3-[[(4E)-1-oxo-4-thiophen-2-ylsulfonyliminonaphthalen-2-yl]amino]benzoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-[[(4E)-1-oxo-4-thiophen-2-ylsulfonyliminonaphthalen-2-yl]amino]benzoic acid
• 化学式: C₂₁H₁₄N₂O₅S₂
• 分子量: 438.5
• InChiKey: JXDMTMODWGATEM-HAVVHWLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  150
• 氢给体数：
  2
• 氢受体数：
  8

文献信息

• PROTEASOME INHIBITORS HAVING CHYMOTRYPSIN-LIKE ACTIVITY
  申请人：Lawrence Harshani

  公开号：US20120142917A1

  公开（公告）日：2012-06-07

  Disclosed herein is the use of HLM-008182, as well as its analogues formed via in-house synthesis, as a potent proteasome inhibitors. A new method was developed for HLM-008182 through a four-step protocol and the method was further optimized to a two step protocol. The synthesis in both protocols was regioselective with TiCl 4 . The reaction was highly efficient with microwave assisted heating and THF as solvent. The modification around the molecule HLM-008182 established primary SAR, indicating that the proteasome inhibition activity was a function of the 2-side chain.

  本文披露了使用HLM-008182及其由内部合成形成的类似物作为有效的蛋白酶体抑制剂。通过四步协议开发了HLM-008182的新方法，并将该方法进一步优化为两步协议。在两种协议的合成中，都使用了TiCl4进行区域选择性反应。微波辅助加热和THF作为溶剂使反应高效。对HLM-008182分子周围的修饰建立了主要的SAR，表明蛋白酶体抑制活性是2侧链的一个功能。
• PROTEASOME INHIBITORS FOR SELECTIVELY INDUCING APOPTOSIS IN CANCER CELLS
  申请人：Lawrence Harshani

  公开号：US20110201609A1

  公开（公告）日：2011-08-18

  The subject invention concerns compounds having activity as inhibitors of proteasomes and methods of using the subject compounds. In one embodiment, a compound of the invention has the chemical structure shown in formula I: wherein R 1 is an organic cyclic ring structure bonded to a sulfonamide structure; R 2 is H, halogen, alkyl, —NR 6 R 7 , or heteroalkyl; R 3 is H, halogen, —OH, —O-alkyl, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —NO 2 , —NH 2 or substituted amines; R 4 is H, alkyl, heteroalkyl, aryl, or heteroaryl, any of which can be optionally substituted with one or more of —NO 2 , alkyl, heteroalkyl, aryl, or heteroaryl, or halogen; R 5 is H, —OH, halogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, —O-alkyl, —O-aryl, heteroalkyl, —NO 2 , —NH 2 , or substituted amine; and R 6 and R 7 are independently H, O, alkyl, aryl, heterocycloalkyl, or heteroaryl, or together can form a heterocycloalkyl or a heteroaryl, any of which can be optionally substituted with one or more of —NO 2 , alkyl, heteroalkyl, aryl, or halogen; or a pharmaceutically acceptable salt or hydrate thereof. In another embodiment, a compound of the invention has the chemical structure shown in formula II: wherein Q, W, X, Y, Z are each independently carbon, oxygen, or nitrogen; R 1 is H, or X 1 R 8 ; R 2 is heteroalkyl, which can be optionally substituted with one or more of —OH, halogen, —C(O)OR 4 , alkyl, heteroalkyl, heterocycloalkyl, or heteroaryl; R 3 is heterocycloalkyl, aryl, heteroaryl, any of which can be optionally substituted with one or more of a halogen or —OH; and R 4 is H or alkyl; R 5 is halogen, alkyl or nitro; R 6 is nitro, X 2 R 9 or a halogen; R 7 is H or alkyl; R 8 is H, alkyl, aryl, CH 2 -alkyl-aryl, -alkyl-C(O)OH, or alkyl-tetrazole (aromatic and aliphatic heterocyclic groups); R 9 is H or alkyl; X 1 is oxygen, nitrogen, or sulfur; X 2 is oxygen, nitrogen, or sulfur; or a pharmaceutically acceptable salt or hydrate thereof.

  本发明涉及作为蛋白酶体抑制剂的化合物及使用该化合物的方法。在一种实施方式中，本发明的化合物具有公式I所示的化学结构：其中，R1是与磺酰胺结构键合的有机环状环结构；R2是H、卤素、烷基、-NR6R7或杂环烷基；R3是H、卤素、-OH、-O-烷基、烷基、环烷基、杂环烷基、芳基、杂芳基、-NO2、-NH2或取代胺；R4是H、烷基、杂烷基、芳基或杂芳基，其中任何一个都可以选择性地取代一个或多个-NO2、烷基、杂烷基、芳基或杂芳基或卤素；R5是H、-OH、卤素、烷基、芳基、杂芳基、环烷基、杂环烷基、-O-烷基、-O-芳基、杂烷基、-NO2、-NH2或取代胺；R6和R7分别是H、O、烷基、芳基、杂环烷基或杂芳基，或者一起形成杂环烷基或杂芳基，其中任何一个都可以选择性地取代一个或多个-NO2、烷基、杂烷基、芳基或卤素；或其药学上可接受的盐或水合物。在另一种实施方式中，本发明的化合物具有公式II所示的化学结构：其中，Q、W、X、Y、Z分别独立地是碳、氧或氮；R1是H或X1R8；R2是杂环烷基，可以选择性地取代一个或多个-OH、卤素、-C（O）OR4、烷基、杂烷基、杂环烷基或杂芳基；R3是杂环烷基、芳基、杂芳基，其中任何一个都可以选择性地取代一个或多个卤素或-OH；R4是H或烷基；R5是卤素、烷基或硝基；R6是硝基、X2R9或卤素；R7是H或烷基；R8是H、烷基、芳基、CH2-烷基-芳基、-烷基-C（O）OH或烷基-四唑（芳香和脂肪族杂环基）；R9是H或烷基；X1是氧、氮或硫；X2是氧、氮或硫；或其药学上可接受的盐或水合物。
• US8466157B2
  申请人：——

  公开号：US8466157B2

  公开（公告）日：2013-06-18
• US8673910B2
  申请人：——

  公开号：US8673910B2

  公开（公告）日：2014-03-18
• [EN] PROTEASOME INHIBITORS FOR SELECTIVELY INDUCING APOPTOSIS IN CANCER CELLS<br/>[FR] INHIBITEURS DES PROTÉASOMES POUR L'INDUCTION SÉLECTIVE DE L'APOPTOSE DANS LES CELLULES CANCÉREUSES
  申请人：H LEE MOFFITT CANCER CT AND RE

  公开号：WO2010005534A2

  公开（公告）日：2010-01-14

  The subject invention concerns compounds having activity as inhibitors of proteasomes and methods of using the subject compounds. In one embodiment, a compound of the invention has the chemical structure shown in Formula (I), wherein R1 is an organic cyclic ring structure bonded to a sulfonamide structure; R2 is H, halogen, alkyl, -NR6R7, or heteroalkyl; R3 is H, halogen, -OH, -O-alkyl, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -NO2, -NH2 or substituted amines; R4 is H, alkyl, heteroalkyl, aryl, or heteroaryl, any of which can be optionally substituted with one or more of -NO2, alkyl, heteroalkyl, aryl, or heteroaryl, or halogen; R5 is H, -OH, halogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -O-alkyl, -O- aryl, heteroalkyl, -NO2, -NH2, or substituted amine; and R6 and R7 are independently H, O, alkyl, aryl, heterocycloalkyl, or heteroaryl, or together can form a heterocycloalkyl or a heteroaryl, any of which can be optionally substituted with one or more of -NO2, alkyl, heteroalkyl, aryl, or halogen; or a pharmaceutically acceptable salt or hydrate thereof. In another embodiment, a compound of the invention has the chemical structure shown in Formula (II), wherein Q, W, X, Y, Z are each independently carbon, oxygen, or nitrogen; R1 is H, or X1R8; R2 is heteroalkyl, which can be optionally substituted with one or more of -OH, halogen, -C(O)OR4, alkyl, heteroalkyl, heterocycloalkyl, or heteroaryl; R3 is heterocycloalkyl, aryl, heteroaryl, any of which can be optionally substituted with one or more of a halogen or -OH; and R4 is H or alkyl; R5 is halogen, alkyl or nitro; R6 is nitro, X2R9 or a halogen; R7 is H or alkyl; R8 is H, alkyl, aryl, CH2-alkyl-aryl, -alkyl-C(O)OH, or alkyl-tetrazole (aromatic and aliphatic heterocyclic groups); R9 is H or alkyl; X1 is oxygen, nitrogen, or sulfur; X2 is oxygen, nitrogen, or sulfur; or a pharmaceutically acceptable salt or hydrate thereof.