methyl 2-<2-(bromomethyl)thien-5-yl>benzoate | 159448-40-5

• 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: methyl 2-<2-(bromomethyl)thien-5-yl>benzoate
• 英文别名: 2-Bromomethyl-5-(2-methoxycarbonylphenyl)thiophene；Methyl 2-[5-(bromomethyl)thiophen-2-yl]benzoate
• CAS: 159448-40-5
• 化学式: C₁₃H₁₁BrO₂S
• 分子量: 311.199
• InChiKey: OHAKPOICYGETMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 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 2-<2-(bromomethyl)thien-5-yl>benzoate 在 sodium hydroxide 、 水 、 sodium hydride 作用下， 以 甲醇 为溶剂， 反应 20.0h， 生成 2-butyl-4-chloro-5-(hydroxymetyl)-1-<<5-(2-carboxyphenyl)thien-2-yl>-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：

  2-甲基噻吩 在 N-溴代丁二酰亚胺(NBS) 、 bis(triphenylphosphine)nickel(II) chloride 、 正丁基锂 、 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 2-<2-(bromomethyl)thien-5-yl>benzoate
  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

• Imidazole ethers having a II antagonist activity
  申请人：Istituto Luso Farmaco D'Italia S.p.A.

  公开号：US05538987A1

  公开（公告）日：1996-07-23

  Compounds of general formula (I) ##STR1## wherein E is O or S; R is C.sub.1 -C.sub.5 straight, branched or cyclic alkyl or C.sub.2 -C.sub.5 alkenyl; X can be H, F, Cl, Br, I, CF.sub.3 ; n is an integer 1 to 4; m is an integer 0 to 4; A and B are 5- or 6- membered aromatic carbocyclic rings optionally containing one or more heteroatoms selected from N, O, S and carrying the substituents R.sub.1, R.sub.2 and R.sub.3, respectively; R.sub.1 can be hydrogen, halogen, C.sub.1 -C.sub.4 alkoxycarbonyl, a sulfonic group or a tetrazole group of formula ##STR2## wherein R.sub.4 can be hydrogen or C.sub.1 -C.sub.5 alkyl; R.sub.2 can be hydrogen or a COOR.sub.4 group (wherein R.sub.4 is hydrogen or C.sub.1 -C.sub.5 alkyl), CN, SO.sub.3 H, PO.sub.3 H or a tetrazole group R.sub.3 ; can be a hydrogen or a moiety of formula (II) B'(R'.sub.2,R'.sub.3) (II) wherein: B.sup.1, R.sup.1.sub.2 have the same meanings reported above for B and R.sub.2, R'.sub.3 is H; with the proviso that when A is phenyl, R.sub.1 is different from H, and the pharmaceutically acceptable salts thereof.

  通式（I）的化合物##STR1##其中E为O或S；R为C.sub.1-C.sub.5直链、支链或环烷基或C.sub.2-C.sub.5烯基；X可以是H、F、Cl、Br、I、CF.sub.3；n为1到4的整数；m为0到4的整数；A和B为5-或6-成员芳香碳环，可选地含有来自N、O、S的一个或多个杂原子，并携带取代基R.sub.1、R.sub.2和R.sub.3，分别；R.sub.1可以是氢、卤素、C.sub.1-C.sub.4烷氧羰基、磺酰基或式的四唑基团##STR2##其中R.sub.4可以是氢或C.sub.1-C.sub.5烷基；R.sub.2可以是氢或COOR.sub.4基团（其中R.sub.4为氢或C.sub.1-C.sub.5烷基）、CN、SO.sub.3 H、PO.sub.3 H或四唑基团R.sub.3；可以是氢或式的一个基团（II）B'(R'.sub.2,R'.sub.3)（II）其中：B.sup.1，R.sup.1.sub.2具有上述B和R.sub.2的相同含义，R'.sub.3为H；但条件是当A为苯时，R.sub.1不同于H，及其药学上可接受的盐。
• 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
• US5538987A
  申请人：——

  公开号：US5538987A

  公开（公告）日：1996-07-23
• [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.