a vehicle (ED50 = 5.3 mg/kg). Modification of the N'-aryl moiety led to the identification of compound 50 (FR182980) which was efficacious in both dosing models (ED50 = 0.034 mg/kg and 0.11 mg/kg, respectively). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(97)10009-8

文献信息

• UREA DERIVATIVES AND THEIR USE AS ACAT-INHIBITORS
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0784612A1

  公开（公告）日：1997-07-23
• [EN] UREA DERIVATIVES AND THEIR USE AS ACAT-INHIBITORS<br/>[FR] DERIVES D'UREE ET LEUR UTILISATION COMME INHIBITEURS DE L'ACAT
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：WO1996010559A1

  公开（公告）日：1996-04-11

  (EN) Urea derivatives of formula (I), wherein R1 is a group of formula (1) (in which R4 is aryl which may have suitable substituent(s), or heterocyclic group which may have suitable substituent(s), and Y is bond, lower alkylene, -S-, -O-, (a), =CH-, -CONH-, (b), (in which R7 is lower alkyl), -NHSO2-, -SO2NH-, -SO2NHCO- or -CONHSO2-); or thiazolyl, imidazolyl, pyrazolyl, pyridyl, thienyl, furyl, isoxazolyl or chromanyl, each of which may have suitable substituent(s); R2 is lower alkyl, lower alkoxy(lower)alkyl, cycloalkyl, ar(lower)alkyl which may have suitable substituent(s), heterocyclic group or heterocyclic(lower)alkyl, R3 is aryl which may have suitable substituent(s) or heterocyclic group which may have suitable substituent(s), and n is 0 or 1, and a pharmaceutically acceptable salt thereof which are useful as a medicament in the treatment of hypercholesterolemia, hyperlipidemia and atherosclerosis.(FR) Cette invention se rapporte à des dérivés d'urée, représentés parr la formule (I), où R1 représente un groupe de la formule (1) (dans laquelle R4 représente aryle qui peut comporter un ou des substitutants appropriés, ou un groupe hétérocyclique qui peut comporter un ou des substituants appropriés; et Y représente une liaison, alkylène inférieur, -S-, -O-, (a), =CH-, -CONH-, (b) (où R7 représente alkyle inférieur), -NHSO2-, -SO2NH-, -SO2NHCO- ou -CONHSO2-); ou alors R1 représente thiazolyle, imidazolyle, pyrazolyle, pyridyle, thiényle, furyle, isoxazolyle ou chromanyle, chacun de ces éléments pouvant comporter un ou des substituants appropriés; R2 représente alkyle inférieur, alcoxy inférieur alkyle(inférieur), cycloalkyle, aralkyle(inférieur) pouvant comporter un ou des substituants appropriés, un groupe hétérocyclique ou alkyle(inférieur) hétérocyclique; R3 représente aryle pouvant comporter un ou des substituants appropriés ou un groupe hétérocyclique pouvant comporter un ou des substituants appropriés; et n est égal à 0 ou à 1; ainsi qu'à un sel pharmaceutiquement acceptacle de ces composés, qui peuvent être utilisés comme médicament dans le traitement de l'hypercholestérolémie, de l'hyperlipidémie et de l'athérosclérose.
• Inhibitors of acyl-CoA: cholesterol O-acyltransferase (ACAT). Part 1: Identification and structure-activity relationships of a novel series of substituted N-alkyl-N-biphenylylmethyl-N′-arylureas
  作者：Akira Tanaka、Takeshi Terasawa、Hiroyuki Hagihara、Yuri Sakuma、Noriko Ishibe、Masae Sawada、Hisashi Takasugi、Hirokazu Tanaka

  DOI：10.1016/s0968-0896(97)10009-8

  日期：1998.1

  A series of N-alkyl-N-biphenylylmethyl-N'-arylurea and related derivatives represented by 1 have been prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyltransferase in vitro and to lower plasma cholesterol levels in cholesterol-fed rats in vivo. Linking of two phenyl groups via oxygen and introduction of fluorine at appropriate positions on the biphenyl moiety improved in vitro and in vivo activity, From this series of analogs, compound 40 (FR179254), which had potent in vitro potency (rabbit intestinal microsomes IC50 = 25 nM), showed excellent plasma cholesterol-lowering activity when administered via the diet (ED50 = 0.045 mg/kg). However, the hypocholesterolemic effect of this compound was moderate when dosed by oral gavage in PEG400 as a vehicle (ED50 = 5.3 mg/kg). Modification of the N'-aryl moiety led to the identification of compound 50 (FR182980) which was efficacious in both dosing models (ED50 = 0.034 mg/kg and 0.11 mg/kg, respectively). (C) 1998 Elsevier Science Ltd. All rights reserved.