methyl 6-diazo-5-oxohexanoate | 76700-84-0

• 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: methyl 6-diazo-5-oxohexanoate
• 英文别名: methyl (6Z)-6-diazo-5-oxohexanoate
• CAS: 76700-84-0
• 化学式: C₇H₁₀N₂O₃
• 分子量: 170.168
• InChiKey: YTHJROJBAKBFFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  12
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  45.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 6-diazo-5-oxohexanoate 在 四溴化碳 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (6E,8Z)-10-Bromo-5-(tert-butyl-diphenyl-silanyloxy)-deca-6,8-dienoic acid methyl ester
  参考文献：
  名称：

  A new general method for the synthesis of lipoxygenase products: preparation of ±5-HETE

  摘要：

  DOI：

  10.1016/s0040-4039(00)88392-6
• 作为产物：
  描述：

  戊二酸单甲酯 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 乙醚 、 苯 为溶剂， 反应 5.5h， 生成 methyl 6-diazo-5-oxohexanoate
  参考文献：
  名称：

  Computer-aided identification of new histone deacetylase 6 selective inhibitor with anti-sepsis activity

  摘要：

  Histone deacetylase (HDAC) inhibitors have been recognized as promising approaches to the treatment of various human diseases including cancer, inflammation, neurodegenerative diseases, and metabolic disorders. Several pan-HDAC inhibitors are currently approved only as anticancer drugs. Interestingly, SAHA (vorinostat), one of clinically available pan-HDAC inhibitors, shows an anti-inflammatory effect at concentrations lower than those required for inhibition of tumor cell growth. It was also reported that HDAC6 selective inhibitor tubastatin A has anti-inflammatory and anti-rheumatic effect. In our efforts to develop novel HDAC inhibitors, we rationally designed various HDAC inhibitors based on the structures of two hit compounds identified by virtual screening of chemical database. Among them, 9a ((E)-N-hydroxy-4-(2-styrylthiazol-4-yl)butanamide) was identified as a HDAC6 selective inhibitor (IC50 values of 0.199 mu M for HDAC6 versus 13.8 mu M for HDAC1), and it did not show significant cytotoxicity against HeLa cells. In vivo biological evaluation of 9a was conducted on a lipopolysaccharide (LPS)-induced mouse model of sepsis. The compound 9a significantly improved 40% survival rate (P = 0.0483), and suppressed the LPS-induced increase of TNF-alpha and IL-6 mRNA expression in the liver of mice. Our study identified novel HDAC6 selective inhibitor 9a, which may serve as a potential lead for the development of anti-inflammatory or anti-sepsis agents. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.03.046

文献信息

• Studies on hypolipidemic agents. II Synthesis of 1-arenesulfonyloxy-2-alkanone derivatives as potent esterase inhibitors and hypolipidemic agents.
  作者：KAZUO OGAWA、TADAFUMI TERADA、YOSHIYUKI MURANAKA、TOSHIHIRO HAMAKAWA、SADAO HASHIMOTO、SETSURO FUJII

  DOI：10.1248/cpb.34.3252

  日期：——

  Many 2-oxoalkyl arenesulfonate derivatives having straight or branched alkyl chains of different lengths, 2-oxoalkyl bis-arenesulfonate derivatives, and alkyl arenesulfonate derivatives having a ketal moiety at the 2-position on the alkyl chain were synthesized, and their esterase-inhibitory activities, as well as hypolipidemic activities, were evaluated.Among these compounds, 1-(2, 4, 6-trimethylbenzenesulfonyloxy)-2-dodecanone (III-1u), and 1-(2, 3, 4, 6-tetramethylbenzenesulfonyloxy)-2-hexanone (III-1w), -2-octanone (III-1x) and -2-decanone (III-1y) exhibited potent esterase-inhibitory activities (IC50=3×10-10, 2×10-10, 2×10<-10> and 3×<-11>M, respectively). However, the sulfonate (XV) having a ketal moiety on the alkyl chain and the bis-sulfonate (XVI) exhibited low inhibitory activities toward esterase in comparison with III and XII. Most of the compounds III and some of the compounds XII exhibited potent hypolipidemic activities corresponding to more than 50% lipid-lowering effect (plasma triglyceride and cholesterol ester) in vivo. The structure-activity relatioinships of these compounds are discussed.

  合成了许多具有直链或支链不同长度烷基链的2-氧代烷基芳磺酸盐衍生物、2-氧代烷基双芳磺酸盐衍生物以及在烷基链的2-位具有缩酮部分的烷基芳磺酸盐衍生物，并评估了它们的酯酶抑制活性及降血脂活性。在这些化合物中，1-(2,4,6-三甲基苯磺酰氧基)-2-十二烷酮（III-1u）、1-(2,3,4,6-四甲基苯磺酰氧基)-2-己烷酮（III-1w）、-2-辛烷酮（III-1x）和-2-癸烷酮（III-1y）表现出强效的酯酶抑制活性（IC50分别为3×10-10、2×10-10、2×10-10和3×10-11M）。然而，相对于III和XII，具有烷基链上缩酮部分的磺酸盐（XV）和双磺酸盐（XVI）对酯酶的抑制活性较低。大多数化合物III和部分化合物XII表现出强效的降血脂活性，对应于体内超过50%的脂质降低效果（血浆甘油三酯和胆固醇酯）。讨论了这些化合物的构效关系。
• New rhodium(II) catalyzed synthesis of 1,4-dicarbonyl compounds from α-diazo ketones using vinyl ethers as two-carbon synthons
  作者：Sengodagounder Muthusamy、Pandurangan Srinivasan

  DOI：10.1016/j.tetlet.2006.06.111

  日期：2006.8

  afforded γ-ketoaldehydes or 1,4-diketones in a facile manner. In this process, oxycyclopropanes are formed as intermediates, and are subsequently ring opened in the presence of the rhodium(II) acetate catalyst to furnish the corresponding 1,4-dicarbonyl compounds. The scope of this protocol has been demonstrated with the synthesis of a serotonin antagonist.

  乙酸铑（II）催化各种α-重氮酮与乙烯基醚的反应，可以轻松地得到γ-酮醛或1,4-二酮。在该方法中，形成氧环丙烷作为中间体，然后在乙酸铑（II）催化剂存在下将其开环以提供相应的1，4-二羰基化合物。血清素拮抗剂的合成证明了该方案的范围。
• Polyene synthesis. Ready construction of retinol-carotene fragments, (.+-.)-6(E)-LTB3 leukotrienes, and corticrocin
  作者：Ernest Wenkert、Ming Guo、Rodolfo Lavilla、Barry Porter、Kishore Ramachandran、Jyh Horng Sheu

  DOI：10.1021/jo00312a031

  日期：1990.12
• Enhancing patency, safety and cost effectiveness of catheters
  作者：HD. Polaschegg、K. Sodemann、B. Feldmer

  DOI：10.1111/j.1755-6686.2002.tb00194.x

  日期：2002.1.3

  SummaryCatheters are generally known to be the last resort for blood access in dialysis. Because of the many problems related to catheter use, catheters are banned from vascular access courses organized by professional societies and the development of catheters and catheter related equipment relies on a few interested medical doctors with limited knowledge of hydraulics and material science. Rather than accepting the need for catheters and the need for improving catheters and catheter related procedures, vascular access meetings typically begin and end with statements saying that the use of fistulas must be increased and catheters must be banned. Several small companies have developed new catheters and catheter related equipment, which potentially overcome many of the problems related to the use of catheters. The authors had the privilege of participating in one of these developments and report about basic features and clinical experience of the DIALOCK® blood access port and an antimicrobial catheter locking solution (CLS) which is used with conventional catheters as well as with the DIALOCK®.
• Wenkert, Ernest; Bakuzis, Marinalva, L. F.; Buckwalter, Brian L., Synthetic Communications, 1981, vol. 11, # 7, p. 533 - 544
  作者：Wenkert, Ernest、Bakuzis, Marinalva, L. F.、Buckwalter, Brian L.、Woodgate, Paul D.

  DOI：——

  日期：——