法克罗芬 | 114012-12-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 法克罗芬
• 中文别名: 3-氨基-2-(4-氯苯基)丙基膦酸
• 英文名称: phaclofen
• 英文别名: (+/-)-3-Amino-2-(4-chlorophenyl)propylphosphonic acid；Phaclofen zwitterion；[3-azaniumyl-2-(4-chlorophenyl)propyl]-hydroxyphosphinate
• CAS: 114012-12-3
• 化学式: C₉H₁₃ClNO₃P
• 分子量: 249.634
• InChiKey: VSGNGLJPOGUDON-UHFFFAOYSA-N

物化性质

• 熔点：
  249-252 °C
• 沸点：
  467.1±55.0 °C(Predicted)
• 密度：
  1.432±0.06 g/cm3(Predicted)
• 溶解度：
  0.1MHCl中的溶解度为13.3 mg/mL
• 稳定性/保质期：

  在常温常压下稳定，应避免与强氧化剂接触。

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  83.6
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 安全说明：
  S26,S36
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338

反应信息

• 作为产物：
  描述：

  1-(4-氯苯基)-2-硝基乙烯 在 镍 盐酸 、 ammonium hydroxide 、 氢气 、 lithium diisopropyl amide 作用下， 以 乙醇 为溶剂， -78.0 ℃ 、100.0 kPa 条件下， 反应 16.0h， 生成 法克罗芬
  参考文献：
  名称：

  An Efficient Synthesis of (±)-3-Amino-2-(4-chlorophenyl)-propylphosphonic Acid (PHACLOFEN)

  摘要：

  本文描述了GABA-B拮抗剂法克洛芬的三步高效合成方法，该方法的特点是将膦酸酯与ß-硝基苯乙烯进行迈克尔加成反应。

  DOI：

  10.1055/s-1989-27279

文献信息

• [EN] PHARMACOLOGICALLY ACTIVE ARYL-SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRAZOLO[1,5-A]PYRIMIDINE À SUBSTITUTION ARYLE PHARMACOLOGIQUEMENT ACTIFS
  申请人：RICHTER GEDEON NYRT

  公开号：WO2018167629A1

  公开（公告）日：2018-09-20

  The present invention relates to new pyrazolo[1,5-a]pyrimidine derivatives of formula (I) or pharmaceutically acceptable salts, biologically active metabolites, pro-drugs, racemates, enantiomers, diastereomers, solvates and hydrates thereof that serve as GABAB receptor positive allosteric modulators. The invention also relates to the process for producing such compounds. The invention further relates to pharmaceutical compositions comprising such compounds optionally in combination with two or more different therapeutic agents and the use of such compounds in methods for treating diseases and conditions mediated and modulated by the GABAB receptor positive allosteric mechanism. The invention also provides a method for manufacture of medicaments useful in the treatment of such disorders.

  本发明涉及通式(I)的新型吡唑并[1,5-a]嘧啶衍生物或其药学上可接受的盐、生物活性代谢物、前药、消旋体、对映体、非对映体、溶剂合物和水合物，它们作为GABAB受体的正变构调节剂。本发明还涉及制备此类化合物的方法。本发明进一步涉及包含此类化合物的药物组合物，可选择性地与两种或更多种不同的治疗剂组合，以及此类化合物在治疗由GABAB受体正变构机制介导和调节的疾病和病症的方法中的用途。本发明还提供了一种用于制造治疗此类疾病的药物的方法。
• [EN] NOVEL PHARMACEUTICAL COMPOSITIONS<br/>[FR] NOUVELLES COMPOSITIONS PHARMACEUTIQUES
  申请人：UNIV OXFORD INNOVATION LTD

  公开号：WO2017089804A1

  公开（公告）日：2017-06-01

  The present invention relates to a pharmaceutical composition comprising a plurality of layered double hydroxide nanoparticles and one or more pharmaceutically acceptable excipients, wherein the at least one aqueously unstable anionic drug compound is intercalated between the layers. The present invention also relates to a process for the preparation of such pharmaceutical compositions, the corresponding layered double hydroxides, as well as methods for their use in stablising unstable anionic drug compounds.

  本发明涉及一种制药组合物，包括多个层状双氢氧化物纳米颗粒和一个或多个药用可接受的赋形剂，其中至少一种易水解的阴离子药物化合物插层在层之间。本发明还涉及一种制备此类制药组合物的方法，相应的层状双氢氧化物，以及用于稳定不稳定的阴离子药物化合物的方法。
• [EN] PHARMACOLOGICALLY ACTIVE ALICYCLIC-SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRAZOLO[1,5-A]PYRIMIDINE À SUBSTITUTION ALICYCLIQUE PHARMACOLOGIQUEMENT ACTIFS
  申请人：RICHTER GEDEON NYRT

  公开号：WO2018167630A1

  公开（公告）日：2018-09-20

  The present invention relates to new pyrazolo[l,5-a]pyrimidine derivatives of formula (I) or pharmaceutical ly acceptable salts, biologically active metabolites, pro-drugs, racemates, enantiomers, diastereomers, solvates and hydrates thereof that serve as GABAB receptor positive allosteric modulators. The invention al so relates to the process for producing such compounds. The invention further relates to pharmaceutical compositions comprising such compounds optionally in combination with two or more different therapeutic agents and the use of such compounds in methods for treating diseases and conditions mediated and modulated by the GABAB receptor positive allosteric mechanism. The invention al so provides a method for manufacture of medicaments useful in the treatment of such disorders.

  本发明涉及公式（I）的新型吡唑并[1,5-a]嘧啶衍生物或其药学上可接受的盐、生物活性代谢物、前药、外消旋体、对映体、非对映异构体、溶剂化物和水合物，它们作为GABAB受体正向变构调节剂。本发明还涉及制备这些化合物的方法。本发明还涉及包含这些化合物的药物组合物，可选地与两种或两种以上不同的治疗剂联合使用，并且这些化合物在治疗GABAB受体正向变构机制介导和调节的疾病和病况的方法中的使用。本发明还提供了一种制造有用于治疗这些疾病的药物的方法。
• Carbamoyl esters that inhibit cholinesterase and release pharmacologically active agents
  申请人：Verheijen C. Jeroen

  公开号：US20050096387A1

  公开（公告）日：2005-05-05

  Carbamoyl esters inhibit cholinesterase activity and, upon hydrolysis release a pharmacologically active agent. In one embodiment, the carbamoyl ester has the following structure: wherein A is selected from the group consisting of an unsubstituted aryl, a substituted aryl, an unsubstituted heteroaryl and a substituted heteroaryl. The carbamoyl esters are employed in methods to treat an individual. The pharmacologically active agent obtained by hydrolysis of the carbamoyl esters can treat, for example, a nervous system condition, a cholinergic deficiency and conditions or diseases associated with a deficiency in a pharmacologically active agent, such as acetylcholine.

  碳酰基酯抑制胆碱酯酶活性，水解后释放出药理活性成分。在一种实施例中，碳酰基酯具有以下结构：其中A选自无取代芳基、取代芳基、无取代杂环芳基和取代杂环芳基的群组。碳酰基酯用于治疗个体的方法中。通过水解碳酰基酯获得的药理活性成分可以治疗例如神经系统疾病、胆碱能缺乏以及与药理活性成分缺乏相关的疾病或病症，例如乙酰胆碱。
• Dopamine analog amide
  申请人：——

  公开号：US20010056116A1

  公开（公告）日：2001-12-27

  The invention involves the formation of a prodrug from a fatty acid carrier and a neuroactive drug. The prodrug is stable in the environment of both the stomach and the bloodstream and may be delivered by ingestion. The prodrug passes readily through the blood brain barrier. Once in the central nervous system, the prodrug is hydrolyzed into the fatty acid carrier and the drug to release the drug. In a preferred embodiment, the carrier is 4, 7, 10, 13, 16, 19 docosahexa-enoic acid and the drug is dopamine. Both are normal components of the central nervous system. The covalent bond between the drug and the carrier preferably is an amide bond, which bond may survive the conditions in the stomach. Thus, the prodrug may be ingested and will not be hydrolyzed completely into the carrier molecule and drug molecule in the stomach.

  该发明涉及使用脂肪酸载体和神经活性药物形成前药。该前药在胃和血液流动环境中稳定，并可通过口服递送。该前药容易穿过血脑屏障。一旦进入中枢神经系统，前药被水解成脂肪酸载体和药物以释放药物。在首选实施方式中，载体是4,7,10,13,16,19二十二碳六烯酸，药物是多巴胺。两者都是中枢神经系统的正常成分。药物和载体之间的共价键通常是酰胺键，这种键可以在胃的条件下存活。因此，前药可以被摄入，并且不会在胃中完全水解成载体分子和药物分子。