2-(1H-imidazol-2-yl)acetic acid hydrochloride | 1297344-60-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(1H-imidazol-2-yl)acetic acid hydrochloride
• 英文别名: 4-imidazoleacetic acid hydrochloride；2-(1H-imidazol-2-yl)acetic acid;hydrochloride
• CAS: 1297344-60-5
• 化学式: C₅H₆N₂O₂*ClH
• mdl: MFCD27996913
• 分子量: 162.576
• InChiKey: UBZJCAXSFAKNQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.42
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  66
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-benzyl 3-(4-(4-fluorophenoxy)phenylcarbamoyl)piperazine-1-carboxylate 、 2-(1H-imidazol-2-yl)acetic acid hydrochloride 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 以67%的产率得到(S)-4-benzyl 4-(2-(1H-imidazol-4-yl)acetyl)-3-(4-(4-fluorophenoxy)phenylcarbamoyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Discovery of a Novel Class of Potent and Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists

  摘要：

  A series of subtype selective sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists are disclosed. Our high-throughput screening campaign revealed hit 1 for which an increase in potency and mouse oral exposure was achieved with minor modifications to the chemical scaffold. In vivo efficacy revealed that at high doses compounds 12 and 15 inhibited tumor growth. Further optimization of our lead series led to the discovery of proline derivatives 37 (XL541) and 38 which had similar efficacy as our first generation analogues at significantly lower doses. Analogue 37 displayed excellent pharmacokinetics and oral exposure in multiple species.

  DOI：

  10.1021/jm201533b
• 作为产物：
  描述：

  2-(1-Tritylimidazol-2-yl)acetic acid 在 盐酸 作用下， 以 水 为溶剂， 反应 1.0h， 以260 mg的产率得到2-(1H-imidazol-2-yl)acetic acid hydrochloride
  参考文献：
  名称：

  开发咪唑链烷酸作为mGAT3选择性GABA摄取抑制剂

  摘要：

  合成了一系列新的潜在的GABA吸收抑制剂，这些抑制剂从1 H-咪唑-4-基乙酸开始，羧酸侧链来自不同的位置，且长度不同，并在四个GABA吸收转运蛋白mGAT1上测试了其抑制能力。 –4在HEK细胞中稳定表达。这项研究还包括了另外两个带有刚性羧酸侧链的双环化合物。生物学测试的结果表明，大多数ω-咪唑链烷酸和链烯酸衍生物作为mGAT3的GABA吸收抑制剂表现出最高的效力。

  DOI：

  10.1016/j.ejmech.2011.01.042

文献信息

• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF ZOLEDRONIC ACID<br/>[FR] PROCEDE AMELIORE DE PREPARATION DE L'ACIDE ZOLEDRONIQUE
  申请人：NATCO PHARMA LTD

  公开号：WO2005063717A1

  公开（公告）日：2005-07-14

  The invention disclosed in this application relates to an improved process for the preparation of zoledronic acid of formula (I) given below which comprises heating at a temperature in the range of 50-80 °C a solution of imidazol-1-ylacetic acid hydrochloride with ortho-phosphoric acid in a solvent medium where boiling point of the solvent used in lesser or close to that of phosphorous trichloride, adding phosphorous trichloride to the reaction mass slowly over a period of 2-3hr at a temperature in the range of 50-80 °C, keeping the resulting reaction mass at a temperature in the range of 50-80 °C for a period of 1-6hr, adding hydrochloric acid to the reaction mass and keeping the reaction mass at a temperature in the range of 60-120 °C, separating the organic solvent from the reaction mass while it is still hot, and diluting the aqueous layer containing zoledronic acid with water miscible solvent. Zoledronic acid is widely used as a bone resorption inhibitor.

  本申请中披露的发明涉及一种改进的制备zoledronic acid（化学式（I）如下）的方法，该方法包括在50-80°C的温度范围内加热imidazol-1-ylacetic acid盐酸盐与正磷酸反应，反应溶液中的溶剂的沸点小于或接近于三氯化磷的沸点，缓慢地在50-80°C的温度范围内在反应混合物中加入三氯化磷，持续时间为2-3小时，将产生的反应混合物保持在50-80°C的温度范围内1-6小时，向反应混合物中加入盐酸并将反应混合物保持在60-120°C的温度范围内，在反应混合物仍然热时将有机溶剂与反应混合物分离，然后用水溶性溶剂稀释含有zoledronic acid的水层。Zoledronic acid被广泛用作骨吸收抑制剂。
• 3-Cyanoquinoline inhibitors of Tpl2 kinase and methods of making and using the same
  申请人：Green Jeffrey Neal

  公开号：US20060264460A1

  公开（公告）日：2006-11-23

  The present invention provides compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , m and n are defined as described herein. The invention also provides methods of making the compounds of formula (I), and methods of treating inflammatory diseases, such as rheumatoid arthritis, in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) to the mammal.

  本发明提供了如下式（I）的化合物及其药用可接受的盐，其中R1、R2、R3、R4、R5、R6、R7、R8、m和n的定义如本文所述。该发明还提供了制备如式（I）化合物的方法，以及治疗炎症性疾病（如类风湿性关节炎）的方法，包括向哺乳动物施用如式（I）化合物的治疗有效量。
• [EN] SPHINGOSINE-1-PHOSPHATE RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS DE SPHINGOSINE-1-PHOSPHATE
  申请人：EXELIXIS INC

  公开号：WO2010045580A1

  公开（公告）日：2010-04-22

  This disclosure relates to sphingosine-1 -phosphate (SlP) receptor antagonists, compositions comprising the SlP receptor antagonists and methods for using and processes for making the SlP receptor antagonists. In particularly, this disclosure relates to sphingosine-1 -phosphate 1 (SlPl) receptor antagonists, compositions comprising the SlPl receptor antagonist and methods for using the SlPl receptor antagonist, such as in the treatment of cancer, and processes for making the SlPl receptor antagonists.

  这项披露涉及神经酰胺-1-磷酸(S1P)受体拮抗剂，包括该S1P受体拮抗剂的组合物以及使用和制备该S1P受体拮抗剂的方法。特别是，这项披露涉及神经酰胺-1-磷酸1(S1P1)受体拮抗剂，包括该S1P1受体拮抗剂的组合物以及使用该S1P1受体拮抗剂的方法，例如在癌症治疗中，并且包括制备该S1P1受体拮抗剂的方法。
• Inhibitors of farnesyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US05661161A1

  公开（公告）日：1997-08-26

  The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit farnesyl-protein transferase. Furthermore, these CAAX analogues differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid antoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

  本发明涉及蛋白质Ras的CAAX基序的类似物，其在体内通过戊烷基化进行修饰。这些CAAX类似物抑制戊烷基蛋白转移酶。此外，这些CAAX类似物与之前描述的抑制戊烷基蛋白转移酶的类似物不同，因为它们没有巯基。缺乏巯基在动物的药代动力学行为方面具有独特的优点，可以防止巯基依赖的化学反应，如迅速的抗氧化和与内源性巯基形成二硫键，从而减少系统毒性。此外，本发明还包括含有这些戊烷基转移酶抑制剂的化疗组合物及其制备方法。
• Peptide derivatives or pharmaceutically acceptable salts thereof, method for producing the same, use of said derivatives and pharmaceutical composition
  申请人：Nebolsin, Vladimir Evgenievich

  公开号：EP2229935A1

  公开（公告）日：2010-09-22

  Derivatives of peptides of general formula or pharmaceutically acceptable salts thereof, their use as the agents possessing antioxidant, antiasthmatic, antihypoxic, antiinflammatory, antiviral, antibacterial, lipid-regulating, antitumor, antimetastatic, glucose lowering, adaptogenic and the other kinds of therapeutic effects, a method to produce them, a pharmaceutical composition or a cosmetic agent comprising as an active agent a peptide derivative of formula (I) or pharmaceutically or cosmetically acceptable salts thereof as well as a method of therapy or prevention of diseases.

  通式肽的衍生物 或其药学上可接受的盐，它们作为具有抗氧化、抗通气、抗缺氧、抗炎、抗病毒、抗菌、调节血脂、抗肿瘤、抗转移、降糖、适应性和其他各种治疗效果的制剂的用途，生产它们的方法，包含式 (I) 肽衍生物或其药学上或化妆品学上可接受的盐作为活性剂的药物组合物或化妆品制剂，以及治疗或预防疾病的方法。