methyl 3,4-dimethoxy-5-nitrobenzoate | 148546-84-3

• 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: methyl 3,4-dimethoxy-5-nitrobenzoate
• CAS: 148546-84-3
• 化学式: C₁₀H₁₁NO₆
• mdl: MFCD12412142
• 分子量: 241.2
• InChiKey: CRSPPWMPFLPNON-UHFFFAOYSA-N

物化性质

• 沸点：
  388.0±37.0 °C(Predicted)
• 密度：
  1.288±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  90.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3,4-dimethoxy-5-nitrobenzoate 在 氢氧化钾 、 硝酸 作用下， 生成 4,5-二甲氧基-2,3-二硝基-苯甲酸
  参考文献：
  名称：

  Klemenc, Monatshefte fur Chemie, 1912, vol. 33, p. 389

  摘要：

  DOI：
• 作为产物：
  描述：

  3,4-二羟基-5-硝基苯甲醛 在 sodium chlorite 、 sodium dihydrogenphosphate 、 氯化亚砜 、 potassium carbonate 作用下， 以 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 8.5h， 生成 methyl 3,4-dimethoxy-5-nitrobenzoate
  参考文献：
  名称：

  Synthesis of Proposed Structure of Aaptoline A, a Marine Sponge-Derived 7,8-Dihydroxyquinoline, and Its Neuroprotective Properties in C. elegans

  摘要：

  通过七个步骤，总产率为52％，成功地合成了提议的aaptoline A结构，这是一种来源于海绵的7,8-二羟基喹啉。合成的关键特点是N-丙炔基苯胺前体的高产率Ag(I)催化的环异构化，以从酸敏感的甲酸氨基苯甲酸甲酯中获得喹啉羧酸骨架。然而，合成的aaptoline A的光谱数据与先前的研究不一致。通过结合2D NMR分析，确认了合成的aaptoline A的结构。对合成的aaptoline A的生物活性的额外研究表明，它具有保护多巴胺能神经元免受MPP+诱导的C. elegans神经毒性的能力。此外，C. elegans中的食物感知能力和运动距离能力在aaptoline A处理后得到显着改善，表明aaptoline A可以在形态和功能上保护多巴胺能神经元。

  DOI：

  10.3390/molecules26195964

文献信息

• Process for the preparation of entacapone and intermediates thereof
  申请人：ESTEVE QUIMICA, S.A.

  公开号：EP1978014A1

  公开（公告）日：2008-10-08

  New preparation process for the preparation of entacapone which comprises converting the 3,4-dimethoxy-5-nitrobenzoic acid into an activated derivative which is reacted with 2-cyano-N,N-diethylacetamide in the presence of a base to give 2-cyano-3-(3,4-dimethoxy-5-nitrophenyl)-N,N-diethyl-3-hydroxyacrylamide; reacting the resulting compound with MHB(OCOR)3 where R is (C1-C4)-alkyl, phenyl, or CF3; and M is a sodium, potassium or ((C1-C4)-alkyl)4N, in the presence of an appropriate solvent to give E-2-cyano-3-3,4-dimethoxy-5-nitrophenyl)-N,N-diethylacrylamide; and finally submitting the compound obtained to a demethylation reaction to yield entacapone. Both 2-cyano-3-(3,4-dimethoxy-5-nitrophenyl)-N,N-diethyl-3-hydroxyacrylamide and E-2-cyano-3-3,4-dimethoxy-5-nitrophenyl)-N,N-diethylacrylamide are new. Entacapone has industrial applicability as antiparkinson's agent.

  新的恩他卡朋制备工艺包括将3,4-二甲氧基-5-硝基苯甲酸转化为活化衍生物，与2-氰基-N,N-二乙基乙酰胺在碱存在下反应，得到2-氰基-3-(3,4-二甲氧基-5-硝基苯基)-N,N-二乙基-3-羟基丙烯酰胺；将所得化合物与MHB(OCOR)3反应，其中R为(C1-C4)-烷基、苯基或CF3；M为钠、钾或((C1-C4)-烷基)4N，在适当溶剂存在下，得到E-2-氰基-3-(3,4-二甲氧基-5-硝基苯基)-N,N-二乙基丙烯酰胺；最后将所得化合物进行去甲基化反应，得到恩他卡朋。2-氰基-3-(3,4-二甲氧基-5-硝基苯基)-N,N-二乙基-3-羟基丙烯酰胺和E-2-氰基-3-(3,4-二甲氧基-5-硝基苯基)-N,N-二乙基丙烯酰胺均为新化合物。恩他卡朋作为抗帕金森病药物具有工业适用性。
• [EN] DERIVATIVES OF PHENYLMETHANONE AS FTO INHIBITORS<br/>[FR] DÉRIVÉS DE PHÉNYLMÉTHANONE UTILISÉS EN TANT QU'INHIBITEURS DE FTO
  申请人：RPXDS CO LTD

  公开号：WO2019129121A1

  公开（公告）日：2019-07-04

  Disclosed herein is a phenyl methanone derivative as an FTO inhibitor. Also disclosed herein is a pharmaceutical composition comprising the same, and a method for reducing food intake or appetite, inhibiting weight gain, promote weight loss, reducing blood glucose, reducing serum LDL, cholesterol, LDL-c, or triglycerides, or treating obesity or an obesity related disease (especially diabetes, hyperglycemia, diabetic nephropathy, hyperlipemia, coronary heart disease, atherosclerosis, hypertension, cardiovascular or cerebrovascular disease, liver, kidney or thyroid diseases) by inhibiting FTO by using the compound disclosed herein.

  本文披露了一种苯甲酮衍生物作为FTO抑制剂。本文还披露了包含该化合物的药物组合物，以及通过使用本文披露的化合物通过抑制FTO来减少食物摄入量或食欲，抑制体重增加，促进体重减轻，降低血糖，降低血清LDL，胆固醇，LDL-c或甘油三酯，或治疗肥胖或肥胖相关疾病（特别是糖尿病，高血糖，糖尿病肾病，高脂血症，冠心病，动脉粥样硬化，高血压，心血管或脑血管疾病，肝脏，肾脏或甲状腺疾病）的方法。
• Benzanilide derivatives as 5-HT1D antagonists
  申请人：GLAXO GROUP LIMITED

  公开号：EP0533267A1

  公开（公告）日：1993-03-24

  The invention provides compounds of the general formula (I) :- or a physiologically acceptable salt or solvate thereof wherein R¹ represents a hydrogen atom, a halogen atom or a group selected from C₁₋₆alkyl and C₁₋₆alkoxy; R² represents a pyridinyl group optionally substituted by one or two substituents selected from halogen atoms, C₁₋₆alkyl, hydroxyC₁₋₆alkyl, C₁₋₆alkoxyC₁₋₆alkyl, C₁₋₆alkoxy, hydroxy, -CN, -NO₂, -CO₂R⁶, -COR⁶, -CONR⁶R⁷ and -(CH₂)mOC(O)C₁₋₄alkyl; R³ represents the group R⁴ and R⁵, which may be the same or different, each independently represent a hydrogen atom or a halogen atom or a group selected from hydroxy, C₁₋₆alkoxy and C₁₋₆alkyl; R⁶, R⁷ and R⁸, which may be the same or different, each independently represent a hydrogen atom or a C₁₋₆alkyl group; and m represents zero or an integer from 1 to 3. The compounds may be used in the treatment or prophylaxis of depression and other CNS disorders.

  本发明提供了通式 (I) :- 的化合物。 或其生理上可接受的盐或溶液 其中 R¹ 代表氢原子、卤素原子或选自 C₁₋₆ 烷基和 C₁₋₆ 烷氧基的基团； R² 代表被一个或两个取代基任选取代的吡啶基，取代基选自卤素原子、C₁₋₆烷基、羟基C₁₋₆烷基、C₁₋₆烷氧基、C₁₋₆烷氧基、羟基、-CN、-NO₂、-CO₂R⁶、-COR⁶、-CONR⁶R⁷ 和-(CH₂)mOC(O)C₁₋₄烷基； R³ 代表以下基团 R⁴ 和 R⁵ 可以相同或不同，各自独立地代表氢原子或卤原子或选自羟基、C₁₋₆烷氧基和 C₁₋₆ 烷基的基团； R⁶、R⁷ 和 R⁸（可以相同或不同）各自独立地代表氢原子或 C₁₋₆烷基；以及 m 代表零或 1 至 3 的整数。 这些化合物可用于治疗或预防抑郁症和其他中枢神经系统疾病。
• Discovery of a Long-Acting, Peripherally Selective Inhibitor of Catechol-<i>O</i>-methyltransferase
  作者：László E. Kiss、Humberto S. Ferreira、Leonel Torrão、Maria João Bonifácio、P. Nuno Palma、Patrício Soares-da-Silva、David A. Learmonth

  DOI：10.1021/jm1001524

  日期：2010.4.22

  Novel nitrocatechol-substituted heterocycles were designed and evaluated for their ability to inhibit catechol-O-methyltransferase (COMT). Replacement of the pyrazole core of the initial hit 4 with a 1,2,4-oxadiazole ring resulted in a series of compounds endowed with longer duration of COMT inhibition. Incorporation of a pyridine N-oxide residue at position 3 of the 1,2,4-oxadiazole ring led to analogue 37f, which was found to possess activity comparable to entacapone and lower toxicity in comparison to tolcapone. Lead structure 37f was systematically modified in order to improve selectivity and duration of COMT inhibition as well as to minimize toxicity. Oxadiazole 37d (2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide (BIA 9-1067)) was identified as a long-acting, purely peripheral inhibitor, which is currently under clinical evaluation as an adjunct to L-Dopa therapy of Parkinson's disease.
• Klemenc, Monatshefte fur Chemie, 1914, vol. 35, p. 95
  作者：Klemenc

  DOI：——

  日期：——