ethyl 2-butyl-4-chloro-1H-imidazole-5-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 2-butyl-4-chloro-1H-imidazole-5-carboxylate
• 英文别名: 2-n-butyl-5-chloro-3H-imidazole-4-carboxylic acid ethyl ester；2-butyl-5-chloro-1H-imidazole-4-carboxylic acid ethyl ester；ethyl 2-butyl-5-chloro-1H-imidazole-4-carboxylate
• 化学式: C₁₀H₁₅ClN₂O₂
• 分子量: 230.694
• InChiKey: HITYWIGPZZXDSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 2-butyl-4-chloro-1H-imidazole-5-carboxylate 在 三苯基膦 、 sodium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 水 为溶剂， 反应 14.5h， 生成 2-n-butyl-5-chloro-3H-imidazole-4-carboxylic acid 3-(3,4-bisbenzyloxyphenyl)propyl ester
  参考文献：
  名称：

  New losartan-hydrocaffeic acid hybrids as antihypertensive-antioxidant dual drugs: Ester, amide and amine linkers

  摘要：

  We report new examples of a series of losartan-hydrocaffeic hybrids that bear novel ester, amide and amine linkers. These compounds were made by linking hydrocaffeic acid to the side chain of losartan at the C-5 position of the imidazole ring through different strategies. Experiments performed in cultured cells demonstrate that these new hybrids retain the ability to block the angiotensin II effect and have increased antioxidant ability. Most of them reduced arterial pressure in rats better or as much as losartan. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.043
• 作为产物：
  描述：

  乙醇 、 咪唑醛 在 sodium cyanide 、 manganese(IV) oxide 、 溶剂黄146 作用下， 以70%的产率得到ethyl 2-butyl-4-chloro-1H-imidazole-5-carboxylate
  参考文献：
  名称：

  血管紧张素II受体及内皮素受体双重拮抗剂

  摘要：

  本公开涉及血管紧张素II受体及内皮素受体双重拮抗剂。具体而言，本公开提供了式I所示化合物及其制备方法。该化合物可用于治疗高血压或肾病等疾病。

  公开号：

  CN112876424A

文献信息

• Novel Angiotensin II Receptor Antagonists. Design, Synthesis, and in Vitro Evaluation of Dibenzo[a,d]cycloheptene and Dibenzo[b,f]oxepin Derivatives. Searching for Bioisosteres of Biphenyltetrazole Using a Three-Dimensional Search Technique
  作者：Ryuichi Kiyama、Tsunetoshi Honma、Kunio Hayashi、Masayoshi Ogawa、Mariko Hara、Masafumi Fujimoto、Toshio Fujishita

  DOI：10.1021/jm00014a024

  日期：1995.7

  Three-dimensional substructure searching (3D search), using the program MACCS-3D, was utilized for designing novel angiotensin II receptor antagonists which contain a bioisostere of the biphenylyltetrazole moiety of DuP 753. A 3D query was prepared from an overlay model of substructures of several potent AII antagonists. The search system retrieved 139 compounds from the database MDDR-3D, which consisted

  使用程序MACCS-3D进行三维子结构搜索（3D搜索），用于设计新型血管紧张素II受体拮抗剂，该拮抗剂包含DuP 753的联苯甲酰四唑部分的生物等排体。从3D子结构的覆盖模型制备3D查询几种有效的AII拮抗剂。该搜索系统从数据库MDDR-3D中检索了139种化合物，其中包括29,400种药用专利化合物。从检索到的化合物中选择三环化合物，然后考虑对覆盖模型的空间适应性和合成可行性进行进化。最后，设计并合成了具有二苯并[a，d]环庚烯或二苯并[b，f] oxepin的各种新型AII拮抗剂。该系列几个成员的受体结合活性（Ki）在10（-10）M范围内，
• 로잘탄 대사체 EXP-3174의 제조방법
  申请人：DAEJEON UNIVERSITY Industry-University Cooperation Foundation 대전대학교 산학협력단(120080024434) Corp. No ▼ 160171-0004131BRN ▼305-82-13385

  公开号：KR20200082424A

  公开（公告）日：2020-07-08

  본 발명은 저렴한 출발물질을 사용하고, 온화한 반응조건에서, 고순도 및 고수율로 로잘탄 대사체 EXP-3174를 제조할 수 있는 제조 방법을 제공한다.

  本发明提供了一种制备EXP-3174洛塞那坦代谢物的方法，该方法使用廉价的起始物质，在温和的反应条件下，可以高纯度和高收率地制备EXP-3174洛塞那坦代谢物。
• Angiotensin II receptor antagonists
  申请人：Pfizer Inc.

  公开号：US05338740A1

  公开（公告）日：1994-08-16

  The present invention relates to novel heterocyclic derivatives of the formula Ar--W--Het wherein Ar, W and Het are as defined below, and related compounds, pharmaceutical compositions comprising such compounds, and the use of such compounds as regulators of the action of angiotensin II in mammals. The compounds of this invention are useful in the treatment and prevention of hypertension, glaucoma, renal disease, congestive heart failure, cognitive dysfunction, and other conditions in which the action of angiotensin II is implicated. This invention also relates to pharmaceutical compositions containing these compounds and to methods of inhibiting angiotensin II in mammals by administration of such compounds.

  本发明涉及公式Ar-W-Het的新型杂环衍生物，其中Ar，W和Het如下所定义，以及相关化合物、包含这些化合物的制药组合物，以及将这些化合物用作哺乳动物中肾素-血管紧张素系统（RAAS）的调节剂的用途。本发明的化合物在治疗和预防高血压、青光眼、肾脏疾病、充血性心力衰竭、认知功能障碍和其他涉及肾素-血管紧张素系统的疾病中具有用途。本发明还涉及包含这些化合物的制药组合物以及通过给予这些化合物来抑制哺乳动物中肾素-血管紧张素系统的方法。
• Azacyclic-heterocyclic compounds as angiotension II receptor antagonists
  申请人：Pfizer Inc.

  公开号：US05789415A1

  公开（公告）日：1998-08-04

  Compounds of the formula ##STR1## wherein: Q is naphthyl, heterocyclic or heterobicyclic; R.sup.1 and R.sup.2, when taken separately, are hydrogen, hydroxy, alkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenyl, heterocyclic or heterobicyclic; R.sup.1 and R.sup.2, when taken together, form a carbocyclic, carbobicyclic, heterocyclic or heterobicyclic group; R.sup.3 is --(CH.sub.2).sub.n COR.sup.4, tetrazolyl, alkyltetrazolyl, triazolyl, alkyltriazolyl, --(CH.sub.2).sub.n CH.sub.2 OH, --SO.sub.2 R.sup.4, --SO.sub.2 NR.sup.5 R.sup.6 or --NHSO.sub.2 R.sup.7 ; R.sup.4 is hydrogen, hydroxy, --NR.sup.5 R.sup.6, --NHSO.sub.2 R.sup.7, alkoxy, alkylthio, --NR.sup.5 R.sup.6, --NHSO.sub.2 R.sup.7 or --OY; n is 0 to 5; Y is a pharmaceutically acceptable cation or a group hydrolyzable under physiological conditions; R.sup.5 and R.sup.6, when taken separately, are hydrogen, alkyl, --CONRR, --COOR or --CO(C.sub.6 H.sub.5); R.sup.5 and R.sup.6, when taken together, form an azacyclic ring; R.sup.7 is alkyl or phenyl; each R is hydrogen or alkyl and X is an azacyclic or azabicyclic group, inhibit angiotensin II in mammals and are useful in treating conditions such as hypertension, congestive heart failure and glaucoma and as the active ingredient in pharmaceutical compositions for treating such conditions.

  化合物的式子为##STR1##其中：Q是萘基，杂环或杂双环基；R1和R2，当单独取时，是氢，羟基，烷基，烷基硫，烷基亚磺酰，烷基磺酰，苯基，杂环或杂双环基；当R1和R2一起取时，形成一个碳环，碳双环，杂环或杂双环基；R3是--(CH2)nCOR4，四唑基，烷基四唑基，三唑基，烷基三唑基，--( )n OH，--SO2R4，--SO2NR5R6或--NHSO2R7；R4是氢，羟基，--NR5R6，--NHSO2R7，烷氧基，烷基硫，--NR5R6，--NHSO2R7或--OY；n为0至5；Y是药物可接受的阳离子或在生理条件下可水解的基团；当R5和R6单独取时，是氢，烷基，--CONRR，--COOR或--CO（C6H5）；当R5和R6一起取时，形成一个氮杂环；R7是烷基或苯基；每个R是氢或烷基，X是氮杂环或氮杂双环基，在哺乳动物中抑制血管紧张素II，对治疗高血压，充血性心力衰竭和青光眼等疾病有用，并作为治疗这些疾病的药物组成部分的有效成分。
• Indole derivatives
  申请人：GLAXO GROUP LIMITED

  公开号：EP0429257A2

  公开（公告）日：1991-05-29

  The invention provides compounds of the general formula (I): or a physiologically acceptable salt or a solvate (e.g. hydrates) thereof in which R¹ represents a hydrogen atom or a halogen atom or a group selected from C₁₋₆ alkyl, C₂₋₆ alkenyl, fluoroC₁₋₆alkyl, -CHO, -CO₂H or -COR⁴; R² represents a hydrogen atom or a halogen atom or the group Ar; R³ represents a hydrogen atom or a group selected from C₁₋₆ alkyl, C₃₋₆alkenyl, C₁₋₆alkoxy, -COR⁴, -SO₂R⁴ or the group Ar; R⁴ represents a group selected from C₁₋₆ alkyl, C₂₋₆ alkenyl, C₁₋₆ alkoxy or the group -NR¹²R¹³; Ar represents the group R⁵ represents a group selected from -CO₂H, -NHSO₂CF₃ or a C-linked tetrazolyl group; R⁶ and R⁷ which may be the same or different each independently represent a hydrogen atom or a halogen atom or a C₁₋₆alkyl group; Het represents an N-linked imidazolyl group substituted at the 2-position by a C₁₋₆alkyl, C₂₋₆alkenyl or a C₁₋₆alkylthio group, the imidazolyl group optionally being substituted by one or two further substituents selected from a halogen atom or a group selected from cyano, nitro, C₁₋₆alkyl, C₂₋₆alkenyl, fluoroC₁₋₆alkyl, -(CH₂)mR⁸, -(CH₂)nCOR⁹, or -(CH₂)pNR¹⁰COR¹¹; or Het represents an N-linked benzimidazolyl group substituted at the 2-position by a C₁₋₆alkyl, C₂₋₆alkenyl or a C₁₋₆alkylthio group; R⁸ represents a hydroxy or C₁₋₆alkoxy group; R⁹ represents a hydrogen atom or a group selected from hydroxy, C₁₋₆alkyl, C₁₋₆alkoxy, phenyl, phenoxy or the group -NR¹²R¹³; R¹⁰ represents a hydrogen atom or a C₁₋₆alkyl group; R¹¹ represents a hydrogen atom or a group selected from C₁₋₆alkyl, C₁₋₆alkoxy, phenyl, phenoxy or the group -NR¹²R¹³; R¹² and R¹³ which may be the same or different each independently represent a hydrogen atom or a C₁₋₄alkyl group or -NR¹²R¹³ forms a saturated heterocyclic ring which has 5 or 6 ring members and may optionally contain in the ring one oxygen atom; m represents an integer from 1 to 4; n represents an integer from 0 to 4; and p represents an integer from 1 to 4; provided that one of R² and R³ represents the group Ar, and that when R² represents the group Ar, R³ represents a hydrogen atom or a group selected from C₁₋₆ alkyl, C₃₋₆ alkenyl, C₁₋₆alkoxy -COR⁴ or -SO₂R⁴, and that when R³ represents the group Ar, R² represents a hydrogen atom or a halogen atom. The compounds may be used in the treatment or prophylaxis of hypertension and diseases associated with cognitive disorders.

  本发明提供通式 (I) 的化合物： 或其生理上可接受的盐或溶液（如水合物），其中 R¹ 代表氢原子或卤原子或选自 C₁₋₆ 烷基、C₂₋₆ 烯基、芴基、-CHO、-CO₂H 或 -COR⁴ 的基团； R² 代表氢原子、卤素原子或基团 Ar； R³ 代表氢原子或选自 C₁₋₆83↩₋₆ 烷基、C₁₋₆烷氧基、-COR⁴、-SO₂R⁴ 或基团 Ar 的基团； R⁴ 代表选自 C₁₋₆ 烷基、C₂₋₆ 烯基、C₁₋₆ 烷氧基或基团 -NR¹²R¹³ 的基团； Ar 代表以下基团 R⁵ 代表选自 -CO₂H、-NHSO₂CF₃ 或 C-链锁四唑基的基团； R⁶ 和 R⁷ 可以相同或不同，各自独立地代表氢原子、卤素原子或 C₁₋₆ 烷基； Het 代表在 2 位被 C₁₋₆烷基、C₂₋₆烯基或 C₁₋₆ 烷硫基取代的 N-连接的咪唑基、咪唑基可任选被一个或两个取代基取代，这两个取代基可选自卤素原子或选自氰基、硝基、C烷基硫代、C烷基硫代、C烷基硫代或C烷基硫代的基团、硝基、C₂₋₆烷基、芴基、-(CH₂)mR⁸、-(CH₂)nCOR⁹或-(CH₂)pNR¹⁰COR¹； 或 Het 代表在 2 位被 C₁₋₆烷基、C₂₋₆烯基或 C₁₋₆ 烷硫基取代的 N-连接的苯并咪唑基团； R⁸ 代表羟基或 C₁₋₆ 烷氧基； R⁹ 代表氢原子或选自羟基、C₁₋₆烷基、C₁₋₆烷氧基、苯基、苯氧基或基团 -NR¹²R¹³ 的基团； R¹⁰ 代表氢原子或 C₁₋₆ 烷基； R¹¹ 代表氢原子或选自 C₁₋₆烷基、C₁₋₆烷氧基、苯基、苯氧基或基团 -NR¹²R¹³ 的基团； R¹² 和 R¹³ 可以相同或不同，各自独立地代表氢原子或 C₁₋₄烷基或 -NR¹²R¹³ 形成饱和杂环，该杂环有 5 或 6 个环成员，环中可选择包含一个氧原子； m 代表 1 至 4 的整数； n 代表 0 至 4 的整数；以及 p 代表 1 至 4 的整数； 条件是 R² 和 R³ 中的一个代表基团 Ar，且当 R² 代表基团 Ar 时，R³ 代表氢原子或选自 C₁₋₆ 烷基的基团、C₃₋₆烯基、C₁₋₆烷氧基-COR⁴或-SO₂R⁴，当 R³ 代表基团 Ar 时，R² 代表氢原子或卤素原子。 这些化合物可用于治疗或预防高血压和与认知障碍有关的疾病。