dimethyl 4-(2-fluorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate | 86408-08-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: dimethyl 4-(2-fluorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate
• 英文别名: dimethyl 4-(2-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 86408-08-4
• 化学式: C₁₇H₁₈FNO₄
• mdl: MFCD01882038
• 分子量: 319.333
• InChiKey: KALSHWKRMSJLAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethyl 4-(2-fluorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate 在 sodium hydroxide 、 硝酸 作用下， 以 甲醇 为溶剂， 反应 6.83h， 生成 2,4-dimethyl-5H-chromeno[3,4-c]pyridin-5-one
  参考文献：
  名称：

  A novel, nonsteroidal inhibitor of androgen binding to the rat androgen binding protein: diethyl [[[3-(2,6-dimethyl-4-pyridinyl)-4-fluorophenyl]amino]methylene]propanedioate

  摘要：

  In vitro binding studies demonstrate the binding specificity of a series of 4-aryl-2,6-dimethylpyridines for the rat epididymal androgen binding protein (rABP). The compounds bound competitively to rABP but have very weak or no demonstrable affinity for rat ventral prostate androgen receptor and human sex hormone binding globulin. In particular, compound 11, diethyl [[[3-(2,6-dimethyl-4-pyridinyl)-4-fluorphenyl]amino]methylene] propanedioate, bound with high affinity to rABP (binding affinity about 1/3 that of the endogenous ligand 5 alpha-dihydrotestosterone). However, additional in vitro binding studies indicated that 11 did not bind to testicular or epididymal ABP from rabbit, rhesus monkey, and human. Nevertheless, the specificity and relatively high affinity of these nonsteroidal compounds make them unique and potentially ideal agents for the study of the role of ABP in spermatogenesis and sperm maturation in the rat.

  DOI：

  10.1021/jm00163a021
• 作为产物：
  描述：

  2-氟苯甲醛 、 乙酰乙酸甲酯 在 氨 作用下， 以 甲醇 为溶剂， 以26%的产率得到dimethyl 4-(2-fluorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate
  参考文献：
  名称：

  1,4-Dihydropyridine antagonist activities at the calcium channel: a quantitative structure-activity relationship approach

  摘要：

  The effect of 46 1,4-dihydropyridine-type calcium channel antagonists on the tonic contractile response of longitudinal muscle strips of guinea pig ileum was determined. 2,6-Dimethyl-3,5-dicarbomethoxy-4-phenyl-1,4-dihydropyridine (13) and 13 ortho-, 15 meta-, and seven para-monosubstituted and 10 polysubstituted aromatic derivatives of 13 were studied. The pharmacological activities of the monosubstituted derivatives were best correlated by eq 10, log 1/C = 0.68 pi + 2.50 sigma m -0.47Lmeta -3.40B1para + 11.31, which had a correlation coefficient of 0.89. The full data set was best correlated by eq 11, log 1/C = 0.62 pi + 1.96 sigma m -0.44Lmeta -3.26B1para -1.51Lmeta' + 14.23, which had a correlation coefficient of 0.90. Equations of similar form but involving an ortho steric term were found to correlate the radioligand binding data for this class of compounds.

  DOI：

  10.1021/jm00119a009

文献信息

• [EN] TREATMENT OF MCI AND ALZHEIMER'S DISEASE<br/>[FR] TRAITEMENT DU TCL ET DE LA MALADIE D'ALZHEIMER
  申请人：UNIV KENTUCKY RES FOUND

  公开号：WO2011142778A1

  公开（公告）日：2011-11-17

  The present invention provides, among other things, therapeutic compositions and methods that can effectively treat, slow or prevent a neurological disease (e.g., a neurodegenerative disease, e.g., mild cognitive impairment (MCI) or Alzheimer's disease (AD)), in particular, based on therapeutically effective amount of nifedipine, oxidized or nitroso nifedipine derivatives, lactam (e.g., a compound of formula (Ic) or (Ic-i), e.g., NFD- L1), thyroxine (T4), triiodothyronine (T3) and combinations thereof.

  本发明提供了治疗组合物和方法，可有效治疗、减缓或预防神经系统疾病（例如，神经退行性疾病，例如轻度认知障碍（MCI）或阿尔茨海默病（AD）），特别是基于治疗有效量的尼群地平、氧化或亚硝基尼群地平衍生物、内酰胺（例如公式（Ic）或（Ic-i）的化合物，例如NFD-L1）、甲状腺素（T4）、三碘甲状腺原氨酸（T3）及其组合物。
• Chiral Phosphoric Acid Catalyzed Enantioselective Desymmetrization of 1,4‐Dihydropyridines by C(sp ³ )−H Bromination
  作者：Min Han、Shi‐qi Zhang、Xin Cui、Qi‐wei Wang、Guang‐xun Li、Zhuo Tang

  DOI：10.1002/anie.202201418

  日期：2022.5.23

  used as substrates to obtain chiral Hantzsch-type 1,4-DHPs, which are frequently contained in pharmaceuticals. The inert C−H bond was converted into a versatile C−Br bond, which enabled the modification of the chiral 1,4-DHP derivatives with high efficiency by nucleophilic substitution. Furthermore, axially chiral 4-aryl pyridines were accessible by central-to-axial chirality conversion.

  容易获得的对称 1,4-二氢吡啶 (1,4-DHP) 被用作底物以获得药物中经常含有的手性 Hantzsch 型 1,4-DHP。惰性 C-H 键被转化为通用的 C-Br 键，从而能够通过亲核取代高效地修饰手性 1,4-DHP 衍生物。此外，轴向手性 4-芳基吡啶可通过中心到轴向手性转换获得。
• Preparation of intermediates to
  申请人：Sterling Drug Inc.

  公开号：US04699984A1

  公开（公告）日：1987-10-13

  Shown is the process which comprises heating 4-(2-fluorophenyl)-2,6-dimethyl-3,5-pyridinedicarboxylic acid to produce a mixture of 4-(2-fluorophenyl)-2,6-dimethylpyridine and 2,4-dimethyl-5H-[1]benzopyrano[3,4-c]pyridin-5-one, separating the components of said mixture and nitrating 4-(2-fluorophenyl)-2,6-dimethylpyridine to produce 4-(2-fluoro-5-nitrophenyl)-2,6-dimethylpyridine. Also shown are the 3-step synthesis of 4-(2-fluorophenyl)-2,6-dimethyl-3,5-pyridinedicarboxylic acid from 2-fluorobenzaldehyde and the five step synthesis of 1-ethyl-6-fluoro-1,4-dihydro-7-(2,6-dimethyl-4-pyridinyl)-4-oxo-3-quinolin ecarboxylic acid, a highly potent antibacterial agent, starting with 4-(2-fluoro-5-nitrophenyl)-2,6-dimethylpyridine. Other intermediates shown in said five step synthesis include 3-(2,6-dimethyl-4-pyridinyl)-4-fluorobenzeneamine and diethyl 4-fluoro-3-(2,6-dimethyl-4-pyridinyl)anilinomethylenemalonate.

  该过程包括加热4-(2-氟苯基)-2,6-二甲基-3,5-吡啶二甲酸，产生4-(2-氟苯基)-2,6-二甲基吡啶和2,4-二甲基-5H-[1]苯并吡喃[3,4-c]吡啶-5-酮的混合物，分离该混合物的组分并对4-(2-氟苯基)-2,6-二甲基吡啶进行硝化，以产生4-(2-氟-5-硝基苯基)-2,6-二甲基吡啶。还展示了从2-氟苯甲醛合成4-(2-氟苯基)-2,6-二甲基-3,5-吡啶二甲酸的三步合成和从4-(2-氟-5-硝基苯基)-2,6-二甲基吡啶开始的1-乙基-6-氟-1,4-二氢-7-(2,6-二甲基-4-吡啶基)-4-氧-3-喹啉羧酸的五步合成，该化合物是一种高效的抗菌剂。在该五步合成中展示了其他中间体，包括3-(2,6-二甲基-4-吡啶基)-4-氟苯胺和二乙酸二乙酯4-氟-3-(2,6-二甲基-4-吡啶基)苯胺甲基亚甲基丙烯酸酯。
• 1-6-naphthyridine derivatives useful in the treatment of blood vessel
  申请人：——

  公开号：US04711901A1

  公开（公告）日：1987-12-08

  The present invention describes 1,6-naphthyridine derivatives of the general formula: ##STR1## wherein R.sup.1 is an unsubstituted or substituted aromtic or heteroaromatic ring, R.sup.2 is a straight-chained or branched alkyl radical containing up to four carbon atoms or a benzyl radical, R.sup.3 is a hydrogen atom, a straight-chained or branched alkyl radical or an alkoxycarbonyl radical containing up to four carbon atoms, R.sup.4 is a straight-chained or branched alkyl radical containing up to four carbons and R.sup.5 is a carbonyl group or a straight-chained, branched or cyclic alkoxycarbonyl radical which contains up to 17 carbon atoms and optionally also contains an oxygen, sulphur or nitrogen atom; as well as the pharamacologically acceptable salts thereof, which are useful for treating diseases of the blood vessels.

  本发明描述了一般式为：##STR1##的1,6-萘啶衍生物，其中R.sup.1是未取代或取代的芳香或杂芳环，R.sup.2是含有最多四个碳原子的直链或支链烷基基团或苯甲基基团，R.sup.3是氢原子，含有最多四个碳原子的直链或支链烷基基团或烷氧羰基基团，R.sup.4是含有最多四个碳原子的直链或支链烷基基团，R.sup.5是羰基基团或含有最多17个碳原子的直链、支链或环状烷氧羰基基团，可选地还含有一个氧、硫或氮原子；以及其药理学上可接受的盐，用于治疗血管疾病。
• 1,6-naphthyridine derivatives useful for treating diseases of the blood
  申请人：Goedecke Aktiengesellschaft

  公开号：US04760081A1

  公开（公告）日：1988-07-26

  The present invention describes 1,6-naphthyridine derivatives of the general formula: ##STR1## wherein R.sup.1 is an unsubstituted or substituted aromatic or heteroaromatic ring, R.sup.2 is a straight-chained or branched alkyl radical containing up to four carbon atoms or a benzyl radical, R.sup.3 is a hydrogen atom, a straight-chained or branched alkyl radicals or an alkoxycarbonyl radical containing up to four carbon atoms, R.sup.4 is a straight-chained or branched alkyl radical containing up to four carbons and R.sup.5 is a carboxyl group or a straight-chained, branched or cyclic alkoxycarbonyl radical which contains up to 17 carbon atoms and optionally also contains an oxygen, sulphur or nitrogen atom; as well as the pharmacologically acceptable salts thereof, which are useful for treating diseases of the blood vessels.

  本发明描述了一种一般式为：## STR1##的1,6-萘啶衍生物，其中R.sup.1是未取代或取代的芳香或杂芳环，R.sup.2是含有最多四个碳原子的直链或支链烷基基团或苄基基团，R.sup.3是氢原子，含有最多四个碳原子的直链或支链烷基基团或烷氧羰基基团，R.sup.4是含有最多四个碳原子的直链或支链烷基基团，R.sup.5是羧基或含有最多17个碳原子的直链、支链或环状烷氧羰基基团，并且还可能包含氧、硫或氮原子的药理学上可接受的盐，用于治疗血管疾病。