[4-Butyl-5-(2'-cyano-biphenyl-4-ylmethyl)-2-methyl-6-oxo-6H-pyrimidin-1-yl]-acetic acid ethyl ester | 136348-11-3

• 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: [4-Butyl-5-(2'-cyano-biphenyl-4-ylmethyl)-2-methyl-6-oxo-6H-pyrimidin-1-yl]-acetic acid ethyl ester
• 英文别名: ethyl [4-butyl-5-[(2'-cyanobiphenyl-4-yl)methyl]-2-methyl-6-oxopyrimidin-1(6H)-yl]acetate；ethyl 2-[4-butyl-5-[[4-(2-cyanophenyl)phenyl]methyl]-2-methyl-6-oxopyrimidin-1-yl]acetate
• CAS: 136348-11-3
• 化学式: C₂₇H₂₉N₃O₃
• 分子量: 443.546
• InChiKey: GKENGMNXTGEYHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  82.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [4-Butyl-5-(2'-cyano-biphenyl-4-ylmethyl)-2-methyl-6-oxo-6H-pyrimidin-1-yl]-acetic acid ethyl ester 在 trimethyltin azide 作用下， 以 甲苯 为溶剂， 反应 30.0h， 生成 ethyl 2-[4-butyl-2-methyl-6-oxo-5-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]pyrimidin-1-yl]acetate
  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：

  2-氰基-4'-溴甲基联苯 在 sodium methylate 、 sodium hydride 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 22.75h， 生成 [4-Butyl-5-(2'-cyano-biphenyl-4-ylmethyl)-2-methyl-6-oxo-6H-pyrimidin-1-yl]-acetic acid ethyl ester
  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

文献信息

• 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。
• Diazaverbindungen
  申请人：CIBA-GEIGY AG

  公开号：EP0435827A2

  公开（公告）日：1991-07-03

  Diazaverbindungen der Formel worin einer der Reste R₁ und R₂ einen gegebenenfalls durch Halogen oder Hydroxy substituierten aliphatischen Kohlenwasserstoffrest oder einen cycloaliphatischen oder araliphatischen Kohlenwasserstoffrest bedeutet, der andere der Reste R₁ und R₂ für die Gruppe der Formel steht, in der Z₁ für Alkylen, O, S(O)m oder N(R) steht, R₅ Carboxy, Halogenalkansulfonylamino, SO₃H, PO₂H₂, PO₃H₂ oder 5-Tetrazolyl bedeutet und die Ringe A und B unabhängig voneinander gegebenenfalls substituiert sind durch einen aliphatischen Kohlenwasserstoffrest, der gegebenenfalls durch O unterbrochen und gegebenenfalls durch Hydroxy oder Halogen substituiert ist, gegebenenfalls durch einen aliphatischen Alkohol verethertes Hydroxy, Halogen, gegebenenfalls verestertes oder amidiertes Carboxy oder 5-Tetrazolyl, und entweder R₃ Halogen, Acyl, einen aromarischen Kohlenwasserstoffrest, gegebenenfalls verestertes oder amidiertes Carboxy, Cyano, SO₃H, PO₃H₂, PO₂H₂, 5-Tetrazolyl, gegebenenfalls substituiertes Sulfamoyl oder Acylamino bedeutet oder für -Z₂-R′ steht, worin Z₂ für eine Bindung oder für O, S(O)m oder N(R) steht und R′ Wasserstoff oder einen aliphatischen Kohlenwasserstoffrest bedeutet, der gegebenenfalls durch O oder S(O)m unterbrochen ist und gegebenenfalls durch Halogen, Hydroxy, gegebenenfalls substituiertes Amino oder gegebenenfalls verestertes oder amidiertes Carboxy substituiert ist, und R₄ einen gegebenenfalls durch O oder S(O)m unterbrochenen aliphatischen Kohlenwasserstoffrest bedeutet, der gegebenenfalls durch gegebenenfalls verestertes oder amidiertes Carboxy, gegebenenfalls mit einem aromatischen Alkohol verethertes Hydroxy, gegebenenfalls substituiertes Amino, S(O)m-R oder einen aromatischen Kohlenwasserstoffrest substituiert ist, oder R₃ und R₄ gemeinsam für Alkylen stehen, wobei R jeweils Wasserstoff oder einen aliphatischen Kohlenwasserstoffrest bedeutet und m jeweils für 0, 1 oder 2 steht, in freier Form oder in Salzform, können als Arzneimittelwirkstoffe verwendet werden und sind in an sich bekannter Weise herstellbar.

  式中的重氮化合物 其中一个基 R₁ 和 R₂ 表示任选被卤素或羟基取代的脂族烃基或环脂族或芳香族烃基，另一个基 R₁ 和 R₂ 表示式中的基团 其中 Z₁是亚烷基、O、S(O)m 或 N(R)，R₅是羧基、卤代烷磺酰氨基、SO₃H、PO₂H₂、PO₃H₂或 5-四唑基，且环 A 和环 B 相互独立地任选被脂族烃基取代、环 A 和环 B 独立地彼此任选被脂族烃基取代，任选被 O 间断，任选被羟基或卤素取代，任选被脂族醇羟基醚化，卤素R₃卤素、酰基、芳香烃基、经酯化或酰胺化的羧基、氰基、SO₃H、PO₃H₂、PO₂H₂、5-四唑基、任选取代的氨基磺酰基或酰氨基，或代表-Z₂-R′，其中 Z₂ 代表键或 O、S(O)m 或 N(R)，R′代表氢或脂肪烃基、Z₂ 表示键或 O、S(O)m 或 N(R)，R′表示氢或脂族烃基，其任选被 O 或 S(O)m 间断并任选被卤素、羟基、任选取代的氨基或任选酯化或酰胺化的羧基取代，R₄ 表示脂族烃基，其任选被 O 或 S(O)m 间断并任选被任选酯化或酰胺化的羧基、任选与芳香醇醚化的羟基、任选取代的氨基、S(O)m 或 N(R)取代，以及任选取代的氨基、S(O)m-R 或芳香烃基，或 R₃ 和 R₄ 共同代表亚烷基，其中 R 在每种情况下代表氢或脂肪烃基，而 m 在每种情况下代表 0、1 或 2。
• Synthesis and angiotensin II receptor antagonist activity of C-linked pyrimidine derivatives
  作者：E Nicolaï、G Curé、J Goyard、M Kirchner、JM Teulon、A Versigny、M Cazes、A Virone-Oddos、F Caussade、A Cloarec

  DOI：10.1016/0223-5234(96)88246-8

  日期：1995.1

  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).