α-Brom-valeriansaeureamid | 59863-66-0

• 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: α-Brom-valeriansaeureamid
• 英文别名: bromo-N-propylacetamide；2-Bromopentanamide
• CAS: 59863-66-0
• 化学式: C₅H₁₀BrNO
• 分子量: 180.044
• InChiKey: SUQPMLQLMVIHIJ-UHFFFAOYSA-N

物化性质

• 熔点：
  78.5-79 °C
• 沸点：
  256.8±23.0 °C(Predicted)
• 密度：
  1.435±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  43.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  α-Brom-valeriansaeureamid 在 双氧水 、 sodium ethanolate 、 乙酸酐 、 溶剂黄146 作用下， 生成 2-ethanesulfonyl-valeric acid amide
  参考文献：
  名称：

  α-Alkylsulfonylamides

  摘要：

  DOI：

  10.1021/ja01267a047
• 作为产物：
  描述：

  2-溴戊酰氯 在 氨 、 水 作用下， 生成 α-Brom-valeriansaeureamid
  参考文献：
  名称：

  The Preparation of Hydroxypyrazines and Derived Chloropyrazines

  摘要：

  DOI：

  10.1021/ja01126a070

文献信息

• Use of imidazoles for the treatment of atherosclerosis
  申请人：Du Pont Merck Pharmaceutical Company

  公开号：US05166214A1

  公开（公告）日：1992-11-24

  This invention relates to imidazoles as inhibitors of acyl-CoA: cholesterol acyltransferase (ACAT), processes for their preparation, and their use as antihypercholesterolemic agents or antiatherosclerotic. The compounds for use in the described method are compounds of Formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are selected independently from H, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 branched alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, C.sub.7 -C.sub.14 araalkyl, phenyl optionally substituted with 1 to 3 groups selected from F, Cl, Br, OH, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.8 branched alkyl, CH.sub.3 S(O).sub.r, NO.sub.2, CF.sub.3, or NR.sup.7 R.sup.8 ; R.sup.3 is H, C.sub.1 -C.sub.6 alkyl, allyl, benzyl, or phenyl optionally substituted with F, Cl, CH.sub.3, CH.sub.3 O, or CF.sub.3 ; R.sup.4 is straight chain C.sub.1 -C.sub.8 alkyl optionally substituted with F; C.sub.3 -C.sub.8 branched alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, C.sub.7 -C.sub.14 aralkyl where the aryl group is optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, F, Br, Cl, NH.sub.2, OH, CN, CO.sub.2 H, CF.sub.3, NO.sub.2, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.7 R.sup.8, or NCOR.sup.7 ; C.sub.3 -C.sub.6 alkenyl or alkynyl, C.sub.1 -C.sub.3 perfluoroalkyl, phenyl optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.8 branched alkyl, C.sub.1 -C.sub.4, alkoxy, F, Br, Cl, NH.sub.2, OH, CN, CO.sub.2 H, CF.sub.3, NO.sub.2, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.7 R.sup.8 or NCOR.sup.7 ; pentafluorophenyl, benzyl optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, F, Br, Cl, NH.sub.2, OH, CN, CO.sub.2 H, CF.sub.3, NO.sub.2, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.7 R.sup.8, or NCOR.sup.7 ; 2-, 3-, or 4- or pyrindinyl, pyrimidinyl, or biphenyl; R.sup.5 is H, C.sub.1 -C.sub.6 alkyl, or benzyl; R.sup.6 is C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 branched alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.8 alkenyl of alkynyl, phenyl optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, F, Br, Cl, NH.sub.2, OH, CN, CO.sub.2 H, CF.sub.3, NO.sub.2, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.7 R.sup.8, or NCOR.sup.7 ; pentafluorophenyl, benzyl optionally substituted with 1 to 3 groups selected from C.sub.1 -C.sub.4 alkyl or alkoxy, F, Br, Cl, NH.sub.2, OH, CN, CO.sub.2 H, CF.sub.3, NO.sub.2, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.7 R.sup.8, or NCOR.sup.7 ; R.sup.7 and R.sup.8 are selected independently from H or C.sub.1 -C.sub.4 alkyl; A is C.sub.2 -C.sub.10 alkyl, C.sub.3 -C.sub.10 branched alkyl, C.sub.3 -C.sub.10 alkenyl, or C.sub.3 -C.sub.10 alkynyl; Y is O; Z is NHR.sup.4, OR.sup.4, or R.sup.4 ; r is 0-2, or a pharmaceutically acceptable salt thereof.

  这项发明涉及咪唑作为酰基辅酶A：胆固醇酰基转移酶（ACAT）的抑制剂，其制备方法以及它们作为抗高胆固醇药物或抗动脉粥样硬化药物的用途。所述方法中用于的化合物为式（I）的化合物：##STR1## 其中R.sup.1和R.sup.2分别选择自H，C.sub.1 -C.sub.8烷基，C.sub.3 -C.sub.8支链烷基，C.sub.3 -C.sub.7环烷基，C.sub.4 -C.sub.10环烷基烷基，C.sub.7 -C.sub.14芳基烷基，苯基，可选择地取代为1至3个来自F，Cl，Br，OH，C.sub.1 -C.sub.4烷氧基，C.sub.1 -C.sub.4烷基，C.sub.3 -C.sub.8支链烷基，CH.sub.3S（O）.sub.r，NO.sub.2，CF.sub.3或NR.sup.7R.sup.8的基团；R.sup.3为H，C.sub.1 -C.sub.6烷基，烯丙基，苄基，或可选择地取代为F，Cl，CH.sub.3，CH.sub.3O或CF.sub.3的苯基；R.sup.4为直链C.sub.1 -C.sub.8烷基，可选择地取代为F；C.sub.3 -C.sub.8支链烷基，C.sub.3 -C.sub.7环烷基，C.sub.4 -C.sub.10环烷基烷基，C.sub.7 -C.sub.14芳基烷基，其中芳基可选择地取代为1至3个来自C.sub.1 -C.sub.4烷基或烷氧基，F，Br，Cl，NH.sub.2，OH，CN，CO.sub.2H，CF.sub.3，NO.sub.2，C.sub.1 -C.sub.4羧烷氧基，NR.sup.7R.sup.8，或NCOR.sup.7；C.sub.3 -C.sub.6烯基或炔基，C.sub.1 -C.sub.3全氟烷基，苯基，可选择地取代为1至3个来自C.sub.1 -C.sub.4烷基，C.sub.3 -C.sub.8支链烷基，C.sub.1 -C.sub.4烷氧基，F，Br，Cl，NH.sub.2，OH，CN，CO.sub.2H，CF.sub.3，NO.sub.2，C.sub.1 -C.sub.4羧烷氧基，NR.sup.7R.sup.8或NCOR.sup.7；五氟苯基，苄基，可选择地取代为1至3个来自C.sub.1 -C.sub.4烷基或烷氧基，F，Br，Cl，NH.sub.2，OH，CN，CO.sub.2H，CF.sub.3，NO.sub.2，C.sub.1 -C.sub.4羧烷氧基，NR.sup.7R.sup.8，或NCOR.sup.7；2-，3-，或4-或吡啶基，嘧啶基，或联苯基；R.sup.5为H，C.sub.1 -C.sub.6烷基，或苄基；R.sup.6为C.sub.1 -C.sub.8烷基，C.sub.3 -C.sub.8支链烷基，C.sub.3 -C.sub.7环烷基，C.sub.3 -C.sub.8烯基或炔基，苯基，可选择地取代为1至3个来自C.sub.1 -C.sub.4烷基或烷氧基，F，Br，Cl，NH.sub.2，OH，CN，CO.sub.2H，CF.sub.3，NO.sub.2，C.sub.1 -C.sub.4羧烷氧基，NR.sup.7R.sup.8，或NCOR.sup.7；五氟苯基，苄基，可选择地取代为1至3个来自C.sub.1 -C.sub.4烷基或烷氧基，F，Br，Cl，NH.sub.2，OH，CN，CO.sub.2H，CF.sub.3，NO.sub.2，C.sub.1 -C.sub.4羧烷氧基，NR.sup.7R.sup.8，或NCOR.sup.7；R.sup.7和R.sup.8分别选择自H或C.sub.1 -C.sub.4烷基；A为C.sub.2 -C.sub.10烷基，C.sub.3 -C.sub.10支链烷基，C.sub.3 -C.sub.10烯基，或C.sub.3 -C.sub.10炔基；Y为O；Z为NHR.sup.4，OR.sup.4，或R.sup.4；r为0-2，或其药用盐。
• Optimization and Evaluation of Novel Antifungal Agents for the Treatment of Fungal Infection
  作者：Ji Won Choi、Kyung-Tae Lee、Siwon Kim、Ye Rim Lee、Hyeon Ji Kim、Kyung Jin Seo、Myung Ha Lee、Seul Ki Yeon、Bo Ko Jang、Sun Jun Park、Hyeon Jeong Kim、Jong-Hyun Park、Dahee Kim、Dong-Gi Lee、Eunji Cheong、Jong-Seung Lee、Yong-Sun Bahn、Ki Duk Park

  DOI：10.1021/acs.jmedchem.1c01299

  日期：2021.11.11

  mortality by fungal infections and the emergence of severe antifungal resistance, there is an urgent need for new antifungal agents. Here, we screened for antifungal activity in our in-house library through the minimum inhibitory concentration test and derived two hit compounds with moderate antifungal activities. The hit compounds’ antifungal activities and drug-like properties were optimized by substituting

  由于真菌感染的发病率和死亡率增加以及严重的抗真菌耐药性的出现，迫切需要新的抗真菌药物。在这里，我们通过最低抑菌浓度测试在我们的内部库中筛选抗真菌活性，并衍生出两种具有中等抗真菌活性的命中化合物。通过取代各种芳环、烷基链和甲基，优化了命中化合物的抗真菌活性和类药特性。在优化的化合物中， 22h是最有前途的候选化合物，具有良好的类药特性，对多种真菌病原体表现出强效、快速的杀菌抗真菌作用，并与一些已知的抗真菌药物具有协同抗真菌活性。此外， 22h被进一步证实可以通过激活多个细胞壁完整性途径来扰乱真菌细胞壁的完整性。此外， 22h在皮下感染小鼠模型和离体人指甲感染模型中均发挥显着的抗真菌功效。
• Synthesis and Structure−Activity Relationship of Pyrazolo[3,4-<i>d</i>]pyrimidines:  Potent and Selective Adenosine A₁ Receptor Antagonists
  作者：Sally-Ann Poulsen、Ronald J. Quinn

  DOI：10.1021/jm960052s

  日期：1996.1.1

  structural differences between the A1 and A2a receptors with respect to the binding of pyrazolo[3,4-d]pyrimidines. This study resulted in prediction that increased A1 affinity could be achieved by incorporation of NH-alkyl substituents at C-4. This was confirmed by synthesis of alpha-[[4-(methylamino)-1-phenylpyrazolo[3,4-d]pyrimidin-6-yl]thiol] hexanamide (15) which was found to have an A1 Ki of 0.745 nM

  合成一系列12个取代的1-苯基吡唑并[3,4-d]嘧啶并评估其对大鼠脑腺苷A1和A2a受体的结合亲和力。为了在受体亚型的分子识别方面定义这些区域，改变了C-4和C-6处的取代基。在C-4处，评估了巯基，甲硫基和氨基取代基的作用，而在C-6处，研究了具有从α-碳延伸的烷基的酰胺。这项研究确定了有效和选择性的腺苷A1受体拮抗剂。在这12种化合物中，最有效的化合物是α-[（4-氨基-1-苯基吡唑并[3,4-d]嘧啶-6-基）硫基]己酰胺（14）；该化合物的A1 Ki为0.939 nM，A2a Ki为88.3 nM，是A1选择性的94倍。在这12种化合物中，选择性最高的是α-[[4-（甲硫基）-1-苯基吡唑并[3，4-d]嘧啶-6-基]硫代]己酰胺（10）; 如果A1 Ki为6.81 nM，A2a Ki> 40 000 nM，则该化合物对A1的选择性是> 5900倍。完整系列的结构-活性关系已确定在吡唑并[3
• Synthese von symmetrisch 2,3-dialkyl-substituierten Maleinsäure-Derivaten
  作者：L. JANITSCHKE、W. KREISER

  DOI：10.1055/s-1976-24029

  日期：——
• α-Bromination of primary nitriles
  作者：Calvin L. Stevens、William Holland

  DOI：10.1021/jo50015a007

  日期：1953.9