2,3-二甲氧基-5-(甲基氨基磺酰基)苯甲酸 | 74651-63-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2,3-二甲氧基-5-(甲基氨基磺酰基)苯甲酸
• 中文别名: 9-氟-7-苯基-1,2,4a,5-四氢-4H-[1,4]氧杂联氮基[4,3-a][1,4]苯并二氮卓
• 英文名称: 2,3-dimethoxy-5-(N-methylsulfamoyl)benzoic acid
• 英文别名: 2,3-dimethoxy-5-methylsulphamoyl benzoic acid；2,3-Dimethoxy-5-((methylamino)sulphonyl)benzoic acid；2,3-dimethoxy-5-(methylsulfamoyl)benzoic acid
• CAS: 74651-63-1
• 化学式: C₁₀H₁₃NO₆S
• mdl: MFCD11537311
• 分子量: 275.282
• InChiKey: XXXLNTRZWHZOCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,3-二甲氧基-5-(甲基氨基磺酰基)苯甲酸 在 三溴化硼 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 N-(4-fluorobenzyl)-2,3-dihydroxy-5-(N-methylsulfamoyl)benzamide
  参考文献：
  名称：

  Design of HIV-1 integrase inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75: A scaffold hopping approach using salicylate and catechol groups

  摘要：

  HIV-1 integrase (IN) is a validated therapeutic target for antiviral drug design. However, the emergence of viral strains resistant to clinically studied IN inhibitors demands the discovery of novel inhibitors that are structurally as well mechanistically different. Herein, we describe the design and discovery of novel IN inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75, which is essential for the HIV-1 integration as an IN cofactor. By merging the pharmacophores of salicylate and catechol, the 2,3-dihydroxybenzamide (5a) was identified as a new scaffold to inhibit the strand transfer reaction efficiently. Further structural modifications on the 2,3-dihydroxybenzamide scaffold revealed that the heteroaromatic functionality attached on the carboxamide portion and the piperidin-1-ylsulfonyl substituted at the phenyl ring are beneficial for the activity, resulting in a low micromolar IN inhibitor (5p, IC(50) = 5 mu M) with more than 40-fold selectivity for the strand transfer over the 3'-processing reaction. More significantly, this active scaffold remarkably inhibited the interaction between IN and LEDGF/p75 cofactor. The prototype example, N-(cyclohexylmethyl)-2,3-dihydroxy-5-(piperidin-1-ylsulfonyl) benzamide (5u) inhibited the IN-LEDGF/p75 interaction with an IC(50) value of 8 mu M. Using molecular modeling, the mechanism of action was hypothesized to involve the chelation of the divalent metal ions inside the IN active site. Furthermore, the inhibitor of IN-LEDGF/p75 interaction was properly bound to the LEDGF/p75 binding site on IN. This work provides a new and efficient approach to evolve novel HIV-1 IN inhibitors from rational integration and optimization of previously reported inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.058
• 作为产物：
  描述：

  2,3-二甲氧基苯甲酸 在 氯磺酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 2,3-二甲氧基-5-(甲基氨基磺酰基)苯甲酸
  参考文献：
  名称：

  一种氨基丙基取代托烷胺类化合物、其药物组 合物及其制备方法和用途

  摘要：

  本发明属于药物化学领域，公开了如下通式(Ⅰ)所示的8‑(3‑氨基丙基)‑3‑外向‑8‑氮杂双环[3.2.1]辛烷‑3‑氨基酰胺类化合物、其药物组合物和用途。该类化合物或其药学上可接受的盐可作为CCR5的拮抗剂，用于制备治疗由CCR5介导的疾病的药物，从而用于制备治疗HIV感染、哮喘、类风湿性关节炎、自身免疫性疾病和慢性梗阻性肺病(COPD)的药物。

  公开号：

  CN106977511B

文献信息

• New substituted heterocyclic benzamides, methods of preparing them and
  申请人：Societe d'Etudes Scientifiques et Industrielle de l'Ile de France

  公开号：US04673686A1

  公开（公告）日：1987-06-16

  There are provided new substituted heterocyclic benzamides and derivatives hereof which provide modifications on the central nervous system.

  这里提供了新的替代杂环苯甲酰胺及其衍生物，这些化合物对中枢神经系统产生改变。
• Azobicycloalkylbenzamides, process for their preparation and pharmaceutical compositions containing them
  申请人：BEECHAM GROUP PLC

  公开号：EP0068700A1

  公开（公告）日：1983-01-05

  Compounds of formula [1], and pharmaceutically acceptable salts and solvent adducts and N-oxides thereof: wherein: n, p and q independently are 0 to 2; Rs is hydrogen or C1-6 alkyl; R, is C1-7 alkyl or a group -(CH2)sR7 where s is 0 to 2 and R7 is a C3-7 cycloalkyl group, or a group (CH2),Ra where t is 1 or 2 and R, is C2-5 alkenyl or a phenyl group optionally substituted by one or two substituents selected from C1-6 alkyl, C1-4 alkoxy, trifluoromethyl and halogen, or a thienyl group; R12 is aminosulphonyl optionally substituted by one or two C1-6 alkyl or C3-8 cycloalkyl, C3-8 cycloalkyl-C1-4 alkyl, phenyl or phenyl C1-4alkyl groups any of which phenyl moieties may be substituted by one or more halogen, trifluoromethyl, C1-6 alkoxy or nitro groups, or N- disubstiuted by C1-6 polymethylene; and either R, is C1-6 alkoxy or C1-6 alkylthio; and one of R2 and R,, is hydrogen and the other is C1-6 alkoxy, C1-6 alkyl or hydroxy; or R, and R2 together are C,.3 alkylenedioxy; and R,, is hydrogen, halogen, CF3, C,.6 alkyl, C1-6 alkoxy, C1-7 acyl, hydroxy, nitro, C1-7 acylamino, amino or aminocarbonyl optionally substituted by one or two C1-6 alkyl, C3-8 cycloalkyl C3-8 cycloalkyl C1-4 alkyl, phenyl or phenyl C1-4 alkyl groups any of which phenyl moieties may be substituted by one or more halogen, trifluoromethyl, C1-6 alkoxy or nitro groups, or N-disubstituted by C4-6 polymethylene.

  式[1]化合物及其药学上可接受的盐类、溶剂加成物和 N-氧化物： 其中 n、p 和 q 独立地为 0 至 2； Rs 是氢或 C1-6 烷基； R，是 C1-7 烷基或基团-(CH2)sR7，其中 s 是 0 至 2，R7 是 C3-7 环烷基，或基团 (CH2),Ra，其中 t 是 1 或 2，R，是 C2-5 烯基或苯基，任选被一个或两个选自 C1-6 烷基、C1-4 烷氧基、三氟甲基和卤素的取代基取代，或被噻吩基取代； R12 是氨基磺酰基，可任选被一个或两个 C1-6 烷基或 C3-8 环烷基、C3-8 环烷基-C1-4 烷基、苯基或苯基 C1-4 烷基取代，其中任何苯基可被一个或多个卤素、三氟甲基、C1-6 烷氧基或硝基取代，或被 C1-6 聚亚甲基二取代；以及 R, 是 C1-6 烷氧基或 C1-6 烷硫基；及 R2 和 R,,中的一个是氢，另一个是 C1-6 烷氧基、C1-6 烷基或羟基；或 R, 和 R2 一起是 C,.3-亚烷基二氧基；和 R，是氢、卤素、CF3、C,.6 烷基、C1-6 烷氧基、C1-7 乙酰基、羟基、硝基、C1-7 乙酰氨基、C1-7 乙酰基酰胺、 C1-7酰氨基、氨基或氨基羰基，可任选被一个或两个C1-6烷基、C3-8环烷基、C3-8环烷基C1-4烷基、苯基或苯基C1-4烷基取代，其中任何苯基可被一个或多个卤素、三氟甲基、C1-6烷氧基或硝基取代，或被C4-6聚亚甲基N-二取代。
• US4263316A
  申请人：——

  公开号：US4263316A

  公开（公告）日：1981-04-21
• US4364867A
  申请人：——

  公开号：US4364867A

  公开（公告）日：1982-12-21
• US4673686A
  申请人：——

  公开号：US4673686A

  公开（公告）日：1987-06-16