ethyl 3-(4-oxopiperidin-1-yl)propanoate | 174774-90-4

• 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 3-(4-oxopiperidin-1-yl)propanoate
• 英文别名: ethyl 3-(4-oxopiperidino)propionate；3-(4-oxo-piperidino)-propionic acid ethyl ester；3-(4-Oxo-piperidino)-propionsaeure-aethylester；3-(4-oxo-piperidin-1-yl)-propionic acid ethyl ester
• CAS: 174774-90-4
• 化学式: C₁₀H₁₇NO₃
• mdl: MFCD14631395
• 分子量: 199.25
• InChiKey: KYBGYVYGAHECAE-UHFFFAOYSA-N

物化性质

• 沸点：
  311.0±27.0 °C(Predicted)
• 密度：
  1.079±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-(4-oxopiperidin-1-yl)propanoate 在 sodium tungstate (VI) dihydrate 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 双氧水 、 正己基锂 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 水 、 溶剂黄146 、 异丙醇 为溶剂， -74.0~90.0 ℃ 、827.39 kPa 条件下， 反应 52.25h， 生成 1-(3,3-bis(3-(methylsulfonyl)phenyl)propyl)-4-(3-(methylsulfonyl)phenyl)piperidine
  参考文献：
  名称：

  ANALOGS OF PRIDOPIDINE, THEIR PREPARATION AND USE

  摘要：

  这项发明提供了一种具有以下结构的隔离化合物或其盐。该发明还提供了一种制备4-(3-(甲磺基)苯基)-1-丙基哌啶-4-醇、1-(3,3-双(3-(甲磺基)苯基)丙基)-4-(3-(甲磺基)苯基)哌啶酮、1,4-双((3-(1-丙基哌啶-4-基)苯基)磺酰基)丁烷、(3R,4S)-4-(3-(甲磺基)苯基)-1-丙基哌啶-3-醇、4-(3-(甲磺基)苯基)-1-丙基哌啶-1-氧化物、1-(2-甲基戊基)-4-(3-(甲磺基)苯基)哌啶、4-(3-(甲磺基亚硫基)苯基)-1-丙基-1,2,3,6-四氢吡啶和4-(3-(甲磺基)苯基)-1-丙基-1,2,3,6-四氢吡啶的过程。该发明还提供了一种用作参考标准的杂质或其盐，用于检测含普利多匹定或其药学上可接受的盐的药物组合物中微量杂质。该发明还提供了一种生产普利多匹定药物产品的过程，包括获得普利多匹定药物物质并将其与适当的赋形剂混合以生产普利多匹定药物产品。该发明还提供了一种生产普利多匹定药物产品的过程。该发明还提供了一种分发普利多匹定药物产品的过程。

  公开号：

  US20150374677A1
• 作为产物：
  描述：

  Tris<2-(ethoxycarbonyl)ethyl>amin 在 sodium ethanolate 、 苯 作用下， 生成 ethyl 3-(4-oxopiperidin-1-yl)propanoate
  参考文献：
  名称：

  Ruzicka; Seidel, Helvetica Chimica Acta, 1922, vol. 5, p. 717

  摘要：

  DOI：

文献信息

• Preparation and Pharmacological Evaluation of Novel Glycoprotein (Gp) IIb/IIIa Antagonists. 2. Condensed Heterocyclic Derivatives.
  作者：Shin'ichiro ONO、Tomohiro YOSHIDA、Kazuhiro MAEDA、Keigo KOSAKA、Yoshihisa INOUE、Teruaki IMADA、Chikara FUKAYA、Norifumi NAKAMURA

  DOI：10.1248/cpb.47.1694

  日期：——

  A novel series of platelet receptor glycoprotein (Gp) IIb/IIIa antagonists with condensed heterocycles as their basic core was synthesized. In an in vitro assay, trans-4-(5-amidinobanzofuran-2-carboxamido)cyclohexyloxyacetic acid 17e and trans-3-[4-(5-amidinobanzofuran-2-carboxamido)cyclohexyl]propionic acid 17f produced marked inhibitions with IC50 values of 0.018 and 0.006 μM, respectively in a human platelet adenosin-5'-diphospate (ADP)-induced aggregation assay; they also exhibited a wide spectrum of inhibition toward major aggregation agonists (ADP, collagen, thrombin, PMA (tumor promoter) and arachidonic acid). These compounds were >2-3 orders of magnitude more effective in inhibiting platelet aggregation than human umbilical vein endothelial cell (HUVEC) binding. The oral administration of 10 mg/kg of either 17e and 17f to guinea pig, resulted in a 60% inhibition of ex vivo platelet aggregation after 5 h. Oral administration of ethyl trans-4-(5-amidinobenzofuran-2-carboxamido)cyclohexyloxyacetate 18e (10 mg/kg) resulted in 80% inhibition of platelet aggregation in dogs for 6 h after oral administration with a return to baseline by 24 h. Ethyl trans-3-[4-(5-amidinobenzofuran-2-carboxamido)cyclohexyl]propionate 18f (AR0598) produced 80% inhibition for 5 h after oral administration. Prodrug 18e showed a good profile in dogs with a long duration of action. 18e (AR0510) was selected as suitable clinical candidate for development as an orally active antithrombotic agent.

  合成了一系列新型的以稠合杂环为基本核心的血小板受体糖蛋白 (Gp) IIb/IIIa 拮抗剂。在体外试验中，反式-4-(5- 氨甲酰苯并呋喃 -2- 羧酰胺基) 环己氧乙酸 17e 和反式-3-[4-(5- 氨甲酰苯并呋喃 -2- 羧酰胺基)环己基] 丙酸 17f 在人血小板腺苷 -5'- 二磷酸 (ADP) 诱导的聚集试验中分别产生了显著的抑制作用，其 IC50 值分别为 0.018 和 0.006 μM;它们对主要的聚集激动剂 (ADP、胶原蛋白、凝血酶、PMA (肿瘤促进剂) 和花生四烯酸) 也表现出广泛的抑制作用。这些化合物在抑制血小板聚集方面比人脐静脉内皮细胞 (HUVEC) 结合的有效性高出 2-3 个数量级。将 17e 和 17f 以 10 mg/kg 的剂量口服给予豚鼠，5 小时后体外血小板聚集抑制率达到 60%。将反式-4-(5- 氨甲酰苯并呋喃 -2- 羧酰胺基) 环己氧乙酸乙酯 18e (10 mg/kg)口服给予狗，6 小时后血小板聚集抑制率达到 80%，24 小时后恢复到基线水平。反式-3-[4-(5- 氨甲酰苯并呋喃 -2- 羧酰胺基)环己基] 丙酸乙酯 18f (AR0598) 在口服给药后产生了 80% 的抑制作用，持续 5 小时。前药 18e 在狗体内显示出良好的特性，具有较长的作用持续时间。因此，18e (AR0510) 被选为适合开发的口服活性抗血栓药物的候选物。
• Carboxylic acid compound having condensed ring, salt thereof and
  申请人：The Green Cross Corporation

  公开号：US05635527A1

  公开（公告）日：1997-06-03

  A novel carboxylic acid compound having a condensed ring, which is represented by the formula (I) ##STR1## wherein each symbol is as defined in the specification, a pharmacologically acceptable salt thereof, a pharmaceutical composition thereof and pharmaceutical use thereof. The novel carboxylic acid compound having a condensed ring and pharmacologically acceptable salt thereof of the present invention have superior GPIIb/IIIa antagonism in mammals inclusive of human; can be administered orally; have long life in blood and low toxicity; and show less side-effects. Accordingly, they are extremely useful for the prophylaxis and treatment of thrombotic diseases and other diseases.

  一种具有紧缩环的新型羧酸化合物，其化学式表示为（I）##STR1## 其中每个符号如规范中所定义，其药理学上可接受的盐，其制药组合物和制药用途。本发明的具有紧缩环的新型羧酸化合物及其药理学上可接受的盐在哺乳动物中包括人类具有优越的GPIIb/IIIa拮抗作用；可以口服；在血液中寿命长且毒性低；并且表现出较少的副作用。因此，它们极其有用于预防和治疗血栓性疾病和其他疾病。
• NOVEL FUSED-RING CARBOXYLIC ACID COMPOUND OR SALT THEREOF, AND MEDICINAL USE THEREOF
  申请人：THE GREEN CROSS CORPORATION

  公开号：EP0712844A1

  公开（公告）日：1996-05-22

  A novel carboxylic acid compound having a condensed ring, which is represented by the formula (I) wherein each symbol is as defined in the specification, a pharmacologically acceptable salt thereof, a pharmaceutical composition thereof and pharmaceutical use thereof. The novel carboxylic acid compound having a condensed ring and pharmacologically acceptable salt thereof of the present invention have superior GPIIb/IIIa antagonism in mammals inclusive of human; can be administered orally; have long life in blood and low toxicity; and show less side-effects. Accordingly, they are extremely useful for the prophylaxis and treatment of thrombotic diseases and other diseases.

  一种具有缩合环的新型羧酸化合物，由式 (I) 表示 其中各符号如说明书中所定义；其药理上可接受的盐；其药物组合物；其药物用途。本发明的具有缩合环的新型羧酸化合物及其药理学上可接受的盐在哺乳动物（包括人类）中具有优异的 GPIIb/IIIa 拮抗作用；可口服给药；在血液中的存活期长且毒性低；副作用小。因此，它们对于预防和治疗血栓性疾病和其他疾病极为有用。
• BENZOXEPINO-11-PIPERIDYLIDENE COMPOUNDS AND PROCESS FOR PRODUCTION THEREOF
  申请人：Fujiyakuhin Co., Ltd.

  公开号：EP1614689A1

  公开（公告）日：2006-01-11

  Provided are a process for producing an acid addition salt of a 3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11-ylidene)piperidino]propionic acid alkyl ester by reacting a 3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11-ylidene)piperidino]propionic acid alkyl ester with an acid, and a process for producing 3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11-ylidene)piperidino]propionic acid using the acid addition salt as an intermediate. By using as an intermediate an acid addition salt of a 3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11-ylidene)piperidino]propionic acid alkyl ester to produce 3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11-ylidene)piperidino]propionic acid, the metals used in the synthetic reaction steps and the organic compounds mainly by-produced during production are readily separated from a reaction liquid by a simple procedure, and the by-products are sufficiently removed without using a purification step by chromatography, thereby enabling mass production and enhancing production efficiency.

  3-[4-(8-氟-5,11-二氢苯并[b]氧代吡啶并[4,3-b]吡啶-11-亚基)哌啶]丙酸烷基酯与酸的反应，以及以酸加成盐为中间体生产 3-[4-(8-氟-5,11-二氢苯并[b]氧代吡啶并[4,3-b]吡啶-11-亚基)哌啶]丙酸的工艺。 以 3-[4-(8-氟-5,11-二氢苯并[b]氧代吡啶并[4,3-b]吡啶-11-亚基)哌啶]丙酸烷基酯的酸加成盐为中间体，制得 3-[4-(8-氟-5,11-二氢苯并[b]氧代吡啶并[4,3-b]吡啶-11-亚基)哌啶]丙酸、合成反应步骤中使用的金属和生产过程中主要副产的有机化合物很容易通过简单的程序从反应液中分离出来，副产物无需使用色谱法进行纯化步骤即可充分去除，从而实现了大规模生产并提高了生产效率。
• Analogs of pridopidine, their preparation and use
  申请人：Schmidt Malle

  公开号：US10130621B2

  公开（公告）日：2018-11-20

  This invention provides an isolated compound having the structure: or a salt thereof. The invention also provides for a process for preparing 4-(3-(methylsulfonyl)phenyl)-1-propylpiperidin-4-ol, 1-(3,3-bis(3-(methylsulfonyl)phenyl)propyl)-4-(3-(methylsulfonyl) phenyl)piperidone, 1,4-bis((3-(1-propylpiperidin-4-yl)phenyl)sulfonyl)butane, (3R,4S)-4-(3-(methylsulfonyl)phenyl)-1-propylpiperidin-3-ol, 4-(3-(methylsulfonyl)phenyl)-1-propylpiperidine 1-oxide, 1-(2-methylpentyl)-4-(3-(methylsulfonyl)phenyl)piperidine, 4-(3-(methylsulfinyl)phenyl)-1-propyl-1,2,3,6-tetrahydropyridne, and 4-(3-(methylsulfonyl)phenyl)-1-propyl-1,2,3,6-tetrahydropyridine. This invention also provides an impurity or a salt thereof for use, as a reference standard to detect trace amounts of the impurity in a pharmaceutical composition comprising pridopidine or a pharmaceutically acceptable salt thereof. This invention further provides a process for producing a pridopidine drug product comprising obtaining a pridopidine drug substance and mixing the pridopidine drug substance with suitable excipients so as to produce the pridopidine drug product. This invention also provides a process for producing a pridopidine drug product. This invention also provides a process of distributing a pridopidine drug product.

  本发明提供了一种具有以下结构的分离化合物： 或其盐类。 本发明还提供了一种制备 4-(3-(甲磺酰基)苯基)-1-丙基哌啶-4-醇、1-(3,3-双(3-(甲磺酰基)苯基)丙基)-4-(3-(甲磺酰基)苯基)哌啶酮、1,4-双((3-(1-丙基哌啶-4-基)苯基)磺酰基)丁烷、(3R、4-(3-(甲磺酰基)苯基)-1-丙基哌啶-3-醇，4-(3-(甲磺酰基)苯基)-1-丙基哌啶 1-氧化物，1-(2-甲基戊基)-4-(3-(甲磺酰基)苯基)哌啶、4-(3-(甲磺酰基)苯基)-1-丙基-1,2,3,6-四氢吡啶，以及 4-(3-(甲磺酰基)苯基)-1-丙基-1,2,3,6-四氢吡啶。 本发明还提供了一种杂质或其盐，用作检测包含普利多哌啶或其药学上可接受的盐的药物组合物中痕量杂质的参考标准。本发明进一步提供了一种生产普利多哌啶药物产品的工艺，包括获得普利多哌啶药物物质并将普利多哌啶药物物质与合适的赋形剂混合以生产普利多哌啶药物产品。本发明还提供了一种生产普利多匹定药物产品的工艺。本发明还提供了一种分配普利多匹定药物产品的工艺。