N-(4-Bromo-3-methyl-5-isoxazolyl)-5-(pyridin-2-yl)thiophene-2-sulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: N-(4-Bromo-3-methyl-5-isoxazolyl)-5-(pyridin-2-yl)thiophene-2-sulfonamide
• 英文别名: N-(4-bromo-3-methyl-5-isoxazolyl)-5-(2-pyridyl)thiophene-2-sulfonamide；N-(4-bromo-3-methyl-1,2-oxazol-5-yl)-5-pyridin-2-ylthiophene-2-sulfonamide
• 化学式: C₁₃H₁₀BrN₃O₃S₂
• 分子量: 400.277
• InChiKey: BLGRMKWIYCDVSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-(3-methyl-5-isoxazolyl)-5-bromothiophene-2-sulfonamide 在 四(三苯基膦)钯 N-溴代丁二酰亚胺(NBS) 、 sodium carbonate 作用下， 以 乙醇 、 氯仿 、 水 、 甲苯 为溶剂， 反应 24.17h， 生成 N-(4-Bromo-3-methyl-5-isoxazolyl)-5-(pyridin-2-yl)thiophene-2-sulfonamide
  参考文献：
  名称：

  The discovery and structure—activity relationships of nonpeptide, low molecular weight antagonists selective for the endothelin ETB receptor

  摘要：

  The systematic modification of the ETA selective N-(5-isoxazolyl)benzene-sulfonamide endothelin antagonists to give ETB selective antagonists is reported. The reversal in selectivity was brought about by substitution of the 4-position with aryl and substituted aryl groups. Of all the aromatic substituents studied, the para-tolyl group gave rise to the most active and selective ETB antagonist. Larger substituents caused a decrease in both ETB activity and selectivity. A similar trend was observed by substitution at the 5-position of the N-(5-isoxazolyl)-2-thiophenesulfonamide ETA receptor antagonists. The para-tolyl group was again found to be optimal for the ETB activity and selectivity. The structural features that were found to be favorable for binding to the ETB receptor, that is, the presence of a linear, conjugated pi-system of definite shape and size, have been successfully incorporated into the design of ETB selective polycyclic aromatic sulfonamides antagonists. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)80010-2

文献信息

• Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin
  申请人：——

  公开号：US20020095041A1

  公开（公告）日：2002-07-18

  Biphenylsulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, bicyclic or tricyclic carbon or heterocyclic ring biphenylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

  提供了二苯基磺胺类化合物和调节或改变内皮素家族肽活性的方法。具体包括使用双环或三环碳或杂环环二苯基磺胺类化合物的方法，通过将该磺胺类化合物与内皮素受体接触来抑制内皮素肽与内皮素受体的结合。还提供了通过给予有效剂量的这些磺胺类化合物或其前药来治疗内皮素介导的疾病的方法，这些化合物能够抑制或增加内皮素的活性。
• N-aryl thienyl-, furyl-, and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin
  申请人：Texas Biotechnology Corp.

  公开号：US06342610B2

  公开（公告）日：2002-01-29

  Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

  提供了噻吩基、呋喃基和吡咯基磺酰胺以及用于调节或改变内皮素肽家族活性的方法。特别是，提供了N-(异恶唑基)噻吩磺酰胺、N-(异恶唑基)呋喃磺酰胺和N-(异恶唑基)吡咯磺酰胺以及使用这些磺酰胺通过将受体与磺酰胺接触来抑制内皮素肽与内皮素受体结合的方法。还提供了通过施用有效量的一个或多个这些磺酰胺或其前药来治疗内皮素介导的疾病的方法，这些磺酰胺或其前药抑制或增加内皮素的活性。
• Thienyl-, furyl-, pyrrolyl- and biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin
  申请人：TEXAS BIOTECHNOLOGY CORPORATION

  公开号：EP1048657A1

  公开（公告）日：2000-11-02

  Biphenylsufonamides of the following formula and methods for modulating or altering the activity of the endothelin family of peptides are provided. The sulfonamides may be used for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide or a pharmaceutically acceptable salt, acid or ester thereof, wherein Ar2 is and wherein Ar1, R13 and R26 are as defined herein.

  提供以下式子的二苯基磺酰胺和调节或改变内皮素家族肽活性的方法。这些磺酰胺可用于通过将受体与磺酰胺或其药学上可接受的盐、酸或酯接触来抑制内皮素肽与内皮素受体的结合，其中Ar2为，Ar1，R13和R26的定义如本文所述。
• [EN] SULFONAMIDES AND DERIVATIVES THEREOF THAT MODULATE THE ACTIVITY OF ENDOTHELIN<br/>[FR] SULFONAMIDES ET LEURS DERIVES MODULANT L'ACTIVITE DE L'ENDOTHELINE
  申请人：IMMUNOPHARMACEUTICS, INC.

  公开号：WO1994027979A1

  公开（公告）日：1994-12-08

  (EN) Sulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided. The sulfonamides have formula (I) in which Ar1 is a 3- or 5-isoxazolyl and Ar2 is selected from among alkyl, including straight and branched chains, aromatic rings, fused aromatic rings and heterocyclic rings, including 5-membered heterocycles with one, two or more heteroatoms and fused ring analogs thereof and 6-membered rings with one, two or more heteroatoms and fused ring analogs thereof. Ar2 is preferably thiophenyl, furyl, pyrrolyl, naphthyl, and phenyl. Compounds in which Ar1 is a 4-halo-substituted isoxazole are more active than the corresponding alkyl-substituted compound and compounds in which Ar1 is substituted at this position with a higher alkyl tend to exhibit greater affinity for ETB receptors than the corresponding lower alkyl-substituted compound.(FR) Sulfonamides et méthodes d'inhibition de la fixation d'une endothéline sur un récepteur de l'endothéline par mise en contact du récepteur et de la sulfonamide. Méthode de traitement des troubles induits par l'entremise de l'endothéline, par administration de quantités efficaces de l'une ou plusieurs de ces sulfonamides ou de leurs prodrogues, inhibant ou favorisant l'activité de l'endothéline. Les sulfonamides sont de la formule (I) où Ar1 est un isoxazolyle 3- ou 5 et Ar2 est choisi parmi des alkyles comportant des chaînes linéaires et ramifiées, des cycles aromatiques, des cycles aromatiques condensés et des hétérocycles y compris des hétérocycles à 5 membres comprenant un, deux ou plus de deux hétéroatomes et leurs analogues condensés, et des cycles à 6 membres comprenant un, deux ou plus de deux hétéroatomes et leurs analogues condensés. Ar2 est de préférence un thiophényle, un furyle, un pyrrolyle, un naphtyle ou un phényle. Les composés dans lesquels Ar1 est un isoxazole 4-halo substitué sont plus actifs que les composés à substitution alkyle correspondants, et les composés où Ar1 est substitué à cette position avec un alkyle supérieur ont tendance à présenter une activité plus grande pour les récepteurs ETB que les composés substitués avec un alkyle inférieur.

  提供了使用这些磺胺类化合物通过与受体接触来抑制内皮素肽与内皮素受体结合的方法。还提供了通过给予这些磺胺类化合物或其前药的有效量来治疗内皮素介导的疾病的方法，这些化合物可以抑制或增加内皮素的活性。这些磺胺类化合物的化学式为（I），其中Ar1为3-或5-异噁唑基，Ar2从烷基（包括直链和支链）、芳香环、融合的芳香环和杂环中选择，包括具有一个、两个或多个杂原子的5-杂环及其融合环的类似物和具有一个、两个或多个杂原子的6-杂环及其融合环的类似物。Ar2最好是噻吩基、呋喃基、吡咯基、萘基和苯基。其中Ar1为4-卤代异噁唑基的化合物比相应的烷基取代化合物更活性，而Ar1在该位置用较高的烷基取代的化合物倾向于表现出比相应的较低烷基取代化合物更大的对ETB受体的亲和力。
• Thienyl-, furyl- and pyrrolyl sulfonamides and derivatives thereof that
  申请人：Texas Biotechnology Corporation

  公开号：US05594021A1

  公开（公告）日：1997-01-14

  Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

  本文提供了硫酰胺类化合物和方法，用于调节或改变内皮素家族肽的活性。特别地，提供了N-(异噁唑基)噻吩基硫酰胺、N-(异噁唑基)呋喃基硫酰胺和N-(异噁唑基)吡咯基硫酰胺，以及使用这些硫酰胺抑制内皮素肽与内皮素受体的结合的方法。还提供了通过给予这些硫酰胺或其前药有效量来治疗内皮素介导的疾病的方法，该硫酰胺或前药抑制或增加内皮素的活性。