3-(2-methylprop-2-en-1-yl)-2-thioxo-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 3-(2-methylprop-2-en-1-yl)-2-thioxo-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-one
• 英文别名: 3-(2-methyl-2-propenyl)-2-sulfanyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one；3-(2-methylprop-2-enyl)-2-sulfanylidene-5,6,7,8-tetrahydro-1H-[1]benzothiolo[2,3-d]pyrimidin-4-one
• 化学式: C₁₄H₁₆N₂OS₂
• mdl: MFCD00809215
• 分子量: 292.426
• InChiKey: KFVNTQPYJUJGSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  92.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(2-methylprop-2-en-1-yl)-2-thioxo-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-one 在 溶剂黄146 、 sodium sulfite 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 8.0h， 生成 2-methyl-2-(dichloro(4-ethoxyphenyl)tellurylmethyl)-2,3,6,7,8,9-hexahydro-5H-benzo[4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidin-5-one
  参考文献：
  名称：

  5,6-二取代的 3-烯基-2-硫代噻吩并[2,3-d]嘧啶-4-one与对烷氧基苯基三氯化物的杂环化

  摘要：

  摘要 5,6-二取代的 3-烯基-2-硫代噻吩并[2,3-d]嘧啶-4-酮通过对-烷氧基苯基三氯化物处理的亲电杂环化导致噻唑啉部分的环化，形成6,7-二取代-2-[二氯-(对烷氧基苯基)碲甲基]-2,3-二氢-5Н-[1,3]噻唑并[3,2-а]噻吩并[2,3-d]嘧啶-5-酮盐酸盐.

  DOI：

  10.1515/hc-2016-0169
• 作为产物：
  描述：

  2-氨基-4,5,6,7-四氢苯并噻酚-3-羧酸乙酯 在 三乙胺 、 sodium hydroxide 作用下， 以 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 4.0h， 生成 3-(2-methylprop-2-en-1-yl)-2-thioxo-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-one
  参考文献：
  名称：

  Development of thieno- and benzopyrimidinone inhibitors of the Hedgehog signaling pathway reveals PDE4-dependent and PDE4-independent mechanisms of action

  摘要：

  From a high content in vivo screen for modulators of developmental patterning in embryonic zebrafish, we previously identified eggmanone (EGM1, 3) as a Hedgehog (Hh) signaling inhibitor functioning downstream of Smoothened. Phenotypic optimization studies for in vitro probe development utilizing a Gli transcription-linked stable luciferase reporter cell line identified EGM1 analogs with improved potency and aqueous solubility. Mechanistic profiling of optimized analogs indicated two distinct scaffold clusters: PDE4 inhibitors able to inhibit downstream of Sufu, and PDE4-independent Hh inhibitors functioning between Smo and Sufu. Each class represents valuable in vitro probes for elucidating the complex mechanisms of Hh regulation. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.03.013

文献信息

• [EN] COMPOUNDS AND METHODS FOR INHIBITION OF HEDGEHOG SIGNALING AND PHOSPHODIESTERASE<br/>[FR] COMPOSÉS ET PROCÉDÉS D'INHIBITION DE LA SIGNALISATION HEDGEHOG ET DE LA PHOSPHODIESTÉRASE
  申请人：UNIV VANDERBILT

  公开号：WO2016040951A1

  公开（公告）日：2016-03-17

  Compounds and compositions, and methods of use thereof, are provided and have utility in inhibiting hedgehog signaling and/or phosphodiesterase-4 activity.

  提供了化合物、组合物及其使用方法，具有抑制刺猬信号和/或磷酸二酯酶4活性的效用。
• Compounds and methods for inhibition of hedgehog signaling and phosphodiesterase
  申请人：Vanderbilt University

  公开号：US10329304B2

  公开（公告）日：2019-06-25

  Compounds and compositions, and methods of use thereof, are provided and have utility in inhibiting hedgehog signaling and/or phosphodiesterase-4 activity.

  所提供的化合物和组合物及其使用方法可用于抑制刺猬信号和/或磷酸二酯酶-4 的活性。
• Compounds and Methods for Inhibition of Hedgehog Signaling and Phosphodiesterase
  申请人：Vanderbilt University

  公开号：US20170190717A1

  公开（公告）日：2017-07-06

  Compounds and compositions, and methods of use thereof, are provided and have utility in inhibiting hedgehog signaling and/or phosphodiesterase-4 activity.
• Development of thieno- and benzopyrimidinone inhibitors of the Hedgehog signaling pathway reveals PDE4-dependent and PDE4-independent mechanisms of action
  作者：Jonathan E. Hempel、Adrian G. Cadar、Charles C. Hong

  DOI：10.1016/j.bmcl.2016.03.013

  日期：2016.4

  From a high content in vivo screen for modulators of developmental patterning in embryonic zebrafish, we previously identified eggmanone (EGM1, 3) as a Hedgehog (Hh) signaling inhibitor functioning downstream of Smoothened. Phenotypic optimization studies for in vitro probe development utilizing a Gli transcription-linked stable luciferase reporter cell line identified EGM1 analogs with improved potency and aqueous solubility. Mechanistic profiling of optimized analogs indicated two distinct scaffold clusters: PDE4 inhibitors able to inhibit downstream of Sufu, and PDE4-independent Hh inhibitors functioning between Smo and Sufu. Each class represents valuable in vitro probes for elucidating the complex mechanisms of Hh regulation. Published by Elsevier Ltd.
• Heterocyclization of 5,6-disubstituted 3-alkenyl-2-thioxothieno[2,3-<i>d</i>]pyrimidin-4-one with <i>p</i>-alkoxyphenyltellurium trichloride
  作者：Mykola Kut、Mikhajlo Onysko、Vasyl Lendel

  DOI：10.1515/hc-2016-0169

  日期：2016.12.1

  Abstract Electrophilic heterocyclization of 5,6-disubstituted 3-alkenyl-2-thioxothieno[2,3-d]pyrimidin-4-ones by treatment with p-alkoxyphenyltellurium trichlorides leads to annulation of the thiazoline moiety with the formation of 6,7-disubstituted-2-[dichloro-(p-alkoxyphenyl)telluromethyl]-2,3-dihydro-5Н-[1,3]thiazolo[3,2-а]thieno[2,3-d]pyrimidin-5-one hydrochlorides.

  摘要 5,6-二取代的 3-烯基-2-硫代噻吩并[2,3-d]嘧啶-4-酮通过对-烷氧基苯基三氯化物处理的亲电杂环化导致噻唑啉部分的环化，形成6,7-二取代-2-[二氯-(对烷氧基苯基)碲甲基]-2,3-二氢-5Н-[1,3]噻唑并[3,2-а]噻吩并[2,3-d]嘧啶-5-酮盐酸盐.