ethyl 1-(2'-cyanobiphenyl-4-yl)methyl-4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate | 144690-96-0

• 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: ethyl 1-(2'-cyanobiphenyl-4-yl)methyl-4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate
• 英文别名: ethyl 1-(2'-cyanobiphenyl-4-yl)methyl-4-(1-hydroxy-1-methylethyl)-2-propyl-1H-imidazole-5-carboxylate；1-[{2'-cyanobiphenyl-4-yl}methyl]-4-(1-hydroxy-1-methylethyl)-2-propylimidazol-5-carboxylic acid ethyl ester；ethyl 3-[[4-(2-cyanophenyl)phenyl]methyl]-5-(2-hydroxypropan-2-yl)-2-propylimidazole-4-carboxylate
• CAS: 144690-96-0
• 化学式: C₂₆H₂₉N₃O₃
• 分子量: 431.535
• InChiKey: PZPSZIYVSFBMGX-UHFFFAOYSA-N

物化性质

• 沸点：
  648.2±55.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  88.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 1-(2'-cyanobiphenyl-4-yl)methyl-4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate 生成 奥美沙坦
  参考文献：
  名称：

  [EN] PREPARATION OF OLMESARTAN MEDOXOMIL
  [FR] PREPARATION D'OLMESARTAN MEDOXOMIL

  摘要：

  本发明提供了一种制备奥美沙坦酯酸甲酯的方法。

  公开号：

  WO2006029056A1
• 作为产物：
  描述：

  diethyl 2-propyl-1H-imidazole-4,5-dicarboxylate hydrochloride 在 potassium carbonate 、 sodium chloride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 异丁酰胺 、 水 、 丙酮 、 甲苯 为溶剂， 反应 6.5h， 生成 ethyl 1-(2'-cyanobiphenyl-4-yl)methyl-4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate
  参考文献：
  名称：

  METHOD FOR PRODUCING 1-BIPHENYLMETHYLIMIDAZOLE COMPOUND

  摘要：

  公开号：

  EP2298763B1

文献信息

• Angiotensin II antagosist 1-biphenylmethylimidazole compounds and their
  申请人：Sankyo Company, Limited

  公开号：US05616599A1

  公开（公告）日：1997-04-01

  Compounds of the following formula (I) or the formula (I).sub.p : ##STR1## wherein R.sup.1 is alkyl or alkenyl; R.sup.2 and R.sup.3 are hydrogen, alkyl, alkenyl, cycloalkyl, aralkyl, aryl, or aryl fused to cycloalkyl; R.sup.4 is hydrogen, alkyl, alkanoyl, alkenoyl, arylcarbonyl, alkoxycarbonyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl, tetrahydrofuryl, a group of formula --SiR.sup.a R.sup.b R.sup.c, in which R.sup.a, R.sup.b and R.sup.c are alkyl or aryl, alkoxymethyl, (alkoxyalkoxy)methyl, haloalkoxymethyl, aralkyl, aryl or alkanoyloxymethoxycarbonyl; R.sup.5 is carboxy or --CONR.sup.8 R.sup.9, wherein R.sup.8 and R.sup.9 hydrogens or alkyl, or R.sup.8 and R.sup.9 together form alkylene; R.sup.6 is hydrogen, alkyl, alkoxy or halogen; R.sup.7 is carboxy or tetrazol-5-yl; R.sub.p.sup.1 is hydrogen, alkyl, cycloalkyl or alkanoyl; R.sub.p.sup.2 is a single bond, alkylene or alkylidene; R.sub.p.sup.3 and R.sub.p.sup.4 are each hydrogen or alkyl; R.sub.p.sup.6 is carboxy or tetrazol-5-yl; and X.sub.p is oxygen or sulfur; and pharmaceutically acceptable salts and esters thereof. The compounds are AII receptor antagonists and thus have hypotensive activity and can be used for the treatment and prophylaxis of hypertension. The compounds may be prepared by reacting a biphenylmethyl compound with an imidazole compound.

  以下式(I)或式(I).sub.p的化合物：其中R.sup.1是烷基或烯基；R.sup.2和R.sup.3是氢、烷基、烯基、环烷基、芳基烷基、芳基或与环烷基融合的芳基；R.sup.4是氢、烷基、烷酰基、烯酰基、芳基羰基、烷氧羰基、四氢吡喃基、四氢硫代吡喃基、四氢噻吩基、四氢呋喃基，具有式--SiR.sup.a R.sup.b R.sup.c的基团，其中R.sup.a、R.sup.b和R.sup.c是烷基或芳基、烷氧甲基、(烷氧基烷氧基)甲基、卤代烷氧甲基、芳基烷基、芳基或烷酰氧甲氧羰基；R.sup.5是羧基或--CONR.sup.8 R.sup.9，其中R.sup.8和R.sup.9是氢或烷基，或R.sup.8和R.sup.9一起形成亚烷基；R.sup.6是氢、烷基、烷氧基或卤素；R.sup.7是羧基或四唑-5-基；R.sub.p.sup.1是氢、烷基、环烷基或烷酰基；R.sub.p.sup.2是单键、烷基或烷基亚甲基；R.sub.p.sup.3和R.sub.p.sup.4分别是氢或烷基；R.sub.p.sup.6是羧基或四唑-5-基；X.sub.p是氧或硫；以及其药学上可接受的盐和酯。这些化合物是AII受体拮抗剂，因此具有降压活性，可用于治疗和预防高血压。这些化合物可以通过将联苯甲基化合物与咪唑化合物反应制备而成。
• PROCESS FOR THE PREPARATION OF OLMESARTAN MEDOXOMIL
  申请人：Zupancic Silvo

  公开号：US20090131680A1

  公开（公告）日：2009-05-21

  The present invention relates to an improved process for the manufacture of olmesartan and pharmaceutically acceptable salts and esters thereof as an active ingredient of a medicament for the treatment of hypertension and related diseases and conditions.

  本发明涉及一种改进的工艺，用于制造奥美沙坦及其药用可接受的盐和酯，作为治疗高血压和相关疾病和症状的药物的活性成分。
• 1-Biphenylimidazole derivatives, their preparation and their therapeutic use
  申请人：Sankyo Company Limited

  公开号：EP0503785A1

  公开（公告）日：1992-09-16

  Compounds of formula (I): in which: R¹ is alkyl or alkenyl; R² and R³ are hydrogen, alkyl, alkenyl, cycloalkyl, aralkyl, aryl, or aryl fused to cycloalkyl; R⁴ is hydrogen, alkyl, alkanoyl, alkenoyl, arylcarbonyl, alkoxycarbonyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl, tetrahydrofuryl, a group of formula -SiRaRbRc, in which Ra, Rb and Rc are alkyl or aryl, alkoxymethyl, (alkoxyalkoxy)methyl, haloalkoxymethyl, aralkyl, aryl or alkanoyloxymethoxycarbonyl; R⁵ is carboxy or a group of formula -CONR⁸R⁹, in which R⁸ and R⁹ are hydrogen atoms or alkyl, or R⁸ and R⁹ together form alkylene; R⁶ is hydrogen, alkyl, alkoxy or halogen; R⁷ is carboxy or tetrazol-5-yl; and pharmaceutically acceptable salts and esters thereof have hypotensive activity and can be used for the treatment and prophylaxis of hypertension. They may be prepared, inter alia, by reacting a biphenylmethyl compound with an imidazole compound.

  式(I)的化合物中：其中，R¹是烷基或烯基；R²和R³是氢、烷基、烯基、环烷基、芳基烷基、芳基或与环烷基融合的芳基；R⁴是氢、烷基、酰基烷基、烯酰基烷基、芳基羰基、烷氧羰基、四氢吡喃基、四氢硫吡喃基、四氢噻吩基、四氢呋喃基、式为-SiRaRbRc的基团，其中Ra、Rb和Rc是烷基或芳基、烷氧甲基、（烷氧基）甲基、卤代烷氧甲基、芳基烷基、芳基或酰氧甲氧羰基；R⁵是羧基或式为-CONR⁸R⁹的基团，其中R⁸和R⁹是氢原子或烷基，或R⁸和R⁹一起形成亚烷基；R⁶是氢、烷基、烷氧基或卤素；R⁷是羧基或四唑-5-基；其药学上可接受的盐和酯具有降压活性，可用于治疗和预防高血压。它们可以通过将联苯甲基化合物与咪唑化合物反应制备而成。
• Angiotensin II antagonist 1-biphenylmethylimidazole compounds and their
  申请人：Sankyo Company, Limited

  公开号：US05646171A1

  公开（公告）日：1997-07-08

  An angiotensin II antagonist of the formula: ##STR1## in which: R.sub.p.sup.1 represents hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl or C.sub.1 -C.sub.6 alkanoyl; R.sub.p.sup.2 represents a single bond, C.sub.1 -C.sub.4 alkylene or C.sub.1 -C.sub.4 alkylidene; R.sub.p.sup.3 and R.sub.p.sup.4 are independently selected from the group consisting of hydrogen and C.sub.1 -C.sub.6 alkyl; R.sub.p.sup.5 represents hydrogen, C.sub.1 -C.sub.4 alkyl, phenyl, naphthyl, benzyl, diphenylmethyl, naphthylmethyl, alkanoyloxyalkyl, cycloalkanecarbonyloxyalkyl, alkoxycarbonyloxyalkyl, cycloalkyloxycarbonyloxyalkyl, (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methyl, (5-alkyl-2-oxo-1,3-dioxolen-4-yl)methyl or phthalaidyl; R.sub.p.sup.6 represents a carboxy or a tetrazol-5-yl; and X.sub.p represents an oxygen or sulfur, and pharmaceutically acceptable salts thereof. The compounds have hypotensive activity and can thus be used for the treatment and prophylaxis of hypertension.

  一种血管紧张素II受体拮抗剂的化学式：##STR1## 其中：R.sub.p.sup.1代表氢，C.sub.1-C.sub.6烷基，C.sub.3-C.sub.6环烷基或C.sub.1-C.sub.6酰基；R.sub.p.sup.2代表单键，C.sub.1-C.sub.4烷基或C.sub.1-C.sub.4烷基亚甲基；R.sub.p.sup.3和R.sub.p.sup.4分别选择自羟基和C.sub.1-C.sub.6烷基的群；R.sub.p.sup.5代表氢，C.sub.1-C.sub.4烷基，苯基，萘基，苄基，二苯甲基，萘甲基，烷酰氧烷基，环烷基羰基氧烷基，烷氧羰基氧烷基，环烷氧羰基氧烷基，（5-苯基-2-氧代-1,3-二氧杂环戊二烯-4-基）甲基，（5-烷基-2-氧代-1,3-二氧杂环戊二烯-4-基）甲基或邻苯二甲酰基；R.sub.p.sup.6代表羧基或四唑-5-基；X.sub.p代表氧或硫，以及其药学上可接受的盐。这些化合物具有降压活性，因此可用于治疗和预防高血压。
• Process For the Preparation of Sartan Derivatives and Intermediates Useful in Such Process
  申请人：Veverka Miroslav

  公开号：US20080312451A1

  公开（公告）日：2008-12-18

  The invention provides a process for the preparation of a sartan derivative of formula (I) (formula as filed in paper form) (I) wherein the substituents have the meaning indicated in the description, or a pharmaceutically acceptable salt thereof, comprising reacting 2-cyanophenylboronic acid or a derivative thereof with a p-halobenzyl-1H-imidazole derivative of formula (VI), (formula as filed in paper form) (VI) wherein (part of formula as filed in paper form), X, Y, R 1 and R 2 are as defined above, and Z is I, Br or Cl, in the presence of a transition metal catalyst and an inorganic or organic base. The invention also provides new intermediates of formula (V), (formula as filed in paper form) (V) wherein M is an alkali metal or an NR 4 R 5 R 6 R 7 group; and of formula (II) (formula as filed in paper form) (II)

  本发明提供了一种制备式(I)（纸质文件中的公式）的Sartan衍生物或其药学上可接受的盐的方法，其中取代基具有说明书中指示的含义，包括在过渡金属催化剂和无机或有机碱的存在下，将2-氰基苯硼酸或其衍生物与式(VI)（纸质文件中的公式）的p-卤苯基-1H-咪唑衍生物反应，其中（公式的一部分如纸质文件中所示），X、Y、R1和R2如上定义，Z为I、Br或Cl。本发明还提供了式(V)（纸质文件中的公式）的新中间体，其中M是碱金属或NR4R5R6R7基团；以及式(II)（纸质文件中的公式）的新中间体。