6-氯-2,2-二甲基-3,4-二氢色烯-4-胺 | 841269-03-2

• 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-氯-2,2-二甲基-3,4-二氢色烯-4-胺
• 英文名称: (RS)-4-amino-6-chloro-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran
• 英文别名: 4-amino-6-chloro-3,4-dihydro-2,2-dimethyl-(2H)-1-benzopyran；4-amino-3,4-dihydro-2,2-dimethyl-6-chloro-2H-1-benzopyran；(6-chloro)-2,2-dimethylchroman-4-amine；6-Chloro-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-4-amine；6-chloro-2,2-dimethyl-3,4-dihydrochromen-4-amine
• CAS: 841269-03-2
• 化学式: C₁₁H₁₄ClNO
• 分子量: 211.691
• InChiKey: YCHLOTPQPGERAD-UHFFFAOYSA-N

物化性质

• 熔点：
  70-73.5 °C
• 沸点：
  279.2±40.0 °C(Predicted)
• 密度：
  1.142±0.06 g/cm3(Predicted)

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

反应信息

• 作为反应物：
  描述：

  对甲氧基苯异氰酸酯 、 6-氯-2,2-二甲基-3,4-二氢色烯-4-胺 以 二氯甲烷 为溶剂， 反应 0.33h， 以51%的产率得到R/S-6-chloro-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

文献信息

• [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
• CHROMANE DERIVATIVES AS TRPV3 MODULATORS
  申请人：Lingam V S Prasadarao

  公开号：US20100311778A1

  公开（公告）日：2010-12-09

  The present invention provides transient receptor potential vanilloid (TRPV) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPV3. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPV3.

  本发明提供了暂时性受体电位香草醛(TRPV)调节剂。特别地，本文所描述的化合物对于治疗或预防由TRPV3调节的疾病、状况和/或疾病非常有用。此外，本文还提供了制备所述化合物的过程、用于其合成的中间体、其制药组合物以及治疗或预防由TRPV3调节的疾病、状况和/或疾病的方法。
• 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.