4-<<<(4-chlorophenyl)sulfonyl>amino>carbonyl>benzoic acid | 105080-63-5

• 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: 4-<<<(4-chlorophenyl)sulfonyl>amino>carbonyl>benzoic acid
• 英文别名: 4-[(4-Chlorophenyl)sulfonylaminocarbonyl] benzene carboxylic acid；4-[(4-Chlorophenyl)sulfonylaminocarbonyl]benzoic acid；4-[(4-chlorophenyl)sulfonylcarbamoyl]benzoic acid
• CAS: 105080-63-5
• 化学式: C₁₄H₁₀ClNO₅S
• 分子量: 339.756
• InChiKey: AFNGAWABOKVXKL-UHFFFAOYSA-N

物化性质

• 密度：
  1.517±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-<<<(4-chlorophenyl)sulfonyl>amino>carbonyl>benzoic acid 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 0.5h， 生成
  参考文献：
  名称：

  Inhibition of Human Neutrophil Elastase with Peptidyl Electrophilic Ketones. 2. Orally Active PG-Val-Pro-Val Pentafluoroethyl Ketones

  摘要：

  Valylprolylvalyl pentafluoroethyl ketones with different N-protecting groups were evaluated in vitro and in vivo as inhibitors of human neutrophil elastase (HNE). Several of these compounds were found to be orally active in HNE-induced rat and hamster lung hemorrhage models. The compound with 4-(4-morpholinylcarbonyl)benzoyl as the protecting group, 71 (MDL 101,146), was studied in greater detail. Hydration and epimerization studies were performed on 71 and related compounds in various media, including human blood serum. Highperformance liquid chromatography studies on a reversed-phase system as a measure of the Lipophilicity of 71. and related compounds revealed a small range of relative retention times wherein the orally active compounds fell. The K-i value determined for 71 vs HNE was 25 nM.

  DOI：

  10.1021/jm00052a013
• 作为产物：
  描述：

  苯甲酸,4-[[[(4-氯苯基)磺酰]氨基]羰基]-,1,1-二甲基乙基酯 在 三氟乙酸 作用下， 以63%的产率得到4-<<<(4-chlorophenyl)sulfonyl>amino>carbonyl>benzoic acid
  参考文献：
  名称：

  Inhibition of human leukocyte elastase (HLE) by N-substituted peptidyl trifluoromethyl ketones

  摘要：

  A series of tripeptides possessing trifluoromethyl or aryl ketone residues at P1 were prepared and evaluated both in vitro and in vivo as potential inhibitors of human leukocyte elastase (HLE). Tripeptides containing non naturally occurring N-substituted glycine residues at the P2-position have been demonstrated to be potent in vitro inhibitors of HLE, with IC50 values in the submicromolar range. Sterically demanding substituents on the P2-nitrogen have no detrimental effect on in vitro potency. The inhibition process presumably acts via hemiketal formation with the active site Ser195 of HLE, and is facilitated by the strongly electron withdrawing trifluoromethyl functionality. Deletion of the amino acid at the P3-subsite region affords inactive compounds. Valine is the preferred residue at the P1-position, whereas the corresponding glycine, alanine, alpha,alpha-dimethylglycine, or phenylalanine analogues are all inactive. The compounds described herein all confer a high degree of in vitro specificity when tested against representative cysteine, aspartyl, metallo, and other serine proteases. One of the most potent in vitro inhibitors is (3RS)-N-[4-[[[(4-chlorophenyl)sulfonyl]amino]carbonyl]phenyl]oxomethyl]-L-valyl-N-(2,3-dihydro-1H-inden-2-yl)glycine N-[3-(1,1,1-trifluoro-4-methyl-2-oxopentyl)]amide (20i; BI-RA-260) (IC50 = 0.084-mu-M). Compound 20i was also tested in hamsters in an elastase-induced pulmonary hemorrhage (EPH) model. In this model, intratracheal (it.) administration of 20i, 5 min prior to HLE challenge, effectively inhibited hemorrhage in a dose-dependent manner with an ED50 of 4.8-mu-g. The inhibitor 20i, 20-mu-g administered it. 24, 48, and 72 h prior to HLE challenge, exhibits significant inhibition against hemorrhage at all time points (97%, 64% and 49%, respectively). In a 21-day chronic model of emphysema in hamsters, 200-mu-g of HLE administered it. caused an elastase-induced emphysema in the lungs which can be quantitated histologically utilizing image analysis. In this assay, 20i significantly inhibited pulmonary lesions associated with septal destruction and increased alveolar spaces, when dosed at 20-mu-g it. 5 min prior to challenge with HLE.

  DOI：

  10.1021/jm00082a005
• 作为试剂：
  描述：

  4-<<<(4-chlorophenyl)sulfonyl>amino>carbonyl>benzoic acid 、 N-L-valyl-N-<3,3,3-trifluoro-1-(1-methylethyl)-2-oxopropyl>-L-prolinamide hydrochloride 在 4-<<<(4-chlorophenyl)sulfonyl>amino>carbonyl>benzoic acid 作用下， 以70的产率得到4-N-(4-氯苯基)磺酰基-1-N-[(2S)-3-甲基-1-氧代-1-[[(2S)-1-(1,1,1-三氟-4-甲基-2-氧代戊烷-3-基)吡咯烷-2-羰基]氨基]丁烷-2-基]苯-1,4-二甲酰胺
  参考文献：
  名称：

  J. Med. Chem. 1994, 37, 4538-4554

  摘要：

  DOI：

文献信息

• Heterocyclic ketones
  申请人：ICI Americas Inc.

  公开号：US05164371A1

  公开（公告）日：1992-11-17

  The invention provides a series of novel heterocyclic ketones of formula I ##STR1## and pharmaceutically acceptable base-addition salts thereof, in which the values of R.sup.4, L, A, X and Q have the meanings defined in the following specification. The compounds of formula I are inhibitors of human leukocytic elastase. The invention also provides pharmaceutical compositions containing a compound of formula I, or a pharmaceutically acceptable base-addition salt thereof, and processes and intermediates for the manufacture of compounds of formula I.

  这项发明提供了一系列新颖的杂环酮化合物，其化学式为I ##STR1## 及其药用可接受的盐，其中R.sup.4、L、A、X和Q的值如下文规定。化合物I的是人类白细胞弹性蛋白酶的抑制剂。该发明还提供了含有化合物I或其药用可接受的盐的药物组合物，以及化合物I的制备过程和中间体。
• Acylated enol derivatives as prodrugs of elastase inhibitors
  申请人：Merrell Pharmaceuticals Inc.

  公开号：US05698523A1

  公开（公告）日：1997-12-16

  This invention relates to acylated enol derivatives of known elastase inhibitors. These compounds are useful in the treatment of various inflammatory diseases, including cystic fibrosis and emphysema or as prodrugs of compounds which are useful in the treatment of said diseases.

  这项发明涉及已知弹性蛋白酶抑制剂的酰化烯醇衍生物。这些化合物在治疗各种炎症性疾病，包括囊性纤维化和肺气肿，或作为治疗这些疾病的有效化合物的前药方面是有用的。
• [EN] CU-AND NI-CATALYZED DECARBOXYLATIVE BORYLATION REACTIONS<br/>[FR] RÉACTIONS DE BORYLATION DÉCARBOXYLATIVE CATALYSÉES PAR CU ET NI
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2018175173A1

  公开（公告）日：2018-09-27

  The invention is directed to methods of converting a carboxylic acid group in a compound, via a redox active ester, to a corresponding boronic ester by treatment with bis(pinacolato)diboron-alkyllithium complex in the presence of a ligand, a Ni(ll) salt or a copper salt, and an Mg(ll) salt, in the presence of an alkyllithium or a lithium hydroxide or alkoxide salt. The product pinacolato boronate ester can be cleaved to provide a boronic acid. The invention is also directed to methods of preparing various compounds of medical value comprising boronic acid groups, and to novel boronic-acid containing compounds of medicinal value, including an atorvastatin boronic acid analog, a vancomycin aglycone boronic acid analog, and boronic acid containing elastase inhibitors mCBK319, mCBK320, mCBK323, and RPX-7009.

  这项发明涉及通过使用双(邻菲罗)二硼烷基锂络合物在配体、Ni(Ⅱ)盐或铜盐以及Mg(Ⅱ)盐的存在下，处理化合物中的羧酸基，通过氧化还原活性酯将其转化为相应的硼酯酯。在存在烷基锂或氢氧化锂或烷氧化锂盐的情况下，所述产品邻菲罗硼酸酯酯可以被裂解以提供硼酸。该发明还涉及制备含硼酸基的医用价值化合物的方法，以及具有药用价值的新型含硼酸基化合物，包括阿托伐他汀硼酸类似物、万古霉素裸核硼酸类似物和含硼酸的弹性蛋白酶抑制剂mCBK319、mCBK320、mCBK323和RPX-7009。
• Peptidic human leukocyte elastase (HLE) inhibitors
  申请人：ZENECA INC.

  公开号：EP0291234A2

  公开（公告）日：1988-11-17

  The invention provides a series of novel heterocyclic ketones of formula I (set out hereinafter) and pharmaceutically acceptable base-addition salts thereof, in which the values of R4, L, A, X and Q have the meanings defined in the following specification. The compounds of formula I are inhibitors of human leukocytic elastase. The invention also provides pharmaceutical compositions containing a compound of formula I, or a pharmaceutically acceptable base-addition salt thereof, and processes and intermediates for the manufacture of compounds of formula I.

  本发明提供了一系列新颖的式 I 杂环酮类化合物（如下所述）及其药学上可接受的碱加成盐，其中 R4、L、A、X 和 Q 的值具有以下说明书中定义的含义。式 I 的化合物是人白细胞弹性蛋白酶的抑制剂。本发明还提供了含有式 I 化合物或其药学上可接受的碱加成盐的药物组合物，以及制造式 I 化合物的工艺和中间体。
• N-substituted amides
  申请人：BOEHRINGER INGELHEIM PHARMACEUTICALS INC.

  公开号：EP0369391A2

  公开（公告）日：1990-05-23

  Compounds of the formula are inhibitors of human leukocyte elastase.

  式中的化合物 是人类白细胞弹性蛋白酶的抑制剂。