ethyl (1-ethoxycarbonyl-4-piperidinylidene)acetate | 123335-55-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: ethyl (1-ethoxycarbonyl-4-piperidinylidene)acetate
• 英文别名: ethyl N-ethoxycarbonyl-4-piperidylideneacetate；ethyl 4-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate
• CAS: 123335-55-7
• 化学式: C₁₂H₁₉NO₄
• 分子量: 241.287
• InChiKey: OXCNJARQOXNNON-UHFFFAOYSA-N

物化性质

• 沸点：
  336.4±35.0 °C(Predicted)
• 密度：
  1.175±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (1-ethoxycarbonyl-4-piperidinylidene)acetate 在 氢溴酸 、 sodium methylate 、 potassium carbonate 作用下， 以 溶剂黄146 、 丙酮 为溶剂， 反应 7.0h， 生成 2-propyl-1-oxa-2,8-diazaspiro<4.5>decan-3-one
  参考文献：
  名称：

  一系列1-oxa-2,8-diazaspiro [4.5] decan-3-ones及其相关化合物作为M1毒蕈碱激动剂的合成及结构活性研究。

  摘要：

  一系列新颖的2,8-二烷基-1-氧杂-2,8-二氮杂螺[4.5] decan-3-one和2,8-二甲基-1,2,8-三氮杂螺[4.5] -decan-3-one （13）与M1毒蕈碱激动剂YM796和RS86有关，是通过羟基脲或甲基肼与α，β-不饱和酯的迈克尔加成反应，然后环化反应合成的。评估了这些化合物对M1和M2受体的结合亲和力和体内毒蕈碱活性：即减轻东passive碱引起的大鼠被动回避任务中的损伤以及诱导体温过低，震颤和流涎。2,8-二甲基-1-恶唑-2,8-二氮杂螺[4.5]十烷-3-酮（6a）对M1和M2受体均表现出高亲和力，显示出健忘活性（0.1 mg / kg，sc）并诱发体温过低（3 mg / kg，sc）。此外，6a刺激大鼠海马切片中的磷酸肌醇水解，表明对M1毒蕈碱受体有部分激动作用。N在6a的N2处甲基的改变增加了M1相对于M2受体的结合亲和力的选择性，但导致M1激动

  DOI：

  10.1248/cpb.43.1523
• 作为产物：
  描述：

  N-乙氧羰基-4-哌啶酮 、 triethyl phosphonoacetic acid 以 乙二醇二甲醚 、 (2S)-N-methyl-1-phenylpropan-2-amine hydrate 、 乙酸乙酯 为溶剂， 生成 ethyl (1-ethoxycarbonyl-4-piperidinylidene)acetate
  参考文献：
  名称：

  Heterocyclic spiro compounds and methods for preparing the same

  摘要：

  以下是通式表示的杂环螺环化合物及其盐：##STR1## 上述化合物作用于毒蕈碱乙酰胆碱受体，从而激活中枢神经系统中的乙酰胆碱神经功能。

  公开号：

  US04940795A1

文献信息

• Synthesis and Structure-Activity Studies of a Series of 1-Oxa-8-azaspiro(4.5)decanes as M1 Muscarinic Agonists.
  作者：Shin-ichi TSUKAMOTO、Mitsuo FUJII、Tomoyuki YASUNAGA、Koyo MATSUDA

  DOI：10.1248/cpb.43.842

  日期：——

  2, 8-Dimethyl-1-oxa-8-azaspiro[4.5]decan-3-one (17), designed by incorporating the tetrahydrofuran ring moiety of muscarone into an 8-azaspiro[4.5]decane skeleton, and related 1-oxa-8-azaspiro[4.5]decanes were synthesized and assessed as M1 muscarinic agonists for the symptomatic treatment of dementia of Alzheimer's type. The compounds were tested for central muscarinic M1 and M2 receptor affinity and in vivo muscarinic activities : namely, amelioration of scopolamine-induced impairment in rat passive avoidance tasks, and induction of hypothermia, tremor, and salivary secretion. Compound 17 exhibited potent muscarinic activities in vitro and in vivo with no selectivity. Systematic modifications of 17 were conducted, and a number of compounds, including the 2-ethyl analogue (18), 3-methylene analogue (29), 3-dithioketal analogues (26, 28), and 3-oxime analogue (37) were found to display preferential affinity for M1 receptors over M2 receptors and, in addition, to exhibit potent antiamnesic activity sufficiently separated from hypothermia-inducing activity, taken as an index of cholinergic side effects, compared with the reference compound RS86 (1). Structure-activity relationships are discussed in comparison with those for muscarone analogues. Of these compounds only two, 2-ethyl-8-methyl-1-oxa-8-azaspiro[4.5]decan-3-one (18) and 2, 8-dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane (29), stimulated phosphoinositide hydrolysis in rat hippocampal slices, indicating partial agonistic activity for M1 muscarinic receptors.The optical resolution of 18 and 29 was performed. Eudismic ratios of both compounds in binding affinity were low, but M1 agonist activity resided preferentially in the (-)-isomers. The absolute configuration of (-)-29 was determined by X-ray crystal structure analysis to be S, being the same as that of muscarone. Based on the in vivo selectivity, (-)-29 was selected for clinical studies.

  2, 8-Dimethyl-1-oxa-8-azaspiro[4.5]decan-3-one (17)，通过将muscarone的四氢呋喃环部分合并到8-azaspiro[4.5]decane骨架中而设计，以及相关的1-oxa合成了-8-氮杂螺[4.5]癸烷并评估其作为M1毒蕈碱激动剂对阿尔茨海默氏型痴呆的对症治疗。测试了这些化合物的中枢毒蕈碱 M1 和 M2 受体亲和力和体内毒蕈碱活性：即改善东莨菪碱诱导的大鼠被动回避任务损伤，以及诱导体温过低、震颤和唾液分泌。化合物17在体外和体内表现出有效的毒蕈碱活性，且无选择性。对 17 个化合物进行了系统修饰，得到了许多化合物，包括 2-乙基类似物 (18)、3-亚甲基类似物 (29)、3-二硫缩酮类似物 (26, 28) 和 3-肟类似物 (37)。发现与 M2 受体相比，对 M1 受体表现出优先的亲和力，此外，与参考化合物 RS86 相比，还表现出与低温诱导活性充分分离的有效抗遗忘活性（作为胆碱能副作用的指标）(1)。讨论了结构-活性关系，并与麝香酮类似物的结构-活性关系进行比较。这些化合物中只有两种，2-乙基-8-甲基-1-氧杂-8-氮杂螺[4.5]癸-3-酮(18)和2, 8-二甲基-3-亚甲基-1-氧杂-8-氮杂螺[4.5]癸烷(29)，刺激大鼠海马切片中的磷酸肌醇水解，表明对M1毒蕈碱受体具有部分激动活性。进行18和29的光学分辨率。两种化合物的结合亲和力的平均比率较低，但 M1 激动剂活性优先存在于 (-)-异构体中。 X射线晶体结构分析确定(-)-29的绝对构型为S，与麝香酮相同。基于体内选择性，选择(-)-29进行临床研究。
• Hydrochloride salts of heterocyclic spiro compounds
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US05412096A1

  公开（公告）日：1995-05-02

  Hydrochloride salts of heterocyclic spiro compounds are provided and can be represented by the following general formula: ##STR1## wherein A represents piperidine or N alkyl piperidine or N alkylene attached to a non adjacent piperidine ring carbon, X is S or O, Y is carbonyl, thiocarbonyl, methylene, R.sup.5 methylene, ##STR2## alk in which R.sup.1 to R.sub.3,R.sub.6,R.sub.7 are H or alkyl, R.sub.4 is H, alkyl, COOH, or ester, or --C alkyl, R.sub.5 is halo, OH,SH, O alkyl, S alkyl, O acyl or S acyl, and Z, and Z.sub.2 are O or S. The above compounds act upon muscarinic acetylcholine receptors, thereby activating the acetylcholine nervous functions in the central nervous system.

  提供杂环螺环化合物的盐酸盐，可用以下一般式表示：##STR1## 其中，A代表哌啶或连接到非相邻哌啶环碳上的N烷基哌啶或N烷基亚碳哌啶，X为S或O，Y为羰基，硫羰基，亚甲基，R.sup.5亚甲基，##STR2## alk其中R.sup.1至R.sub.3，R.sub.6，R.sub.7为H或烷基，R.sub.4为H，烷基，COOH或酯，或--C烷基，R.sub.5为卤素，OH，SH，O烷基，S烷基，O酰基或S酰基，Z和Z.sub.2为O或S。上述化合物作用于毒蕈碱乙酰胆碱受体，从而激活中枢神经系统中的乙酰胆碱神经功能。
• Delphinium plant named ‘ET DLP 824’
  申请人：Bisschop Elisabeth

  公开号：USPP034653P2

  公开（公告）日：2022-10-11

  A new and distinct cultivar of Delphinium plant named ‘ET DLP 824’, characterized by its relatively compact, upright and sturdy plant habit; relatively short internodes; dark green-colored leaves; freely flowering habit; moderately strong to strong flowering stems with dense inflorescences with numerous white-colored flowers; and good garden performance.

  一种新的独特的翠雀属植物品种，命名为“ET DLP 824”，其特征为植株相对紧凑、直立、结实；节间相对较短；叶片呈深绿色；花期自由；开花茎适中到强壮，花序密集，有许多白色花朵；在花园中表现良好。
• Heterocyclic spiro compounds and their preparation
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP0311313A2

  公开（公告）日：1989-04-12

  Heterocyclic spiro compounds repreented by the following general formula and salts thereof: The above compounds act upon muscarinic acetylcholine receptors, thereby activating the acetylcholine nervous functions in the central nervous system.

  由以下通式表示的杂环螺化合物及其盐类： 上述化合物作用于毒蕈碱乙酰胆碱受体，从而激活中枢神经系统中的乙酰胆碱神经功能。
• Synthesis of a Thiomuscarone Analog
  作者：Gideon Shapiro、Yair Lavi

  DOI：10.3987/com-90-5592

  日期：——

  A novel synthesis of the thiomuscarone analog, 1-thia-2,8-dimethyl-3-oxo-8-azaspiro[4.5]decane (4) has been achieved. Other thiolan-3-ones which are highly substituted in the 5-position should be available by this method which provides an alternative to the classical Michael reaction-Dieckmann sequence.