2-Methyl-4-(3-nitrophenyl)-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridin-3-carbonsaeureethylester | 89267-47-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-Methyl-4-(3-nitrophenyl)-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridin-3-carbonsaeureethylester
• 英文别名: ethyl-2-methyl-4-(3-nitrophenyl)-5-oxo-1,4,5,7-tetrahydrofuro<3,4-b>-3-pyridinecarboxylate；ethyl 1,4,5,7-tetrahydro-2-methyl-4-(3-nitrophenyl)-5-oxofuro[3,4-b]pyridine-3-carboxylate；Ethyl 2-methyl-4-(3-nitrophenyl)-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridine-3-carboxylate；ET 2-ME-4-(3-Nitro-PH)-5-oxo-1,4,5,7-tetrahydrofuro(3,4-B)pyridine-3-carboxylate；ethyl 2-methyl-4-(3-nitrophenyl)-5-oxo-4,7-dihydro-1H-furo[3,4-b]pyridine-3-carboxylate
• CAS: 89267-47-0
• 化学式: C₁₇H₁₆N₂O₆
• 分子量: 344.324
• InChiKey: ZYQOLGCHSLBXFG-UHFFFAOYSA-N

物化性质

• 熔点：
  173-176 °C
• 沸点：
  554.9±50.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-Methyl-4-(3-nitrophenyl)-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridin-3-carbonsaeureethylester 在 硫酸 、 硝酸 作用下， 以59%的产率得到ethyl-2-methyl-4-(3-nitrophenyl)-5-oxo-5,7-dihydrofuro<3,4-b>3-pyridinecarboxylate
  参考文献：
  名称：

  Goerlitzer; Bartke, Pharmazie, 2002, vol. 57, # 10, p. 672 - 678

  摘要：

  DOI：
• 作为产物：
  描述：

  2-bromomethyl-3,5-dicarboethoxy-4-(3-nitrophenyl)-6-methyl-1,4-dihydropyridine 生成 2-Methyl-4-(3-nitrophenyl)-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridin-3-carbonsaeureethylester
  参考文献：
  名称：

  Synthesis of Novel Asymmetrical 1,4‐Dihydropyridine Derivatives

  摘要：

  Asymmetrical 1,4-dihydropyridine esters 3a and 3i-k were synthesized from the symmetrical precursor 1 through the intermediate 2-bromomethyl derivative 2. Then, compound 3a was subjected to a different transformation for preparation of 1,4-dihydropyridine derivatives 3b-h.

  DOI：

  10.1080/00397910500297305

文献信息

• Circulation-active hydroxy-tetra-hydropyridinelactones
  申请人：Bayer Aktiengesellschaft

  公开号：US04647568A1

  公开（公告）日：1987-03-03

  Hydroxytetrahydropyridinelactones of the formula ##STR1## in which R represents a phenyl, naphthyl, thienyl, furyl, pyrryl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, quinolyl, isoquinolyl, indolyl, benzimidazolyl, quinazolyl, quinoxalyl, thionaphthenyl, isothionaphthenyl, chromonyl, thiochromonyl, chromenyl, thiochromenyl, benzoxadiazolyl or benzthiadiazolyl radical, and the stated radicals may carry 1 to 3 identical or different substituents from the group comprising C.sub.1 -C.sub.20 -alkyl, C.sub.2 -C.sub.20 -alkenyl, C.sub.2 -C.sub.20 -alkinyl, C.sub.1 -C.sub.20 -alkoxy, fluorine, chlorine, bromine, iodine, trifluoromethyl, monofluoro-C.sub.1 -C.sub.10 -alkoxy, polyfluoro-C.sub.1 -C.sub.10 -alkoxy, hydroxyl, amino, mono-C.sub.1 -C.sub.10 -alkylamino, di-C.sub.1 -C.sub.10 -alkylamino, nitro, cyano, azido, carboxyl, carb-C.sub.1 -C.sub.10 -alkoxy, carboxamido, sulphonamido, SO.sub.m -alkyl (m=0 to 2, 1 to 20 C atoms), phenyl, benzyl, benzyloxy or benzylthio, it being possible for the 4 last-mentioned substituents to carry 1 to 3 radicals from the group comprising C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.5 -alkoxy, C.sub.1 -C.sub.5 -alkylthio, fluorine, chlorine, bromine, iodine, cyano, nitro, azido, hydroxyl, trifluoromethyl, amino, C.sub.1 -C.sub.6 -alkylamino or di-C.sub.1 -C.sub.6 -alkylamino, R.sup.1 represents a straight-chain, branched or cyclic saturated or unsaturated hydrocarbon radical which has 1-20 C atoms, may be interrupted in the chain by 1 or 2 oxygen or sulphur atoms and may be optionally substituted by one or more fluorine atoms, NO.sub.2, C.sub.3 -C.sub.12 -trialkyl-silyl, hydroxyl, chlorine, bromine, iodine or cyano, R.sup.2 represents hydrogen, --NH.sub.2, --CHO, cyano, --CH.sub.2 OH or a straight-chain or branched saturated or unsaturated hydrocarbon radical having 1 to 8 C atoms, R.sup.3 represents hydrogen or a straight-chain or branched C.sub.1 -C.sub.10 -alkyl radical which may be interrupted in the alkyl chain by one or two oxygen atoms and may be optionally substituted by fluorine, chlorine, bromine, iodine, --CN, --NH.sub.2, --OH or morpholino, which can be used as cardiotonics for improving the contractility of the heart. Moveover, they increase the flow of Ca.sup.++ into the cells and can therefore be employed as antihypotonics, for lowering the blood sugar level, for reducing the swelling of mucous membranes and for influencing the salt balance and/or fluid balance.

  化学式为##STR1##的羟基四氢吡啶内酯化合物，其中R代表苯基、萘基、噻吩基、呋喃基、吡咯基、吡唑基、咪唑基、噁唑基、异噁唑基、噻唑基、吡啶基、吡嗪基、嘧啶基、吡嗪啉基、喹啉基、异喹啉基、吲哚基、苯并咪唑基、喹唑基、喹喔啉基、硫代萘基、异硫代萘基、香豆素基、硫代香豆素基、香豆素基、硫代香豆素基、苯并噁二唑基或苯并噻二唑基基团，所述基团可以携带1至3个相同或不同的取代基，所述取代基来自于C.sub.1-C.sub.20-烷基、C.sub.2-C.sub.20-烯基、C.sub.2-C.sub.20-炔基、C.sub.1-C.sub.20-烷氧基、氟、氯、溴、碘、三氟甲基、单氟-C.sub.1-C.sub.10-烷氧基、多氟-C.sub.1-C.sub.10-烷氧基、羟基、氨基、单-C.sub.1-C.sub.10-烷基氨基、双-C.sub.1-C.sub.10-烷基氨基、硝基、氰基、偶氮基、羧基、羧基-C.sub.1-C.sub.10-烷氧基、羧酰胺基、磺酰胺基、SO.sub.m-烷基（m=0到2，1到20个C原子）、苯基、苄基、苄氧基或苄硫基，其中后4个取代基可以携带1至3个来自C.sub.1-C.sub.5-烷基、C.sub.1-C.sub.5-烷氧基、C.sub.1-C.sub.5-烷硫基、氟、氯、溴、碘、氰基、硝基、偶氮基、羟基、三氟甲基、氨基、C.sub.1-C.sub.6-烷基氨基或双-C.sub.1-C.sub.6-烷基氨基的基团，R.sup.1代表具有1-20个C原子的直链、支链或环状饱和或不饱和的碳氢基团，可以通过1或2个氧或硫原子在链中间中断，并且可以被一个或多个氟原子、NO.sub.2、C.sub.3-C.sub.12-三烷基硅基、羟基、氯、溴、碘或氰取代，R.sup.2代表氢、--NH.sub.2、--CHO、氰、--CH.sub.2OH或具有1至8个C原子的直链或支链饱和或不饱和的碳氢基团，R.sup.3代表氢或直链或支链C.sub.1-C.sub.10-烷基团，该烷基链可以通过一个或两个氧原子在烷基链中断，并且可以被氟、氯、溴、碘、--CN、--NH.sub.2、--OH或morpholino取代，这些化合物可以作为心脏强心剂，以改善心脏的收缩能力。此外，它们增加了Ca.sup.++进入细胞的流量，因此可以用作抗低血压剂，降低血糖水平，减少黏膜肿胀以及影响盐平衡和/或液体平衡。
• Meyer; Scherling; Karl, Arzneimittel-Forschung/Drug Research, 1983, vol. 33, # 11, p. 1528 - 1534
  作者：Meyer、Scherling、Karl

  DOI：——

  日期：——
• Zhang, Jian; Jin, Long Fei, Journal of the Chemical Society of Pakistan, 2011, vol. 33, # 6, p. 916 - 921
  作者：Zhang, Jian、Jin, Long Fei

  DOI：——

  日期：——
• Antagonism of 4-substituted 1,4-dihydropyridine-3,5-dicarboxylates toward voltage-dependent L-type Ca2+ channels CaV1.3 and CaV1.2
  作者：Che-Chien Chang、Song Cao、Soosung Kang、Li Kai、Xinyong Tian、Prativa Pandey、Sara Fernandez Dunne、Chi-Hao Luan、D. James Surmeier、Richard B. Silverman

  DOI：10.1016/j.bmc.2010.03.038

  日期：2010.5

  L-type Ca2+ channels in mammalian brain neurons have either a Ca(V)1.2 or Ca(V)1.3 pore-forming subunit. Recently, it was shown that Ca(V)1.3 Ca2+ channels underlie autonomous pacemaking in adult dopaminergic neurons in the substantia nigra pars compacta, and this reliance renders them sensitive to toxins used to create animal models of Parkinson's disease. Antagonism of these channels with the dihydropyridine antihypertensive drug isradipine diminishes the reliance on Ca2+ and the sensitivity of these neurons to toxins, pointing to a potential neuroprotective strategy. However, for neuroprotection without an antihypertensive side effect, selective Ca(V)1.3 channel antagonists are required. In an attempt to identify potent and selective antagonists of Ca(V)1.3 channels, 124 dihydropyridines (4-substituted-1,4-dihydropyridine3,5-dicarboxylic diesters) were synthesized. The antagonism of heterologously expressed Ca(V)1.2 and Ca(V)1.3 channels was then tested using electrophysiological approaches and the FLIPR Calcium 4 assay. Despite the large diversity in substitution on the dihydropyridine scaffold, the most Ca(V)1.3 selectivity was only about twofold. These results support a highly similar dihydropyridine binding site at both Ca(V)1.2 and Ca(V)1.3 channels and suggests that other classes of compounds need to be identified for Ca(V)1.3 selectivity. (c) 2010 Elsevier Ltd. All rights reserved.
• US4647568A
  申请人：——

  公开号：US4647568A

  公开（公告）日：1987-03-03