methyl 3-<4-(bromomethyl)phenyl>thiophene-2-carboxylate | 154082-05-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: methyl 3-<4-(bromomethyl)phenyl>thiophene-2-carboxylate
• 英文别名: Methyl 3-[4-(bromomethyl)phenyl]thiophene-2-carboxylate
• CAS: 154082-05-0
• 化学式: C₁₃H₁₁BrO₂S
• 分子量: 311.199
• InChiKey: OJEQFBQNIBHDRT-UHFFFAOYSA-N

物化性质

• 沸点：
  394.1±42.0 °C(predicted)
• 密度：
  1.470±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-<4-(bromomethyl)phenyl>thiophene-2-carboxylate 在 sodium hydroxide 、 sodium tetrahydroborate 、 水 、 potassium carbonate 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.5h， 生成 2-butyl-4-chloro-5-(hydroxymetyl)-1-<<1-(2-carboxythien-3-yl)-4-phenyl>methyl>-1H-imidazole
  参考文献：
  名称：

  Nonpeptide Angiotensin II Receptor Antagonists. Synthesis, in vitro Activity, and Molecular Modeling Studies of N-[(Heterobiaryl)methyl]imidazoles

  摘要：

  With the aim of explaining the influence of the structural changes on the biphenylic moiety on the activity, a series of N-[(heterobiaryl)methyl]imidazoles (I), constructed on the model of DuPont compounds by replacing either the central or terminal phenyl ring with a heteroaromatic one, such as furan, thiophene, thiazole, and pyridine, was synthesized. Compared to the reference DuPont compound (EXP-7711), all the heterobiaryl derivatives showed a reduced potency both in receptor binding (rat adrenal capsular membranes) and in the functional assay (angiotensin II-induced contraction of rabbit aorta strips). The lower activity was justified by the extensive molecular modeling studies, which took into consideration the conformational and electrostatic features of several heterobiaryl derivatives. On the basis of the results obtained, it was hypothesized that the central aromatic ring of the biarylic portion works as a spacer, orienting in the right way the terminal phenyl ring, whose electronic distribution is, instead, crucial to its fitting well with a lipophilic pocket at the receptor site.

  DOI：

  10.1021/jm00049a012
• 作为产物：
  描述：

  3-碘噻吩-2-羧酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 bis(triphenylphosphine)nickel(II) chloride 、 叔丁基锂 、 zinc(II) chloride 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 反应 3.0h， 生成 methyl 3-<4-(bromomethyl)phenyl>thiophene-2-carboxylate
  参考文献：
  名称：

  Nonpeptide Angiotensin II Receptor Antagonists. Synthesis, in vitro Activity, and Molecular Modeling Studies of N-[(Heterobiaryl)methyl]imidazoles

  摘要：

  With the aim of explaining the influence of the structural changes on the biphenylic moiety on the activity, a series of N-[(heterobiaryl)methyl]imidazoles (I), constructed on the model of DuPont compounds by replacing either the central or terminal phenyl ring with a heteroaromatic one, such as furan, thiophene, thiazole, and pyridine, was synthesized. Compared to the reference DuPont compound (EXP-7711), all the heterobiaryl derivatives showed a reduced potency both in receptor binding (rat adrenal capsular membranes) and in the functional assay (angiotensin II-induced contraction of rabbit aorta strips). The lower activity was justified by the extensive molecular modeling studies, which took into consideration the conformational and electrostatic features of several heterobiaryl derivatives. On the basis of the results obtained, it was hypothesized that the central aromatic ring of the biarylic portion works as a spacer, orienting in the right way the terminal phenyl ring, whose electronic distribution is, instead, crucial to its fitting well with a lipophilic pocket at the receptor site.

  DOI：

  10.1021/jm00049a012

文献信息

• Imidazopyridinderivate als Angiotensin II Antagonisten
  申请人：MERCK PATENT GmbH

  公开号：EP0595151A2

  公开（公告）日：1994-05-04

  Neue Imidazopyridinderivate der Formel I worin R bedeutet und X, -Y=Z-, R1, R2, R3, R4 und R5 die in Patentanspruch 1 angegebenen Bedeutungen haben, sowie deren Salze zeigen Angiotensin II-antagonistische Eigenschaften und können zur Behandlung von Hypertension, Aldosteronismus, Herzinsuffizienz und erhöhtem Augeninnendruck sowie von Störungen des Zentralnervensystems verwendet werden.

  式 I 的新咪唑吡啶衍生物 其中 R 和 X、-Y=Z-、R1、R2、R3、R4 和 R5 具有权利要求 1 中给出的含义，它们的盐类具有血管紧张素 II 拮抗特性，可用于治疗高血压、醛固酮增多症、心功能不全、眼内压增高以及中枢神经系统疾病。
• IMIDAZOLE ETHERS HAVING A II ANTAGONIST ACTIVITY
  申请人：INSTITUTO LUSO FARMACO D'ITALIA S.p.a.

  公开号：EP0652869A1

  公开（公告）日：1995-05-17
• US5405964A
  申请人：——

  公开号：US5405964A

  公开（公告）日：1995-04-11
• [EN] IMIDAZOLE ETHERS HAVING A II ANTAGONIST ACTIVITY<br/>[FR] ETHERS DE L'IMIDAZOLE AYANT UNE ACTIVITE ANTAGONISTE DES RECEPTEURS A L'ANGIOTENSINE II
  申请人：INSTITUTO LUSO FARMACO D'ITALIA S.P.A.

  公开号：WO1994002467A1

  公开（公告）日：1994-02-03

  (EN) Compounds of general formula (I), the processes for the preparation and the use thereof as therapeutical agents. The described compounds have A II antagonist properties and they can be used in various cardiovascular disorders.(FR) L'invention concerne les composés ayant la formule générale (I), les procédés pour leur préparation et leur utilisation comme agents thérapeutiques. Les composés décrits ont une activité antagoniste de l'angiotensine II et ils peuvent être utilisés pour traiter différents troubles cardiovasculaires.
• Nonpeptide Angiotensin II Receptor Antagonists. Synthesis, in vitro Activity, and Molecular Modeling Studies of N-[(Heterobiaryl)methyl]imidazoles
  作者：Aldo Salimbeni、Renato Canevotti、Fabio Paleari、Fabrizio Bonaccorsi、Anna R. Renzetti、Laura Belvisi、Gianpaolo Bravi、Carlo Scolastico

  DOI：10.1021/jm00049a012

  日期：1994.11

  With the aim of explaining the influence of the structural changes on the biphenylic moiety on the activity, a series of N-[(heterobiaryl)methyl]imidazoles (I), constructed on the model of DuPont compounds by replacing either the central or terminal phenyl ring with a heteroaromatic one, such as furan, thiophene, thiazole, and pyridine, was synthesized. Compared to the reference DuPont compound (EXP-7711), all the heterobiaryl derivatives showed a reduced potency both in receptor binding (rat adrenal capsular membranes) and in the functional assay (angiotensin II-induced contraction of rabbit aorta strips). The lower activity was justified by the extensive molecular modeling studies, which took into consideration the conformational and electrostatic features of several heterobiaryl derivatives. On the basis of the results obtained, it was hypothesized that the central aromatic ring of the biarylic portion works as a spacer, orienting in the right way the terminal phenyl ring, whose electronic distribution is, instead, crucial to its fitting well with a lipophilic pocket at the receptor site.