2,2’-(4-溴-1-亚丁烯基)双[3-甲基噻吩] | 109857-81-0

• 物质功能分类: 医药中间体 - 杂环化合物 - 噻吩类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 中文名称: 2,2’-(4-溴-1-亚丁烯基)双[3-甲基噻吩]
• 中文别名: 4-溴-1,1-双(3-甲基-2-噻吩)-1-丁烯；2,2'-(4-溴-1-亚丁烯基)双[3-甲基噻吩]
• 英文名称: 4,4-bis(3-methyl-thiophen-2-yl)-but-3-en-1-yl bromide
• 英文别名: 4-bromo-1,1-bis(3-methyl-2-thienyl)-1-butene；2,2'-(4-Bromobut-1-ene-1,1-diyl)bis(3-methylthiophene)；2-[4-bromo-1-(3-methylthiophen-2-yl)but-1-enyl]-3-methylthiophene
• CAS: 109857-81-0
• 化学式: C₁₄H₁₅BrS₂
• 分子量: 327.309
• InChiKey: KRXSGXVUQKRSCK-UHFFFAOYSA-N

物化性质

• 密度：
  1.374

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  2,2’-(4-溴-1-亚丁烯基)双[3-甲基噻吩] 在 sodium hydroxide 、 potassium carbonate 、 potassium iodide 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 48.0h， 生成 噻加宾
  参考文献：
  名称：

  The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid (Tiagabine) as an anticonvulsant drug candidate

  摘要：

  A series of different synthetic approaches to novel GABA uptake inhibitors are described, leading to examples which are derivatives of nipecotic acid and guvacine, substituted at nitrogen by 4,4-diaryl-3-butenyl or 2-(diphenylmethoxy)ethyl moieties. The in vitro value for inhibition of [H-3]-GABA uptake in rat synaptosomes was determined for each compound. It was found that the most potent examples are those having a substituent in an ''ortho'' position in one or both aromatic/heteroaromatic groups. The majority of the compounds described are structurally related to tiagabine, (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid hydrochloride (NNC 05-0328) and some of the reasoning behind the selection of this compound as a drug candidate is summarized.

  DOI：

  10.1021/jm00064a005
• 作为产物：
  描述：

  cyclopropylbis(3-methyl-2-thienyl)methanol 以46的产率得到2,2’-(4-溴-1-亚丁烯基)双[3-甲基噻吩]
  参考文献：
  名称：

  N-(butenyl substituted) azaheterocyclic carboxylic acids

  摘要：

  在1-位置具有3-羧基哌啶-1-基，3-羧基四氢吡啶-1-基或3-羧甲基吡咯烷-1-基，并在4-位置上选择性地取代呋喃基，噻吩基，吡啶基和/或吡咯基的1-氨基丁-3-烯衍生物，能够增强GABA能神经递质的传递。

  公开号：

  US05010090A1

文献信息

• Design, synthesis and SAR studies of GABA uptake inhibitors derived from 2-substituted pyrrolidine-2-yl-acetic acids
  作者：Tobias Steffan、Thejavathi Renukappa-Gutke、Georg Höfner、Klaus T. Wanner

  DOI：10.1016/j.bmc.2015.01.035

  日期：2015.3

  design and synthesis of a series of 2-substituted pyrrolidine-2-yl-acetic acid as core structures and the N-arylalkyl derivatives thereof as potential GABA transport inhibitors. The 2-position in the side chain of pyrrolidine-2-yl-acetic acid derivatives was substituted with alkyl, hydroxy and amino groups to modulate the activity and selectivity to mGAT1 and mGAT4 proteins. SAR studies of the compounds

  在本文中，我们公开了一系列2-取代的吡咯烷-2-基-乙酸作为核心结构以及其N-芳基烷基衍生物作为潜在的GABA转运抑制剂的设计和合成。吡咯烷-2-基-乙酸衍生物的侧链中的2位被烷基，羟基和氨基取代，以调节对mGAT1和mGAT4蛋白的活性和选择性。对四种小鼠GABA转运蛋白（mGAT1-mGAT4）进行的化合物的SAR研究表明，对2-羟基-2-吡咯烷-2-基-乙酸衍生物具有显着的效力和亚型选择性。外消旋体rac-（u）-13c的效能最高（pIC 505.67）在GABA吸收试验中对mGAT1的选择性和mGAT1的选择性。实际上，的效力外消旋- （Û） - 13C在hGAT-1（PIC 50 6.14）比其在MGAT1效力更高。这些摄取结果外消旋- （Û） - 13C是符合结合亲和力到前述蛋白质MGAT1（对ķ我6.99）和hGAT-1（P ķ我7.18）由MS根据NO711作为标记结合测定
• Compositions and methods for the treatment of epilepsy
  申请人：Kandula Mahesh

  公开号：US09290486B1

  公开（公告）日：2016-03-22

  The invention relates to the compounds of formula I and formula II or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I or formula II; and methods for treating or preventing neurological diseases may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of epilepsy, bipolar disorder, trigeminal neuralgia, attention-deficit hyperactivity disorder, partial seizures, adjunctive therapy for partial, myoclonic, tonic-clonic seizures and schizophrenia, neuropathic pain, seizures, Tourette syndrome, Alzheimer's disease, autism, bipolar disorder and anxiety disorder, bipolar disorder, mania, phantom limb syndrome, complex regional pain syndrome, paroxysmal extreme pain disorder, neuromyotonia, intermittent explosive disorder, borderline personality disorder, myotonia congenita and post-traumatic stress disorder.

  该发明涉及公式I和公式II的化合物或其药用可接受的盐，以及其多晶形、溶剂合物、对映体、立体异构体和水合物。包括有效量的公式I或公式II化合物的药物组合物；以及用于治疗或预防神经系统疾病的方法可以制成口服、颊下、直肠、局部、经皮、经粘膜、静脉、肠道给药、糖浆或注射剂。这种组合物可用于治疗癫痫、躁郁症、三叉神经痛、注意力缺陷多动障碍、部分性癫痫发作、部分、肌阵挛、强直-阵挛性癫痫及精神分裂症、神经性疼痛、癫痫、抽动症、阿尔茨海默病、自闭症、躁郁症和焦虑症、躁郁症、狂躁症、幻肢综合征、复杂性区域性疼痛综合征、发作性极端疼痛综合征、神经肌痉挛、间歇性爆发障碍、边缘型人格障碍、遗传性肌张力过高和创伤后应激障碍的治疗。
• Syntheses, Calcium Channel Antagonist and Anticonvulsant Activities of Substituted 1,4-Dihydro-3,5-pyridinedicarboxylates Containing Various 3-Alkyl Ester Substituents
  作者：Sai-Hay Yiu、Edward E. Knaus

  DOI：10.1002/ardp.19973300109

  日期：——

  5‐pyridinedicarboxylates 10–20 containing an amine, quaternary ammonium, aryl(heteroaryl)alkenyl, 4 ‐ (4‐fluorophenyl)‐piperazin‐1‐yl or methoxy moiety in the C‐3 alkyl ester R‐substituent in combination with a C‐4 phenyl ring bearing a 2,3‐Cl2, 3‐NO2, 3‐NMe2, 4‐NMe2 or 3,4,5‐(OMe)3 X‐substituent were prepared using the Hantzsch 1,4‐dihydropyridine reaction. In vitro calcium channel antagonist activity (CCA)

  一组 3-烷基 5-异丙基 4-芳基-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸酯 10-20 含有胺、季铵、芳基（杂芳基）烯基、4-（4 -氟苯基) -哌嗪 - C-3烷基酯R-取代基中的1-基或甲氧基部分与带有2,3-Cl2、3-NO2、3-NMe2、4-NMe2的C-4苯环组合或 3,4,5- (OMe) 3 X- 取代基使用 Hantzsch 1,4-二氢吡啶反应制备。使用豚鼠回肠纵向平滑肌测定法测定体外钙通道拮抗剂活性(CCA)。在C-4 3-硝基苯基系列化合物中，C-3酯R-取代基是CCA活性的决定因素，其中相对效力顺序为-CH2CH2CH=C-(2-甲基苯基)2±-CH2CH2NMe2.HCl>- CH2CH2CH = C-(3-甲基-2-噻吩基) 2> -CH2CH2 + NMe3 I-。C-4苯基X-取代基的位置和性质也是CCA活性的决定因素，其中相对活性顺序为3-NMe2>4-NMe2>3
• Ring-chain tautomerism in 2,2-bis(2-thienyl)tetrahydrofurans: preparation of [butene-2H5]-tiagabine
  作者：John M. Herbert、Trevor W. Mathers

  DOI：10.1002/jlcr.1787

  日期：2010.7

  A concise preparation of [butene-2H5]-tiagabine hydrochloride starting from [2H6]-γ-butyrolactone is described. It was necessary to ring-open the labeled γ-butyrolactone precursor before the addition of 2-thienyllithium to avoid cyclisation of the intermediate to a 2,2-bis(2-thienyl)tetrahydrofuran. Copyright © 2010 John Wiley & Sons, Ltd.

  描述了从 [2H6]-γ-丁内酯开始的 [丁烯-2H5]-tiagabine 盐酸盐的简明制备。有必要在添加 2-噻吩基锂之前将标记的 γ-丁内酯前体开环，以避免中间体环化为 2,2-双（2-噻吩基）四氢呋喃。版权所有 © 2010 John Wiley & Sons, Ltd.
• Azetidine derivatives as novel γ-aminobutyric acid uptake inhibitors: Synthesis, biological evaluation, and structure–activity relationship
  作者：Mark R. Faust、Georg Höfner、Jörg Pabel、Klaus T. Wanner

  DOI：10.1016/j.ejmech.2010.02.029

  日期：2010.6

  In this study azetidine derivatives representing conformationally constrained GABA or β-alanine analogs were evaluated for their potency as GABA-uptake inhibitors. The study comprised derivatives substituted in 2- as well as in 3-position with either an acetic acid moiety or a carboxylic acid function. In addition, azetidine derivatives bearing a tetrazole ring as a bioisosteric substitute for a carboxylic

  在这项研究中，评估了代表构象受限的GABA或β-丙氨酸类似物的氮杂环丁烷衍生物作为GABA吸收抑制剂的功效。该研究包括在2-位和3-位被乙酸部分或羧酸官能团取代的衍生物。另外，还包括带有四唑环的氮杂环丁烷衍生物作为羧酸基团的生物等位替代物。探索了3-羟基-3-（4-甲氧基苯基）氮杂环丁烷衍生物作为已知的GABA摄取抑制剂NNC-05-2045的类似物，该抑制剂表现出氮杂环丁烷环而不是后者中存在的哌啶环。既，Ñ -未被取代的化合物以及它们的Ñ从生物学上评估了对-烷基化的亲脂性衍生物对GAT-1和GAT-3转运蛋白的亲和力。发现具有4,4-二苯基丁烯基或4,4-双（3-甲基-2-噻吩基）丁烯基部分作为亲脂性残基的氮杂环丁烷-2-基乙酸衍生物在GAT-1上显示出最高的效价，IC 50值为分别为2.83±0.67μM和2.01±0.77μM。这些化合物中最有效的GAT-3抑制剂似乎是β-丙氨酸类似物1-