(p-iodophenoxy)acetyl chloride | 20143-44-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (p-iodophenoxy)acetyl chloride
• 英文别名: <4-Iod-phenoxy>-acetylchlorid；2-(4-iodophenoxy)acetyl chloride
• CAS: 20143-44-6
• 化学式: C₈H₆ClIO₂
• 分子量: 296.492
• InChiKey: DXYJATYNWNDZJC-UHFFFAOYSA-N

物化性质

• 沸点：
  308.1±22.0 °C(Predicted)
• 密度：
  1.847±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 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：

  (p-iodophenoxy)acetyl chloride 以 吡啶 为溶剂， 反应 10.0h， 生成 3-(2-Hydroxy-ethyl)-2-(4-iodo-phenoxymethyl)-3H-quinazolin-4-one
  参考文献：
  名称：

  Khan; Saksena, Pharmazie, 1988, vol. 43, # 12, p. 864 - 865

  摘要：

  DOI：
• 作为产物：
  描述：

  对碘苯氧乙酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (p-iodophenoxy)acetyl chloride
  参考文献：
  名称：

  具有抗药性的蚊子乙酰胆碱酯酶1的非共价抑制剂。

  摘要：

  昆虫的抗药性显着威胁通过在传播疾病的昆虫的媒介控制中使用杀虫剂获得的重要利益。为了开发新的杀虫剂候选物，迫切需要发现具有杀虫活性的新化学实体。在这里，我们介绍必需酶乙酰胆碱酯酶1（AChE1）的基于苯氧乙酰胺的抑制剂的设计，合成和生物学评估。AChE1是经过验证的杀虫剂靶标，可用于控制例如疟疾，登革热和寨卡病毒感染的蚊媒。所述抑制剂将蚊子对人AChE的选择性与对赋予耐药性的突变G122S的高效力相结合。事实证明，结合使用单一化合物具有两个方面的挑战。抑制剂-蛋白质复合物的结构-活性关系分析和分子动力学模拟提供了阐明这些特性的分子基础的见解。我们还表明，抑制剂表现出对传播疾病的蚊子具有体内杀虫活性。我们的发现支持AChE1的非共价，选择性和抗性破坏抑制剂的概念，将其作为未来杀虫剂开发的有前途的方法。

  DOI：

  10.1021/acs.jmedchem.8b01060

文献信息

• Cloxacepride and related compounds: a new series of orally active antiallergic compounds
  作者：Gunter Metz、M. H. Pindell、H. L. Chen

  DOI：10.1021/jm00361a022

  日期：1983.7

  4-[[(p-Chlorophenoxy)acetyl]amino]-5-chloro-2-methoxy-N-[2-(diethylamino)ethyl]benzamide (cloxacepride, 1), exhibited substantial oral antiallergic potential in a reaginic PCA test in rats over a wide range of antigenic challenge times. Available reference compounds with oral activity, such as doxantrazole and 7-(2-hydroxyethoxy)-9-oxoxanthene-2-carboxylic acid (AH 7725, 4), were active only when administered

  4-[[（对-氯苯氧基）乙酰基]氨基] -5-氯-2-甲氧基-N- [2-（二乙基氨基）乙基]苯甲酰胺（cloxacepride，1）在PCA测试中显示出明显的口服抗过敏潜力。大鼠在广泛的抗原挑战时间内。现有的具有口服活性的参考化合物，例如多沙唑和7-（2-羟基乙氧基）-9-氧杂蒽-2-羧酸（AH 7725，4），仅在激发前15分钟给药才具有活性：4，尤其是效果不一致。氯吡格雷的口服ED50值为46-49 mg / kg，与茶碱相当，静脉注射2 mg / kg的铬糖酸二钠（DSCG）可立即攻击。口服ED50剂量后，1显示出比茶碱更慢的发作和更长的作用持续时间。全身性过敏反应和抗组胺活性的抑制作用的缺乏表明了特异性作用或尿素性抗原抗体反应。根据必需的取代基，研究和讨论了各种化学修饰的构效关系。
• Dichloroaniline derivatives
  申请人：Glaxo Group Limited

  公开号：US04943591A1

  公开（公告）日：1990-07-24

  The invention provides compounds of the general formula (I) ##STR1## wherein X represents a C.sub.1-6 alkylene, C.sub.2-6 alkenylene or C.sub.2-6 alkynylene chain and Y represents a bond, or a C.sub.1-4 alkylene, C.sub.2-4 alkenylene or C.sub.2-4 alkynylene chain with the proviso that the sum total of carbon atoms in X and Y is not more than 8; Ar represents a phenyl group optionally substituted by one or more substituents selected from halogen atoms or the groups C.sub.1-3 alkyl, nitro, --(CH.sub.2).sub.q R [where R is hydroxy, C.sub.1-3 alkoxy, --NR.sup.3 R.sup.4 (where R.sup.3 and R.sup.4 each represent a hydrogen atom, or a C.sub.1-4 alkyl group, or --NR.sup.3 R.sup.4 forms a saturated heterocyclic amino group which has 5-7 ring members and optionally contains in the ring one or more atoms selected from --O-- or --S-- or a group --NH-- or --N(CH.sub.3)--), --NR.sup.5 COR.sup.6 (where R.sup.5 represents a hydrogen atom or a C.sub.1-4 alkyl group, and R.sup.6 represents a hydrogen atom or a C.sub.1-4 alkyl, C.sub.1-4 alkoxy or --NR.sup.3 R.sup.4 group), and q represents an integer from 0 to 3], --NR.sup.5 COR.sup.19 (where R.sup.5 is as defined above and R.sup.19 represents a phenyl group), --(CH.sub.2).sub.r R.sup.7 [where R.sup.7 represents --NR.sup.5 SO.sub.2 R.sup.8 (where R.sup.8 represents a C.sub.1-4 alkyl, phenyl or --NR.sup.3 R.sup.4 group), --NR.sup.5 COCH.sub.2 N(R.sup.5).sub.2 (where each of the groups R.sup.5 represents a hydrogen atom or a C.sub.1-4 alkyl group), --COR.sup.9 (where R.sup.9 represents hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4), --SR.sup.10 (where R.sup.10 is a hydrogen atom, or a C.sub.1-4 alkyl group optionally substituted by hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4), --SOR.sup.10, --SO.sub.2 R.sup.10, --CN, or --NR.sup.11 R.sup.12 (where R.sup.11 and R.sup.12 represent a hydrogen atom or a C.sub.1-4 alkyl group, at least one of which is C.sub.2-4 alkyl substituted by a hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4), and r represents an integer from 0 to 3], --O(CH.sub.2).sub.q COR.sup.9 (where q and R.sup.9 are as defined above), or --O(CH.sub.2).sub.t R.sup.13 [where R.sup.13 represents hydroxy, NR.sup.3 R.sup.4, NR.sup.11 R.sup.12 or a C.sub.1-4 alkoxy group optionally substituted by hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4, and t is an integer 2 or 3], or Ar is a phenyl group substituted by an alkylenedioxy group --O(CH.sub.2).sub.p O-- where p is 1 or 2; R.sup.1 and R.sup.2 each represents a hydrogen atom or a C.sub.1-3 alkyl group, with the proviso that the sum total of carbon atoms in R.sup.1 and R.sup.2 is not more than 4; and physiologically acceptable salts and solvates (e.g. hydrates) thereof. The compounds of formula (I) have a stimulant action at .beta..sub.2 -adrenoreceptors and are useful, in particular, in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.

  本发明提供了一般式(I)的化合物：##STR1## 其中，X代表C.sub.1-6烷基，C.sub.2-6烯基或C.sub.2-6炔基链，Y代表键或C.sub.1-4烷基，C.sub.2-4烯基或C.sub.2-4炔基链，但X和Y中碳原子的总和不超过8；Ar代表苯基，可选地由一个或多个取代基选自卤素原子或C.sub.1-3烷基，硝基，--(CH.sub.2).sub.qR [其中R为羟基，C.sub.1-3烷氧基，--NR.sup.3R.sup.4（其中R.sup.3和R.sup.4各代表氢原子或C.sub.1-4烷基，或--NR.sup.3R.sup.4形成有5-7个环成员的饱和杂环氨基，其中环中可选地包含一个或多个原子选自--O--或--S--或--NH--或--N(CH.sub.3)--），--NR.sup.5COR.sup.6（其中R.sup.5代表氢原子或C.sub.1-4烷基，R.sup.6代表氢原子或C.sub.1-4烷基，C.sub.1-4烷氧基或--NR.sup.3R.sup.4基），q代表0至3的整数]，--NR.sup.5COR.sup.19（其中R.sup.5如上定义，R.sup.19代表苯基），--(CH.sub.2).sub.rR.sup.7 [其中R.sup.7代表--NR.sup.5SO.sub.2R.sup.8（其中R.sup.8代表C.sub.1-4烷基，苯基或--NR.sup.3R.sup.4基），--NR.sup.5COCH.sub.2N(R.sup.5).sub.2（其中每个R.sup.5代表氢原子或C.sub.1-4烷基），--COR.sup.9（其中R.sup.9代表羟基，C.sub.1-4烷氧基或NR.sup.3R.sup.4），--SR.sup.10（其中R.sup.10为氢原子或可选地由羟基，C.sub.1-4烷氧基或NR.sup.3R.sup.4取代的C.sub.1-4烷基），--SOR.sup.10，--SO.sub.2R.sup.10，--CN或--NR.sup.11R.sup.12（其中R.sup.11和R.sup.12代表氢原子或C.sub.1-4烷基，至少有一个是由羟基，C.sub.1-4烷氧基或NR.sup.3R.sup.4取代的C.sub.2-4烷基），r代表0至3的整数]，--O(CH.sub.2).sub.qCOR.sup.9（其中q和R.sup.9如上定义），或--O(CH.sub.2).sub.tR.sup.13 [其中R.sup.13代表羟基，NR.sup.3R.sup.4，NR.sup.11R.sup.12或可选地由羟基，C.sub.1-4烷氧基或NR.sup.3R.sup.4取代的C.sub.1-4烷氧基，t为2或3]，或Ar是由烷二氧基基团--O(CH.sub.2).sub.pO-取代的苯基，其中p为1或2；R.sup.1和R.sup.2各代表氢原子或C.sub.1-3烷基，但R.sup.1和R.sup.2中碳原子的总和不超过4；以及其生理上可接受的盐和溶剂（例如水合物）。式(I)的化合物在.beta..sub.2-肾上腺素受体上具有兴奋作用，并且特别适用于治疗与可逆性气道阻塞有关的疾病，如哮喘和慢性支气管炎。
• Dichloroaniline derivatives for the therapy or prophylaxysis of a
  申请人：Glaxo Group Limited

  公开号：US05006556A1

  公开（公告）日：1991-04-09

  The invention provides compounds of the general formula (I) ##STR1## wherein X represents a C.sub.1-6 alkylene, C.sub.2-6 alkenylene or C.sub.2-6 alkynylene chain and Y represents a bond, or a C.sub.1-4 alkylene, C.sub.2-4 alkenylene or C.sub.2-4 alkynylene chain with the proviso that the sum total of carbon atoms in X and Y is not more than 8; Ar represents a phenyl group optionally substituted by one or more substituents selected from halogen atoms or the groups C.sub.1-3 alkyl, nitro, --(CH.sub.2)qR [where R is hydroxy, C.sub.1-3 alkoxy, --NR.sup.3 R.sup.4 (where R.sup.3 and R.sup.4 each represent a hydrogen atom, or a C.sub.1-4 alkyl group, or --NR.sup.3 R.sup.4 forms a saturated heterocyclic amino group which has 5-7 ring members and optionally contains in the ring one or more atoms selected from --O-- or --S-- or a group --NH-- or --N(CH.sub.3)--), --NR.sup.5 COR.sup.6 (where R.sup.5 represents a hydrogen atom or a C.sub.1-4 alkyl group, and R.sup.6 represents a hydrogen atom or a C.sub.1-4 alkyl, C.sub.1-4 alkoxy or --NR.sup.3 R.sup.4 group), and q represents an integer from 0 to 3], --NR.sup.5 COR.sup.19 (where R.sup.5 is as defined above and R.sup.19 represents a phenyl group), --(CH.sub.2).sub.r R.sup.7 [where R.sup.7 represents --NR.sup.5 SO.sub.2 R.sup.8 (where R.sup.8 represents a C.sub.1-4 alkyl, phenyl or --NR.sup.3 R.sup.4 group), --NR.sup.5 COCH.sub.2 N(R.sup.5).sub.2 (where each of the groups R.sup.5 represents a hydrogen atom or a C.sub.1-4 alkyl group), --COR.sup.9 (where R.sup.9 represents hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4), --SR.sup.10 (where R.sup.10 is a hydrogen atom, or a C.sub.1-4 alkyl group optionally substituted by hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4), --SOR.sup.10, --SO.sub.2 R.sup.10, --CN, or --NR.sup.11 R.sup.12 (where R.sup.11 and R.sup.12 represent a hydrogen atom or a C.sub.1-4 alkyl group, at least one of which is C.sub.2-4 alkyl substituted by a hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4 group), and r represents an integer from 0 to 3], --O(CH.sub.2).sub.q COR.sup.9 (where q and R.sup.9 are as defined above), or --O(CH.sub.2).sub.t R.sup.13 [where R.sup.13 represents hydroxy, NR.sup.3 R.sup.4, NR.sup.11 R.sup.12 or a C.sub.1-4 alkoxy group optionally substituted by hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4, and t is an integer 2 or 3], or Ar is a phenyl group substituted by an alkylenedioxy group --O(CH.sub.2).sub.p O-- where p is 1 or 2; R.sup.1 and R.sup.2 each represents a hydrogen atom or a C.sub.1-3 alkyl group, with the proviso that the sum total of carbon atoms in R.sup.1 and R.sup.2 is not more than 4; and physiologically acceptable salts and solvates (e.g. hydrates) thereof. The compounds of formula (I) have a stimulant action at .beta..sub.2 -adrenoreceptors and are useful, in particular, in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.

  本发明提供了一般式（I）的化合物：##STR1## 其中X代表C.sub.1-6烷基，C.sub.2-6烯基或C.sub.2-6炔基链，Y代表键或C.sub.1-4烷基，C.sub.2-4烯基或C.sub.2-4炔基链，但X和Y中碳原子的总和不超过8；Ar代表苯基，可选地取代一个或多个取代基，所述取代基选择自卤原子或C.sub.1-3烷基、硝基、--(CH.sub.2)qR [其中R为羟基、C.sub.1-3烷氧基、--NR.sup.3R.sup.4（其中R.sup.3和R.sup.4分别代表氢原子，或C.sub.1-4烷基，或--NR.sup.3R.sup.4形成有5-7个环成员的饱和杂环氨基，可选地在环中包含一个或多个选择自--O--或--S--或--NH--或--N(CH.sub.3)--的原子或基），--NR.sup.5COR.sup.6（其中R.sup.5代表氢原子或C.sub.1-4烷基，R.sup.6代表氢原子或C.sub.1-4烷基、C.sub.1-4烷氧基或--NR.sup.3R.sup.4基），q代表0至3的整数]、--NR.sup.5COR.sup.19（其中R.sup.5如上定义，R.sup.19代表苯基），--(CH.sub.2).sub.rR.sup.7 [其中R.sup.7代表--NR.sup.5SO.sub.2R.sup.8（其中R.sup.8代表C.sub.1-4烷基、苯基或--NR.sup.3R.sup.4基）、--NR.sup.5COCH.sub.2N(R.sup.5).sub.2（其中R.sup.5的每个基代表氢原子或C.sub.1-4烷基）、--COR.sup.9（其中R.sup.9代表羟基、C.sub.1-4烷氧基或NR.sup.3R.sup.4）、--SR.sup.10（其中R.sup.10为氢原子或C.sub.1-4烷基，可选地被羟基、C.sub.1-4烷氧基或NR.sup.3R.sup.4取代）、--SOR.sup.10、--SO.sub.2R.sup.10、--CN或--NR.sup.11R.sup.12（其中R.sup.11和R.sup.12代表氢原子或C.sub.1-4烷基，至少一个基被羟基、C.sub.1-4烷氧基或NR.sup.3R.sup.4取代，且其中至少一个基为C.sub.2-4烷基），r代表0至3的整数]、--O(CH.sub.2).sub.qCOR.sup.9（其中q和R.sup.9如上定义），或--O(CH.sub.2).sub.tR.sup.13 [其中R.sup.13代表羟基、NR.sup.3R.sup.4、NR.sup.11R.sup.12或C.sub.1-4烷氧基，可选地被羟基、C.sub.1-4烷氧基或NR.sup.3R.sup.4取代，t为2或3]，或Ar为取代有烷二氧基基团--O(CH.sub.2).sub.pO-的苯基，其中p为1或2；R.sup.1和R.sup.2各代表氢原子或C.sub.1-3烷基，但R.sup.1和R.sup.2中碳原子的总和不超过4；以及其生理上可接受的盐和溶剂（例如水合物）。式（I）化合物在β.sub.2-肾上腺素受体上具有兴奋作用，特别适用于治疗与可逆气道阻塞相关的疾病，例如哮喘和慢性支气管炎。
• Metz; Specker, Arzneimittel-Forschung/Drug Research, 1980, vol. 30, # 116, p. 2014 - 2019
  作者：Metz、Specker

  DOI：——

  日期：——
• Structure–Activity Relationships for Amide-, Carbamate-, And Urea-Linked Analogues of the Tuberculosis Drug (6<i>S</i>)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5<i>H</i>-imidazo[2,1-<i>b</i>][1,3]oxazine (PA-824)
  作者：Adrian Blaser、Brian D. Palmer、Hamish S. Sutherland、Iveta Kmentova、Scott G. Franzblau、Baojie Wan、Yuehong Wang、Zhenkun Ma、Andrew M. Thompson、William A. Denny

  DOI：10.1021/jm2012276

  日期：2012.1.12

  Analogues of clinical tuberculosis drug (6S)-2-nitro-6-[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824), in which the OCH2 linkage was replaced with amide, carbamate, and urea functionality, were investigated as an alternative approach to address oxidative metabolism, reduce lipophilicity, and improve aqueous solubility. Several soluble monoaryl examples displayed moderately improved (similar to 2- to 4-fold) potencies against replicating Mycobacterium tuberculosis but were generally inferior inhibitors under anaerobic (nonreplicating) conditions. More lipophilic biaryl derivatives mostly displayed similar or reduced potencies to these in contrast to the parent biaryl series. The leading biaryl carbamate demonstrated exceptional metabolic stability and a 5-fold better efficacy than the parent drug in a mouse model of acute M. tuberculosis infection but was poorly soluble. Bioisosteric replacement of this biaryl moiety by arylpiperazine resulted in a soluble, orally bioavailable carbamate analogue providing identical activity in the acute model, comparable efficacy to OPC-67683 in a chronic infection model, favorable pharmacokinetic profiles across several species, and enhanced safety.