ethyl 5-bromo-3,3-dimethyl-pentanoate | 123469-83-0

• 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: ethyl 5-bromo-3,3-dimethyl-pentanoate
• 英文别名: ethyl 5-bromo-3,3-dimethylvalerate；BrCH2CH2CMe2CH2CO2Et；5-bromo-3,3-dimethyl-valeric acid ethyl ester；5-Brom-3,3-dimethyl-valeriansaeure-aethylester；5-bromo-3,3-dimethylpentanoic acid ethyl ester；Ethyl 5-bromo-3,3-dimethylpentanoate
• CAS: 123469-83-0
• 化学式: C₉H₁₇BrO₂
• 分子量: 237.137
• InChiKey: LYUGLLMDRXJRGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  12
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ethyl 5-bromo-3,3-dimethyl-pentanoate 在 sodium hydroxide 、 sodium hydride 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  结合血栓烷受体拮抗作用和血栓烷合酶抑制作用的药物：[[[[2-（1H-咪唑-1-基）亚乙基]氨基]氧基]链烷酸。

  摘要：

  描述了结合血栓烷-A2（TxA2）受体拮抗作用和血栓烷合酶抑制作用的一类新化合物。第一个系列（E）-和（Z）-[[[[2-（1H-咪唑-1-基）亚乙基]氨基]氧基]戊酸显示相关的血栓烷合酶抑制与弱TxA2受体拮抗作用有关，而一系列前者在结构上衍生自（+/-）-（E）-[[[[2-（1H-咪唑-1-基）-3-苯基亚丙基]氨基]氧基]戊酸的戊酸显示有效且均衡的双重活动。讨论了重要的单一活动和双重活动的结构要求。后一个系列的两个紧密同源物，（+/-）-（E）-5-[[[[1-环己基-2-（1H-咪唑-1-基）-3-苯基亚丙基]氨基]氧基]戊酸23c及其对氟苯基类似物23m在凝结期间抑制大鼠全血中TxB2的产生，IC50为0.06和0。37 microM拮抗[3H] SQ 29548与洗涤的人血小板的结合，IC50分别为0.08和0.02 microM。选择这两种化合物进行进一步的药理评估，结果显

  DOI：

  10.1021/jm00047a016
• 作为产物：
  描述：

  4,4-二甲基-2,6-二氧代哌啶-3,5-二甲腈 在 sodium tetrahydroborate 、 硫酸 、 水 、 氢溴酸 、 乙酸酐 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 162.0h， 生成 ethyl 5-bromo-3,3-dimethyl-pentanoate
  参考文献：
  名称：

  The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase

  摘要：

  Betaine-homocysteine S-methyltransferase (BHMT) is an important zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. In the liver, BHMT performs to half of the homocysteine remethylation. In this study, we systematically investigated the tolerance of the enzyme for modifications at the "homocysteine" part of the previously reported potent inhibitor (R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid (1). In the new compounds, which are S-alkylated homocysteine derivatives, we replaced the carboxylic group in the "homocysteine" part of inhibitor 1 with different isosteric moieties (tetrazole and oxadiazolone); we suppressed the carboxylic negative charge by amidations; we enhanced acidity by replacing the carboxylate with phosphonic or phosphinic acids; and we introduced pyrrolidine steric constraints. Some of these compounds display high affinity toward human BHMT and may be useful for further pharmacological studies of this enzyme. Although none of the new compounds were more potent inhibitors than the reference inhibitor 1, this study helped to completely define the structural requirements of the active site of BHMT and revealed the remarkable selectivity of the enzyme for homocysteine. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.039

文献信息

• Structure−Activity Study of New Inhibitors of Human Betaine-Homocysteine <i>S</i>-Methyltransferase
  作者：Václav Vaněk、Miloš Buděšínský、Petra Kabeleová、Miloslav Šanda、Milan Kožíšek、Ivona Hančlová、Jana Mládková、Jiří Brynda、Ivan Rosenberg、Markos Koutmos、Timothy A. Garrow、Jiří Jiráček

  DOI：10.1021/jm8015798

  日期：2009.6.25

  BHMT inhibitors. The inhibitors were designed to mimic the hypothetical transition state of BHMT substrates and consisted of analogues with NH, N(CH3), or N(CH3)2 groups separated from the homocysteine sulfur atom by a methylene, ethylene, or a propylene spacer. Only the inhibitor with the N(CH3) moiety and ethylene spacer gave moderate inhibition. This result led us to prepare two inhibitors lacking

  甜菜碱高半胱氨酸小号-methyltransferase（BHMT）催化甲基从甜菜碱转移到1-高半胱氨酸，得到二甲基甘氨酸和升-甲硫氨酸。在这项研究中，我们制备了一系列新的 BHMT 抑制剂。这些抑制剂旨在模拟 BHMT 底物的假设过渡态，由具有 NH、N(CH 3 ) 或 N(CH 3 ) 2基团的类似物组成，这些基团通过亚甲基、亚乙基或丙烯间隔基与同型半胱氨酸硫原子隔开. 只有具有 N(CH 3 ) 部分和乙烯间隔基的抑制剂产生中等抑制作用。这一结果促使我们制备了两种在S 中缺少氮原子的抑制剂。-连接的烷基链：( RS , RS )-5-(3-氨基-3-羧基丙硫基)-3-甲基戊酸和( RS )-5-(3-氨基-3-羧基丙硫基)-3,3-二甲基戊酸. 这两种化合物都是 BHMT 的高效抑制剂。BHMT 不能耐受这些抑制剂中真正的甜菜碱模拟物，尤其是氮原子的发现令人惊讶，并引发了关于 BHMT
• Carboxylic acid derivatives, processes for the preparation thereof and
  申请人：Boehringer Mannheim GmbH

  公开号：US04609673A1

  公开（公告）日：1986-09-02

  The present invention provides carboxylic acid derivatives of the general formula: ##STR1## wherein R is a hydrogen atom, alkyl, a metal cation or an ammonium or alkylammonium ion, R.sub.1 is a hydrogen atom, a hydroxyl group or an alkyl, O-alkyl,O-benzyl or O-acyl radical, R.sub.2 is a hydrogen atom or an alkyl, aryl or aralkyl radical, n is 0, 1 or 2 and R.sub.3 is an acyl radical, this radical being (a) a straight-chained or branched, saturated or unsaturated alkanoyl radical containing 2 to 11 carbon atoms; or (b) the radical ##STR2## in which A is a straight-chained or branched, saturated or unsaturated aliphatic hydrocarbon radical containing up to 4 carbon atoms, which is optionally substituted by hydroxyl, and B is a straight-chained or branched, saturated or unsaturated aliphatic hydrocarbon radical containing up to 8 carbon atoms, which is optionally substituted one or more times by hydroxyl, carboxyl or phenyl, or B is a phenyl or cycloalkyl radical; or (c) the radical ##STR3## in which A and B have the same meanings as in (b) and R.sub.4 is a hydrogen atom or an alkyl or aralkyl radical; as well as the pharmacologically acceptable salts thereof. The present invention also provides processes for the preparation of these compounds, as well as pharmaceutical compositions containing them.

  本发明提供了通式为：其中R是氢原子、烷基、金属阳离子或铵盐或烷基铵离子，R.sub.1是氢原子、羟基或烷基，O-烷基、O-苄基或O-酰基基团，R.sub.2是氢原子或烷基、芳基或芳基烷基基团，n为0、1或2，R.sub.3是酰基基团，该基团为(a)含有2至11个碳原子的直链或支链、饱和或不饱和的烷酰基基团；或(b)基团：其中A是含有最多4个碳原子的直链或支链、饱和或不饱和脂肪烃基团，可选地被羟基取代，B是含有最多8个碳原子的直链或支链、饱和或不饱和脂肪烃基团，可选地被羟基、羧基或苯基取代，或B是苯基或环烷基基团；或(c)基团：其中A和B的含义与(b)中相同，R.sub.4是氢原子或烷基或芳基烷基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基团的羟基酰基基
• Substituted sulphonamides, pharmaceuticals thereof and methods of using
  申请人：Boehringer Mannheim GmbH

  公开号：US04981873A1

  公开（公告）日：1991-01-01

  The present invention concerns compounds of the formula: ##STR1## where R.sub.1 is an alkyl or alkenyl radical containing up to 6 carbon atoms, a cycloalkyl radical containing 3 to 7 carbon atoms, an aralkyl, aralkenyl or aryl radical in which the aryl radical or moiety can be substituted one or more times by halogen, C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkoxy, hydroxyl, trifluoromethyl, cyano, nitro, amino, C.sub.1 -C.sub.6 -alkylamino, C.sub.2 -C.sub.12 -dialkylamino, C.sub.1 -C.sub.6 -acylamino, C.sub.1 -C.sub.16 -acyl, C.sub.1 -C.sub.6 -alkylsulphenyl, -sulphinyl or -sulphonyl or by azido, R.sub.2 is hydrogen atom or a C.sub.1 -C.sub.6 -alkyl, aralkyl, aralkenyl or acyl radical, A and B are saturated or unsaturated alkylene chains containing up to 10 carbon atoms which can be substituted one or more times by C.sub.1 -C.sub.3 -alkyl radicals, the sum of carbon atoms in chains A and B being at least 4 and at most 11, Q is an oxygen or sulphur atom, a sulphonyl or sulphinyl group or an amino group --N(R.sub.2)--, R.sub.2 having the same meaning as above, and Y is a free carboxylic acid group or a carboxylic acid ester, carboxylic acid amide, hydroxymethyl or tetrazolyl radical; the pharmacologically acceptable salts thereof and the optically active and E-Z isomers thereof, as well as mixtures thereof. These compounds are useful as they have an antagonistic action towards thromboxane A.sub.2 as well as against prostaglandin endoperoxide. They inhibit the aggregation of blood platelets and prevent the constriction of the smooth musculature as well as bronchoconstriction.

  本发明涉及以下化合物：##STR1## 其中，R1是含有6个碳原子以下的烷基或烯基基团，含有3至7个碳原子的环烷基基团，芳基烷基，芳基烯基或芳基基团，其中芳基基团或基团可以被卤素，C1-C6烷基，C1-C6烷氧基，羟基，三氟甲基，氰基，硝基，氨基，C1-C6烷基氨基，C2-C12二烷基氨基，C1-C6酰胺基，C1-C16酰基，C1-C6烷基磺酰基，-磺酰基或-磺酸基或-偶氮基取代一次或多次。R2是氢原子或C1-C6烷基，芳基烷基，芳基烯基或酰基基团，A和B是饱和或不饱和的含有10个碳原子以下的烷基链，可以被C1-C3烷基基团取代一次或多次，链A和B的碳原子总数至少为4且最多为11，Q是氧原子或硫原子，磺酰基或磺酰基基团或氨基-N（R2）-，其中R2与上述相同，Y是自由羧酸基或羧酸酯，羧酸酰胺，羟甲基或四唑基基团；以及其药学上可接受的盐和光学活性和E-Z异构体，以及其混合物。这些化合物具有抗血栓素A2和前列腺素内过氧化物的拮抗作用。它们抑制血小板聚集并防止平滑肌收缩以及支气管收缩。
• Biologically active compounds
  申请人：Smith Kline & French Laboratories Limited

  公开号：US04997847A1

  公开（公告）日：1991-03-05

  The invention relates to phenylsulphonamidolkanoic acids which have thromboxane A.sub.2 receptor antagonist activity.

  该发明涉及具有血栓素A.sub.2受体拮抗活性的苯磺酰胺基烷酸。
• Neue Carbonsäure-Derivate, Verfahren zu ihrer Herstellung sowie diese Verbindungen enthaltende Arzneimittel
  申请人：BOEHRINGER MANNHEIM GMBH

  公开号：EP0149201A1

  公开（公告）日：1985-07-24

  Neue Carbonsäure-Derivate der Formel I in der R H, Alkyl, ein Metall-Kation, Ammonium, Alkylammonium R1 H, OH, Alkyl, O-Alkyl, O-Benzyl, O-Acyl R2 H, Alkyl, Aryl, Aralkyl n 0, 1, 2 und R3 einen Acyl-Rest bedeuten, deren pharmakologisch verträgliche Salze, Verfahren zu deren Herstellung sowie Arzneimittel mit lipidsenkender Wirkung, die diese Substanzen enthält.

  式 I 的新羧酸衍生物 其中 R 是 H、烷基、金属阳离子、铵、烷基铵 R1 是 H、OH、烷基、O-烷基、O-苄基、O-酰基 R2 是 H、烷基、芳基、芳烷基 n 是 0、1、2，R3 是酰基、它们的药理耐受盐、它们的制备工艺以及含有这些物质的具有降血脂活性的药物。