Ethyl 2-[(2'-cyanobiphenyl-4-yl)methyl]-3-oxoheptanoate | 137860-02-7

• 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 2-[(2'-cyanobiphenyl-4-yl)methyl]-3-oxoheptanoate
• 英文别名: ethyl 2-[[4-(2-cyanophenyl)phenyl]methyl]-3-oxoheptanoate
• CAS: 137860-02-7
• 化学式: C₂₃H₂₅NO₃
• 分子量: 363.456
• InChiKey: KEVDVLZBIYZVHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  67.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl 2-[(2'-cyanobiphenyl-4-yl)methyl]-3-oxoheptanoate 在 sodium methylate 、 三氯氧磷 作用下， 反应 14.25h， 生成 4'-(4-Butyl-6-methoxy-2-methyl-pyrimidin-5-ylmethyl)-biphenyl-2-carbonitrile
  参考文献：
  名称：

  Synthesis and angiotensin II receptor antagonist activity of C-linked pyrimidine derivatives

  摘要：

  The synthesis and pharmacological activity of nonpeptide angiotensin II (Ang II) receptor antagonists are presented. These 3-N-substituted pyrimidine-4(3H)-one and 4-O,N,S-substituted pyrimidine derivatives represent a series of C-linked biphenyl tetrazole Ang II antagonists. In vitro, they displayed a high affinity for rat adrenal Ang II receptors, several compounds causing more than 60% displacement of [I-125]Sar(1)-Ile(8)-Ang II from the rat adrenal Ang II receptor at 10(-7) M. In vivo, several compounds displayed a high oral antihypertensive activity in renal hypertensive rat with decreases in systolic arterial pressure (SAP) greater than 60 mmHg 10 mg/kg. 2-[2-Methyl-4-oxo-6-n-propyl-5-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]pyrimidin-3-yl]ethanol hydrochloride (compound 17) was compared with Losartan in the renal artery-ligated rat model. It was shown that at 3 mg/kg po, 17 induced a maximal decrease in mean arterial pressure (MAP) of 60.8 mmHg, which was similar to that was observed with Losartan (maximal decrease of 60 mmHg at 3 mg/kg) with a long duration of action (greater than 16 h).

  DOI：

  10.1016/0223-5234(96)88246-8
• 作为产物：
  描述：

  3-氧代庚酸乙酯 、 2-氰基-4'-溴甲基联苯 在 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 以93%的产率得到Ethyl 2-[(2'-cyanobiphenyl-4-yl)methyl]-3-oxoheptanoate
  参考文献：
  名称：

  C联吡唑衍生物的合成及其血管紧张素II受体拮抗剂活性。

  摘要：

  介绍了新的非肽血管紧张素II（AII）受体拮抗剂的合成和药理活性。这些5-O-取代的和5-C-取代的3-烷基吡唑衍生物代表了一系列新的拮抗剂，并导致在肾动脉结扎的大鼠模型中发现具有有效口服降压活性的化合物。在体外，它们显示出对大鼠肾上腺AII受体的高度亲和力。体内结构活性关系研究表明，4- [2'-（1H-四唑-5-基）联苯-4-基]甲基部分对于口服活性很重要，并且烷基取代基在1-的关键作用或2位。在口服给药的情况下，总体上发现5-C衍生物比5-O衍生物更有效。UP 221-78，5-羟甲基-3-正丙基-1-（2,2,2-三氟乙基）-4- [[2'

  DOI：

  10.1248/cpb.42.1617

文献信息

• Synthesis and SAR Studies of Novel Triazolopyrimidine Derivatives as Potent, Orally Active Angiotensin II Receptor Antagonists
  作者：Eric Nicolai、Gerard Cure、Joel Goyard、Maud Kirchner、Jean-Marie Teulon、Annie Versigny、Michele Cazes、Francois Caussade、Angela Virone-Oddos、Alix Cloarec

  DOI：10.1021/jm00041a016

  日期：1994.7

  The synthesis and pharmacological activity of new nonpeptide angiotensin II (AII) receptor antagonists are presented. These [1,2,4]-triazolo[1,5-c]pyrimidine and 1,2,4-triazolo[4,3-c]pyrimidine derivatives represent a new class of bicyclic antagonists that produced a potent, oral antihypertensive activity in the renal artery-ligated rat model. In vitro, they displayed a high affinity for rat adrenal

  介绍了新的非肽血管紧张素II（AII）受体拮抗剂的合成和药理活性。这些[1,2,4]-三唑并[1,5-c]嘧啶和1,2,4-三唑并[4,3-c]嘧啶衍生物代表了一类新的双环拮抗剂，可产生有效的口服降压活性在肾动脉结扎的大鼠模型中。在体外，它们表现出对大鼠肾上腺AII受体的高度亲和力，并被发现对AT1受体亚型具有特异性。SAR研究表明，8- [2'-（（1H-四唑-5-基）联苯-4-基]甲基对于口服活性很重要，并且烷基取代基在5和7位上起着至关重要的作用。在[1,5-c]和[4,3-c]系列之间没有发现显着差异。UP 269-6（5-甲基-7-正丙基8-[[2'-（1H-四唑-5-基）联苯-4-基]甲基]-[1,2,4]-三唑并[ 1,5-c]嘧啶-2（3H）-one，选择衍生物29）作为前导化合物。它被证明是一种高效的抗高血压衍生物（肾结扎大鼠在1 mg / kg po时平均动脉压降低39
• Synthesis and Angiotensin II Receptor Antagonist Activity of C-Linked Pyrazole Derivatives.
  作者：Eric NICOLAI、Gerard CURE、Joel GOYARD、Maud KIRCHNER、Jean-Marie TEULON、Annie VERSIGNY、Michele CAZES、Angela VIRONE-ODDOS、Francois CAUSSADE、Alix CLOAREC

  DOI：10.1248/cpb.42.1617

  日期：——

  The synthesis and pharmacological activity of new nonpeptide angiotensin II (AII) receptor antagonists are presented. These 5-O-substituted and 5-C-substituted 3-alkylpyrazole derivatives represent a new series of antagonists and have led to the discovery of compounds with potent oral antihypertensive activity in a renal artery-ligated rat model. In vitro, they displayed a high affinity for rat adrenal

  介绍了新的非肽血管紧张素II（AII）受体拮抗剂的合成和药理活性。这些5-O-取代的和5-C-取代的3-烷基吡唑衍生物代表了一系列新的拮抗剂，并导致在肾动脉结扎的大鼠模型中发现具有有效口服降压活性的化合物。在体外，它们显示出对大鼠肾上腺AII受体的高度亲和力。体内结构活性关系研究表明，4- [2'-（1H-四唑-5-基）联苯-4-基]甲基部分对于口服活性很重要，并且烷基取代基在1-的关键作用或2位。在口服给药的情况下，总体上发现5-C衍生物比5-O衍生物更有效。UP 221-78，5-羟甲基-3-正丙基-1-（2,2,2-三氟乙基）-4- [[2'
• HETEROMONOCYCLIC COMPOUND AND USE THEREOF
  申请人：Kuroita Takanobu

  公开号：US20080207654A1

  公开（公告）日：2008-08-28

  A compound represented by the formula (I): wherein R1 is an oxo group, ═N—R or the like; a group represented by the formula: is a group represented by the formula: R2 is a group represented by the formula: R3 and R4 are each H, or C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylamino, di(C1-C6)alkylamino or C1-C6 alkylthio, each of which is optionally substituted; and R5 is H, or C1-C6 alkyl, C2-C6 alkenyl, cyclic group, each of which is optionally substituted, —CO—R8 or —O—R8′, or a salt thereof. The compound of the present invention is useful as a drug for the prophylaxis or treatment of circulatory diseases, metabolic diseases and/or central nervous system diseases.

  化合物的化学式为(I)，其中R1为氧代基，═N—R或类似基团；式中的基团表示为：其中R2为式中的基团；R3和R4分别为H，或C1-C6烷基，C3-C6环烷基，C1-C6烷氧基，C1-C6烷基氨基，二(C1-C6)烷基氨基或C1-C6烷基硫基，每个基团均可选地被取代；R5为H，或C1-C6烷基，C2-C6烯基，环状基团，每个基团均可选地被取代，—CO—R8或—O—R8′，或其盐。本发明的化合物可用作预防或治疗循环系统疾病、代谢性疾病和/或中枢神经系统疾病的药物。
• Substituted pyrimidines and [1,2, 4] triazoles and the use thereof for treating prophylaxis, cardiovascular diseases, metabolic diseases and/or central nervous system diseases
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US07998968B2

  公开（公告）日：2011-08-16

  A compound represented by the formula (I): wherein R1 is an oxo group, ═N—R or the like; a group represented by the formula: is a group represented by the formula: R2 is a group represented by the formula: R3 and R4 are each H, or C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylamino, di(C1-C6)alkylamino or C1-C6 alkylthio, each of which is optionally substituted; and R5 is H, or C1-C6 alkyl, C2-C6 alkenyl, cyclic group, each of which is optionally substituted, —CO—R8 or —O—R8′, or a salt thereof. For example, the compound may be substituted pyrimidines and pharmaceutical compositions of the formula (I) where X=—CR3; X1=—CR2 or —NR2; and X2=—CR5 or —NR5. The compound of the present invention is useful as a drug for the prophylaxis or treatment of cardiovascular diseases, metabolic diseases and/or central nervous system diseases.

  化合物的化学式为(I)：其中R1是氧代基，═N—R或类似的基团；由式子表示的基团：是由式子表示的基团：R2是由式子表示的基团：R3和R4分别是H，或C1-C6烷基，C3-C6环烷基，C1-C6烷氧基，C1-C6烷基氨基，二(C1-C6)烷基氨基或C1-C6烷基硫基，每个基团都可以选择性地被取代；而R5是H，或C1-C6烷基，C2-C6烯基，环状基团，每个基团都可以选择性地被取代，—CO—R8或—O—R8′，或其盐。例如，该化合物可以是取代的嘧啶，并且具有化学式(I)的制药组合物，其中X=—CR3；X1=—CR2或—NR2；X2=—CR5或—NR5。本发明的化合物可用作预防或治疗心血管疾病、代谢性疾病和/或中枢神经系统疾病的药物。
• Heteromonocyclic compound or a salt thereof having strong antihypertensive action, insulin sensitizing activity and the like production thereof and use thereof for prophylaxis or treatment of cardiovascular diseases, metabolic diseases and/or central nervous system diseases
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US07803940B2

  公开（公告）日：2010-09-28

  A compound represented by the formula (I): wherein R1 is an oxo group, ═N—R or the like; a group represented by the formula: is a group represented by the formula: R2 is a group represented by the formula: R3 and R4 are each H, or C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylamino, di(C1-C6)alkylamino or C1-C6 alkylthio, each of which is optionally substituted; and R5 is H, or C1-C6 alkyl, C2-C6 alkenyl, cyclic group, each of which is optionally substituted, —CO—R8 or —O—R8′, or a salt thereof. The compound of the present invention is useful as a drug for the prophylaxis or treatment of cardiovascular diseases, metabolic diseases and/or central nervous system diseases.

  化合物的化学式为(I)，其中R1代表氧代基，═N—R或类似基团；式中代表的基团为：R2代表式中代表的基团；R3和R4分别代表氢、C1-C6烷基、C3-C6环烷基、C1-C6烷氧基、C1-C6烷基氨基、双(C1-C6)烷基氨基或C1-C6烷基硫基，每个基团都可以选择性地被取代；R5代表氢、C1-C6烷基、C2-C6烯基、环状基团，每个基团都可以选择性地被取代，—CO—R8或—O—R8′，或其盐。本发明的化合物可用作预防或治疗心血管疾病、代谢性疾病和/或中枢神经系统疾病的药物。