2-(3-hydroxyphenyl)-5-methylthiophene-3-carboxamide | 1245740-21-9

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 2-(3-hydroxyphenyl)-5-methylthiophene-3-carboxamide
• 英文别名: 2-(3-hydroxy-phenyl)-5-methyl-thiophene-3-carboxylic acid amide
• CAS: 1245740-21-9
• 化学式: C₁₂H₁₁NO₂S
• 分子量: 233.291
• InChiKey: NGRSOIINRAFCIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  91.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-hydroxyphenyl)-5-methylthiophene-3-carboxamide 、 phenylhexyl isocyanate 生成 ST4069
  参考文献：
  名称：

  CARBAMATE DERIVATIVES IN PARTICULAR FOR THE TREATMENT OF NEUROLOGICAL DISORDERS

  摘要：

  本发明涉及一种新的I式碳酸酯衍生物，其制备方法以及含有该衍生物的制药组合物，用于治疗神经系统疾病，如神经病性疼痛和焦虑症。

  公开号：

  US20120252865A1
• 作为产物：
  描述：

  2-(3-methoxyphenyl)-5-methylthiophene-3-carboxamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 以95%的产率得到2-(3-hydroxyphenyl)-5-methylthiophene-3-carboxamide
  参考文献：
  名称：

  Discovery of Potent Inhibitors of Human and Mouse Fatty Acid Amide Hydrolases

  摘要：

  Fatty acid amide hydrolase (FAAH, EC 3.5.1.99) is the main enzyme catabolizing endocannabinoid fatty acid amides. FAAH inactivation promotes beneficial effects upon pain and anxiety without the side effects accompanying agonists of type-1 cannabinoid receptors. Aiming at discovering new selective FAAH inhibitors, we developed a series of compounds (5a-u) characterized by a functionalized heteroaromatic scaffold. Particularly, 5c and 5d were identified as extremely potent, noncompetitive, and reversible FAAH inhibitors endowed with a remarkable selectivity profile and lacking interaction with the hERG channels. In vivo antinociceptive activity was demonstrated for 5c, 5d, and 5n at a dose much lower than that able to induce either striatal and limbic stereotypies or anxiolytic activity, thus outlining their potential to turn into optimum preclinical candidates. Aiming at improving pharmacokinetic properties and metabolic stability of 5d, we developed a subset of nanomolar dialyzable FAAH inhibitors (5v-z), functionalized by specific polyethereal lateral chains and fluorinated aromatic rings.

  DOI：

  10.1021/jm300689c

文献信息

• [EN] CARBAMATE DERIVATIVES IN PARTICULAR FOR THE TREATMENT OF NEUROLOGICAL DISORDERS<br/>[FR] DÉRIVÉS CARBAMATES EN PARTICULIER POUR LE TRAITEMENT DE TROUBLES NEUROLOGIQUES
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2010105930A1

  公开（公告）日：2010-09-23

  The present invention relates to new carbamate derivatives of formula I, processes for their preparation, and to pharmaceutical compositions containing them for the treatment of neurological disorders, such as neuropathic pain and anxiety.

  本发明涉及一类新的氨基甲酸衍生物，其化学式为I，包括它们的制备方法，以及包含这些化合物的药物组合物，用于治疗神经系统疾病，如神经性疼痛和焦虑。
• Development of novel multipotent compounds modulating endocannabinoid and dopaminergic systems
  作者：Alessandro Grillo、Giulia Chemi、Simone Brogi、Margherita Brindisi、Nicola Relitti、Filomena Fezza、Domenico Fazio、Laura Castelletti、Elisabetta Perdona、Andrea Wong、Stefania Lamponi、Alessandra Pecorelli、Mascia Benedusi、Manuela Fantacci、Massimo Valoti、Giuseppe Valacchi、Fabrizio Micheli、Ettore Novellino、Giuseppe Campiani、Stefania Butini、Mauro Maccarrone、Sandra Gemma

  DOI：10.1016/j.ejmech.2019.111674

  日期：2019.12

  potential treatment of complex and multifactorial diseases as well as for addictions and also smoke cessation. In this frame, following our interest in the development of molecules able to modulate either the endocannabinoid or the dopaminergic system, and given the multiple and reciprocal interconnections between them, we decided to merge the pharmacophoric elements of some of our early leads for

  多元药理学方法可能有助于发现用于研究或可能治疗复杂和多因素疾病以及成瘾和戒烟的药理学工具。在此框架中，随着我们对能够调节内源性大麻素或多巴胺能系统的分子的发展兴趣，并鉴于它们之间的相互联系，我们决定合并一些早期潜在客户的药效学元素以鉴定新分子作为能够调节两个系统的工具。我们在此描述了化合物5a-j的合成和生物学特征，这些化合物的合成和生物学特征是受我们的有效和选择性脂肪酸酰胺水解酶（FAAH）抑制剂（3a-c）以及多巴胺D2或D3受体亚型（4a，b）的配体的启发。尤其，大多数新分子显示出与目标靶标相互作用的纳摩尔浓度。在计算机上研究了所开发化合物（5a-j）的药物似然性，同时通过实验对hERG亲和力，选择性谱（对某些内源性大麻素系统蛋白），细胞毒性谱（对成纤维细胞和星形胶质细胞）和致突变性（Ames试验）进行了研究。决定。代谢研究也可用于补充化合物3a和5c的初步药物相似性分析。有趣的是，评估了神经母细胞瘤细胞系（IMR
• Development of potent and selective FAAH inhibitors with improved drug-like properties as potential tools to treat neuroinflammatory conditions
  作者：Alessandro Papa、Silvia Pasquini、Francesca Galvani、Mariarosaria Cammarota、Chiara Contri、Gabriele Carullo、Sandra Gemma、Anna Ramunno、Stefania Lamponi、Beatrice Gorelli、Simona Saponara、Katia Varani、Marco Mor、Giuseppe Campiani、Francesca Boscia、Fabrizio Vincenzi、Alessio Lodola、Stefania Butini

  DOI：10.1016/j.ejmech.2022.114952

  日期：2023.1