6-methoxycarbonyl-3-thia-hexanal | 93546-02-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 6-methoxycarbonyl-3-thia-hexanal
• 英文别名: methyl 7-oxo-5-thiaheptanoate；Methyl 4-(2-oxoethylsulfanyl)butanoate
• CAS: 93546-02-2
• 化学式: C₇H₁₂O₃S
• 分子量: 176.236
• InChiKey: RTBOJXMRNQMXRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  11
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  68.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-methoxycarbonyl-3-thia-hexanal 在 1-pentynyl copper 、 六甲基磷酰三胺 、 4-二甲氨基吡啶 、 叔丁基锂 、 甲基磺酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 10.33h， 生成 (7-Z)-11,15-O-bis(tert-butyldimethylsilyl)-5-thia-Δ⁷-prostaglandin E1 methyl ester
  参考文献：
  名称：

  Synthesis of thiaprostaglandin E1 derivatives.

  摘要：

  一系列新型硫代前列腺素，即4-硫代-、5-硫代-、6-硫代-和7-硫代前列腺素E1甲酯（3b、4b、5b和6b），通过使用手性共同合成砌块（R）-4-叔丁基二甲基甲硅烷氧基-2-环戊烯酮（1）的三组分偶联反应合成。在这些硫代前列腺素中，7-硫代前列腺素E1甲酯显示出最强的血小板聚集抑制活性。

  DOI：

  10.1248/cpb.33.1815

文献信息

• Novel 5-thiaprostaglandin, process for production thereof, and pharmaceutical use thereof
  申请人：TEIJIN LIMITED

  公开号：EP0112633A2

  公开（公告）日：1984-07-04

  The present invention relates to novel 5-thiaprostaglandin which include 5-thiaprostaglandin E1 derivative, Δ7-5-thiaprostaglandin E1, 5-thiaprostaglandin A,, and Δ7-5-thiaprostaglandin A1; to process for producing these compounds; and to pharmaceutical uses of these compounds, especially as anti-ulcer or antitumor agent.

  本发明涉及新型5-硫前列腺素，包括5-硫前列腺素E1衍生物、Δ7-5-硫前列腺素E1、5-硫前列腺素A和Δ7-5-硫前列腺素A1；涉及生产这些化合物的工艺；还涉及这些化合物的医药用途，特别是作为抗溃疡剂或抗肿瘤剂。
• Aromatic derivative and preparation method thereof
  申请人：TEIJIN LIMITED

  公开号：EP0273678A2

  公开（公告）日：1988-07-06

  1. An aromatic derivative having the formula (I) or the salt thereof: wherein R1 and R2 independently represent a hydrogen atom, hydroxyl, a halogen atom, or OR3 wherein R3 is C1-C10 alkyl; A-B represents a hydrocarbon moiety having 1 to 10 carbon atoms and containing at least one double bond or a sulfur-or oxygen-containing hydrocarbon moiety having 1 to 10 carbon atoms; n is an integer of 2 to 4; X represents a group NH-; and Y represents a hydrogen atom; alkyl having 1 to 5 carbon atomswhich may be substituted with aryl; alkenyl having 2 to 5 carbon atoms which may be substituted with aryl or aryl substituted with at least one C1-C5 alkoxy; aryl which may be substituted with at least one carboxy or C1-C5 alkoxycarbonyl or C1-C5 alkoxy; provided that, when R1 and R2 are both hydrogen, the moiety -A-B-(CH2)n-X-Y does not represent -CH = CH (CH2)n-COOR4 wherein n = 2 to 4 and R4 is hydrogen or C1-C5 alkyl.

  1.具有式（I）的芳香族衍生物或其盐： 其中 R1 和 R2 独立地代表氢原子、羟基、卤素原子或 OR3，其中 R3 是 C1-C10 烷基；A-B 代表具有 1 至 10 个碳原子并含有至少一个双键的烃基或具有 1 至 10 个碳原子的含硫或含氧的烃基；n 是 2 至 4 的整数；X 代表基团 NH-；Y 代表氢原子；具有 1 至 5 个碳原子的烷基，可被芳基取代；具有 2 至 5 个碳原子的烯基，可被芳基取代或被至少一个 C1-C5 烷氧基取代的芳基；可被至少一个羧基或 C1-C5 烷氧基羰基或 C1-C5 烷氧基取代的芳基；但当 R1 和 R2 均为氢时，分子 -A-B-(CH2)n-X-Y 不代表 -CH = CH (CH2)n-COOR4，其中 n = 2 至 4，R4 为氢或 C1-C5 烷基。
• Design and synthesis of a selective EP4-receptor agonist. Part 3: 16-phenyl-5-thiaPGE1 and 9-β-halo derivatives with improved stability
  作者：T Maruyama

  DOI：10.1016/s0968-0896(02)00031-7

  日期：2002.6

  To identify a new selective EP4-agonist with improved chemical stability, further chemical modification of those reported previously was continued. We focused our attention on chemical modification of the alpha chain of 3,7-dithiaPGE(1), and selected 5-thiaPGE(1), as a new chemical lead, Introduction of an optimized omega to chain to the 5-thiaPG skeleton afforded in-methoxymethyl derivative 33a, which showed the most potent EP4-receptor agonist activity and good subtype-selectivity both in vitro and in vivo. 9beta-HaloPGF derivatives were also synthesized and biologically evaluated in an attempt to block self-degradation of the beta-hydroxyketone moiety. Among these series, 39a and 39b showed potent agonist activity and good subtype-selectivity. Structure-activity relationships (SARs) are also discussed. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Discovery of novel prostaglandin analogs as potent and selective EP2/EP4 dual agonists
  作者：Tohru Kambe、Toru Maruyama、Yoshihiko Nakai、Hideyuki Yoshida、Hiroji Oida、Takayuki Maruyama、Nobutaka Abe、Akio Nishiura、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmc.2012.02.018

  日期：2012.4

  To identify potent EP2/EP4 dual agonists with excellent subtype selectivity, a series of c-lactam prostaglandin E analogs bearing a 16-phenyl x-chain were synthesized and evaluated. Structural hybridization of 1 and 2, followed by more detailed chemical modification of the benzoic acid moiety, led us to the discovery of a 2-mercaptothiazole-4-carboxylic acid analog 3 as the optimal compound in the series. An isomer of this compound, the 2-mercaptothiazole-5-carboxylic acid analog 13, showed 34-fold and 13-fold less potent EP2 and EP4 receptor affinities, respectively. Structure activity relationship data from an in vitro mouse receptor binding assay are presented. Continued evaluation in an in vivo rat model of another 2-mercaptothiazole-4-carboxylic acid analog 17, optimized for sustained compound release from PLGA microspheres, demonstrated its effectiveness in a rat bone fracture-healing model following topical administration. (C) 2012 Elsevier Ltd. All rights reserved.
• Discovery of a novel EP2/EP4 dual agonist with high subtype-selectivity
  作者：Tohru Kambe、Toru Maruyama、Masayuki Nakano、Yoshihiko Nakai、Tadahiro Yoshida、Naoki Matsunaga、Hiroji Oida、Akira Konaka、Takayuki Maruyama、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmcl.2011.10.109

  日期：2012.1

  A series of gamma-lactam prostaglandin E(1) analogs bearing a 16-phenyl moiety in the omega-chain and aryl moiety in the alpha-chain were synthesized and biologically evaluated. Among the tested compounds, gamma-lactam PGE analog 3 designed as a structural hybrid of 1 and 2 was discovered as the most optimized EP2/EP4 dual agonist with excellent subtype-selectivity (K(i) values: mEP2 = 9.3 nM, mEP4 = 0.41 nM). A structure-activity relationship study is presented. (C) 2011 Elsevier Ltd. All rights reserved.