4'-<(6-butyl-1,4-dihydro-2-methyl-4-oxo-5-pyrimidinyl)methyl><1,1'-biphenyl>-2-carbonitrile | 135689-65-5

• 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'-<(6-butyl-1,4-dihydro-2-methyl-4-oxo-5-pyrimidinyl)methyl><1,1'-biphenyl>-2-carbonitrile
• 英文别名: 4'-[(4-butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile；4'-[(4-butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]-[1,1'-biphenyl]-2-carbonitrile；4'-[(4-Butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile；2-[4-[(4-butyl-2-methyl-6-oxo-1H-pyrimidin-5-yl)methyl]phenyl]benzonitrile
• CAS: 135689-65-5
• 化学式: C₂₃H₂₃N₃O
• 分子量: 357.455
• InChiKey: BLYSKSPZMKMURZ-UHFFFAOYSA-N

物化性质

• 沸点：
  556.0±60.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  65.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4'-<(6-butyl-1,4-dihydro-2-methyl-4-oxo-5-pyrimidinyl)methyl><1,1'-biphenyl>-2-carbonitrile 在 sodium methylate 、 三氯氧磷 作用下， 反应 11.0h， 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：

  2-氰基-4'-溴甲基联苯 在 sodium methylate 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 38.25h， 生成 4'-<(6-butyl-1,4-dihydro-2-methyl-4-oxo-5-pyrimidinyl)methyl><1,1'-biphenyl>-2-carbonitrile
  参考文献：
  名称：

  新型三唑并嘧啶衍生物作为有效的口服活性血管紧张素II受体拮抗剂的合成和SAR研究。

  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[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

  DOI：

  10.1021/jm00041a016

文献信息

• N-3-Substituted Pyrimidinones as Potent, Orally Active, AT1 Selective Angiotensin II Receptor Antagonists
  作者：Aldo Salimbeni、Renato Canevotti、Fabio Paleari、Davide Poma、Saturnino Caliari、Francesco Fici、Rocco Cirillo、Anna R. Renzetti、Alessandro Subissi

  DOI：10.1021/jm00024a008

  日期：1995.11

  A novel series of nonpeptide angiotensin II (A II) antagonists containing a pyrimidinone ring which carries a C-linked biphenyltetrazole moiety and a carboxyheteroaryl group on the 3-position have been prepared. Their affinity for the AT1 receptor was determined in a binding assay on rat adrenal cortical membranes. The in vivo antihypertensive properties were tested by evaluating the inhibition of

  制备了一系列新的非肽血管紧张素II（A II）拮抗剂，该拮抗剂包含嘧啶酮环，该嘧啶酮环在3位上带有C连接的联苯四唑部分和羧基杂芳基。通过对大鼠肾上腺皮质膜的结合试验确定它们对AT1受体的亲和力。通过评估对A II的升压反应的抑制，然后进行静脉和内服给药，来测试体内的抗高血压特性。与其他已知的A II拮抗剂（例如DUP）相比，广泛的分子建模研究（包括分子静电势分布的比较，构象分析和A II计算药效团模型上的覆盖物）用于评估新化合物的结构参数。 -753和SK＆F 108566）。根据建模研究，在嘧啶酮环的3-位引入（羧基杂芳基）甲基部分导致衍生物的效力增加。甲基2-[[[4-丁基-2-甲基-6-氧代-5-] [[2'-（1H-四唑-5-基）] [1,1'-联苯] -4-基]甲基] -1 -（6H）-嘧啶基]甲基] -3-噻吩羧酸酯（3k，LR-B / 081），是该系列中最有效的化合物之一（Ki
• COMPOUND CONTAINING A NOVEL 4-ALKOXYPYRIMIDINE STRUCTURE AND MEDICINE CONTAINING SAME
  申请人：Miura Toru

  公开号：US20120322819A1

  公开（公告）日：2012-12-20

  Disclosed is novel compound and medicinal formulation containing same, possessing both angiotensin II receptor blocking and PPARγ activation effect, of use as a medicine for prevention and/or treatment of hypertension, heart disease, angina pectoris, cerebrovascular disorder, cerebral circulatory disturbances, post-ischemic peripheral circulatory damage, renal disease, arteriosclerosis, inflammatory disorder, type 2 diabetes, diabetic complications, insulin resistance syndrome, syndrome X, metabolic syndrome and hyperinsulinaemia. Further disclosed is the general formula I (where one or both of R 1 and R 2 represent a C 1-6 alkyl group, R 3 represents a C 1-6 alkyl group which may contain one or more substituent groups selected from group A, or a C 3-8 cycloalkyl group which may contain one or more substituent groups selected from group B.) which represents the compound, and salts thereof, solvates thereof, and medicinal compositions containing any of these.

  本文披露了一种新型化合物和含有该化合物的药物配方，具有同时具有抗血管紧张素II受体阻断和PPARγ激活作用的特性，可用作预防和/或治疗高血压、心脏病、心绞痛、脑血管疾病、脑循环障碍、缺血后周围循环损伤、肾脏疾病、动脉硬化、炎症性疾病、2型糖尿病、糖尿病并发症、胰岛素抵抗综合征、X综合征、代谢综合征和高胰岛素血症的药物。进一步披露了一般式I（其中R1和/或R2代表C1-6烷基基团，R3代表一个C1-6烷基基团，可以含有从A组中选择的一个或多个取代基，或者一个C3-8环烷基基团，可以含有从B组中选择的一个或多个取代基。）代表该化合物，以及其盐、溶剂化合物和含有这些化合物的药物组成物。
• 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。