2-(2,4-dichlorophenylthio)propanoic acid | 119424-79-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(2,4-dichlorophenylthio)propanoic acid
• 英文别名: 2-(2,4-Dichlorophenylsulfanyl)-propionic acid；2-(2,4-dichlorophenyl)sulfanylpropanoic acid
• CAS: 119424-79-2
• 化学式: C₉H₈Cl₂O₂S
• 分子量: 251.133
• InChiKey: XECKVRUWGDNORW-UHFFFAOYSA-N

物化性质

• 沸点：
  366.2±42.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2,4-dichlorophenylthio)propanoic acid 在 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 N-(4-fluorobenzyl)-2-[(2,4-dichlorophenyl)sulfonyl]propanamide
  参考文献：
  名称：

  Synthesis and structure–activity relationships of novel phenoxyacetamide inhibitors of the Pseudomonas aeruginosa type III secretion system (T3SS)

  摘要：

  The increasing prevalence of drug-resistant bacterial infections is driving the discovery and development not only of new antibiotics, but also of inhibitors of virulence factors that are crucial for in vivo pathogenicity. One such virulence factor is the type III secretion system (T3SS), which plays a critical role in the establishment and dissemination of Pseudomonas aeruginosa infections. We have recently described the discovery and characterization of a series of inhibitors of P. aeruginosa T3SS based on a phenoxyacetamide scaffold. To better characterize the factors involved in potent T3SS inhibition, we have conducted a systematic exploration of this structure, revealing several highly responsive structure-activity relationships indicative of interaction with a specific target. Most of the structural features contributing to potency were additive, and combination of those features produced optimized inhibitors with IC50 values <1 mu M. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.011
• 作为产物：
  描述：

  2,4-二氯苯硫酚 在 水 、 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 2-(2,4-dichlorophenylthio)propanoic acid
  参考文献：
  名称：

  Synthesis and structure–activity relationships of novel phenoxyacetamide inhibitors of the Pseudomonas aeruginosa type III secretion system (T3SS)

  摘要：

  The increasing prevalence of drug-resistant bacterial infections is driving the discovery and development not only of new antibiotics, but also of inhibitors of virulence factors that are crucial for in vivo pathogenicity. One such virulence factor is the type III secretion system (T3SS), which plays a critical role in the establishment and dissemination of Pseudomonas aeruginosa infections. We have recently described the discovery and characterization of a series of inhibitors of P. aeruginosa T3SS based on a phenoxyacetamide scaffold. To better characterize the factors involved in potent T3SS inhibition, we have conducted a systematic exploration of this structure, revealing several highly responsive structure-activity relationships indicative of interaction with a specific target. Most of the structural features contributing to potency were additive, and combination of those features produced optimized inhibitors with IC50 values <1 mu M. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.011

文献信息

• Selenium analogs of phenoxypropionic and phenoxyacetic herbicides
  作者：Jerzy Zakrzewski、Bogumiła Huras、Anna Kiełczewska、Maria Krawczyk

  DOI：10.1515/znb-2018-0128

  日期：2018.12.19

  derivatives were dimerized with elemental selenium in the presence of CuO as catalyst to the corresponding diselenides. Diselenides were reduced with NaBH4 to a selenide anion and condensed with either propionic or chloroacetic acid to achieve the selenium analogs of phenoxyacetic herbicides. These selenium analogs show moderate herbicidal and fungistatic activity.

  摘要苯氧乙酸除草剂的硒类似物，即 2-(2,4-二氯苯氧基)丙酸 (2,4-DP)、2-(2,4-二氯苯氧基)乙酸 (2,4-D)、2-(4 -氯-2-甲基苯氧基）丙酸（MCPP）、2-（4-氯-2-甲基苯氧基）乙酸（MCPA）、2-（2,4,5-三氯苯氧基）丙酸（2,4,5- TP) 和 2-(2,4,5-三氯苯氧基) 乙酸 (2,4,5-T) 分两步合成。在CuO作为催化剂的情况下，碘芳基衍生物与元素硒二聚化为相应的二硒化物。二硒化物用 NaBH4 还原为硒化物阴离子，并与丙酸或氯乙酸缩合以获得苯氧基乙酸除草剂的硒类似物。这些硒类似物显示出中等的除草和抑真菌活性。
• Pyrimidine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US04851519A1

  公开（公告）日：1989-07-25

  Compounds of the formula ##STR1## wherein R.sup.1 is halogen, C.sub.1-4 -alkyl, halo-(C.sub.1-4 -alkyl) or C.sub.2-4 -alkanoyl, R.sup.2 is hydrogen, hydroxy, C.sub.1-4 alkoxy, C.sub.1-4 -alkylthio or phenyl-(C.sub.1-4 -alkoxy) or , when X is O, also acyloxy, R.sup.3 is hydrogen or C.sub.1-4 -alkyl, R.sup.4 is a carbocyclic group or a heterocyclic group, R.sup.5 is hydrogen or fluorine, m stands for zero, 1 or 2, X is O or NH and Y is a direct bond, --CH.dbd.CH--, --C.tbd.C-- or a group of the formula of --(Z).sub.n --A-- (a) in which A is a C.sub.1-8 alkylene group which is optionally substituted by one or two phenyl groups, Z is O, S, SO or SO.sub.2 and n stands for zero or 1, with the proviso that R.sup.1 is different from iodine, when R.sup.2 is hydroxy or benzoyloxy, R.sup.3 is hydrogen, R.sup.4 is unsubstituted phenyl, R.sup.5 is hydrogen, m stands for zero, X is O, and Y is a direct bond, and tautomers thereof, which possess antiviral activity and can therefore be used in the form of medicaments for the control and prevention of viral infections are described. The compounds of formula I can be prepared according to known methods.

  式为##STR1##的化合物，其中R.sup.1是卤素，C.sub.1-4-烷基，卤代-(C.sub.1-4-烷基)或C.sub.2-4-酰基，R.sup.2是氢，羟基，C.sub.1-4烷氧基，C.sub.1-4-烷基硫醚或苯基-(C.sub.1-4-烷氧基)，当X为O时，还可以是酰氧基，R.sup.3是氢或C.sub.1-4-烷基，R.sup.4是碳环基或杂环基，R.sup.5是氢或氟，m代表零、1或2，X是O或NH，Y是直接键，--CH.dbd.CH--，--C.tbd.C--或具有--(Z).sub.n--A--(a)式的基团，在该式中A是C.sub.1-8烷基烯基，可以选择地被一个或两个苯基取代，Z是O，S，SO或SO.sub.2，n代表零或1，但R.sup.1不同于碘时，当R.sup.2是羟基或苯甲酰氧基，R.sup.3是氢，R.sup.4是未取代的苯基，R.sup.5是氢，m代表零，X是O，Y是直接键，以及它们的互变异构体，具有抗病毒活性，因此可用作药物形式用于控制和预防病毒感染。根据已知方法可以制备式I的化合物。
• Mutations in the Pseudomonas aeruginosa Needle Protein Gene <i>pscF</i> Confer Resistance to Phenoxyacetamide Inhibitors of the Type III Secretion System
  作者：Nicholas O. Bowlin、John D. Williams、Claire A. Knoten、Matthew C. Torhan、Tommy F. Tashjian、Bing Li、Daniel Aiello、Joan Mecsas、Alan R. Hauser、Norton P. Peet、Terry L. Bowlin、Donald T. Moir

  DOI：10.1128/aac.02795-13

  日期：2014.4

  The type III secretion system (T3SS) is a clinically important virulence mechanism in Pseudomonas aeruginosa that secretes and translocates effector toxins into host cells, impeding the host's rapid innate immune response to infection. Inhibitors of T3SS may be useful as prophylactic or adjunctive therapeutic agents to augment the activity of antibiotics in P. aeruginosa infections, such as pneumonia and bacteremia. One such inhibitor, the phenoxyacetamide MBX 1641, exhibits very responsive structure-activity relationships, including striking stereoselectivity, in its inhibition of P. aeruginosa T3SS. These features suggest interaction with a specific, but unknown, protein target. Here, we identify the apparent molecular target by isolating inhibitor-resistant mutants and mapping the mutation sites by deep sequencing. Selection and sequencing of four independent mutants resistant to the phenoxyacetamide inhibitor MBX 2359 identified the T3SS gene pscF , encoding the needle apparatus, as the only locus of mutations common to all four strains. Transfer of the wild-type and mutated alleles of pscF , together with its chaperone and cochaperone genes pscE and pscG , to a Δ pscF P. aeruginosa strain demonstrated that each of the single-codon mutations in pscF is necessary and sufficient to provide secretion and translocation that is resistant to a variety of phenoxyacetamide inhibitor analogs but not to T3SS inhibitors with different chemical scaffolds. These results implicate the PscF needle protein as an apparent new molecular target for T3SS inhibitor discovery and suggest that three other chemically distinct T3SS inhibitors interact with one or more different targets or a different region of PscF.

  摘要 III型分泌系统（T3SS）是铜绿假单胞菌中一种临床上重要的毒力机制。 铜绿假单胞菌 Ⅲ型分泌系统（T3SS）是铜绿假单胞菌的一种重要临床毒力机制，它能将效应毒素分泌并转运到宿主细胞中，从而阻碍宿主对感染做出快速的先天免疫反应。T3SS 抑制剂可作为预防或辅助治疗药物，增强抗生素在铜绿假单胞菌感染中的活性。 铜绿假单胞菌 感染（如肺炎和菌血症）的抗生素活性。其中一种抑制剂是苯氧乙酰胺 MBX 1641，它对铜绿假单胞菌的抑制表现出非常灵敏的结构-活性关系，包括显著的立体选择性。 铜绿假单胞菌 T3SS。这些特征表明它与一个特定但未知的蛋白质靶点相互作用。在这里，我们通过分离抑制剂抗性突变体并通过深度测序绘制突变位点图，确定了明显的分子靶标。对四个对苯氧乙酰胺抑制剂 MBX 2359 具有抗性的独立突变体进行筛选和测序，确定了 T3SS 基因 pscF 是所有四个菌株唯一共同的突变位点。将野生型和突变等位基因的 的野生型和突变等位基因 及其伴侣蛋白和辅助伴侣蛋白基因 pscE 和 基因 转变为 Δ pscF 铜绿微囊藻 菌株中的每个单密码子突变都证明了 单密码子突变 中的每个单密码子突变对提供分泌和转运是必要且足够的，这些分泌和转运对多种苯氧乙酰胺抑制剂类似物具有抗性，但对具有不同化学支架的 T3SS 抑制剂没有抗性。这些结果表明，PscF 针蛋白显然是发现 T3SS 抑制剂的一个新分子靶点，并表明其他三种化学性质不同的 T3SS 抑制剂与 PscF 的一个或多个不同靶点或不同区域相互作用。
• Method of treating herpes simplex viral infection employing pyrimidine
  申请人：Hoffmann-La Roche Inc.

  公开号：US05010060A1

  公开（公告）日：1991-04-23

  Compounds of the formula ##STR1## wherein R.sup.1 is halogen, C.sub.1-4 -alkyl, halo-(C.sub.1-4 -alkyl) or C.sub.2-4 -alkanoyl, R.sup.2 is hydrogen, hydroxy, C.sub.1-4 -alkoxy, C.sub.1-4 -alkylthio or phenyl-(C.sub.1-4 -alkoxy) or, when X is O, also acyloxy, R.sup.3 is hydrogen or C.sub.1-4 -alkyl, R.sup.4 is a carbocyclic group or a heterocyclic group, R.sup.5 is hydrogen or fluorine, m stands for zero, 1 or 2, X is O or NH and Y is a direct bond, --CH.dbd.CH--, --C.tbd.C-- or a group of the formula of --(Z).sub.n --A-- (a) in which A is a C.sub.1-8 -alkylene group which is optionally substituted by one or two phenyl groups, is O, S, SO or SO.sub.2 and n stands for zero or 1, with the proviso that R.sup.1 is different from iodine, when R.sup.2 is hydroxy or benzoyloxy, R.sup.3 is hydrogen, R.sup.4 is unsubstituted phenyl, R.sup.5 is hydrogen, m stands for zero, X is O, and Y is a direct bond, and tautomers thereof, which possess antiviral activity and can therefore be used in the form of medicaments for the control and prevention of viral infections are described. The compounds of formula I can be prepared according to known methods.

  化合物的化学式为##STR1## 其中，R.sup.1是卤素，C.sub.1-4-烷基，卤代-(C.sub.1-4-烷基)或C.sub.2-4-酰基，R.sup.2是氢，羟基，C.sub.1-4-烷氧基，C.sub.1-4-烷基硫基或苯基-(C.sub.1-4-烷氧基)，或者当X是O时，也可以是酰氧基，R.sup.3是氢或C.sub.1-4-烷基，R.sup.4是一个碳环基或杂环基，R.sup.5是氢或氟，m代表零，1或2，X是O或NH，Y是直接键，--CH.dbd.CH--，--C.tbd.C--或式为--(Z).sub.n--A--(a)的基团，其中A是C.sub.1-8-烷基，可选地被一个或两个苯基取代，是O，S，SO或SO.sub.2，n代表零或1，但R.sup.1不同于碘时，当R.sup.2是羟基或苯甲酰氧基，R.sup.3是氢，R.sup.4是未取代的苯基，R.sup.5是氢，m代表零，X是O，Y是直接键，以及它们的互变异构体，具有抗病毒活性，因此可以用作药物的形式，用于控制和预防病毒感染。化合物I的制备可以按照已知方法进行。
• Fawcett et al., Annals of Applied Biology, 1955, vol. 43, p. 342,343, 344
  作者：Fawcett et al.

  DOI：——

  日期：——