4-(乙基氧基)-3-氧代丁酸甲酯 | 415678-65-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 中文名称: 4-(乙基氧基)-3-氧代丁酸甲酯
• 英文名称: methyl γ-ethoxyacetoacetate
• 英文别名: methyl 4-ethoxy-3-oxobutanoate；γ-ethoxyacetoacetic acid methyl ester；methyl 4-(ethyloxy)-3-oxobutanoate
• CAS: 415678-65-8
• 化学式: C₇H₁₂O₄
• 分子量: 160.17
• InChiKey: SGEADHKTXGGOEZ-UHFFFAOYSA-N

物化性质

• 沸点：
  225.0±15.0 °C(Predicted)
• 密度：
  1.060±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  11
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2918990090
• 危险性防范说明：
  P305+P351+P338
• 危险性描述：
  H227,H315,H319,H335
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  4-(乙基氧基)-3-氧代丁酸甲酯 在 dirhodium tetraacetate 4-二甲氨基吡啶 、 三乙胺 、 甲烷磺酰基叠氮化物 作用下， 以 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 生成 (Z)-4-[(2,4-dimethyl-3-pentyloxy)carbonylmethylidene]-2-methyl-1,3-dioxolane
  参考文献：
  名称：

  Ruthenium(II) Porphyrin Catalyzed Formation of (Z)-4-Alkyloxycarbonyl- methylidene-1,3-dioxolanes from γ-Alkoxy-α-diazo-β-ketoesters

  摘要：

  [GRAPHICS]Ruthenum(II) porphyrins and dirhodium(II) acetate catalyze cyclization of gamma-alkoxy-alpha-diazo-beta-ketoesters to (Z)-4-(alkyloxycarbonylmethylidene)-1,3-dioxolanes selectively (ca. 68% yield) with no formation of 3(2H)-furanones. Reacting a diazo ketoester with [Ru-II(TTP)(CO)] [H2TTP = meso-tetrakis(p-tolyl) porphyrin] in toluene afforded a ruthenium carbenoid complex, which has been isolated and spectroscopically characterized. A mechanism involving hydrogen atom migration from the C-H bond to the ruthenium carbenoid is proposed.

  DOI：

  10.1021/ol010283f
• 作为产物：
  描述：

  monomethyl monopotassium malonate 、 2-Ethoxy-1-imidazol-1-yl-ethanone 在 magnesium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 4-(乙基氧基)-3-氧代丁酸甲酯
  参考文献：
  名称：

  乙酰丙酮铁催化分子内C-H烷氧基化合成O-杂环

  摘要：

  C-H 键的分子内烷氧基化可以将结构和官能团的复杂性迅速引入看似简单或惰性的前体中。由于四氢呋喃 (THF) 基序普遍存在于各种药物、农用化学品和天然产品中，因此这种转化尤为重要。尽管已知用于生成功能化 THF 的各种合成方法，但大多数都表现出有限的官能团耐受性，并且缺乏用于制备用于药理学目的的分子中普遍存在的螺环或稠合双环和三环醚单元的证明。在此，我们报道了一种分子内 C-H 烷氧基化，使用市售的乙酰丙酮铁 (Fe(acac) 2) 作为催化剂。建议该反应通过形成由 N 2产生的乙烯基碳自由基来进行挤压，它介导近端 H 原子的提取，然后是快速的 C-O 键形成自由基重组步骤。使用同位素标记研究（乙烯基 C-D 掺入）、自由基时钟底物的开环和 Hammett 分析探索自由基机制，并通过密度泛函理论 (DFT) 计算进一步证实。观察到富电子 C-H 键（叔、醚）的反应性提高，而需要更大的催化

  DOI：

  10.1021/jacs.1c02074

文献信息

• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2010120854A1

  公开（公告）日：2010-10-21

  The invention is directed to to substituted indazole derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R1 - R6 and X are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically leukemia and cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及取代吲唑衍生物。具体而言，本发明涉及根据公式I的化合物：其中R1-R6和X在此定义。本发明的化合物是PDK1的抑制剂，可用于治疗由组成性激活的ACG激酶（如癌症，特别是白血病、乳腺癌、结肠癌和肺癌）引起的疾病。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物来抑制PDK1活性和治疗相关疾病的方法。
• Pyrrolopyridazinone Compound
  申请人：Hagihara Masahiko

  公开号：US20090036453A1

  公开（公告）日：2009-02-05

  The present invention discloses a pyrrolopyridazinone compound represented by the formula (1): wherein R 1 represents C 1 -C 2 alkyl group or halogeno C 1 -C 2 alkyl group, R 2 repersents C 3 -C 5 cycloalkyl group, (C 3 -C 5 cycloalkyl)C 1 -C 2 alkyl group or C 1 -C 3 alkyl group, R 3 represents hydrogen atom, or methylene group or cis-vinylene group for forming substituted oxygen-containing hetero ring in combination with group —O—R 2 , R 4 represents hydrogen atom, halogen atom, C 1 -C 8 alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, hydroxy C 3 -C 6 alkenyl group, hydroxy C 3 -C 6 alkynyl group, C 1 -C 6 alkyl group substituted by substituent(s) selected from Substituent group (a), C 3 -C 6 cycloalkyl group which may be substituted by substituent(s) selected from Substituent group (b), “C 1 -C 3 alkyl group which is substituted by C 3 -C 6 cycloalkyl group which may be substituted by substituent(s) selected from Substituent group (b), and which may be substituted by a hydroxy group”, an aromatic ring group or heteroaromatic ring group each of which may be substituted by a substituent(s) selected from Substituent group (c) or “C 1 -C 2 alkyl group which is substituted by aromatic ring group or heteroaromatic ring group each of which may be substituted by group(s) selected from Substituent group (c), and which may be substituted by a hydroxy group”, Substituent group (a) represents a halogen atom, hydroxy group, cyano group, carboxy group, C 1 -C 5 alkoxy group, halogeno C 1 -C 4 alkoxy group, C 3 -C 6 cycloalkoxy group, (C 3 -C 6 cycloalkyl)C 1 -C 2 alkoxy group, C 1 -C 4 alkoxycarbonyl group, C 2 -C 4 alkanoyl group, C 2 -C 4 alkanoyloxy group or C 1 -C 4 alkyl-substituted amino group, Substituent group (b) represents a hydroxy group or a halogen atom, Substituent group (c) represents a halogen atom, a hydroxy group, a cyano group, a nitro group, a carboxy group, C 1 -C 5 alkoxy group, C 1 -C 4 alkoxycarbonyl group, C 2 -C 4 alkanoyloxy group, C 1 -C 4 alkyl-substituted amino group or a C 1 -C 4 alkyl group which may be substituted by a substituent(s) selected from the group consisting of (a halogen atom, a hydroxy group and a carboxy group), or a pharmaceutically acceptable salt thereof.

  本发明公开了一种由式（1）表示的吡咯吡啶二酮化合物：其中，R1代表C1-C2烷基或卤代C1-C2烷基，R2代表C3-C5环烷基、（C3-C5环烷基）C1-C2烷基或C1-C3烷基，R3代表氢原子，或与基团-O-R2结合形成取代含氧杂环的亚甲基或顺式乙烯基，R4代表氢原子、卤素原子、C1-C8烷基、C2-C6烯基、C2-C6炔基、羟基C3-C6烯基、羟基C3-C6炔基、由从取代基团（a）中选择的取代基团取代的C1-C6烷基，可由从取代基团（b）中选择的取代基团取代的C3-C6环烷基，可由从取代基团（b）中选择的取代基团取代的C1-C3烷基，且可由羟基取代，芳香环基或杂芳香环基，每个都可由从取代基团（c）中选择的取代基团取代或由取代基团（c）选择的基团取代的C1-C2烷基，且可由羟基取代，取代基团（a）表示卤素原子、羟基、氰基、羧基、C1-C5烷氧基、卤代C1-C4烷氧基、C3-C6环烷氧基、（C3-C6环烷基）C1-C2烷氧基、C1-C4烷氧羰基、C2-C4酰基、C2-C4酰氧基或C1-C4烷基取代的氨基基团，取代基团（b）表示羟基或卤素原子，取代基团（c）表示卤素原子、羟基、氰基、硝基、羧基、C1-C5烷氧基、C1-C4烷氧羰基、C2-C4酰氧基、C1-C4烷基取代的氨基基团或可由从由卤素原子、羟基和羧基组成的基团中选择的取代基团取代的C1-C4烷基，或其药学上可接受的盐。
• PYRROLOPYRIDAZINONE COMPOUND AS PDE4 INHIBITOR
  申请人：Ube Industries, Ltd.

  公开号：EP1982986B1

  公开（公告）日：2012-03-07
• Potent and Orally Bioavailable GPR142 Agonists as Novel Insulin Secretagogues for the Treatment of Type 2 Diabetes
  作者：Narihiro Toda、Xiaolin Hao、Yasuyuki Ogawa、Kozo Oda、Ming Yu、Zice Fu、Yi Chen、Yongjae Kim、Mike Lizarzaburu、Sarah Lively、Shauna Lawlis、Michiko Murakoshi、Futoshi Nara、Nobuaki Watanabe、Jeff D. Reagan、Hui Tian、Angela Fu、Alykhan Motani、Qingxiang Liu、Yi-Jyun Lin、Run Zhuang、Yumei Xiong、Peter Fan、Julio Medina、Leping Li、Masanori Izumi、Ryo Okuyama、Satoshi Shibuya

  DOI：10.1021/ml400186z

  日期：2013.8.8

  GPR142 is a G protein-coupled receptor that is predominantly expressed in pancreatic beta-cells. GPR142 agonists stimulate insulin secretion in the presence of high glucose concentration, so that they could be novel insulin secretagogues with reduced or no risk of hypoglycemia. We report here the optimization of HTS hit compound 1 toward a proof of concept compound 33, which showed potent glucose lowering effects during an oral glucose tolerance test in mice and monkeys.
• EP1982986A1
  申请人：——

  公开号：EP1982986A1

  公开（公告）日：2008-10-22