1,4-苯并二氧六环-2-甲酰胺 | 147031-85-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 中文名称: 1,4-苯并二氧六环-2-甲酰胺
• 中文别名: 1,4-苯并二氧六环-2-硫代甲酰胺；2,3-二氢-1,4-苯并二噁英-2-硫代甲酰胺
• 英文名称: 2,3-dihydro-1,4-benzodioxine-2-carbothioamide
• 英文别名: 2,3-dihydro-1,4-benzodioxine-3-carbothioamide
• CAS: 147031-85-4
• 化学式: C₉H₉NO₂S
• 分子量: 195.242
• InChiKey: ZOHVHNZPAGHKKO-UHFFFAOYSA-N

物化性质

• 熔点：
  180 °C
• 溶解度：
  >29.3 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  76.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  1,4-苯并二氧六环-2-甲酰胺 在 copper(II) bis(trifluoromethanesulfonate) 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 0.25h， 以78%的产率得到3,5-bis-(2,3-dihydrobenzo[1,4]dioxin-2-yl)-[1,2,4]thiadiazole
  参考文献：
  名称：

  铜 (II) 介导的硫代酰胺的同源偶联用于合成 1,2,4-噻二唑

  摘要：

  开发了铜 (II) 介导的硫代酰胺的高选择性氧化环化反应，以提供 3,5-二取代的 1,2,4-噻二唑。铜物种在这种转化中起着关键作用，并且在最佳反应条件下可以容忍不同的官能团。

  DOI：

  10.1002/ejoc.201402194
• 作为产物：
  描述：

  2,3-二氢苯并[1,4]二恶烷-2-甲腈 在 硫化氢 、 三乙胺 作用下， 以 吡啶 为溶剂， 反应 24.0h， 以95%的产率得到1,4-苯并二氧六环-2-甲酰胺
  参考文献：
  名称：

  Amide-oximes et hydroximates benzodioxaniques: synthèse de nouveaux composés et étude en neuropsycho-pharmacologie

  摘要：

  The authors describe the O(N)-(dialkylaminoalkyl) amide-oximes, benzodioxanic hydroximates and also the acetylated derivatives of the former compounds (I) which are detoxified. The hydroximates are obtained without structural ambiguity from thiono-esters. Pharmacological testing via the main methods shows that some of these new compounds possess imipraminic, and others neuroleptic properties.

  DOI：

  10.1016/0223-5234(92)90111-d

文献信息

• PIPERIDINE-AMIDE DERIVATIVES
  申请人：Andjelkovic Mirjana

  公开号：US20080300279A1

  公开（公告）日：2008-12-04

  The invention is concerned with novel piperidine-amide derivatives of formula (I) wherein R 1 , R 2 , X and Y are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds inhibit L-CPT1 and may be used to treat diseases associated with L-CPT1.

  这项发明涉及式（I）中的新型哌啶酰胺衍生物，其中R1、R2、X和Y如描述和权利要求中定义，并且其生理上可接受的盐和酯。这些化合物抑制L-CPT1，可用于治疗与L-CPT1相关的疾病。
• Discovery of 2-Aminothiazole-4-carboxamides, a Novel Class of Muscarinic M3 Selective Antagonists, through Solution-Phase Parallel Synthesis
  作者：Yufu Sagara、Morihiro Mitsuya、Minaho Uchiyama、Yoshio Ogino、Toshifumi Kimura、Norikazu Ohtake、Toshiaki Mase

  DOI：10.1248/cpb.53.437

  日期：——

  Synthesis and structure–activity relationship of a new class of muscarinic M3 selective antagonists were described. In the course of searching for a muscarinic M3 antagonist with a structure distinct from those of the 2-(4,4-difluorocyclopentyl)-2-phenylacetamide derivatives, we identified a thiazole-4-carboxamide derivative (1) as a lead compound in our in-house chemical collection. Since this compound (1) showed relatively low binding affinity (Ki=140 nM) for M3 receptors in the human binding assays, we tried to improve its potency and selectivity for M3 over M1 and M2 receptors by derivatization of 1 through a combinatorial approach. A solution-phase parallel synthesis effectively contributed to the optimization of each segment of 1. Thus, we have identified a cyclooctenylmethyl derivative (3e) and a cyclononenylmethyl derivative (3f) as representative M3 selective antagonists in this class.

  描述了一类新的选择性抗美洲豹M3受体拮抗剂的合成和结构-活性关系。在寻找一种结构与2-(4,4-二氟环戊基)-2-苯乙酰胺衍生物不同的抗美洲豹M3受体拮抗剂的过程中，我们在内部化学库中识别出了一种噻唑-4-氨基甲酸酯衍生物（1）作为领先化合物。由于该化合物（1）在人体结合实验中对M3受体的结合亲和力较低（Ki=140 nM），我们尝试通过组合化学方法对1进行衍生化，以提高其对M3受体的效能和对M1及M2受体的选择性。溶液相平行合成有效地促进了1的每个片段的优化。因此，我们识别出环辛烯基甲基衍生物（3e）和环壬烯基甲基衍生物（3f）作为该类抗美洲豹M3受体选择性拮抗剂的代表。
• Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 2
  作者：Marie Grimstrup、Øystein Rist、Jean-Marie Receveur、Thomas M. Frimurer、Trond Ulven、Jesper M. Mathiesen、Evi Kostenis、Thomas Högberg

  DOI：10.1016/j.bmcl.2009.12.015

  日期：2010.2

  Structure-activity relationships have been established by exploring the eastern and western side of 5-thiazolyleacetic acids as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. Benzhydryl motifs in the 2-position of the thiazole was found to be most advantageous. The 4-thiazole position should either carry 3- or 4-fluorophenyl rings or a 4-pyridyl suitably substituted in the flanking 2-position. Several compounds with single digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained. The compound series display a good PK profile and selectivity over a large number of other targets. (C) 2009 Elsevier Ltd. All rights reserved.
• US8039487B2
  申请人：——

  公开号：US8039487B2

  公开（公告）日：2011-10-18
• [EN] PIPERIDINE-AMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE PIPÉRIDINE-AMIDE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2008145596A1

  公开（公告）日：2008-12-04

  [EN] The invention is concerned with novel piperidine- amide derivatives of formula (I) wherein R1, R2, X and Y are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds inhibit L-CPT1 and can be used as medicaments.
  [FR] L'invention concerne des nouveaux dérivés de pipéridine-amide de formule (I) dans laquelle R1, R2, X et Y sont tels que définis dans la description et dans les revendications, ainsi que leurs sels et esters physiologiquement acceptables. Ces composés inhibent L-CPT1 et peuvent être utilisés comme médicaments.