3,4-dihydro-2-dimethoxymethyl-4-hydroxy-2-methyl-6-nitro-2H-1-benzopyran | 146821-83-2

• 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: 3,4-dihydro-2-dimethoxymethyl-4-hydroxy-2-methyl-6-nitro-2H-1-benzopyran
• 英文别名: 2-dimethoxymethyl-2-methyl-4-hydroxy-6-nitro-3,4-dihydro-2H-1-benzopyran；2-(Dimethoxymethyl)-2-methyl-6-nitro-3,4-dihydrochromen-4-ol
• CAS: 146821-83-2
• 化学式: C₁₃H₁₇NO₆
• 分子量: 283.281
• InChiKey: ROJXUMCKSCWJTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  93.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,4-dihydro-2-dimethoxymethyl-4-hydroxy-2-methyl-6-nitro-2H-1-benzopyran 在 4-二甲氨基吡啶 、 lithium hydroxide 、 对甲苯磺酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， 反应 16.5h， 生成 (2S)-2-methyl-2-([1,3]dioxolan-2-yl)-6-nitro-2H-1-benzopyran
  参考文献：
  名称：

  A Novel Anti-Ischemic ATP-Sensitive Potassium Channel (K_ATP) Opener without Vasorelaxation:  N-(6-Aminobenzopyranyl)-N‘-benzyl-N‘ ‘-cyanoguanidine Analogue

  摘要：

  This paper describes the design, synthesis, and biological evaluation of a novel anti-ischemic compound, (2S,3S,4R)-N-(6-amino-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-benzopyranyl)-N'-benzyl-N " -cyanoguanidine (33), and the structure-activity relationships leading to the discovery of this compound. Compound 33 significantly reduced the myocardial infarct zone to area at risk (IZ/AAR) in the ischemic myocardium rat model with high cardioselectivity. Since the cardioprotective effect of compound 33 is reversed by ATP-sensitive potassium channel (K-ATP) blockers, its anti-ischemic effect appears to be at least mediated by K-ATP opening. In addition, compound 33 shows good protective activity on neuronal cells against oxidative stress, and therefore it is suggested that compound 33 may have therapeutic potential both in cardio- and in neuroprotection.

  DOI：

  10.1021/jm010183f
• 作为产物：
  描述：

  3,4-dihydro-2-dimethoxymethyl-2-methyl-6-nitro-4-oxo-2H-1-benzopyran 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 3,4-dihydro-2-dimethoxymethyl-4-hydroxy-2-methyl-6-nitro-2H-1-benzopyran
  参考文献：
  名称：

  N-((6-(取代氨基)-2-甲基-2H-苯并-2-基)甲基)-N-甲基苯磺酰胺衍生物的新型5-脂氧合酶抑制剂的开发

  摘要：

  5-脂氧合酶（5-LO）是多种抗炎药物开发的重要药物靶点之一。在此，我们设计、优化并合成了一种新型N -((6-(取代氨基)-2-甲基-2H-苯并-2-基)甲基) -N-甲基苯磺酰胺衍生物作为潜在的5-LO抑制剂。根据体外研究，包括酶活性测定（1 μM 抑制率≥78%）和细胞测定（1 μM 抑制率≥72%），合成的化合物中，10a、10b 和 10g 对 5- LO表现出抑制活性。 1μM）。使用花生四烯酸诱导的耳水肿小鼠模型选择10b以进一步提高体内效率。口服10b成功抑制了耳部水肿和髓过氧化物酶活性（MPO活性）。分子对接研究表明，化合物10b与 5-LO 的 Ile126 和 Val110之间存在烷基和 pi-烷基相互作用，以及与 Arg138 之间的氢键是关键的蛋白质-配体相互作用。

  DOI：

  10.1002/bkcs.12772

文献信息

• Benzopyran derivatives and processes for the preparation thereof
  申请人：Korea Research Institute of Chemical Technology

  公开号：US05236935A1

  公开（公告）日：1993-08-17

  The present invention relates to novel benzopyran derivatives of formula (I) which have superior selectivity in the treatment of hypertension by lowering blood pressure with a relaxation activity on vascular smooth muscle. The present invention also relates to processes for preparing such compounds; and to a pharmaceutical compositions containing such compounds as an active ingredient. ##STR1## wherein: R.sub.1 is --CN, --NO.sub.2, --OCX.sub.1 X.sub.2 X.sub.3, --NH.sub.2, --NHSO.sub.2 R.sup.A, ##STR2## --SO.sub.2 R.sup.C or --SO.sub.2 NR.sup.C R.sup.D wherein X.sub.1, X.sub.2 and X.sub.3 are, each independently, a fluorine, chlorine or hydrogen atom; R.sup.A and R.sup.B are, each independently, an amino, C.sub.1-6 alkoxy, C.sub.1-6 alkyl group or an optionally substituted phenyl group; and R.sup.C and R.sup.D are a hydrogen atom, or a C.sub.1-6 alkyl group or an optionally substituted phenyl group with a halogen atom, or a straight or branched C.sub.1-3 alkyl group; R.sub.2 is ##STR3## wherein R.sup.E is a hydrogen atom, or a C.sub.1-6 alkyl, cyclopropyl, cyclopropylmethyl or benzyl group; R.sup.F is --COR.sup.A or --CSR.sup.A ; X is O, S or NR.sup.C, and n is an integer from 0 to 3, wherein R.sup.A and R.sup.C have the same meanings as defined above; R.sub.3 is a C.sub.1-4 straight or branched alkyl group; and R.sub.4 is ##STR4## wherein R.sup.G and R.sup.H are, each independently, a C.sub.-16 alkyl group or an optionally substituted phenyl group; A and B are, each independently, S or O; and Z is a C.sub.1-3 straight or branched alkyl group.

  本发明涉及具有式（I）的新型苯并吡喃衍生物，其在治疗高血压方面具有优越的选择性，通过放松血管平滑肌降低血压。本发明还涉及制备这类化合物的方法；以及含有这类化合物作为活性成分的药物组合物。其中：R₁为--CN，--NO₂，--OCX₁X₂X₃，--NH₂，--NHSO₂Rᴬ，--SO₂Rᶜ或--SO₂NRᶜRᴰ，其中X₁，X₂和X₃分别为氟，氯或氢原子；Rᴬ和Rᴮ分别为氨基，C₁-₆烷氧基，C₁-₆烷基或可选择取代的苯基；Rᶜ和Rᴰ为氢原子，或C₁-₆烷基或可选择取代的苯基与卤原子，或直链或支链C₁-₃烷基；R₂为，其中Rᴱ为氢原子，或C₁-₆烷基，环丙基，环丙基甲基或苄基；Rᶠ为--CORᴬ或--CSRᴬ；X为O，S或NRᶜ，n为0到3的整数，其中Rᴬ和Rᶜ的含义如上定义；R₃为C₁-₄直链或支链烷基；R₄为，其中Rᴳ和Rᴴ分别为C₁-₁₆烷基或可选择取代的苯基；A和B分别为S或O；Z为C₁-₃直链或支链烷基。
• Novel benzopyran derivatives and processes for the preparation thereof
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY

  公开号：EP0514935B1

  公开（公告）日：1995-11-08
• US5236935A
  申请人：——

  公开号：US5236935A

  公开（公告）日：1993-08-17
• A Novel Anti-Ischemic ATP-Sensitive Potassium Channel (<i>K</i>_ATP) Opener without Vasorelaxation:  <i>N</i>-(6-Aminobenzopyranyl)-<i>N‘</i>-benzyl-<i>N‘ ‘</i>-cyanoguanidine Analogue
  作者：Sung-eun Yoo、Kyu Yang Yi、Sunkyung Lee、Jeehee Suh、Nakjeong Kim、Byung Ho Lee、Ho Won Seo、Sun-Ok Kim、Dong-Ha Lee、Hong Lim、Hwa Sup Shin

  DOI：10.1021/jm010183f

  日期：2001.11.1

  This paper describes the design, synthesis, and biological evaluation of a novel anti-ischemic compound, (2S,3S,4R)-N-(6-amino-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-benzopyranyl)-N'-benzyl-N " -cyanoguanidine (33), and the structure-activity relationships leading to the discovery of this compound. Compound 33 significantly reduced the myocardial infarct zone to area at risk (IZ/AAR) in the ischemic myocardium rat model with high cardioselectivity. Since the cardioprotective effect of compound 33 is reversed by ATP-sensitive potassium channel (K-ATP) blockers, its anti-ischemic effect appears to be at least mediated by K-ATP opening. In addition, compound 33 shows good protective activity on neuronal cells against oxidative stress, and therefore it is suggested that compound 33 may have therapeutic potential both in cardio- and in neuroprotection.
• Development for a new 5‐lipoxygenase inhibitors of <scp><i>N</i></scp>‐((6‐(substituted‐amino)‐<scp>2‐methyl‐2<i>H</i></scp>‐chromen‐2‐yl)methyl)‐<scp><i>N</i></scp>‐methyl benzenesulfonamide derivatives
  作者：Young‐Chang Kim、Aizhan Abdildinova、Ye Jin Shin、Dong Kyun Han、Jong Yeon Hwang、Hyae Gyeong Cheon、Young‐Dae Gong

  DOI：10.1002/bkcs.12772

  日期：2023.11

  significant drug targets for the development of various anti-inflammatory drugs. Herein, we designed, optimized, and synthesized a novel N-((6-(substituted-amino)-2-methyl-2H-chromen-2-yl)methyl)-N-methylbenzenesulfonamide derivatives as potential 5-LO inhibitors. Among the synthesized compounds, 10a, 10b, and 10g exhibited inhibitory activity toward 5-LO according to the in vitro studies including enzyme activity

  5-脂氧合酶（5-LO）是多种抗炎药物开发的重要药物靶点之一。在此，我们设计、优化并合成了一种新型N -((6-(取代氨基)-2-甲基-2H-苯并-2-基)甲基) -N-甲基苯磺酰胺衍生物作为潜在的5-LO抑制剂。根据体外研究，包括酶活性测定（1 μM 抑制率≥78%）和细胞测定（1 μM 抑制率≥72%），合成的化合物中，10a、10b 和 10g 对 5- LO表现出抑制活性。 1μM）。使用花生四烯酸诱导的耳水肿小鼠模型选择10b以进一步提高体内效率。口服10b成功抑制了耳部水肿和髓过氧化物酶活性（MPO活性）。分子对接研究表明，化合物10b与 5-LO 的 Ile126 和 Val110之间存在烷基和 pi-烷基相互作用，以及与 Arg138 之间的氢键是关键的蛋白质-配体相互作用。