tert-butyl N-(4-(1,1,3,3-tetraoxidobenzo[d][1,3,2]dithiazol-2-yl)phenyl)carbamate | 1239013-79-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl N-(4-(1,1,3,3-tetraoxidobenzo[d][1,3,2]dithiazol-2-yl)phenyl)carbamate
• 英文别名: tert-butyl (4-(1,1,3,3-tetraoxidobenzo[d][1,3,2]dithiazol-2-yl)phenyl)carbamate；tert-butyl N-[4-(1,1,3,3-tetraoxo-1λ6,3λ6,2-benzodithiazol-2-yl)phenyl]carbamate
• CAS: 1239013-79-6
• 化学式: C₁₇H₁₈N₂O₆S₂
• 分子量: 410.472
• InChiKey: SVDMLDSGRYXZRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl N-(4-(1,1,3,3-tetraoxidobenzo[d][1,3,2]dithiazol-2-yl)phenyl)carbamate 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 生成 N-(4-(1,1,3,3-tetraoxidobenzo[d][1,3,2]dithiazol-2-yl)phenyl)nicotinamide
  参考文献：
  名称：

  Discovery, Synthesis, and Structure–Activity Relationship Development of a Series of N-4-(2,5-Dioxopyrrolidin-1-yl)phenylpicolinamides (VU0400195, ML182): Characterization of a Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 (mGlu₄) with Oral Efficacy in an Antiparkinsonian Animal Model

  摘要：

  There is an increasing amount of literature data showing the positive effects on preclinical antiparkinsonian rodent models with selective positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)). However, most of the data generated utilize compounds that have not been optimized for druglike properties, and as a consequence, they exhibit poor pharmacokinetic properties and thus do not cross the blood-brain barrier. Herein, we report on a series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides with improved PK properties with excellent potency and selectivity as well as improved brain exposure in rodents. Finally, ML182 was shown to be orally active in the haloperidol induced catalepsy model, a well-established antiparkinsonian model.

  DOI：

  10.1021/jm200956q
• 作为产物：
  描述：

  1,2-苯二磺酰二氯 、 特定基氨基甲酸脂酶 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 tert-butyl N-(4-(1,1,3,3-tetraoxidobenzo[d][1,3,2]dithiazol-2-yl)phenyl)carbamate
  参考文献：
  名称：

  [EN] SUBSTITUTED 1,1,3,3-TETRAOXIDOBENZO[D][1,3,2]DITHIAZOLES AS MGLUR4 ALLOSTERIC POTENTIATORS, COMPOSITIONS, AND METHODS OF TREATING NEUROLOGICAL DYSFUNCTION
  [FR] 1,1,3,3-TÉTRAOXYDOBENZO[D][1,3,2]DITHIAZOLES SUBSTITUÉS EN TANT QUE POTENTIALISATEURS ALLOSTÉRIQUES DE MGLUR4, COMPOSITIONS ET PROCÉDÉS DE TRAITEMENT D'UN DYSFONCTIONNEMENT NEUROLOGIQUE

  摘要：

  用于代谢型谷氨酸受体4（mGluR4）的变构增强剂/正变构调节剂的化合物及其使用方法。

  公开号：

  WO2010088406A1

文献信息

• [EN] SUBSTITUTED 1,1,3,3-TETRAOXIDOBENZO[D][1,3,2]DITHIAZOLES AS MGLUR4 ALLOSTERIC POTENTIATORS, COMPOSITIONS, AND METHODS OF TREATING NEUROLOGICAL DYSFUNCTION<br/>[FR] 1,1,3,3-TÉTRAOXYDOBENZO[D][1,3,2]DITHIAZOLES SUBSTITUÉS EN TANT QUE POTENTIALISATEURS ALLOSTÉRIQUES DE MGLUR4, COMPOSITIONS ET PROCÉDÉS DE TRAITEMENT D'UN DYSFONCTIONNEMENT NEUROLOGIQUE
  申请人：UNIV VANDERBILT

  公开号：WO2010088406A1

  公开（公告）日：2010-08-05

  Compounds useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4) and methods of using the compounds.

  用于代谢型谷氨酸受体4（mGluR4）的变构增强剂/正变构调节剂的化合物及其使用方法。
• SUBSTITUTED 1,1,3,1-TETRAOXIDOBENZO[D][1,3,2]DITHIAZOLES AS MGLUR4 ALLOSTERIC POTENTIATORS, COMPOSITIONS, AND METHODS OF TREATING NEUROLOGICAL DYSFUNCTION
  申请人：Conn P. Jeffrey

  公开号：US20110319429A1

  公开（公告）日：2011-12-29

  Compounds useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4) and methods of using the compounds.

  该专利描述了一种化合物，可作为代谢型谷氨酸受体亚型4（mGluR4）的异构增强剂/正异构调节剂，并提供了使用该化合物的方法。
• Substituted 1,1,3,1-tetraoxidobenzo[D][1,3,2]dithiazoles as MGLUR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
  申请人：Conn P. Jeffrey

  公开号：US08658650B2

  公开（公告）日：2014-02-25

  Compounds useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4) and methods of using the compounds.

  本发明涉及一种作为代谢型谷氨酸受体亚型4（mGluR4）的异构增强剂/正异构调节剂有用的化合物以及使用这些化合物的方法。
• US8658650B2
  申请人：——

  公开号：US8658650B2

  公开（公告）日：2014-02-25
• Discovery, Synthesis, and Structure–Activity Relationship Development of a Series of <i>N</i>-4-(2,5-Dioxopyrrolidin-1-yl)phenylpicolinamides (VU0400195, ML182): Characterization of a Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 (mGlu₄) with Oral Efficacy in an Antiparkinsonian Animal Model
  作者：Carrie K. Jones、Darren W. Engers、Analisa D. Thompson、Julie R. Field、Anna L. Blobaum、Stacey R. Lindsley、Ya Zhou、Rocco D. Gogliotti、Satyawan Jadhav、Rocio Zamorano、Jim Bogenpohl、Yoland Smith、Ryan Morrison、J. Scott Daniels、C. David Weaver、P. Jeffrey Conn、Craig W. Lindsley、Colleen M. Niswender、Corey R. Hopkins

  DOI：10.1021/jm200956q

  日期：2011.11.10

  There is an increasing amount of literature data showing the positive effects on preclinical antiparkinsonian rodent models with selective positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)). However, most of the data generated utilize compounds that have not been optimized for druglike properties, and as a consequence, they exhibit poor pharmacokinetic properties and thus do not cross the blood-brain barrier. Herein, we report on a series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides with improved PK properties with excellent potency and selectivity as well as improved brain exposure in rodents. Finally, ML182 was shown to be orally active in the haloperidol induced catalepsy model, a well-established antiparkinsonian model.