7-溴苯并[B]噻吩-2-羧酸乙酯 | 1355171-39-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 中文名称: 7-溴苯并[B]噻吩-2-羧酸乙酯
• 英文名称: ethyl 7-bromobenzo[b]thiophene-2-carboxylate
• 英文别名: Ethyl 7-bromo-1-benzothiophene-2-carboxylate；ethyl 7-bromo-1-benzothiophene-2-carboxylate
• CAS: 1355171-39-9
• 化学式: C₁₁H₉BrO₂S
• 分子量: 285.161
• InChiKey: QMDPVCJTYPUFDS-UHFFFAOYSA-N

物化性质

• 沸点：
  370.3±22.0 °C(Predicted)
• 密度：
  1.553±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H312,H315,H319,H332,H335
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  7-溴苯并[B]噻吩-2-羧酸乙酯 在 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以90%的产率得到7-溴-1-苯并噻吩-2-羧酸
  参考文献：
  名称：

  A Novel α2/α4 Subtype-selective Positive Allosteric Modulator of Nicotinic Acetylcholine Receptors Acting from the C-tail of an α Subunit

  摘要：

  Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChR) are important therapeutic candidates as well as valuable research tools. We identified a novel type II PAM, (R)-7-bromo-N-(piperidin-3-yl)benzo[b]thiophene-2-carboxamide (Br-PBTC), which both increases activation and reactivates desensitized nAChRs. This compound increases acetylcholine-evoked responses of 2* and 4* nAChRs but is without effect on 3* or 6* nAChRs (* indicates the presence of other nAChR subunits). Br-BPTC acts from the C-terminal extracellular sequences of 4 subunits, which is also a PAM site for steroid hormone estrogens such as 17-estradiol. Br-PBTC is much more potent than estrogens. Like 17-estradiol, the non-steroid Br-PBTC only requires one 4 subunit to potentiate nAChR function, and its potentiation is stronger with more 4 subunits. This feature enables Br-BPTC to potentiate activation of (42)(62)3 but not (62)(2)3 nAChRs. Therefore, this compound is potentially useful in vivo for determining functions of different 6* nAChR subtypes. Besides activation, Br-BPTC affects desensitization of nAChRs induced by sustained exposure to agonists. After minutes of exposure to agonists, Br-PBTC reactivated short term desensitized nAChRs that have at least two 4 subunits but not those with only one. Three 4 subunits were required for Br-BPTC to reactivate long term desensitized nAChRs. These data suggest that higher PAM occupancy promotes channel opening more efficiently and overcomes short and long term desensitization. This C-terminal extracellular domain could be a target for developing subtype or state-selective drugs for nAChRs.

  DOI：

  10.1074/jbc.m115.676551
• 作为产物：
  描述：

  3-溴-2-氟苯甲醛 、 巯基乙酸乙酯 在 三乙胺 作用下， 以 乙腈 为溶剂， 以95%的产率得到7-溴苯并[B]噻吩-2-羧酸乙酯
  参考文献：
  名称：

  A Novel α2/α4 Subtype-selective Positive Allosteric Modulator of Nicotinic Acetylcholine Receptors Acting from the C-tail of an α Subunit

  摘要：

  Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChR) are important therapeutic candidates as well as valuable research tools. We identified a novel type II PAM, (R)-7-bromo-N-(piperidin-3-yl)benzo[b]thiophene-2-carboxamide (Br-PBTC), which both increases activation and reactivates desensitized nAChRs. This compound increases acetylcholine-evoked responses of 2* and 4* nAChRs but is without effect on 3* or 6* nAChRs (* indicates the presence of other nAChR subunits). Br-BPTC acts from the C-terminal extracellular sequences of 4 subunits, which is also a PAM site for steroid hormone estrogens such as 17-estradiol. Br-PBTC is much more potent than estrogens. Like 17-estradiol, the non-steroid Br-PBTC only requires one 4 subunit to potentiate nAChR function, and its potentiation is stronger with more 4 subunits. This feature enables Br-BPTC to potentiate activation of (42)(62)3 but not (62)(2)3 nAChRs. Therefore, this compound is potentially useful in vivo for determining functions of different 6* nAChR subtypes. Besides activation, Br-BPTC affects desensitization of nAChRs induced by sustained exposure to agonists. After minutes of exposure to agonists, Br-PBTC reactivated short term desensitized nAChRs that have at least two 4 subunits but not those with only one. Three 4 subunits were required for Br-BPTC to reactivate long term desensitized nAChRs. These data suggest that higher PAM occupancy promotes channel opening more efficiently and overcomes short and long term desensitization. This C-terminal extracellular domain could be a target for developing subtype or state-selective drugs for nAChRs.

  DOI：

  10.1074/jbc.m115.676551

文献信息

• [EN] MODULATORS FOR NICOTINIC ACETYLCHOLINE RECEPTOR α2 AND α4 SUBUNITS<br/>[FR] MODULATEURS POUR LES SOUS-UNITÉS Α2 ET Α4 DE RÉCEPTEUR NICOTINIQUE DE L'ACÉTYLCHOLINE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2016191366A1

  公开（公告）日：2016-12-01

  Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChR) are important therapeutic candidates as well as valuable research tools. We identified a novel type II PAM, (R)-7-bromo-N-(piperidin-3-yl)benzo[b]thiophene-2-carboxamide (Br-PBTC), which both increases activation and reactivates desensitized nAChRs. This compound increases acetylcholine-evoked responses of α2* and α4* nAChRs, but is without effect on α3* or α6* nAChRs ("*" indicates presence of other nAChR subunits). Br-BPTC binds to the C-terminal extracellular sequences of a4 subunits, which is also a PAM site for steroid hormone estrogens such as 17-β estradiol. Br-PBTC is much more potent than estrogens. Like 17-P-estradiol, the non-steroid Br-PBTC only requires one α4 subunit to potentiate nAChR function, and its potentiation is stronger with more a4 subunits. This feature enables Br-BPTC to potentiate activation of (α4β2)(α6β2)β3 but not (α6β2)2β3 nAChRs. Various bioactive analogs of Br-PBTC are provided.

  正向变构调节剂（PAMs）对尼古丁乙酰胆碱受体（nAChR）是重要的治疗候选药物，同时也是有价值的研究工具。我们发现了一种新型II型PAM，(R)-7-溴-N-(哌啶-3-基)苯并[b]噻吩-2-甲酰胺（Br-PBTC），它既增加了激活，又重新激活了脱敏的nAChRs。这种化合物增加了α2*和α4* nAChRs对乙酰胆碱的响应，但对α3*或α6* nAChRs没有影响（"*"表示存在其他nAChR亚基）。Br-BPTC结合到α4亚基的C端外胞外序列，这也是类固醇激素雌激素如17-β雌二醇的PAM位点。Br-PBTC比雌激素更有效。与17-β雌二醇一样，非类固醇Br-PBTC只需要一个α4亚基来增强nAChR功能，并且随着更多的α4亚基，其增强作用更强。这个特性使Br-BPTC能够增强(α4β2)(α6β2)β3而不是(α6β2)2β3 nAChRs的激活。提供了各种生物活性类似物的Br-PBTC。
• WO2023/125376
  申请人：——

  公开号：——

  公开（公告）日：——
• A Novel α2/α4 Subtype-selective Positive Allosteric Modulator of Nicotinic Acetylcholine Receptors Acting from the C-tail of an α Subunit
  作者：Jingyi Wang、Alexander Kuryatov、Zhuang Jin、Jack Norleans、Theodore M. Kamenecka、Paul J. Kenny、Jon Lindstrom

  DOI：10.1074/jbc.m115.676551

  日期：2015.11

  Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChR) are important therapeutic candidates as well as valuable research tools. We identified a novel type II PAM, (R)-7-bromo-N-(piperidin-3-yl)benzo[b]thiophene-2-carboxamide (Br-PBTC), which both increases activation and reactivates desensitized nAChRs. This compound increases acetylcholine-evoked responses of 2* and 4* nAChRs but is without effect on 3* or 6* nAChRs (* indicates the presence of other nAChR subunits). Br-BPTC acts from the C-terminal extracellular sequences of 4 subunits, which is also a PAM site for steroid hormone estrogens such as 17-estradiol. Br-PBTC is much more potent than estrogens. Like 17-estradiol, the non-steroid Br-PBTC only requires one 4 subunit to potentiate nAChR function, and its potentiation is stronger with more 4 subunits. This feature enables Br-BPTC to potentiate activation of (42)(62)3 but not (62)(2)3 nAChRs. Therefore, this compound is potentially useful in vivo for determining functions of different 6* nAChR subtypes. Besides activation, Br-BPTC affects desensitization of nAChRs induced by sustained exposure to agonists. After minutes of exposure to agonists, Br-PBTC reactivated short term desensitized nAChRs that have at least two 4 subunits but not those with only one. Three 4 subunits were required for Br-BPTC to reactivate long term desensitized nAChRs. These data suggest that higher PAM occupancy promotes channel opening more efficiently and overcomes short and long term desensitization. This C-terminal extracellular domain could be a target for developing subtype or state-selective drugs for nAChRs.