2-cyclohexyl-8-(vinylsulfonyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one | 1253926-01-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 2-cyclohexyl-8-(vinylsulfonyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one
• 英文别名: 2-Cyclohexyl-8-ethenesulfonyl-1,3,8-triaza-spiro[4.5]dec-1-en-4-one；2-cyclohexyl-8-ethenylsulfonyl-1,3,8-triazaspiro[4.5]dec-1-en-4-one
• CAS: 1253926-01-0
• 化学式: C₁₅H₂₃N₃O₃S
• 分子量: 325.432
• InChiKey: WYORIZDGZYRRGE-UHFFFAOYSA-N

物化性质

• 沸点：
  483.7±55.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  87.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-cyclohexyl-8-(vinylsulfonyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one 在 N-甲基二环己基胺 、 palladium 10% on activated carbon 、 氢气 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 N-甲基吡咯烷酮 、 乙醇 、 溶剂黄146 、 乙酸乙酯 为溶剂， 反应 49.5h， 生成 2-cyclohexyl-8-(phenethylsulfonyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one
  参考文献：
  名称：

  Development of a Novel Human Parathyroid Hormone Receptor 1 (hPTHR1) Agonist (CH5447240), a Potent and Orally Available Small Molecule for Treatment of Hypoparathyroidism

  摘要：

  During the course of derivatization of HTS hit 4a, we have identified a novel small-molecule hPTHRl agonist, l-(3,5-dimethyl-4-(2-((2-((lR,4R)-4-methylcyclohexyl)-4-oxo-l,3,8-triazaspiro[4.5]dec-l-en-8-yl)sulfonyl)ethyl)-phenyl)-l-methylurea (CH5447240, 141). Compound 141 exhibited a potent in vitro hPTHRl agonist effect with EC20 of 3.0 mu M and EC50 of 12 mu M and showed excellent physicochemical properties, such as high solubility in fasted state simulated intestinal fluid and good metabolic stability in human liver microsomes. Importantly, 141 showed 55% oral bioavailability and a significantly elevated serum calcium level in hypocalcemic model rats.

  DOI：

  10.1021/acs.jmedchem.8b00182
• 作为产物：
  描述：

  4-氨基-4-氰基-哌啶-1-羧酸叔丁酯 在 盐酸 、 4-二甲氨基吡啶 、 双氧水 、 三乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 8.0h， 生成 2-cyclohexyl-8-(vinylsulfonyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one
  参考文献：
  名称：

  Development of a Novel Human Parathyroid Hormone Receptor 1 (hPTHR1) Agonist (CH5447240), a Potent and Orally Available Small Molecule for Treatment of Hypoparathyroidism

  摘要：

  During the course of derivatization of HTS hit 4a, we have identified a novel small-molecule hPTHRl agonist, l-(3,5-dimethyl-4-(2-((2-((lR,4R)-4-methylcyclohexyl)-4-oxo-l,3,8-triazaspiro[4.5]dec-l-en-8-yl)sulfonyl)ethyl)-phenyl)-l-methylurea (CH5447240, 141). Compound 141 exhibited a potent in vitro hPTHRl agonist effect with EC20 of 3.0 mu M and EC50 of 12 mu M and showed excellent physicochemical properties, such as high solubility in fasted state simulated intestinal fluid and good metabolic stability in human liver microsomes. Importantly, 141 showed 55% oral bioavailability and a significantly elevated serum calcium level in hypocalcemic model rats.

  DOI：

  10.1021/acs.jmedchem.8b00182

文献信息

• Spiroimidazolone derivative
  申请人：Esaki Toru

  公开号：US09169254B2

  公开（公告）日：2015-10-27

  The present invention relates to a compound represented by the following formula (1): wherein W, X, Y, R1, R2, R33, R34, m and n are as defined in the claims, or a pharmacologically acceptable salt thereof.

  本发明涉及一种由以下式(1)表示的化合物：其中W、X、Y、R1、R2、R33、R34、m和n如权利要求中所定义，或其药学上可接受的盐。
• Synthesis and Biological Evaluations of Novel Human Parathyroid Hormone 1 Receptor (hPTHR1) Agonists Bearing Bicyclic Aromatic Moiety
  作者：Yoshikazu Nishimura、Toru Esaki、Yoshiaki Isshiki、Yoshiyuki Furuta、Takashi Emura、Yoshiaki Watanabe、Masateru Ohta、Shinichi Arai、Hiroshi Noda、Masaru Shimizu、Tatsuya Tamura、Haruhiko Sato

  DOI：10.1002/cmdc.202300589

  日期：2024.3

  This study provides a synthesis and structure-activity relationship of biaryl spiroimidazolone compounds with PTHR1 agonist activity. The aromatic group and ethyl linker of compound 2a were converted to improve activity and solubility. The resulting compound 2j increased the bone mineral density of ovariectomized rats as PTH1–34. The SAR and in vivo effects are discussed.

  本研究提供了具有 PTHR1 激动剂活性的联芳基螺酰咪唑酮化合物的合成和构效关系。化合物2a的芳香基团和乙基连接基被转化以提高活性和溶解度。所得化合物2j增加了卵巢切除大鼠的骨矿物质密度（PTH1-34）。讨论了 SAR 和体内效应。
• SPIROIMIDAZOLONE DERIVATIVE
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP2433940B9

  公开（公告）日：2015-10-28
• US9169254B2
  申请人：——

  公开号：US9169254B2

  公开（公告）日：2015-10-27
• US9487517B2
  申请人：——

  公开号：US9487517B2

  公开（公告）日：2016-11-08