4-amino-3,4-dihydro-2,2-dimethyl-6-fluoro-(2H)-1-benzopyran | 226922-93-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 4-amino-3,4-dihydro-2,2-dimethyl-6-fluoro-(2H)-1-benzopyran
• 英文别名: 6-fluoro-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-4-amine；6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-amine
• CAS: 226922-93-6
• 化学式: C₁₁H₁₄FNO
• 分子量: 195.237
• InChiKey: LLWCBPNSRBRTGN-UHFFFAOYSA-N

物化性质

• 沸点：
  244.1±40.0 °C(Predicted)
• 密度：
  1.099±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 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：
  3

反应信息

• 作为反应物：
  描述：

  4-amino-3,4-dihydro-2,2-dimethyl-6-fluoro-(2H)-1-benzopyran 在 2-氯-1-甲基吡啶碘化物 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 38.0h， 生成 2-(tert-butyl)-3-(6-fluoro-2,2-dimethylchroman-4-yl)-1-hydroxy-1-methylguanidine
  参考文献：
  名称：

  OXADIAZOLINE COMPOUND AND FORMULATION FOR CONTROLLING HARMFUL ORGANISMS

  摘要：

  本发明提供一种由式(I)表示的化合物（在式(I)中，R1代表取代或未取代的C1-6烷基基团，R2代表取代或未取代的C1-8烷基基团，R3代表氢原子或取代或未取代的C1-6烷基基团，A代表取代或未取代的o-苯基基团，取代或未取代的苯基基团等，B代表氧基，取代或未取代的氧甲基基团等，Q代表取代或未取代的o-苯基基团）或其盐。

  公开号：

  US20200170254A1
• 作为产物：
  描述：

  4-氟苯基醋酸酯 在 四氢吡咯 、 盐酸 、 sodium tetrahydroborate 、 三氯化铝 、 硫酸 作用下， 以 甲醇 为溶剂， 生成 4-amino-3,4-dihydro-2,2-dimethyl-6-fluoro-(2H)-1-benzopyran
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm040789e

文献信息

• Sulfonamide-substituted chromans, processes for their preparation, their use as a medicament or diagnostic, and medicament comprising them
  申请人：Hoechst Aktiengesellschaft

  公开号：US06191164B1

  公开（公告）日：2001-02-20

  Sulfonamide-substituted chromans, processes for their preparation, their use as a medicament or a diagnostic, and medicament comprising them Chromans of the formula I and of the formula 1a having the meanings R(A), R(B), R(C) and R(1) to R(8) indicated in the claims are outstandingly suitable for preparing a medicament for blocking the K+ channel which is opened by cyclic adenosine monophosphate (cAMP); and further for preparing a medicament for inhibiting gastric acid secretion; for the treatment of ulcers of the stomach and of the intestinal region, in particular of the duodenum, for the treatment of reflux esophagitis, for the treatment of diarrheal illnesses, for the treatment and prevention of all types of arrhythmias including ventricular and supraventricular arrhythmias, and for the control of reentry arrhythmias and for the prevention of sudden heart death as a result of ventricular fibrillation.

  磺胺基取代的色苷，其制备方法，其用作药物或诊断的用途，以及包含它们的药物 具有下式I的色苷和下式1a的色苷，其中在权利要求中指示的R(A)、R(B)、R(C)和R(1)到R(8)的含义，非常适合制备用于阻断由环磷酸腺苷单磷酸（cAMP）打开的K+通道的药物；进一步用于制备用于抑制胃酸分泌的药物；用于治疗胃和肠道溃疡，特别是十二指肠的药物；用于治疗反流性食道炎；用于治疗腹泻疾病；用于治疗和预防包括室性和房性心律失常在内的所有类型心律失常；用于控制再入性心律失常和预防由室颤引起的突发心脏死亡。
• TRPV1 ANTAGONISTS
  申请人：AbbVie Inc.

  公开号：US20130345255A1

  公开（公告）日：2013-12-26

  Disclosed herein are compounds of formula (I) or pharmaceutically acceptable salts, prodrugs, or combinations thereof, wherein X 1 , L, R x , R y , R z , R 1 , R 2 , A, m, n, p, q, and r are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

  本文披露了具有以下结构的化合物（I）或药用盐、前药或其组合物，其中X1、L、Rx、Ry、Rz、R1、R2、A、m、n、p、q和r在规范中有定义。还披露了包含这些化合物的组合物以及使用这些化合物和组合物治疗疾病和疾病的方法。
• Design, Synthesis, and Pharmacological Evaluation of <i>R/S</i>-3,4-Dihydro-2,2-dimethyl- 6-halo-4-(phenylaminocarbonylamino)-2<i>H</i>-1-benzopyrans:  Toward Tissue-Selective Pancreatic β-Cell <i>K</i>_ATP Channel Openers Structurally Related to (±)-Cromakalim
  作者：Sophie Sebille、David Gall、Pascal de Tullio、Xavier Florence、Philippe Lebrun、Bernard Pirotte

  DOI：10.1021/jm060161z

  日期：2006.7.1

  (+/-)-cromakalim and acting as pancreatic beta-cell potassium channel openers, several R/S-3,4-dihydro-2,2-dimethyl-6-halo-4-(phenylaminocarbonylamino)-2H-1-benzopyrans with or without a substituent on the phenyl ring in the 4-position were synthesized. Their activity on rat-insulin-secreting cells and rat aorta rings was compared to that of the K(ATP) channel activators (+/-)-cromakalim, diazoxide, (+/-)-pinacidil

  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
• [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