5-氯磺酰基-2,3-二甲氧基苯甲酸 | 74651-62-0

• 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: 5-氯磺酰基-2,3-二甲氧基苯甲酸
• 中文别名: 2-戊基-3-甲基-5-庚基呋喃
• 英文名称: 5-chlorosulfonyl-2,3-dimethoxybenzoic acid
• 英文别名: 2,3-dimethoxy-5-chlorosulphonyl benzoic acid；5-Chlorosulphonyl-2,3-dimethoxybenzoic acid
• CAS: 74651-62-0
• 化学式: C₉H₉ClO₆S
• mdl: MFCD09048188
• 分子量: 280.686
• InChiKey: TWHADRKVBHEANG-UHFFFAOYSA-N

物化性质

• 沸点：
  462.9±45.0 °C(Predicted)
• 密度：
  1.503±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  98.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-氯磺酰基-2,3-二甲氧基苯甲酸 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 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 38.5h， 生成 N-(thiophen-2-ylmethyl)-2,3-dihydroxy-5-(piperidin-1-ylsulfonyl)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 作用下， 以54%的产率得到5-氯磺酰基-2,3-二甲氧基苯甲酸
  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

• N-(1-Methyl-2-pyrrolidinylmethyl)-2,3-dimethoxy-5-methylsulfamoyl
  申请人：Societe d'Etudes Scientifiques et Industrielles de l'Ile de France

  公开号：US04263316A1

  公开（公告）日：1981-04-21

  The present invention relates to a novel veratramide, N-(1-methyl-2-pyrroinyl-methyl)-2,3-dimethoxy-5-methylsulphamoyl benzamide, its pharmacologically acceptable acid addition salts, its quaternary ammonium salts, its oxides and its levorotatory and dextrorotatory isomers and their use in the treatment of disorders of the lower urinary apparatus.

  本发明涉及一种新型的维拉特酰胺，N-(1-甲基-2-吡咯烷基甲基)-2,3-二甲氧基-5-甲基磺酰苯甲酰胺，其药理学上可接受的酸盐、季铵盐、氧化物和其左旋和右旋异构体，以及它们在下尿道疾病治疗中的应用。
• Nor-tropane derivatives, and their application in therapeutics
  申请人：Delalande S.A.

  公开号：US04434170A1

  公开（公告）日：1984-02-28

  Novel 3 .beta.-aroylamino and 3 .beta.-heteroaroylamino nor-tropanes and granatanes are provided having the general formula: ##STR1## Wherein n=1 or 2, R represents a benzyl or a substituted benzyl group and A-CO represents one of a specific range of aroyl groups. The compounds of the invention are useful in the treatment of psychism or digestive troubles.

  提供了具有以下通式的Novel 3 .beta.-aroylamino和3 .beta.-heteroaroylamino nor-tropanes和granatanes： 其中n = 1或2，R代表苄基或取代苄基基团，A-CO代表特定范围的芳酰基之一。该发明的化合物在治疗精神或消化问题方面有用。
• Alkylthio derivatives of azabicyclobenzamides, their preparation and pharmaceutical compositions
  申请人：BEECHAM GROUP PLC

  公开号：EP0067615A1

  公开（公告）日：1982-12-22

  Pharmaceutical compositions comprising compounds of formula (I) or pharmaceutically acceptable salts and/or N-oxides and/or solvates thereof: wherein: R1 is a C1-6 alkoxy or C1-6 alkylthio group; and one of R2, R3 and R4 is hydrogen, the second is C1-6 alkylthio and the third is selected from the class of substituents consisting of hydrogen, halogen, CF3, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-7 acyl, C1-7 acylamino, C1-6 alkylsulphonyl, C1-6 alkylsulphinyl, hydroxy, nitro or amino, aminocarbonyl or aminosulphonyl optionally N-substituted by one or two C1-6 alkyl groups; or R1 is joined to R2 to form C1-2 alkylenedioxy; and one of R3 and R4 is C1-6 alkylthio and the other is selected from the class of substituents defined above; R5 is hydrogen or C1-6 alkyl; R6 is C1-7 alkyl or a group -(CH2)sR7 where s is 0 to 2 and R7 is a C3-8 cycloalkyl group, or a group -(CH2) Ra where t is 1 or 2 and R8 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; and p and q are independently 0 to 2 and a pharmaceutically acceptable carrier, novel compounds within formula (I) having useful pharmacological activity and a process for their preparation.

  包含式 (I) 化合物或其药学上可接受的盐和/或 N-氧化物和/或溶剂的药物组合物： 其中 R1是C1-6烷氧基或C1-6烷硫基；R2、R3和R4中的一个是氢，第二个是C1-6烷硫基，第三个选自氢、卤素、CF3、C1-6烷基、C1-6烷氧基、C1-6烷硫基、C1-7酰基、C1-7酰氨基、C1-6烷基磺酰基、C1-6烷基亚磺酰基、羟基、硝基或由一个或两个C1-6烷基任选N-取代的氨基、氨基羰基或氨基磺酰基组成的取代基类别；或 R1 与 R2 连接形成 C1-2 亚烷基二氧基；R3 和 R4 中的一个为 C1-6 亚烷基硫代，另一个选自上文定义的取代基类别； R5 是氢或 C1-6 烷基； R6 是 C1-7 烷基或基团-(CH2)sR7，其中 s 是 0 至 2，R7 是 C3-8 环烷基，或基团-(CH2)Ra，其中 t 是 1 或 2，R8 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，或被一个噻吩基取代；和 p 和 q 独立地为 0 至 2，以及一种药学上可接受的载体。
• 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。
• Azabicycloalkyl benzamides, process for their preparation and pharmaceutical compositions containing them
  申请人：BEECHAM GROUP PLC

  公开号：EP0069482A1

  公开（公告）日：1983-01-12

  Compounds of formula (I) and pharmaceutically acceptable salts thereof: wherein: n, p and q independently are 0 to 2; R5 is hydrogen of C1-6 alkyl; R6 is C1-7 alkyl or a group -(CH2)sR7 where s is 0 to 2 and R7 is a C3-8 cycloalkyl group, or a group -(CH2)tR8 where t is 1 or 2 and R8 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 C1-6 alkylsulphonyl; and either R1 is C1-6 alkoxy or C1-6 alkylthio; and one of R2 and R11 is hydrogen and the other is C1-6 alkoxy, C1-6 alkyl or hydroxy; or R, and R2 together are C1-3 alkylenedioxy; and R11 is hydrogen, halogen, CF3, C1-6 alkoxy, hydroxy, nitro, C1-7 acyl, amino, C1-7 acylamino, 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 of N-disubstituted by C4-6 polymethylene, having useful pharmacological activity, a process for their preparation and their use.

  式(I)化合物及其药学上可接受的盐类： 其中 n、p 和 q 分别为 0 至 2； R5 是 C1-6 烷基中的氢 R6 是 C1-7 烷基或基团-(CH2)sR7，其中 s 是 0 至 2，R7 是 C3-8 环烷基；或基团-(CH2)tR8，其中 t 是 1 或 2，R8 是 C2-5 烯基或苯基，可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；或噻吩基； R12 是 C1-6 烷基磺酰基；以及 R1 是 C1-6 烷氧基或 C1-6 烷硫基；以及 R2 和 R11 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 合在一起是 C1-3 烷二氧基； 和 R11 是氢、卤素、CF3、C1-6 烷氧基、羟基、硝基、C1-7 乙酰基、氨基、C1-7 乙酰氨基、任选被一个或两个 C1-6 烷基、C3-8 环烷基、C3-8 环烷基 C1-4 烷基取代的氨基羰基、苯基或苯基 c1-4 烷基，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，N-被 C4-6 聚亚甲基二取代，具有有用的药理活性，其制备方法和用途。