2-methoxy-4-nitro-N-o-tolyl-benzenesulfonamide | 1204290-57-2

• 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-methoxy-4-nitro-N-o-tolyl-benzenesulfonamide
• 英文别名: 2-methoxy-N-(2-methylphenyl)-4-nitrobenzenesulfonamide
• CAS: 1204290-57-2
• 化学式: C₁₄H₁₄N₂O₅S
• 分子量: 322.342
• InChiKey: MDLRQPWLTMYDGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-methoxy-4-nitro-N-o-tolyl-benzenesulfonamide 在 sodium tetrahydroborate 、 nickel(II) chloride hexahydrate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 4-amino-2-methoxy-N-o-tolyl-benzenesulfonamide
  参考文献：
  名称：

  Synthesis and biological evaluation of naphthoquinone analogs as a novel class of proteasome inhibitors

  摘要：

  Screening of the NCI Diversity Set-1 identified PI-083 (NSC-45382) a proteasome inhibitor selective for cancer over normal cells. Focused libraries of novel compounds based on PI-083 chloronaphthoquinone and sulfonamide moieties were synthesized to gain a better understanding of the structure-activity relationship responsible for chymotrypsin-like proteasome inhibitory activity. This led to the demonstration that the chloronaphthoquinone and the sulfonamide moieties are critical for inhibitory activity. The pyridyl group in PI-083 can be replaced with other heterocyclic groups without significant loss of activity. Molecular modeling studies were also performed to explore the detailed interactions of PI-083 and its derivatives with the beta 5 and beta 6 subunits of the 20S proteasome. The refined model showed an H-bond interaction between the Asp-114 and the sulfonamide moiety of the PI-083 in the beta 6 subunit. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.038
• 作为产物：
  描述：

  2-甲氧基-4-硝基苯磺酰氯 、 邻甲苯胺 在 吡啶 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 0.17h， 以79%的产率得到2-methoxy-4-nitro-N-o-tolyl-benzenesulfonamide
  参考文献：
  名称：

  Synthesis and biological evaluation of naphthoquinone analogs as a novel class of proteasome inhibitors

  摘要：

  Screening of the NCI Diversity Set-1 identified PI-083 (NSC-45382) a proteasome inhibitor selective for cancer over normal cells. Focused libraries of novel compounds based on PI-083 chloronaphthoquinone and sulfonamide moieties were synthesized to gain a better understanding of the structure-activity relationship responsible for chymotrypsin-like proteasome inhibitory activity. This led to the demonstration that the chloronaphthoquinone and the sulfonamide moieties are critical for inhibitory activity. The pyridyl group in PI-083 can be replaced with other heterocyclic groups without significant loss of activity. Molecular modeling studies were also performed to explore the detailed interactions of PI-083 and its derivatives with the beta 5 and beta 6 subunits of the 20S proteasome. The refined model showed an H-bond interaction between the Asp-114 and the sulfonamide moiety of the PI-083 in the beta 6 subunit. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.038

文献信息

• 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。
• Proteasome inhibitors for selectively inducing apoptosis in cancer cells
  申请人：Lawrence Harshani

  公开号：US08673910B2

  公开（公告）日：2014-03-18

  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: or a pharmaceutically acceptable salt or hydrate thereof. In another embodiment, a compound of the invention has the chemical structure shown in formula II: or a pharmaceutically acceptable salt or hydrate thereof.

  本发明涉及具有蛋白酶体抑制剂活性的化合物以及使用该化合物的方法。在一种实施例中，本发明的化合物具有公式I所示的化学结构：或其药学上可接受的盐或水合物。在另一种实施例中，本发明的化合物具有公式II所示的化学结构：或其药学上可接受的盐或水合物。
• 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.
• Synthesis and biological evaluation of naphthoquinone analogs as a novel class of proteasome inhibitors
  作者：Harshani R. Lawrence、Aslamuzzaman Kazi、Yunting Luo、Robert Kendig、Yiyu Ge、Sanjula Jain、Kenyon Daniel、Daniel Santiago、Wayne C. Guida、Saïd M. Sebti

  DOI：10.1016/j.bmc.2010.06.038

  日期：2010.8

  Screening of the NCI Diversity Set-1 identified PI-083 (NSC-45382) a proteasome inhibitor selective for cancer over normal cells. Focused libraries of novel compounds based on PI-083 chloronaphthoquinone and sulfonamide moieties were synthesized to gain a better understanding of the structure-activity relationship responsible for chymotrypsin-like proteasome inhibitory activity. This led to the demonstration that the chloronaphthoquinone and the sulfonamide moieties are critical for inhibitory activity. The pyridyl group in PI-083 can be replaced with other heterocyclic groups without significant loss of activity. Molecular modeling studies were also performed to explore the detailed interactions of PI-083 and its derivatives with the beta 5 and beta 6 subunits of the 20S proteasome. The refined model showed an H-bond interaction between the Asp-114 and the sulfonamide moiety of the PI-083 in the beta 6 subunit. (C) 2010 Elsevier Ltd. All rights reserved.