1-benzyl-4,5-diphenylimidazole-2-carboxaldehyde | 135098-44-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-benzyl-4,5-diphenylimidazole-2-carboxaldehyde
• 英文别名: 1-benzyl-2-formyl-4,5-diphenylimidazole；1-Benzyl-2-formyl-4,5-diphenyl-imidazole；1-benzyl-4,5-diphenylimidazole-2-carbaldehyde
• CAS: 135098-44-1
• 化学式: C₂₃H₁₈N₂O
• 分子量: 338.409
• InChiKey: IUNRJDVBZAJQQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-benzyl-4,5-diphenylimidazole-2-carboxaldehyde 在 palladium on activated charcoal 氨 、 氢气 、 sodium 、 4-甲基苯磺酸吡啶 作用下， 以 四氢呋喃 、 乙酸乙酯 、 甲苯 为溶剂， 反应 18.5h， 生成 2-(4,5,6,7-tetrahydro-1,3-dioxepin-2-yl)-4,5-diphenylimidazole
  参考文献：
  名称：

  Acyl-CoA:Cholesterol O-Acyltransferase (ACAT) Inhibitors. 2. 2-(1,3-Dioxan-2-yl)-4,5-diphenyl-1H-imidazoles as Potent Inhibitors of ACAT

  摘要：

  The second in this series of papers concerns our further investigations into the search for a potent bioavailable acyl-CoA:cholesterol O-acyltransferase (ACAT) inhibitor suitable for the treatment of atherosclerosis. The design, synthesis, and structure-activity relationship for a series of ACAT inhibitors based on the 2-(1,3-dioxan-2-yl)-4,5-diphenyl-1H-imidazole pharmacophore are described. Compounds such as 13a bearing simple alkyl or hydroxymethyl substituents at the 5-position of the 1,3-dioxane ring are potent bioavailable inhibitors of the rat hepatic microsomal enzyme in vitro (IC50 < 100 nM) but are only weak inhibitors of the human hepatic enzyme. We have found however that 1,3-dioxanes substituted at the 5-cis position with pyrazolylalkyl or aminoalkyl groups are potent inhibitors in vitro of human macrophage ACAT, the potency depending on the nature of the terminal heterocycle and the length of the alkyl chain. An ex vivo bioassay described herein demonstrates that potent inhibitors such as 13t (IC50 = 10 nM) which contain lipophilic terminal heterocycles do not appear to be systemically available. Less potent but more water soluble compounds such as 13h (IC50 = 60 nM) and 13n (IC50 = 70 nM) are absorbed following oral dosing and achieve plasma levels significantly in excess of their IC50 for ACAT inhibition. These compounds are therefore possible candidates for further investigation as oral antiatherosclerotic agents.

  DOI：

  10.1021/jm9505876
• 作为产物：
  描述：

  4,5-二苯基咪唑 在 正丁基锂 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 生成 1-benzyl-4,5-diphenylimidazole-2-carboxaldehyde
  参考文献：
  名称：

  5,10,15,20-四（N-保护的咪唑-2-基）卟啉

  摘要：

  已显示标题卟啉的实例可以由适当的N-保护的咪唑-2-甲醛和吡咯在回流的丙酸中制备：随后的脱保护，提供了合成5,10,15,20-四（合成的咪唑）的途径-2-基）卟啉（TIP）。

  DOI：

  10.1016/0040-4020(96)00520-0

文献信息

• Imidazoles
  申请人：RHONE POULENC RORER LIMITED

  公开号：EP0506437A1

  公开（公告）日：1992-09-30

  Imidazole derivatives of the formula: wherein R¹ represents optionally substituted phenyl, R² represents alkyl optionally substituted by hydroxy, X¹ represents a bond, oxygen, -S(0)n-, -CH₂0- or - CH₂N(R⁶)-, wherein n is 0, 1 or 2 and R⁶ represents hydrogen, alkyl, acyl alkylsulphonyl or, -C(X³)NR⁷R⁸, wherein X³ represents oxygen or sulphur and R⁷ and R⁸ represent hydrogen, alkyl, or optionally substituted phenyl, m is zero or 1 to 8, X² represents a bond, oxygen, -S(0)p- wherein p is 0, 1 or 2, or a group -C(0)NR⁴-, -C(S)NR⁴-, -OC(0)NR⁴-, -OC(S)NR⁴-, -NR⁴C(0)- or -NR⁴C(S)-, wherein R⁴ represents hydrogen or alkyl and R³ represents optionally substituted heterocyclyl, or cycloalkyl or, except when X¹ and X² are direct bonds, R³ represents optionally substituted phenyl, or R³ represents amino, alkylamino, benzylamino, benzyl(alkyl)amino, dialkylamino, aminoalkyl, alkylaminoalkyl, benzylaminoalkyl, benzyl(alkyl)aminoalkyl or dialkylaminoalkyl, or a cyclic imino group, and salts thereof possess useful pharmacological properties.

  Imidazole衍生物的化学式如下： 其中R¹代表可选择取代的苯基，R²代表可选择取代的烷基，其上带有羟基，X¹代表键，氧，-S(0)n-，-CH₂0-或- CH₂N(R⁶)-，其中n为0，1或2，R⁶代表氢，烷基，酰基烷基磺酰基或，-C(X³)NR⁷R⁸，其中X³代表氧或硫，R⁷和R⁸代表氢，烷基，或可选择取代的苯基，m为零或1至8，X²代表键，氧，-S(0)p-，其中p为0，1或2，或一个基团-C(0)NR⁴-，-C(S)NR⁴-，-OC(0)NR⁴-，-OC(S)NR⁴-，-NR⁴C(0)-或-NR⁴C(S)-，其中R⁴代表氢或烷基，R³代表可选择取代的杂环烷基，或环烷基或，除非X¹和X²是直接键，R³代表可选择取代的苯基，或R³代表氨基，烷基氨基，苄基氨基，苄(烷基)氨基，二烷基氨基，氨基烷基，烷基氨基烷基，苄基氨基烷基，苄(烷基)氨基烷基或二烷基氨基烷基，或一个环状亚胺基团，及其盐具有有用的药理学性质。
• Imidazoles useful as antiatherosclerotic agents
  申请人：Rhone-Poulenc Rorer S.A.

  公开号：US05102900A1

  公开（公告）日：1992-04-07

  Imidazole derivatives of the formula: ##STR1## are described wherein R.sup.1 represents halogen, alkyl or alkoxy, n is 0 to 5, R.sup.2 represents hydrogen or alkyl, R.sup.3 represents hydrogen or alkyl optionally substituted by halogen, hydroxy, acyloxy, alkoxy, hydroxyalkoxy, acyloxyalkoxy, or by optionally substituted phenyl, or the groups R.sup.3 and the carbon atom to which they are attached together form a cycloalkane or cycloalkene group. They are pharmaceutically useful as antiatherosclerotic agents.

  描述了公式为：##STR1## 的咪唑衍生物，其中R.sup.1代表卤素，烷基或烷氧基，n为0至5，R.sup.2代表氢或烷基，R.sup.3代表氢或烷基，可选择地被卤素，羟基，酰氧基，烷氧基，羟基烷氧基，酰氧基烷氧基，或可选择地被取代的苯基取代，或者R.sup.3和它们所连接的碳原子一起形成环烷基或环烯基。它们在药学上有抗动脉粥样硬化的作用。
• US5102900A
  申请人：——

  公开号：US5102900A

  公开（公告）日：1992-04-07
• [EN] IMIDAZOL DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR APPLICATIONS
  申请人：RHONE-POULENC RORER LIMITED

  公开号：WO1992005148A1

  公开（公告）日：1992-04-02

  (EN) Imidazole derivatives of the formula (I): [DPIM]-X-Z-Y wherein [DPIM] is a 4,5-diphenylimidazol-2-yl grouping in which the phenyl groups are optionally substituted by halogen, alkyl or alkoxy, X represents a direct bond or alkylene, alkenylene or alkynylene of up to 3 carbon atoms, Z represents a direct bond or, when X is other than a direct bond, Z represents oxygen, -O-CH2- or -NH-, and Y represents alkoxycarbonyl, optionally substituted alkyl, optionally substituted phenyl or heterocyclyl, or a group of formula (II), (III), (IV), wherein m is 2, 3 or 4, p is 0, 1, 2, 3, 4 or 5, q is 0 or 1, r is 1, 2, 3 or 4, provided that formulae (III) and (IV) each represents a 5-, 6- or 7-membered ring, and Q represents optionally substituted methylene, and pharmaceutically acceptable salts thereof possess useful pharmacological properties.(FR) Dérivés d'imidazoles de la formule (I): [DPIM]-X-Z-Y dans laquelle [DPIM] représente un groupement 4, 5-diphénylimidazole-2-yl dans lequel les groupes phényle sont éventuellement substitués par halogène, alkyle ou alkoxy, X représente une liaison directe ou alkylène, alkénylène ou alkynylène comportant jusqu'à 3 atomes de carbone, Z représente oxygène, -O-CH2 ou -NH- et Y représente alkoxycarbonyle, éventuellement alkyle substitué, éventuellement phényle ou hétérocyclyle substitués ou un groupe de formule (II), (III), (IV), dans lequel m est 2 , 3 ou 4, p est 0, 1, 2, 3, 4 ou 5, q est 0 ou 1, r est 1, 2, 3 ou 4, dans la mesure où les formules (III) et (IV) représentent chacune un composé cyclique à 5, 6 ou 7 éléments et Q représente éventuellement méthylène substitué, ainsi que leurs sels acceptables sur le plan pharmaceutique, possédant des propriétés pharmacologiques efficaces.
• [EN] IMIDAZOLES
  申请人：RHONE-POULENC RORER LIMITED

  公开号：WO1992017470A1

  公开（公告）日：1992-10-15

  (EN) Imidazole derivatives of formula (I), wherein R1 represents optionally substituted phenyl, R2 represents alkyl optionally substituted by hydroxy, X1 represents a bond, oxygen, -S(O)n-, -CH2O- or - CH2N(R6)-, wherein n is 0, 1 or 2 and R6 represents hydrogen, alkyl, acyl alkylsulphonyl or, -C(X3)NR7R8, wherein X3 represents oxygen or sulphur and R7 and R8 represent hydrogen, alkyl, or optionally substituted phenyl, m is zero or 1 to 8, X2 represents a bond, oxygen, -S(O)p-wherein p is 0, 1 or 2, or a group -C(O)NR4-, -C(S)NR4-, -OC(O)NR4-, -OC(S)NR4-, -NR4C(O)- or -NR4C(S)-, wherein R4 represents hydrogen or alkyl and R3 represents optionally substituted heterocyclyl, or cycloalkyl or, except when X1 and X2 are direct bonds, R3 represents optionally substituted phenyl, or R3 represents amino, alkylamino, benzylamino, benzyl(alkyl)amino, dialkylamino, aminoalkyl, alkylaminoalkyl, benzylaminoalkyl, benzyl(alkyl)aminoalkyl or dialkylaminoalkyl, or a cyclic imino group, and salts thereof possess useful pharmacological properties.(FR) On décrit des dérivés de formule (I), dans laquelle R1 représente phényle éventuellement substitué, R2 représente alkyle éventuellement substitué par hydroxy, X1 représente une liaison, oxygène, -S(O)n-, -CH2O- ou -CH2N(R6)-, où n est 0, 1 ou 2 et R6 représente hydrogène, alkyle, acyle, alkylsulphonyle ou -C(X3)NR7R8, où X3 représente oxygène ou soufre et R7 et R8 représentent hydrogène, alkyle ou phényle éventuellement substitué, m est zéro ou 1 à 8, X2 représente une liaison, oxygène, -S(O)p-, où p est 0, 1 ou 2, ou un groupe -C(O)NR4-, -C(S)NR4-, -OC(O)NR4-, -OC(S)NR4-, -NR4C(O)-, ou -NR4C(S)-, où R4 représente hydrogène ou alkyle et R3 représente hétérocyclyle éventuellement substitué, ou cylcloalkyle ou, sauf lorsque X1 et X2 sont des liaisons directes, R3 représente phényle éventuellement substitué, ou R3 représente amino, alkylamino, benzylamino, benzyl(alkyl)amino, dialkylamino, aminoalkyle, alkylaminoalkyle, benzylaminoalkyle, benzyl(alkyl)aminoalkyle ou dialkylaminoalkyle, ou un groupe imino cyclique, et leurs sels. Lesdits composés présentent des propriétés pharmacologiques utiles.