N-[(2S)-5-(6-methyl-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide | 1045805-41-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: N-[(2S)-5-(6-methyl-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide
• 英文别名: 2-Propanesulfonamide,N-[(2S)-2,3-dihydro-5-(6-methyl-3-pyridinyl)-1H-inden-2-yl]-；N-[(2S)-5-(6-methylpyridin-3-yl)-2,3-dihydro-1H-inden-2-yl]propane-2-sulfonamide
• CAS: 1045805-41-1
• 化学式: C₁₈H₂₂N₂O₂S
• 分子量: 330.451
• InChiKey: OCJKHBCJMIOPJS-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-溴-2-甲基吡啶 、 N-[(2S)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide 在 caesium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 0.5h， 以57%的产率得到N-[(2S)-5-(6-methyl-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide
  参考文献：
  名称：

  Discovery of N-[(2S)-5-(6-Fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide, a Novel Clinical AMPA Receptor Positive Modulator

  摘要：

  A series of AMPA receptor positive allosteric modulators has been optimized from poorly penetrant leads to identify molecules with excellent preclinical pharmacokinetics and CNS penetration. These discoveries led to 17i, a potent, efficacious CNS penetrant molecule with an excellent pharmacokinetic profile across preclinical species, which is well tolerated and is also orally bioavailable in humans.

  DOI：

  10.1021/jm1005429

文献信息

• Compounds which potentiate glutamate receptor and uses thereof in medicine
  申请人：Bradley Marcus Daniel

  公开号：US20070161638A1

  公开（公告）日：2007-07-12

  Compounds of formula (I) or a pharmaceutically acceptable salt, solvate or prodrug thereof, are disclosed: wherein R 1 is C 1-6 alkyl, haloC 1-6 alkyl, C 2-6 alkenyl, amino, monoC 1-4 alkylamino or diC 1-4 alkylamino; R 2 and R 3 , which may be the same or different, are hydrogen, halogen, C 1-6 alkyl, haloC 1-6 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, cyano, amino, monoC 1-4 alkylamino or diC 1-4 alkylamino; each R 4 , which may be the same or different, is C 1-6 alkyl, halogen, C 1-6 alkyl, haloC 1-6 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, cyano, nitro, amino, monoC 1-4 alkylamino or diC 1-4 alkylamino; p is 0, 1 or 2; n is 1 or 2; R 5 and R 6 , which may be the same or different, are hydrogen, halogen, C 1-6 alkyl, haloC 1-6 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, cyano, amino, monoC 1-4 alkylamino or diC 1-4 alkylamino; and Het is thienyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, pyrrolyl, quinolyl, thiazolyl or furyl, each of which may be substituted by one or more groups independently selected from the list consisting of C 1-6 alkyl, C 1-6 alkoxy, acetyl, halogen, haloC 1-6 alkyl, cyano, nitro, amino, monoC 1-4 alkylamino and diC 1-4 alkylamino. Methods of preparation of the compounds, and uses thereof in medicine, for example treatment of schizophrenia, are also disclosed.

  公开了公式（I）的化合物或其药学上可接受的盐，溶剂化物或前药，其中R1为C1-6烷基，卤代C1-6烷基，C2-6烯基，氨基，单C1-4烷基氨基或双C1-4烷基氨基；R2和R3，可以相同也可以不同，为氢，卤素，C1-6烷基，卤代C1-6烷基，C1-4烷氧基，卤代C1-4烷氧基，氰基，氨基，单C1-4烷基氨基或双C1-4烷基氨基；每个R4，可以相同也可以不同，为C1-6烷基，卤素，C1-6烷基，卤代C1-6烷基，C1-4烷氧基，卤代C1-4烷氧基，氰基，硝基，氨基，单C1-4烷基氨基或双C1-4烷基氨基；p为0、1或2；n为1或2；R5和R6，可以相同也可以不同，为氢，卤素，C1-6烷基，卤代C1-6烷基，C1-4烷氧基，卤代C1-4烷氧基，氰基，氨基，单C1-4烷基氨基或双C1-4烷基氨基；Het为噻吩基，吡啶基，嘧啶基，吡嗪基，嘧啶基，吡嗪啉基，咪唑基，吡唑基，吡咯基，喹啉基，噻唑基或呋喃基，每个基团都可以由独立于C1-6烷基，C1-6烷氧基，乙酰基，卤素，卤代C1-6烷基，氰基，硝基，氨基，单C1-4烷基氨基和双C1-4烷基氨基的一个或多个基团进行取代。还公开了制备这些化合物的方法以及它们在医学上的用途，例如用于治疗精神分裂症。
• Modulation of AMPA/kainate Receptors for the Treatment of Hypoglycemia
  申请人：Vanderklish Peter

  公开号：US20200397751A1

  公开（公告）日：2020-12-24

  Methods for modulating the levels of glucagon and blood glucose of a mammal are provided. In the subject methods, a positive allosteric modulator of AMPA/kainate receptors is administered to a host. The subject methods find use in applications where it is desired to increase one or both of the glucagon and blood glucose levels in a mammalian host. The subject methods find use in applications where it is desired to decrease the size, or breadth, of the circadian range of blood glucose levels in a mammalian host. The subject methods also find use in applications where it is desired to decrease the frequency, severity, or occurrence of hypoglycemia in a mammalian host. Finally, the subject method finds use in applications where it is desired to decrease the frequency, severity, or occurrence of nocturnal hypoglycemia in a mammalian host, particularly that which occurs in diabetics as a result of therapy with insulins or insulin analogs or other glucose lowering agents, or combinations of such agents.
• US7618969B2
  申请人：——

  公开号：US7618969B2

  公开（公告）日：2009-11-17
• Discovery of <i>N</i>-[(2<i>S</i>)-5-(6-Fluoro-3-pyridinyl)-2,3-dihydro-1<i>H</i>-inden-2-yl]-2-propanesulfonamide, a Novel Clinical AMPA Receptor Positive Modulator
  作者：Simon E. Ward、Mark Harries、Laura Aldegheri、Daniele Andreotti、Stuart Ballantine、Benjamin D. Bax、Andrew J. Harris、Andy J. Harker、Jesper Lund、Rosemary Melarange、Anna Mingardi、Claudette Mookherjee、Julie Mosley、Marta Neve、Beatrice Oliosi、Roberto Profeta、Kathrine J. Smith、Paul W. Smith、Simone Spada、Kevin M. Thewlis、Shahnaz P. Yusaf

  DOI：10.1021/jm1005429

  日期：2010.8.12

  A series of AMPA receptor positive allosteric modulators has been optimized from poorly penetrant leads to identify molecules with excellent preclinical pharmacokinetics and CNS penetration. These discoveries led to 17i, a potent, efficacious CNS penetrant molecule with an excellent pharmacokinetic profile across preclinical species, which is well tolerated and is also orally bioavailable in humans.