1-甲基-1,2,5,6-四氢烟酸乙酯 | 28125-84-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 中文名称: 1-甲基-1,2,5,6-四氢烟酸乙酯
• 英文名称: Homoarecoline
• 英文别名: ethyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate；ethyl 1-methyl-3,6-dihydro-2H-pyridine-5-carboxylate
• CAS: 28125-84-0
• 化学式: C₉H₁₅NO₂
• mdl: MFCD00465883
• 分子量: 169.224
• InChiKey: UNARQANIGOBIHM-UHFFFAOYSA-N

物化性质

• 沸点：
  228.8±28.0 °C(Predicted)
• 密度：
  1.038±0.06 g/cm3(Predicted)
• 保留指数：
  1307

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  1-甲基-1,2,5,6-四氢烟酸乙酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 溴 、 potassium acetate 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 1-甲基-5-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)-1,2,3,6-四氢吡啶
  参考文献：
  名称：

  一种合成N-取代-1,2,3,6-四氢吡啶-5-硼酸 酯的方法

  摘要：

  本发明公开了一种合成N‑取代‑1,2,3,6‑四氢吡啶‑5‑硼酸酯的方法。以N‑取代‑1,2,3,6‑四氢吡啶‑5‑羧酸(酯)为原料，与卤素加成，然后碱性条件消除形成烯基卤，随后金属钯催化下与联硼酯偶联后得到N‑取代‑1,2,3,6‑四氢吡啶‑5‑硼酸酯。该方法得到中间体烯基卤不存在异构体，分离容易，得到的产品纯度高，为该类化合物的合成提供了一条比较简洁的途径。

  公开号：

  CN105503924B
• 作为产物：
  描述：

  3-哌啶甲酸乙酯 在 palladium on activated charcoal Oxone 、 正丁基锂 、 氢气 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 二异丙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 、 丙酮 、 甲苯 为溶剂， 反应 1.5h， 生成 1-甲基-1,2,5,6-四氢烟酸乙酯
  参考文献：
  名称：

  Intriguing Influence of the Solvent on the Regioselectivity of Sulfoxide Thermolysis in β-Amino-α-sulfinyl Esters

  摘要：

  The sulfoxide thermolysis of the diastereoisomeric methyl (3R,4aS, 10R)-6-methoxy-1-methyl-3-(phenylisulfinyl)-1,2,3,4,4a,5,10,10a-oct hydrobenzo[g]quinoline-3-carboxylates 3a and Yb in toluene yields, by loss of benzenesulfenic acid, an almost 1 : 1 mixture of the vinylogous urethane 2b and the isomeric alpha-aminoethyl enoate 2a. When this elimination is performed in acetic acid, the enoate 2a is formed rather selectively. The same solvent effects on the regioselectivity of the elimination of benzenesulfenic acid are observed with a simple sulfoxide of ethyl piperidine-3-carboxylate (7).

  DOI：

  10.1002/1522-2675(200205)85:5<1399::aid-hlca1399>3.0.co;2-r

文献信息

• Cholinergic Agents: Effect of Methyl Substitution in a Series of Arecoline Derivatives on Binding to Muscarinic Acetylcholine Receptors
  作者：Walter H. Moos、Stephen C. Bergmeier、Linda L. Coughenour、Robert E. Davis、Fred M. Hershenson、Jeffrey A. Kester、James S. McKee、John G. Marriott、Roy D. Schwarz、Haile Tecle、Anthony J. Thomas

  DOI：10.1002/jps.2600811012

  日期：1992.10

  Arecoline, arecaidine, and a series of derivatives, differing by the presence or absence of methyl groups at positions on the periphery of the molecule, were prepared, and their binding to muscarinic acetylcholine receptors was tested. On the basis of this study, muscarinic agonism for arecoline series is governed by strict structure-activity relationships, as previously observed for other agonist

  制备了槟榔碱，槟榔碱和一系列衍生物，它们的区别在于分子外围位置上甲基的存在与否，并测试了它们与毒蕈碱型乙酰胆碱受体的结合。在这项研究的基础上，对槟榔碱系列的毒蕈碱激动作用受严格的结构-活性关系控制，如先前在其他激动剂系列中观察到的那样。在本系列槟榔碱衍生物中，氮取代的变化很小。
• Physiologically active 1,2,4,-oxa- and thiadiazoles
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US04952587A1

  公开（公告）日：1990-08-28

  The present invention provides a compound of formula I or a salt or prodrug thereof: ##STR1## wherein the dotted circle represents one or two double bonds in any position in the 5-membered ring; X, Y and Z independently represent oxygen, sulphur, nitrogen or carbon, provided that at least one of X, Y and Z represents oxygen, sulphur or nitrogen; A represents a group of formula II: ##STR2## in which R.sup.1 represents hydrogen, hydroxy, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, hydroxy(C.sub.1-6)alkyl, halogen, amino, cyano, --CONR.sup.6 R.sup.7 or --SO.sub.2 NR.sup.6 R.sup.7, in which R.sup.6 and R.sup.7 independently represent hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; R.sup.2 represents hydrogen, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy or C.sub.1-6 alkylcarbonyl; V represents nitrogen, ##STR3## and W represents oxygen, sulphur or ##STR4## in which R.sup.8 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; E represents a bond or a straight or branched alkylene chain containing from 1 to 5 carbon atoms, and optionally being substituted with hydroxy or phenyl; and F represents: (a) a non-aromatic azacyclic or azabicyclic ring system; or (b) a group of formula --NR.sup.a R.sup.b, in which R.sup.a and R.sup.b independently represent hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl or aryl(C.sub.1-6)alkyl; which compounds are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; and presenile and senile dementia.

  本发明提供了化合物I的结构或其盐或前药：其中虚线圆圈代表5-成员环中任意位置的一个或两个双键；X、Y和Z独立地代表氧、硫、氮或碳，但至少一个X、Y和Z代表氧、硫或氮；A代表结构II的一个基团：其中R.sup.1代表氢、羟基、C.sub.1-6烷基、C.sub.2-6烯基、C.sub.2-6炔基、C.sub.1-6烷氧基、羟基(C.sub.1-6)烷基、卤素、氨基、氰基、--CONR.sup.6 R.sup.7或--SO.sub.2 NR.sup.6 R.sup.7，其中R.sup.6和R.sup.7独立地代表氢、C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基；R.sup.2代表氢、卤素、C.sub.1-6烷基、C.sub.1-6烷氧基或C.sub.1-6烷基羰基；V代表氮，W代表氧、硫或其中R.sup.8代表氢、C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基；E代表键或含有1至5个碳原子的直链或支链烷基链，可选地被羟基或苯基取代；F代表：(a)非芳香性氮杂环或氮杂双环系统；或(b)结构--NR.sup.a R.sup.b的一个基团，其中R.sup.a和R.sup.b独立地代表氢、C.sub.1-6烷基、C.sub.2-6烯基、C.sub.2-6炔基或芳基(C.sub.1-6)烷基；这些化合物在治疗精神分裂症（例如精神分裂症和狂躁症）、焦虑、酒精或药物戒断、疼痛、胃排空延缓、胃功能障碍（如消化不良、消化性溃疡、反流性食道炎和胀气）、偏头痛、恶心呕吐以及老年性痴呆症等方面有用。
• Five-membered ring systems with bonded azacyclic ring substituents
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0328200A1

  公开（公告）日：1989-08-16

  The present invention provides a compound of formula I or a salt or prodrug thereof: wherein the dotted circle represents one or two double bonds in any position in the 5-membered ring; X, Y and Z independently represent oxygen, sulphur, nitrogen or carbon, provided that at least one of X, Y and Z represents oxygen, sulphur or nitrogen; A represents a group of formula II: in which: R' represents hydrogen, hydroxy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, hydroxy(C1-6)alkyl, halogen, amino, cyano, -CONR6R7 or -S02NR6R7, in which R6 and R7 independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; R2 represents hydrogen, halogen, C1 -6 alkyl, C1 -s alkoxy or C1 -6 alkylcarbonyl; V represents nitrogen, - CH or - C -; and W represents oxygen, sulphur or - NR8, in which R8 represents hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; E represents a bond or a straight or branched alkylene chain containing from 1 to 5 carbon atoms, and optionally being substituted with hydroxy or phenyl; and F represents: . a) a non-aromatic azacyclic or azabicyclic ring system; or b) a group of formula -NRaRb, in which Ra and Rb independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-s alkynyl or aryl(C1-6)alkyl; which compounds are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; and presenile and senile dementia.

  本发明提供了式 I 的化合物或其盐或原药： 其中圆点代表五元环任意位置上的一个或两个双键； X、Y和Z独立地代表氧、硫、氮或碳，条件是X、Y和Z中至少有一个代表氧、硫或氮； 其中 R'代表氢、羟基、C1-6 烷基、C2-6 烯基、C2-6 炔基、C1-6 烷氧基、羟基（C1-6）烷基、卤素、氨基、氰基、-CONR6R7 或 -S02NR6R7，其中 R6 和 R7 独立地代表氢、C1-6 烷基、C2-6 烯基或 C2-6 烷炔基； R2 代表氢、卤素、C1-6 烷基、C1-s 烷氧基或 C1-6 烷基羰基； V 代表氮、- CH 或 - C -；以及 W 代表氧、硫或- NR8，其中 R8 代表氢、C1-6 烷基、C2-6 烯基或 C2-6 烷炔基； E 代表键或含有 1 至 5 个碳原子的直链或支链亚烷基链，可选择被羟基或苯基取代； 以及 F 代表 a) 非芳氮杂环或氮杂环环系；或 b) 式-NRaRb 的基团，其中 Ra 和 Rb 独立代表氢、C1-6 烷基、C2-6 烯基、C2-s 烷炔基或芳基（C1-6）烷基。这些化合物可用于治疗精神病（如精神分裂症和躁狂症）、焦虑、戒酒或戒毒、疼痛、胃淤血、胃功能障碍（如消化不良、消化性溃疡、反流性食道炎和胀气）、偏头痛、恶心和呕吐以及先天性和老年性痴呆。
• Novel 5-HT3 antagonists. Indole oxadiazoles
  作者：C. J. Swain、R. Baker、C. Kneen、J. Moseley、J. Saunders、E. M. Seward、G. Stevenson、M. Beer、J. Stanton、K. Watling

  DOI：10.1021/jm00105a021

  日期：1991.1

  The synthesis and biochemical evaluation of a series of indole oxadiazole 5-HT3 antagonists are described. The key pharmacophoric elements have been defined as a basic nitrogen, a linking group capable of H-bonding interactions, and an aromatic moiety. The steric limitations of the aromatic binding site have been determined by substitution about the indole ring. Variation of the heterocyclic linking group has shown that while two hydrogen-bonding interactions are possible, only one is essential for high affinity. The environment of the basic nitrogen has been investigated and shown to be optimal when constrained within an azabicyclic system. These results have been incorporated into a proposed binding model for the 5-HT3 antagonist binding site, in which the optimum distance between the aromatic binding site and the basic amine is 8.4-8.9 angstrom and the steric limitations are defined by van der Waals difference mapping.
• 2-Oxotetrahydro-1,3-oxazine: A Useful Interamediate for the Preparation of Tetrahydropyridine, Indolizidine, and Quinolizidine Skeletons
  作者：Takushi Kurihara、Yoshitaka Matsubara、Hirotaka Osaki、Sinya Harusawa、Ryuji Yoneda

  DOI：10.3987/com-89-s77

  日期：——