E2508 Tosylate | 685886-34-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: E2508 Tosylate
• 英文别名: N-(cyclopropylmethyl)-7-[2,6-dimethoxy-4-(methoxymethyl)phenyl]-2-ethyl-N-[(tetrahydro-2H-pyran-4-yl)methyl]pyrazolo[1,5-a]pyridin-3-amine, 4-methylbenzenesulfonate；N-cyclopropylmethyl-N-{7-[2,6-dimethoxy-4-(methoxymethyl)-phenyl]-2-ethylpyrazolo[1,5-a]pyridine-3-yl}-N-(tetrahydro-2H-pyran-4-ylmethyl)amine p-toluenesulfonate；N-(Cyclopropylmethyl)-7-(2,6-dimethoxy-4-(methoxymethyl)phenyl)-2-ethyl-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazolo(1,5-a)pyridin-3-amine 4-methylbenzenesulfonate；N-(cyclopropylmethyl)-7-[2,6-dimethoxy-4-(methoxymethyl)phenyl]-2-ethyl-N-(oxan-4-ylmethyl)pyrazolo[1,5-a]pyridin-3-amine;4-methylbenzenesulfonic acid
• CAS: 685886-34-4
• 化学式: C₇H₈O₃S*C₂₉H₃₉N₃O₄
• 分子量: 665.851
• InChiKey: NOWKXPVUFWKFHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.61
• 重原子数：
  47
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  tert-butyl N-(7-bromo-2-ethylpyrazolo[1,5-a]pyridin-3-yl)carbamate 在 盐酸 、 四(三苯基膦)钯 、 barium hydroxide octahydrate 、 三乙酰氧基硼氢化钠 、 sodium hydride 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.33h， 生成 E2508 Tosylate
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of Pyrazolo[1,5-a]pyridine Derivatives: Potent and Orally Active Antagonists of Corticotropin-Releasing Factor 1 Receptor

  摘要：

  Design, synthesis, and structure activity relationships of a series of 3-dialkylamino-7-phenyl pyrazolo[1,5-a]pyridines (I) as selective antagonists of the corticotropin-releasing factor 1 (CRF1) receptor are described. The most prominent compound to emerge from this work, 46 (E2508), exhibits potent in vitro activity, excellent drug-like properties, and robust oral efficacy in animal models of stress-related disorders. It has advanced into clinical trials.

  DOI：

  10.1021/jm300259r

文献信息

• Process for production of pyrazole-fused ring derivatives
  申请人：Negi Shigeto

  公开号：US20070191613A1

  公开（公告）日：2007-08-16

  An object of the invention is to find out intermediates usful for the synthesis of pyrazol-fused ring derivatives (such as 7-phenylpyrazolo[1,5-a]pyridine derivatives) and a method for producing the same. A method for producing compound represented by the general formula (II), wherein Z 1 and Z 2 each independently represents a methine group or a nitrogen atom; R 1 represents an ethyl group or the like; R 5 represents a hydrogen atom or the like; R 2 and R 3 each independently represents a C 1-6 alkyl group or the like, salts thereof, or solvates of both, comprising the step of: reacting a compound represented by the general formula (I), wherein Z 1 , Z 2 , R 5 , R 1 , R 2 and R 3 each has the same definition as described above, with an organometallic reagent; and then reacting the resulting product with pentafluoroiodobenzene.

  本发明的目的是找出用于合成吡唑融合环衍生物（例如7-苯基吡唑并[1,5-a]吡啶衍生物）的中间体以及生产方法。一种生产通用式（II）所代表的化合物的方法，其中Z1和Z2分别独立表示亚甲基基团或氮原子；R1表示乙基基团或类似物；R5表示氢原子或类似物；R2和R3分别独立表示C1-6烷基基团或类似物，它们的盐或两者的溶剂，包括以下步骤：将通用式（I）所代表的化合物与有机金属试剂反应；然后将所得产物与五氟化碘苯反应。
• METHOD FOR PREPARATION OF PHARMACEUTICAL COMPOSITION HAVING IMPROVED DISINTEGRADABILITY
  申请人：Eisai R&D Management Co., Ltd.

  公开号：EP1938842A1

  公开（公告）日：2008-07-02

  There exists a strong desire both for pharmaceutical compositions which rapidly exhibit pharmacological effects without an increase in the size of the dosage form or a decline in quality due to interactions between a pharmaceutically active ingredient and the disintegrant, and also for a method of preparing such pharmaceutical compositions. Such a desire is especially acute with regard to, for example, preparations which contain a drug such as an analgesic or a quick-acting hypoglycemic drug that requires the rapid appearance of pharmacological effects following administration, preparations which have a high content of the pharmaceutically active ingredient, and preparations which contain two or more different active pharmaceutical ingredients. Thus, the object of the present invention is to improve the disintegratability of the pharmaceutical compositions without increasing the size of the dosage form and without a decline in quality due to interactions between the pharmaceutically active ingredient and the disintegrant. The present invention provides a method for preparing a pharmaceutical composition having a rapid disintegration time, comprising: blending, in the pharmaceutical composition containing a pharmaceutically active ingredient, at least one disintegrant and at least one water-soluble salt having a pH being from 3 to 9 in an aqueous solution of 2.5% concentration. The invention also provides a premix composition obtained by the preliminary mixture of a disintegrant with a water-soluble inorganic salt having a pH being from 3 to 9 in an aqueous solution of 2.5% concentration.

  人们强烈希望药物组合物能迅速显示药理作用，而不会因药物活性成分与崩解剂之间的相互作用而导致剂型体积增大或质量下降，同时也希望有一种方法来制备这种药物组合物。例如，对于含有镇痛药或速效降糖药等需要在给药后迅速产生药理作用的药物的制剂、具有高含量药物活性成分的制剂以及含有两种或两种以上不同药物活性成分的制剂，这种愿望尤为迫切。因此，本发明的目的是改善药物组合物的崩解性，同时不增加剂型的体积，也不会因药物活性成分与崩解剂之间的相互作用而导致质量下降。本发明提供了一种制备具有快速崩解时间的药物组合物的方法，包括：在含有药物活性成分的药物组合物中，混合至少一种崩解剂和至少一种 pH 值为 3 至 9 的水溶性盐，其水溶液的浓度为 2.5%。本发明还提供了一种预混组合物，它是由一种崩解剂与一种水溶性无机盐在浓度为 2.5%的水溶液中初步混合而成，该无机盐的 pH 值为 3 至 9。
• METHOD FOR PREPARATION OF PHARMACEUTICAL COMPOSITION HAVING IMPROVED DISINTEGRATABILITY AND PHARMACEUTICAL COMPOSITION MANUFACTURED BY SAME METHOD
  申请人：Ueki Yosuke

  公开号：US20080214557A1

  公开（公告）日：2008-09-04

  There exists a strong desire both for pharmaceutical compositions which rapidly exhibit pharmacological effects without an increase in the size of the dosage form or a decline in quality due to interactions between a pharmaceutically active ingredient and the disintegrant, and also for a method of preparing such pharmaceutical compositions. Such a desire is especially acute with regard to, for example, preparations which contain a drug such as an analgesic or a quick-acting hypoglycemic drug that requires the rapid appearance of pharmacological effects following administration, preparations which have a high content of the pharmaceutically active ingredient, and preparations which contain two or more different pharmaceutically active ingredients. Thus, the object of the present invention is to improve the disintegratability of the pharmaceutical compositions without increasing the size of the dosage form and without a decline in quality due to interactions between the pharmaceutically active ingredient and the disintegrant. The present invention provides a method for preparing a pharmaceutical composition having a rapid disintegration time, comprising: blending, in the pharmaceutical composition containing a pharmaceutically active ingredient, at least one disintegrant and at least one water-soluble salt having a pH being from 3 to 9 in an aqueous solution of 2.5% concentration. The invention also provides a premix composition obtained by the preliminary mixture of a disintegrant with a water-soluble inorganic salt having a pH of from 3 to 9 in an aqueous solution of 2.5% concentration.
• US7858809B2
  申请人：——

  公开号：US7858809B2

  公开（公告）日：2010-12-28
• Synthesis and Structure–Activity Relationships of Pyrazolo[1,5-<i>a</i>]pyridine Derivatives: Potent and Orally Active Antagonists of Corticotropin-Releasing Factor 1 Receptor
  作者：Yoshinori Takahashi、Shigeki Hibi、Yorihisa Hoshino、Koichi Kikuchi、Kogyoku Shin、Kaoru Murata-Tai、Masae Fujisawa、Mitsuhiro Ino、Hisashi Shibata、Masahiro Yonaga

  DOI：10.1021/jm300259r

  日期：2012.6.14

  Design, synthesis, and structure activity relationships of a series of 3-dialkylamino-7-phenyl pyrazolo[1,5-a]pyridines (I) as selective antagonists of the corticotropin-releasing factor 1 (CRF1) receptor are described. The most prominent compound to emerge from this work, 46 (E2508), exhibits potent in vitro activity, excellent drug-like properties, and robust oral efficacy in animal models of stress-related disorders. It has advanced into clinical trials.