4-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromene-4-carbonitrile | 1001582-11-1

• 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-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromene-4-carbonitrile
• 英文别名: 4-hydroxy-2,2-dimethylchroman-4-carbonitrile；4-hydroxy-2,2-dimethyl-3H-chromene-4-carbonitrile
• CAS: 1001582-11-1
• 化学式: C₁₂H₁₃NO₂
• 分子量: 203.241
• InChiKey: BLRBZWRJBGBVGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  53.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromene-4-carbonitrile 在 potassium carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 3.33h， 生成 4'-imino-2,2-dimethyl-3'-[4-acetamidobenzyl]-2,3-dihydro-2'H-spiro[chromene-4,5'-[1,3]oxazolidin]-2'-one
  参考文献：
  名称：

  Synthesis and biological evaluation of 5-membered spiro heterocycle-benzopyran derivatives against myocardial ischemia

  摘要：

  The activation of ATP-sensitive potassium channels (K-ATP), play a key role in an endogenous "self-defence" mechanism, known as ischemic preconditioning (IPC), which is fundamentally involved in the protection of the heart against the ischemia/reperfusion injury. Presently, it is widely accepted that IPC is mainly (albeit not exclusively) mediated by the activation of K-ATP channels expressed in the mitochondrial inner membrane (mito-K-ATP) rather than the sarcoplasmatic ones (sarc-K-ATP). Consistently, exogenous activation of K-ATP channels by pharmacological tools can be viewed as one of the most promising strategies for the therapy of myocardial ischemia. As part of our research program devoted to the synthesis and the evaluation of new cardioprotective agents, we extensively studied several six-membered spiro-heterocycle-benzopyran compounds endowed of a significant anti-ischemic activity. The positive results obtained, prompted us to further explore the influence on the biopharmacological effects, of the spiro-substitution at C4 benzopyran nucleus by replacing the six-membered spirocycle of the most active compounds with 5-membered-one.The preliminary evaluation of the new compounds on cultured H9c2 cardiomyoblasts exposed to anoxia/reperfusion and on Langendorff-perfused rat hearts submitted to ischemia/reperfusion cycles, showed that some of them can exert a cardioprotective effect. This anti-ischemic activity was antagonized by 5-hydroxydecanoic acid, a selective blocker of mito-K-ATP channels, confirming the involvement of this channel in the cardioprotective activity. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.003
• 作为产物：
  描述：

  3,4-dihydro-2,2-dimethyl-4-[(trimethylsilyl)oxy]-2H-1-benzopyran-4-carbonitrile 在 盐酸 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以89%的产率得到4-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromene-4-carbonitrile
  参考文献：
  名称：

  Synthesis and biological evaluation of 5-membered spiro heterocycle-benzopyran derivatives against myocardial ischemia

  摘要：

  The activation of ATP-sensitive potassium channels (K-ATP), play a key role in an endogenous "self-defence" mechanism, known as ischemic preconditioning (IPC), which is fundamentally involved in the protection of the heart against the ischemia/reperfusion injury. Presently, it is widely accepted that IPC is mainly (albeit not exclusively) mediated by the activation of K-ATP channels expressed in the mitochondrial inner membrane (mito-K-ATP) rather than the sarcoplasmatic ones (sarc-K-ATP). Consistently, exogenous activation of K-ATP channels by pharmacological tools can be viewed as one of the most promising strategies for the therapy of myocardial ischemia. As part of our research program devoted to the synthesis and the evaluation of new cardioprotective agents, we extensively studied several six-membered spiro-heterocycle-benzopyran compounds endowed of a significant anti-ischemic activity. The positive results obtained, prompted us to further explore the influence on the biopharmacological effects, of the spiro-substitution at C4 benzopyran nucleus by replacing the six-membered spirocycle of the most active compounds with 5-membered-one.The preliminary evaluation of the new compounds on cultured H9c2 cardiomyoblasts exposed to anoxia/reperfusion and on Langendorff-perfused rat hearts submitted to ischemia/reperfusion cycles, showed that some of them can exert a cardioprotective effect. This anti-ischemic activity was antagonized by 5-hydroxydecanoic acid, a selective blocker of mito-K-ATP channels, confirming the involvement of this channel in the cardioprotective activity. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.003

文献信息

• Ungesättigte N-Benzopyranyllactame
  申请人：HOECHST AKTIENGESELLSCHAFT

  公开号：EP0337179A1

  公开（公告）日：1989-10-18

  Beschrieben werden Verbindungen I mit R¹ gleich H, Alkyl, Alkoxy, CO Alkyl, COOH, Carboxyalkyl, CONR₂, CN, NO₂, Alkylsulfi(o)nyl, Arylsulfi(o)nyl; R² gleich H, OH, Alkoxy, Alkyl, Alkylcarbonyl, R³/R⁴ gleich Alkyl, m gleich null oder eins, X gleich -CR⁶=CR⁷-(-CR⁸=CR⁹-)-n (R⁶ bis R⁹ gleich H, Alkyl) mit n gleich null oder 1. Sie sind wirksame Antihypertensiva und Spasmolytika für Blase, Darm, Galle, Uterus, Trachea und Ureter.

  所述化合物 I 其中 R¹ 是 H、烷基、烷氧基、CO 烷基、COOH、羧基、CONR₂、CN、NO₂、烷硫基、芳硫基；R² 是 H、OH、烷氧基、烷基、烷基羰基，R³/R⁴ 是烷基，m 是 0 或 1，X 是-CR⁶=CR⁷-(-CR⁸=CR⁹-)-n（R⁶ 至 R𠞙 是 H、烷基），n 等于 0 或 1。它们是膀胱、肠道、胆囊、子宫、气管和输尿管的有效降压和解痉剂。
• WO2008/7210
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] NITROGENOUS N-SUBSTITUTED 4-SPIRO-HETEROCYCLIC 2, 2 -DIMETHYLCHROMANE DERIVATIVES<br/>[FR] DÉRIVÉS AZOTÉS DE 2, 2 -DIMÉTHYLCHROMANE 4-SPIRO-HÉTÉROCYCLIQUES À SUBSTITUTION N
  申请人：UNIV PISA

  公开号：WO2008007210A2

  公开（公告）日：2008-01-17

  [EN] A compound having the following general formula:(I) wherein - * represents a chiral center; - R0 is selected from the group comprised of : a carbonyl or thiocarbonyl group, an alkyl group (methylene, ethylene, or methylcarbonyl or methyl-thiocarbonyl group; - Y is selected from the group comprised of: a CH2 group, a C=O group, a C=S group, a C=NH group; - A is selected from the group comprised of: a -CONH- group, a - COO- group, a -CO- group, an alkyl group (C1-C3), alkylcarbonyl group, a carbonyl group, a thiocarbonyl group, an alkylthiocarbonyl group, a sulphonic group, an alkylsulphonic group; - R1 is selected from the group comprised of: a hydrogen atom, an alkyl group, (methyl, ethyl, propyl, isopropyl, butyl, iso-butyl or tert-butyl, an alkoxy group (methoxy, ethoxy, n-propyloxy, iso-propyloxy), an halide atom (F, Cl, Br, I), a trifluoromethyl group, a cyanide group, a nitro group, a hydroxy group, an amine group, an alkylamine group, an alkylamide (acetamide, trifluoroacetamide, propionamide) or alkylsulphonamide (methanesulphonamide, ethanesulphonamide) group. - -R2 is selected from the group comprised of: a hydrogen atom, an alkyl group with C1-C4 carbon atoms (methyl, ethyl, propyl, isopropyl, butyl, isobutyl or terbutyl), a carboxyl group, an alkoxy group (methoxy, ethoxy, n-propyloxy, iso-propyloxy), an halide atom (F, Cl, Br, I), a cyanide group, a nitro group, a trifluoromethyl group, a hydroxy group, a thioalkyl group (C1, C2, C3); an amine group of NR3R4 type where R3 and R4 can be indifferently a hydrogen atom, an alkyl, alkylsulphonic (methanesulphonic, ethanesulphonic), acyl (acetyl, propionyl), trifluoroalkyl group.
  [FR] Composé de formule générale (I) dans laquelle * représente un centre chiral, R0 est choisi dans le groupe constitué par un groupe carbonyle ou thiocarbonyle, un goupe alkyle (méthylène, éthylène ou un groupe méthylcarbonyle ou méthylthiocarbonyle), Y est choisi dans le groupe constitué par un groupe CH2, un groupe C=O, un groupe C=S, un groupe C=NH, A est choisi dans le groupe constitué par un groupe -CONH-, un groupe - COO-, un groupe -CO-, un groupe alkyle (C1-C3), un groupe alkylcarbonyle, un groupe carbonyle, un groupe thiocarbonyle, un groupe alkylthiocarbonyle, un groupe sulfonique, un groupe alkylsulfonique, R1 est choisi dans le groupe constitué par un atome d'hydrogène, un groupe alkyle, (méthyle, éthyle, propyle, isopropyle, butyle, iso-butyle ou tert-butyle), un groupe alcoxy (méthoxy, éthoxy, n-propyloxy, iso-propyloxy), un atome d'ahlogénure (F, Cl, Br, I), un groupe trifluorométhyle, un groupe cyanure, un groupe nitro, un groupe hydroxy, un groupe amine, un groupe alkylamine, un groupe alkylamide (acétamide, trifluoroacétamide, propionamide) ou alkylsulfonamide (méthanesulfonamide, éthanesulfonamide), R2 est choisi dans le groupe constitué par un atome d'hydrogène, un groupe alkyle ayant C1-C4 atomes de carbone (méthyle, éthyle, propyle, isopropyle, butyle, isobutyle ou tertbutyle), un groupe carboxyle, un groupe alcoxy (méthoxy, éthoxy, n-propyloxy, iso-propyloxy), un atome d'halogénure (F, Cl, Br, I), un groupe cyanure, un groupe nitro, un groupe trifluorométhyle, un groupe hydroxy, un groupe thioalkyle (C1, C2, C3); un groupe amine du type NR3R4 dans laquelle R3 et R4 peuvent représenter indifféremment un atome d'hydrogène, un goupe alkyle, alkylsulfonique (méthanesulfonique, éthanesulfonique), acyle (acétyle, propionyle), trifluoroalkyle.
• Synthesis and biological evaluation of 5-membered spiro heterocycle-benzopyran derivatives against myocardial ischemia
  作者：Simona Rapposelli、Maria Cristina Breschi、Vincenzo Calderone、Maria Digiacomo、Alma Martelli、Lara Testai、Michael Vanni、Aldo Balsamo

  DOI：10.1016/j.ejmech.2011.01.003

  日期：2011.3

  The activation of ATP-sensitive potassium channels (K-ATP), play a key role in an endogenous "self-defence" mechanism, known as ischemic preconditioning (IPC), which is fundamentally involved in the protection of the heart against the ischemia/reperfusion injury. Presently, it is widely accepted that IPC is mainly (albeit not exclusively) mediated by the activation of K-ATP channels expressed in the mitochondrial inner membrane (mito-K-ATP) rather than the sarcoplasmatic ones (sarc-K-ATP). Consistently, exogenous activation of K-ATP channels by pharmacological tools can be viewed as one of the most promising strategies for the therapy of myocardial ischemia. As part of our research program devoted to the synthesis and the evaluation of new cardioprotective agents, we extensively studied several six-membered spiro-heterocycle-benzopyran compounds endowed of a significant anti-ischemic activity. The positive results obtained, prompted us to further explore the influence on the biopharmacological effects, of the spiro-substitution at C4 benzopyran nucleus by replacing the six-membered spirocycle of the most active compounds with 5-membered-one.The preliminary evaluation of the new compounds on cultured H9c2 cardiomyoblasts exposed to anoxia/reperfusion and on Langendorff-perfused rat hearts submitted to ischemia/reperfusion cycles, showed that some of them can exert a cardioprotective effect. This anti-ischemic activity was antagonized by 5-hydroxydecanoic acid, a selective blocker of mito-K-ATP channels, confirming the involvement of this channel in the cardioprotective activity. (C) 2011 Elsevier Masson SAS. All rights reserved.