阿前列素 | 83997-19-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 阿前列素
• 英文名称: (1S,5S,6R,7R)-6-<3(R)-Cyclopentyl-3-hydroxy-E-1-propenyl>-7-hydroxybicyclo<3.3.0>octan-E-Δ^3,δ-pentanoic Acid
• 英文别名: ATAPROST；(5E)-5-[(3aS,4R,5R,6aS)-4-[(E,3S)-3-cyclopentyl-3-hydroxyprop-1-enyl]-5-hydroxy-3,3a,4,5,6,6a-hexahydro-1H-pentalen-2-ylidene]pentanoic acid
• CAS: 83997-19-7
• 化学式: C₂₁H₃₂O₄
• 分子量: 348.483
• InChiKey: DKLGLHQHLFISGJ-YLBFUXKPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl (1R,5S,6S,7R)-6-tert-butyldimethylsilyloxymethyl-7-tetrahydropyranyloxybicyclo<3.3.0>oct-2-ene-3-γ-pentenoate 在 (苯甲酸甲酯)三羰基铬 咪唑 、 sodium hydroxide 、 sodium tetrahydroborate 、 pyridine-SO3 complex 、 四丁基氟化铵 、 氢气 、 sodium hydride 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， -25.0~120.0 ℃ 、6.86 MPa 条件下， 反应 28.5h， 生成 阿前列素
  参考文献：
  名称：

  使用芳烃三羰基铬络合物催化的加氢立体控制合成环外烯烃。I.碳环素及其类似物的有效合成。

  摘要：

  描述了碳环素及其类似物（2-7）的有效合成，其中1,3-二烯的立体有规1,4-氢加氢成内部单烯起关键作用。也就是说，芳烃.Cr（CO）3络合物催化的二烯13和58的1,4-氢化可以高收率从Corey内酯获得，在高H2压力下，立体定向地得到环外烯烃14和61，收率很好。然后将这些中间体按照常规方法转化为可治疗的碳环素（2）及其类似物3-7。

  DOI：

  10.1248/cpb.39.309

文献信息

• [EN] IMPROVED PEPTIDE PHARMACEUTICALS FOR TREATMENT OF NASH AND OTHER DISORDERS<br/>[FR] COMPOSÉS PHARMACEUTIQUES PEPTIDIQUES AMÉLIORÉS UTILISÉS POUR LE TRAITEMENT D'UNE STÉATOHÉPATITE NON ALCOOLIQUE ET D'AUTRES TROUBLES
  申请人：SPITFIRE PHARMA INC

  公开号：WO2019136158A1

  公开（公告）日：2019-07-11

  The disclosure provides peptide products comprising a peptide covalently attached to a surfactant moiety which have improved properties, including increased duration of action and bioavailability. The peptide products are useful for treating insulin resistance, diabetes, obesity, metabolic syndrome and cardiovascular diseases, and conditions associated therewith, such as NASH and PCOS.

  该披露提供了包括肽共价连接到表面活性剂基团的肽产品，具有改善的特性，包括增加作用持续时间和生物利用度。这些肽产品可用于治疗胰岛素抵抗、糖尿病、肥胖、代谢综合征和心血管疾病，以及相关的疾病，如NASH和PCOS。
• PULMONARY HYPERTENSION TREATING AGENT
  申请人：THE UNIVERSITY OF TOKYO

  公开号：US20160368895A1

  公开（公告）日：2016-12-22

  [Problem] The present invention addresses the problem of providing a compound that is useful for preventing or treating diseases associated with malfunctioning of PGI2 receptors, in particular, pulmonary hypertension. [Solution] A positive allosteric regulator of a PGI2 receptor which comprises a compound represented by formula (1) or a pharmaceutically acceptable salt, hydrate or solvate thereof. (1) (In the formula, R1 is a branched chain or cyclic alkyl or alkenyl having 3 to 10 carbon atoms which may be substituted, R2 is a hydrogen atom or an alkyl having 1 to 6 carbon atoms which may be substituted, R3 is 1 to 4 substituents which are the same or different independently selected from the group consisting of a hydrogen atom, a halogen atom, an alkyl having 1 to 6 carbon atoms which may be substituted, and an alkoxy having 1 to 6 carbon atoms which may be substituted, and A is an aryl which may be substituted or a heteroaryl which may be substituted.)

  [问题] 本发明解决了提供一种化合物的问题，该化合物可用于预防或治疗与PGI2受体功能失调相关的疾病，特别是肺动脉高压。[解决方案] PGI2受体的正向变构调节剂，包括由式（1）表示的化合物或其药用可接受的盐、水合物或溶剂。 (1) （在该式中，R1是具有3到10个碳原子的支链烷基或环烷基，可能被取代，R2是氢原子或具有1到6个碳原子的烷基，可能被取代，R3是1到4个取代基，它们是相同或不同地独立选择自由基团，包括氢原子、卤原子、可能被取代的具有1到6个碳原子的烷基和可能被取代的具有1到6个碳原子的烷氧基，A是可能被取代的芳基或可能被取代的杂环芳基。）
• NICOTINAMIDE RIBOSIDE DERIVATIVES AND THEIR USES
  申请人：GANAPATI Gangadhara

  公开号：US20180362570A1

  公开（公告）日：2018-12-20

  The disclosure provides derivatives of both the oxidized form and the reduced form of nicotinamide riboside (NR) and nicotinic acid riboside (NAR). The NR and NAR derivatives have improved stability and bioavailability compared to NR and NAR, and can increase cellular NAD + levels and improve mitochondrial function. Therefore, the NR and NAR derivatives are useful for treating mitochondrial diseases, mitochondria-related diseases and conditions, and other disorders and conditions.

  该披露提供了烟酰胺核苷酸（NR）和烟酸核苷酸（NAR）的氧化形式和还原形式的衍生物。与NR和NAR相比，NR和NAR衍生物具有更好的稳定性和生物利用度，并且可以增加细胞NAD+水平并改善线粒体功能。因此，NR和NAR衍生物对治疗线粒体疾病、与线粒体相关的疾病和症状以及其他疾病和症状具有用处。
• NICOTINYL RIBOSIDE COMPOUNDS AND THEIR USES
  申请人：MitoPower, LLC

  公开号：US20200397807A1

  公开（公告）日：2020-12-24

  The disclosure provides nicotinamide riboside (NR), the reduced form of NR (NRH), nicotinic acid riboside (NAR), the reduced form of NAR (NARH), derivatives thereof, compositions thereof and uses thereof. The NR and NAR derivatives have improved stability and bioavailability compared to NR and NAR. NR, NRH, NAR, NARH, and derivatives thereof can increase cellular NAD + levels and enhance mitochondrial and cellular function and cell viability. Therefore, NR, NRH, NAR, NARH, and derivatives thereof, whether alone or in combination with one or more additional therapeutic agents (e.g., a mitochondrial uncoupler or/and a PARP inhibitor), are useful for treating mitochondrial diseases, mitochondria-related diseases and conditions, metabolic disorders, and other disorders and conditions.

  该披露提供烟酰胺核糖苷（NR）、烟酰胺核糖苷的还原形式（NRH）、烟酸核糖苷（NAR）、烟酸核糖苷的还原形式（NARH）、以及它们的衍生物、组合物和用途。与NR和NAR相比，NR和NAR的衍生物具有更好的稳定性和生物利用度。NR、NRH、NAR、NARH和它们的衍生物可以增加细胞NAD+水平，增强线粒体和细胞功能以及细胞存活能力。因此，NR、NRH、NAR、NARH和它们的衍生物，无论是单独使用还是与一个或多个额外治疗剂（例如线粒体解耦蛋白抑制剂和/或PARP抑制剂）结合使用，都可用于治疗线粒体疾病、与线粒体相关的疾病和症状、代谢紊乱以及其他疾病和症状。
• Microparticles With Modified Release of At Least One Active Principle and Oral Pharmaceutical Form Comprising Same
  申请人：Dargelas Frederic

  公开号：US20090220611A1

  公开（公告）日：2009-09-03

  The invention concerns microparticulate systems with modified release of oral active principle(s). The invention aims at providing a novel pharmaceutical with time-dependent and pH-dependent release mechanism, enabling: a) the latent period preceding the release of the active principle in the stomach; b) the pH triggering the release of the active principle in the intestine; c) the release speed of the active principle. This is achieved through the use of coated microparticles made from particles of active principle each coated with two coating films A and B. A comprises: film-forming (co)polymer (A1) insoluble in fluids of the gastrointestinal tract; ethylcellulose (co)polymer (A2) soluble in fluids of the gastrointestinal tract; plasticizing polyvinylpyrrolidone (A3); castor oil/optionally a surfactant and/or magnesium stearate lubricant (A4). B comprises a hydrophilic polymer (B1) bearing ionized groups with neutral pH (EUDRAGIT® L100-55) and a hydrophobic compound (B2) (LUBRITAB®). The invention also concerns medicines based on said microparticles.

  该发明涉及具有口服活性原理改性释放的微粒系统。该发明旨在提供一种具有时间依赖性和pH依赖性释放机制的新型药物，实现：a）在胃中释放活性原理之前的潜伏期；b）在肠道中触发释放活性原理的pH值；c）活性原理的释放速度。这是通过使用由活性原理颗粒制成的被包覆的微粒来实现的，每个微粒都涂有两层涂膜A和B。A包括：在胃肠道液体中不溶解的成膜（共）聚合物（A1）；在胃肠道液体中可溶解的乙基纤维素（共）聚合物（A2）；增塑剂聚乙烯吡咯烷酮（A3）；蓖麻油/可选的表面活性剂和/或硬脂酸镁润滑剂（A4）。B包括具有中性pH的离子化基团的亲水性聚合物（B1）（EUDRAGIT® L100-55）和疏水化合物（B2）（LUBRITAB®）。该发明还涉及基于这些微粒的药物。