1'-methyl-3H-spiro[isobenzofuran-1,4'-piperidine] | 56657-95-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异香豆素
• 英文名称: 1'-methyl-3H-spiro[isobenzofuran-1,4'-piperidine]
• 英文别名: 1,3-dihydro-1'-methylspiro[isobenzofuran-1,4'-piperidine]；1''-methyl-3H-spiro[2-benzofuran-1,4''-piperidine]；1'-methylspiro[1H-2-benzofuran-3,4'-piperidine]
• CAS: 56657-95-5
• 化学式: C₁₃H₁₇NO
• 分子量: 203.284
• InChiKey: DZVDLNBMBMYHGT-UHFFFAOYSA-N

物化性质

• 熔点：
  78-80 °C
• 沸点：
  310.4±42.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1'-methyl-3H-spiro[isobenzofuran-1,4'-piperidine] 以76%的产率得到
  参考文献：
  名称：

  PARHAM W. E.; EGBERG D. C.; SAYED Y. A.; THRAIKILL R. W.; KEYSER G. E.; N+, J. ORG. CHEM. , 1976, 41, NO 15, 2628-2633

  摘要：

  DOI：
• 作为产物：
  描述：

  4-(2-hydroxymethyl-phenyl)-1-methyl-piperidin-4-ol 在 盐酸 、 溶剂黄146 作用下， 生成 1'-methyl-3H-spiro[isobenzofuran-1,4'-piperidine]
  参考文献：
  名称：

  1,3-Dihydrospiro[isobenzofuran]s and derivatives thereof

  摘要：

  描述了一种替代1,3-二氢螺[异苯并呋喃]的新型化合物和制备方法。这些化合物可用作镇静剂、止痛剂和它们的中间体。

  公开号：

  US03962259A1

文献信息

• Modulators of Cystic Fibrosis Transmembrane Conductance Regulator
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：US20160095858A1

  公开（公告）日：2016-04-07

  The present invention features a compound of formula I: or a pharmaceutically acceptable salt thereof, where R 1 , R 2 , R 3 , W, X, Y, Z, n, o, p, and q are defined herein, for the treatment of CFTR mediated diseases, such as cystic fibrosis. The present invention also features pharmaceutical compositions, method of treating, and kits thereof.

  本发明涉及一种具有以下化学式I的化合物： 或其药用可接受的盐，其中R 1 ，R 2 ，R 3 ，W，X，Y，Z，n，o，p和q在此处定义，用于治疗CFTR介导的疾病，如囊性纤维化。本发明还涉及药物组合物、治疗方法和相关工具包。
• [EN] MODULATORS OF VASOPRESSIN RECEPTORS WITH THERAPEUTIC POTENTIAL<br/>[FR] MODULATEURS DES RÉCEPTEURS DE LA VASOPRESSINE À POUVOIR THÉRAPEUTIQUE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2014127350A1

  公开（公告）日：2014-08-21

  Compounds comprising piperazines, piperidines, spiro-furanopiperidines, and analogs thereof are provided that are modulators, such as positive allosteric modulators, of one or more subclasses of vasopressin receptors. The compounds can be selective modulators of one or more subclasses of vasopressin receptors. Compounds of the invention can be used in the treatment of a condition wherein modulating a vasopressin receptor is medically indicated for treatment of the condition.

  提供了包含哌嗪、哌啶、螺环呋喃哌啶及其类似物的化合物，这些化合物是利钠素受体的调节剂，如正向变构调节剂，可以调节一个或多个亚类别的利钠素受体。这些化合物可以是一个或多个亚类别的利钠素受体的选择性调节剂。本发明的化合物可用于治疗需要调节利钠素受体的情况。
• [EN] 1',3'-DISUBSTITUTED-4-PHENYL-3,4,5,6-TETRAHYDRO-2H, 1'H-[1, 4'] BIPYRIDINYL-2'-ONES<br/>[FR] 4-PHÉNYL-3,4,5,6-TÉTRAHYDRO-2H,1'H-[1, 4'] BIPYRIDINYL-2'-ONES 1', 3'-DISUSBSTITUÉES
  申请人：ORTHO MCNEIL JANSSEN PHARM

  公开号：WO2009033704A1

  公开（公告）日：2009-03-19

  The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) wherein all radicals are as defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors - subtype 2 ('mGluR2') which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及新型化合物，特别是根据式（I）中定义的新型吡啶酮衍生物，其中所有基团均如申请和权利要求中所定义。根据本发明的化合物是代谢型受体亚型2（'mGluR2'）的阳性变构调节剂，用于治疗或预防与谷氨酸功能障碍相关的神经系统和精神疾病，以及mGluR2代谢型受体亚型涉及的疾病。具体来说，这些疾病是来自焦虑、精神分裂症、偏头痛、抑郁症和癫痫等中枢神经系统疾病的选择性疾病。本发明还涉及制备这种化合物和组合物的药物组合物和方法，以及利用这种化合物预防和治疗mGluR2涉及的疾病。
• PYRIMIDINE COMPOUND
  申请人：Matsushima Yuji

  公开号：US20110053912A1

  公开（公告）日：2011-03-03

  A novel and excellent method for preventing and/or treating diseases related to a cannabinoid type 2 receptor, based on an agonistic action on a cannabinoid type 2 receptor. It was found that a hetero ring derivative mainly having two substituents, for example, a pyrimidine-5-carboxamide derivative having a substituent amino group at the 2-position, exhibits a potent agonistic action on a cannabinoid type 2 receptor, and can be an agent for preventing and/or treating diseases related to a cannabinoid type 2 receptor such as inflammatory diseases, pain, and the like.

  一种预防和/或治疗与大麻素2型受体相关疾病的新颖优秀方法，基于对大麻素2型受体的激动作用。发现一种异核环衍生物主要具有两个取代基，例如，在2-位置具有取代基氨基的嘧啶-5-羧酰胺衍生物，表现出对大麻素2型受体的强效激动作用，可以成为预防和/或治疗与大麻素2型受体相关疾病，如炎症性疾病、疼痛等的药物。
• .sigma. Ligands with Subnanomolar Affinity and Preference for the .sigma.2 Binding Site. 2. Spiro-Joined Benzofuran, Isobenzofuran, and Benzopyran Piperidines
  作者：Ejner K. Moltzen、Jens Perregaard、Eddi Meier

  DOI：10.1021/jm00011a020

  日期：1995.5

  structural factors governing sigma 1/sigma 2 affinity and selectivity within this class of compounds. The N-substituent in spiro[isobenzofuran-1(3H),4'-piperidines] is highly important, both for affinity and selectivity. Spiropiperidines with no or small N-substituents (H, Me, Et) exert very low affinity for both sigma 1 and sigma 2 binding sites (IC50(sigma 1, sigma 2) > 100 nM), whereas medium-sized substituents

  合成了螺[异苯并呋喃-1（3H），4'-哌啶]及相应的苯并呋喃和苯并吡喃衍生物，并作为σ配体进行了评估。这些化合物与Lu 28-179（1'-[4- [1-（4-氟苯基）-1H-吲哚-3-基] -1-丁基]螺[异苯并呋喃-1（3H），4'-哌啶]已被证明是选择性的sigma 2配体，其亲和力在亚纳摩尔范围内。该研究的目的是确定在这类化合物中控制sigma 1 / sigma 2亲和力和选择性的结构因素。螺[异苯并呋喃-1（3H），4'-哌啶]中的N-取代基对于亲和力和选择性都非常重要。没有或只有少量N取代基（H，Me，Et）的螺哌啶对sigma 1和sigma 2结合位点都具有非常低的亲和力（IC50（sigma 1，sigma 2）> 100 nM），而中等大小的取代基（例如Pr，Bu，Ph（CH2）2）会产生有效但非选择性的化合物（IC50（sigma 1，sigma 2）= 2-5