6-溴-3,4-二氢-2,2-二甲基-2H-1-苯并吡喃-4-胺 | 226922-92-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 6-溴-3,4-二氢-2,2-二甲基-2H-1-苯并吡喃-4-胺
• 中文别名: 4-氨基-6-溴-3,4-二氢-2,2-二甲基-2H-1-苯并吡喃
• 英文名称: 4-amino-6-bromo-3,4-dihydro-2,2-dimethyl-(2H)-1-benzopyran
• 英文别名: 6-Bromo-2,2-dimethylchroman-4-amine；6-bromo-2,2-dimethyl-3,4-dihydrochromen-4-amine
• CAS: 226922-92-5
• 化学式: C₁₁H₁₄BrNO
• 分子量: 256.142
• InChiKey: PXJLFYGCARIYEH-UHFFFAOYSA-N

物化性质

• 沸点：
  293.0±40.0 °C(Predicted)
• 密度：
  1.351

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2932999099
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储温度应保持在2-8°C，并请避免光照。

反应信息

• 作为反应物：
  描述：

  对甲氧基苯异氰酸酯 、 6-溴-3,4-二氢-2,2-二甲基-2H-1-苯并吡喃-4-胺 以 二氯甲烷 为溶剂， 反应 0.33h， 以38%的产率得到R/S-6-bromo-3,4-dihydro-2,2-dimethyl-4-(4-methoxyphenylaminocarbonylamino)-2H-1-benzopyran
  参考文献：
  名称：

  R / S-3,4-二氢-2,2-二甲基-6-卤代-4-（苯基氨基羰基氨基）-2H-1-苯并吡喃的设计，合成和药理学评估：朝向组织选择性胰腺β细胞KATP通道在结构上与（+/-）-cromakalim有关的开瓶器。

  摘要：

  在寻找一系列与（+/-）-cromakalim结构相关并充当胰腺β细胞钾通道开放剂的苯并吡喃类化合物时，一些R / S-3,4-dihydro-2,2-methyldimethyl-6-halo合成了在4-位的苯环上具有或没有取代基的-4-（苯基氨基羰基氨基）-2H-1-苯并吡喃。将它们对大鼠胰岛素分泌细胞和大鼠主动脉环的活性与K（ATP）通道激活剂（+/-）-cromakalim，二氮嗪，（+/-）-pinacidil和化合物4的活性进行了比较。结构活性这种关系表明，对胰腺组织的最明显的抑制活性是通过在C-4苯环（药物37-42）上引入一个间位或对位电子吸收基团（一个氯原子）而获得的。这样的分子与母体化合物（+/-）-cromakalim不同，胰组织对血管组织的选择性也很高。用R / S-6-氯-4-（3-氯苯基氨基羰基氨基）-3,4-二氢-2,2-二甲基-2H-1-b恩佐吡喃进行的放射

  DOI：

  10.1021/jm060161z
• 作为产物：
  描述：

  4-溴苯基乙酸酯 在 四氢吡咯 、 盐酸 、 sodium tetrahydroborate 、 三氯化铝 、 硫酸 作用下， 以 甲醇 为溶剂， 反应 10.0h， 生成 6-溴-3,4-二氢-2,2-二甲基-2H-1-苯并吡喃-4-胺
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of K<SUB>ATP</SUB>-channel Openers Related to Cromakalim: Introduction of Arylsulphonylurea Moieties

  摘要：

  DOI：

  10.1211/146080899128734587

文献信息

• [EN] NOVEL COMPOUNDS HAVING INHIBITORY ACTIVITY AGAINST GLUCOSYLCERAMIDE SYNTHASE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PROCESSES FOR PREPARING THE SAME, AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME<br/>[FR] NOUVEAUX COMPOSÉS AYANT UNE ACTIVITÉ INHIBITRICE CONTRE LA GLUCOSYLCÉRAMIDE SYNTHASE OU SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CEUX-CI, LEURS PROCÉDÉS DE PRÉPARATION, ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT
  申请人：YUHAN CORP

  公开号：WO2021096241A1

  公开（公告）日：2021-05-20

  The present invention provides a novel compound having a chromane, isochromane, thiochromane, or tetrahydroquinoline moiety or pharmaceutically acceptable salt thereof, a process for the preparation thereof, a pharmaceutical composition comprising the same and a use thereof. The compound having a chromane, isochromane, thiochromane, or tetrahydroquinoline moiety or pharmaceutically acceptable salt thereof has an inhibitory activity against glucosylceramide synthase (GCS), and therefore can be usefully applied for preventing or treating various diseases associated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachs disease, Parkinson's disease, etc.

  本发明提供了一种具有色烷、异色烷、硫色烷或四氢喹啉基团的新化合物或其药用可接受盐，其制备方法，包含该化合物的药物组合物及其用途。具有色烷、异色烷、硫色烷或四氢喹啉基团或其药用可接受盐的化合物对葡萄糖基鞘氨醇合酶（GCS）具有抑制作用，因此可有益地应用于预防或治疗与GCS相关的各种疾病，如戈谢病、法布里病、泰萨病、帕金森病等。
• [EN] BENZOPYRAN DERIVATIVES, METHOD OF PRODUCTION AND USE THEREOF<br/>[FR] DERIVES DE BENZOPYRANE, PROCEDE DE PRODUCTION ET D'UTILISATION DE CEUX-CI
  申请人：UNIV LIEGE

  公开号：WO2005075463A1

  公开（公告）日：2005-08-18

  The invention relates to novel benzopyran derivatives of formula (I), to their method of production, to composition comprising the derivatives and use thereof. Formula (I) wherein: R1, R2, R3 and R4 are independently hydrogen, halogen, C1-6-alkyl. C3-8­-cycloalkyl, hydroxy, C1-6-alkoxy, C1-6-alkoxy-C1-6-alkyl, nitro, amino, cyano, cyanomethyl, perhalomethyl, C1-6-monoalkyl- or dialkylamino, sulfamoyl, C1-6-alkylthio, C1-6-alkylsulfonyl, C1-6-alkylsulfinyl, formyl, C1-6-alkylcarbonylamino, R8arylthio, R8arylsulfinyl, R8arylsulfonyl, C1-6-alkoxycarbonyl, C1-6-alkoxycarbonyl-C1-6-alkyl, carbamoyl, carbamoylmethyl, C1-6-monoalkyl- or dialkylaminocarbonyl, C1-6-monoalkyl- or dialkylaminothiocarbonyl, ureido, C1-6-monoalkyl- or dialkylaminocarbonylamino, thioureido, C1-6-monoalkyl- or dialkylaminothiocarbonylamino, C1-6-monoalkyl- or dialkylaminosulfonyl, carboxy, carboxy-C1-6-alkyl, acyl, R8aryl, R8aryl-C1-6-alkyl, R8aryloxy; R5 and R6 are each independently hydrogen, C1-6-alkyl or, R5 and R6 taken together with the carbon atom to which they are attached form a 3- to 6-membered carbocyclic ring; R7 is 2-, 3- or 4-pyridyl optionally mono- or polysubstituted by R1; R7 is 2- or 3-thienyl optionally mono- or polysubstituted substituted by R1 or R7 is phenyl optionally mono- or polysubstituted by R1 with the exception of or R7 representing C6H5 ; R8 is hydrogen, halogen, C1-6-alkyl, C3-8-cycloalkyl, hydroxy, C1-6-alkoxy, nitro, amino, cyano, cyanomethyl, perhalomethyl; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture or any polymorphic and tautomeric form.

  该发明涉及公式（I）的新型苯并吡喃衍生物，以及它们的生产方法、包含这些衍生物的组合物和它们的用途。公式（I）中：R1、R2、R3和R4独立地为氢、卤素、C1-6-烷基、C3-8-环烷基、羟基、C1-6-烷氧基、C1-6-烷氧基-C1-6-烷基、硝基、氨基、氰基、氰甲基、全卤甲基、C1-6-单烷基或二烷基氨基、磺酰胺基、C1-6-烷基硫基、C1-6-烷基磺酰基、C1-6-烷基亚磺酰基、甲酰基、C1-6-烷基羰胺基、R8芳基硫基、R8芳基亚磺酰基、R8芳基磺酰基、C1-6-烷氧羰基、C1-6-烷氧羰基-C1-6-烷基、氨基甲酰基、氨基甲基、C1-6-单烷基或二烷基氨基甲酰基、C1-6-单烷基或二烷基氨基硫酰基、脲基、C1-6-单烷基或二烷基氨基甲酰胺基、硫脲基、C1-6-单烷基或二烷基氨基硫酰胺基、C1-6-单烷基或二烷基氨基磺酰基、羧基、羧基-C1-6-烷基、酰基、R8芳基、R8芳基-C1-6-烷基、R8芳氧基；R5和R6各自独立地为氢、C1-6-烷基或者R5和R6与它们连接的碳原子一起形成3-至6-成员的碳环；R7为2-、3-或4-吡啶基，可选地通过R1单取代或多取代；R7为2-或3-噻吩基，可选地通过R1单取代或多取代，或者R7为苯基，可选地通过R1单取代或多取代，但不包括R7代表C6H5；R8为氢、卤素、C1-6-烷基、C3-8-环烷基、羟基、C1-6-烷氧基、硝基、氨基、氰基、氰甲基、全卤甲基；或其与药学上可接受的酸或碱形成的盐，或任何光学异构体或光学异构体混合物，包括消旋混合物或任何多形和互变异构体。
• New R/S-3,4-dihydro-2,2-dimethyl-6-halo-4-(phenylaminothiocarbonylamino)-2H-1-benzopyrans structurally related to (±)-cromakalim as tissue-selective pancreatic β-cell KATP channel openers
  作者：Sophie Sebille、Pascal de Tullio、Xavier Florence、Bénédicte Becker、Marie-Hélène Antoine、Catherine Michaux、Johan Wouters、Bernard Pirotte、Philippe Lebrun

  DOI：10.1016/j.bmc.2008.03.065

  日期：2008.5

  the vascular smooth muscle tissue (relaxation of aorta rings). The biological activity of these new dimethylchroman derivatives was further compared to that of (+/-)-cromakalim, (+/-)-pinacidil, diazoxide and BPDZ 73. Structure-activity relationships indicated that an improved potency for the pancreatic tissue was obtained by introducing a meta- or a para-electron-withdrawing group such as a chlorine

  本工作旨在探索一系列与（+/-）结构相关的R / S-3,4-二氢-2,2-二甲基-6-卤代4-（苯基氨基硫代羰基氨基）-2H-1-苯并吡喃-cromakalim，在4位和6位上有不同取代。这些推定的ATP敏感性钾通道激活剂（K（ATP））的生物学效应在体外在胰腺内分泌组织上（抑制胰岛素释放）和在血管平滑肌组织上（主动脉环松弛）进行了表征。进一步将这些新的二甲基苯并二氢吡喃衍生物的生物活性与（+/-）-cromakalim，（+/-）-吡那地尔，二氮嗪和BPDZ 73的生物活性进行了比较。构效关系表明，通过在C-4苯环上引入间位或对位电子吸收基团（例如氯原子），可以获得胰腺组织增强的效力，而与卤素原子的性质无关苯并吡喃核的6位。大多数原始的二甲基苯并二氢吡喃硫脲在抑制胰岛素释放方面比其“脲”同系物更有效，甚至比二氮嗪更有效。此外，与（+/-）-cromakalim或（+/-）-吡那地尔不同
• 4,6-Disubstituted 2,2-Dimethylchromans Structurally Related to the K_ATP Channel Opener Cromakalim: Design, Synthesis, and Effect on Insulin Release and Vascular Tone
  作者：Sophie Sebille、Pascal de Tullio、Bénédicte Becker、Marie-Hélène Antoine、Stéphane Boverie、Bernard Pirotte、Philippe Lebrun

  DOI：10.1021/jm040789e

  日期：2005.1.1

  Five series (ureas, thioureas, carbamates, sulfonylureas, and amides) of 4,6-disubstituted-2,2dimethylchromans structurally related to cromakalim were prepared and evaluated, as putative ATP-sensitive potassium channel activators, on rat pancreatic islets and rat aorta rings. The biological data indicate that most compounds were, like the reference molecule cromakalim, more active on the vascular smooth muscle tissue (myorelaxant effect on 30 mM KCl induced contractions of rat aorta rings) than on the pancreatic tissue (inhibition of 16.7 mM glucose induced insulin release from rat pancreatic islets). However, some drugs (8h, 8i, 9f, 9g, 9h, and 9i) markedly inhibited insulin release and exhibited an activity equivalent or greater than that of diazoxide. Compounds 9h and 9i were also found to be more active on pancreatic beta-cells than on vascular smooth muscle cells. Last, the amide 6b was selected in order to examine its mechanism of action on vascular smooth muscle cells. Pharmacological results suggest that the compound acted as a K-ATP channel opener. In conclusion, the present data indicate that appropriate structural modifications can generate dimethylchromans with pharmacological profiles different from that of cromakalim.
• New R/S-3,4-dihydro-2,2-dimethyl-2H-1-benzopyrans as KATP channel openers: Modulation of the 4-position
  作者：Xavier Florence、Sophie Sebille、Pascal de Tullio、Philippe Lebrun、Bernard Pirotte

  DOI：10.1016/j.bmc.2009.09.041

  日期：2009.11

  The present work aimed at exploring a series of diversely 4-arylthiourea-substituted R/S-3,4-dihydro-2,2-dimethyl- 6-halo-2H-1-benzopyrans structurally related to (+/-)-cromakalim. These new compounds were examined in vitro as putative potassium channel openers (PCOs) on rat pancreatic islets (inhibition of insulin release) as well as on rat aorta rings (relaxation of aorta ring) and their activity was compared to that of the reference K-ATP channel activators (+/-)-cromakalim, (+/-)-pinacidil, diazoxide and of previously reported cromakalim analogues. Structure-activity relationships indicated that the most pronounced inhibitory activity on the insulin secretory process was obtained with molecules bearing a strong metaor para-electron-withdrawing group (CN or NO2) on the phenyl ring of the arylthiourea moiety at the 4-position of the benzopyran nucleus (compounds 12-23). Among those, R/S-6-chloro-4-(4-cyanophenylaminothiocarbonylamino)-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran (16) was found to be the most potent benzopyran-type inhibitor of insulin release ever described. Most of these original benzopyran derivatives show increased selectivity for pancreatic versus vascular tissue. Radioisotopic investigations indicated that these new compounds activated pancreatic KATP channels. (C) 2009 Elsevier Ltd. All rights reserved.