3-(azepan-1-ylsulfonyl)-4-methoxybenzoic acid | 299181-35-4

• 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: 3-(azepan-1-ylsulfonyl)-4-methoxybenzoic acid
• 英文别名: 3-(azepane-1-sulfonyl)-4-methoxy-benzoic acid
• CAS: 299181-35-4
• 化学式: C₁₄H₁₉NO₅S
• mdl: MFCD00814139
• 分子量: 313.375
• InChiKey: SSIIBIGRHVVLAP-UHFFFAOYSA-N

物化性质

• 沸点：
  512.7±60.0 °C(Predicted)
• 密度：
  1.310±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  92.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(azepan-1-ylsulfonyl)-4-methoxybenzoic acid 、 (R)-1-cyano-N-(4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)pyrrolidine-3-carboxamide 在 O‑(6‑chlorobezotriazol‑1‑yl)‑N,N,N,N‑tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以34 %的产率得到(R)-N-(5-(3-(azepan-1-ylsulfonyl)-4-methoxybenzoyl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)-1-cyanopyrrolidine-3-carboxamide
  参考文献：
  名称：

  抑制剂、探针和 PROTAC 的开发为研究活细胞中的 PARK7 提供了完整的工具箱

  摘要：

  小分子抑制剂、基于活性的探针 (ABP) 和蛋白水解靶向嵌合体 (PROTAC) 等多种化学工具的集成推进了临床药物发现，并促进了对靶向蛋白质的各个生物学方面的探索。在此，我们报告了针对与帕金森病和癌症有关的人类帕金森病蛋白 7 (PARK7/DJ-1) 开发的化学工具箱。通过结合结构指导设计、小型化文库合成和高通量筛选，我们鉴定了两种有效的化合物JYQ-164和JYQ-173 ，通过共价和选择性地靶向其关键残基 Cys106，在体外和细胞内抑制 PARK7。利用JYQ-173 ，我们进一步开发了一种可渗透细胞的 Bodipy 探针JYQ-196 ，用于在活细胞中共价标记 PARK7，以及一流的 PARK7 降解剂JYQ-194 ，可选择性诱导其在人类细胞中的蛋白酶体降解。我们的研究提供了一个有价值的工具箱，以增强对细胞环境中 PARK7 生物学的理解，并为治疗干预开辟了新的机会。

  DOI：

  10.1021/acs.jmedchem.3c02410
• 作为产物：
  描述：

  大茴香酸 在 吡啶 作用下， 以 乙酸乙酯 为溶剂， 反应 4.0h， 生成 3-(azepan-1-ylsulfonyl)-4-methoxybenzoic acid
  参考文献：
  名称：

  Development and characterization of 3-(benzylsulfonamido)benzamides as potent and selective SIRT2 inhibitors

  摘要：

  Inhibitors of sirtuin-2 deacetylase (SIRT2) have been shown to be protective in various models of Huntington's disease (HD) by decreasing polyglutamine aggregation, a hallmark of HD pathology. The present study was directed at optimizing the potency of SIRT2 inhibitors containing the neuroprotective sulfobenzoic acid scaffold and improving their pharmacology. To achieve that goal, 176 analogues were designed, synthesized, and tested in deacetylation assays against the activities of major human sirtuins SIRT1-3. This screen yielded 15 compounds with enhanced potency for SIRT2 inhibition and 11 compounds having SIRT2 inhibition equal to reference compound AK-1. The newly synthesized compounds also demonstrated higher SIRT2 selectivity over SIRT1 and SIRT3. These candidates were subjected to a dose-response bioactivity assay, measuring an increase in alpha-tubulin K40 acetylation in two neuronal cell lines, which yielded five compounds bioactive in both cell lines and eight compounds bioactive in at least one of the cell lines tested. These bioactive compounds were subsequently tested in a tertiary polyglutamine aggregation assay, which identified five inhibitors. ADME properties of the bioactive SIRT2 inhibitors were assessed, which revealed a significant improvement of the pharmacological properties of the new entities, reaching closer to the goal of a clinically-viable candidate. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.02.003

文献信息

• [EN] BENZAMIDE COMPOUNDS AND RELATED METHODS OF USE<br/>[FR] COMPOSÉS BENZAMIDE ET LEURS PROCÉDÉS D'UTILISATION CONNEXES
  申请人：UNIV NORTHWESTERN

  公开号：WO2014100833A1

  公开（公告）日：2014-06-26

  Benzamide compounds and derivatives thereof, as can be used for selective inhibition of the SIRT2 enzyme and/or therapeutic use in the treatment of Huntington's disease.

  苯甲酰胺化合物及其衍生物，可用于选择性抑制SIRT2酶和/或在亨廷顿病的治疗中用于治疗用途。
• [EN] ARYL SULFONIC ACIDS AND DERIVATIVES AS FSH ANTAGONISTS<br/>[FR] ACIDES SULFONIQUES ARYLES ET DERIVES TELS QUE LES ANTAGONISTES FSH
  申请人：AMERICAN HOME PROD

  公开号：WO2000058277A1

  公开（公告）日：2000-10-05

  This invention provides compounds of formula (I) having the structure wherein Q is hydrogen or -SO2R1; X is a bond, O, S(O)¿n?, -CH=CH-, -CH2CH2-, -C C-, or -CH2S(O)nCH2-; R?1¿ is OH, NH¿2?, C1 to C6 alkoxy, C1 to C3 perfluoroalkoxy; Ar is (a) or (b); Ar' is (c) or (d); R?2 and R4¿ are each, independently, hydrogen, OR6, -S(O)¿m?R?6, -NHR6, -N(R6)¿2, or -CH2SO2CH3; R?3 and R5¿ are each, independently, hydrogen, -NO¿2?, -NH2, -SO2R?9¿, or -CH¿2R?9; R6 is hydrogen, C¿1? to C6 alkyl, C3 to C6 alkenyl, -CH2CH2Z, -CH2COR?7, -CH¿2CH=CHCOR7, (e), (f) or (g); Y¿1? and Y?3¿ are each, independently, N, or CH; Y?2 and Y4¿ are each independently, O, S, or NR?13; R7 is -OR8, -NHR8, -N(R8)¿2, or -NHCH2CH2OR8; Z is -OR¿8?, -OCH2CH2OR?8, -N(R8)¿2, or (h); R8 is hydrogen or C1 to C3 alkyl; R9 is C1 to C6 alkyl, C3 to C6 alkenyl, OH, NHR?10, N(R10)¿2, CH2COR11, -CH2CH=CHCOR11, or (i); R10 is C1 to C3 alkyl, C3 to C4 alkenyl, phenyl, -CH2CH2OCH3, or -(j); R?11 is -OR12, -NHR12, -N(R12)¿2, or -NHCH2CH2OR12; R12 is hydrogen, or C¿1? to C3 alkyl; R?13¿ is hydrogen, or C¿1? to C3 alkyl; W is a bond, CH2, CH2CH2, O, S(O)q, NCHO, NCOCH3, or NR?12¿; m is 0 - 2; n is 0 - 2; q is 0 - 2, with the proviso that R?2 and R3¿ are not both hydrogen; or pharmaceutically acceptable salt thereof, which are useful as contraceptive agents.

  本发明提供了具有结构式(I)的化合物，其中Q为氢或-SO2R1; X为键，O，S(O)n，-CH=CH-，-CH2CH2-，-CC-或-CH2S(O)nCH2-; R1为OH，NH2，C1到C6烷氧基，C1到C3全氟烷氧基; Ar为(a)或(b); Ar'为(c)或(d); R2和R4分别独立地为氢，OR6，-S(O)mR6，-NHR6，-N(R6)2或-CH2SO2CH3; R3和R5独立地为氢，-NO2，-NH2，-SO2R9或-CH2R9; R6为氢，C1到C6烷基，C3到C6烯基，-CH2CH2Z，-CH2COR7，-CH2CH=CHCOR7，(e)，(f)或(g); Y1和Y3独立地为N或CH; Y2和Y4独立地为O，S或NR13; R7为-OR8，-NHR8，-N(R8)2或-NHCH2CH2OR8; Z为-OR8，-OCH2CH2OR8，-N(R8)2或(h); R8为氢或C1到C3烷基; R9为C1到C6烷基，C3到C6烯基，OH，NHR10，N(R10)2，CH2COR11，-CH2CH=CHCOR11或(i); R10为C1到C3烷基，C3到C4烯基，苯基，-CH2CH2OCH3或-(j); R11为-OR12，-NHR12，-N(R12)2或-NHCH2CH2OR12; R12为氢或C1到C3烷基; R13为氢或C1到C3烷基; W为键，CH2，CH2CH2，O，S(O)q，NCHO，NCOCH3或NR12; m为0-2; n为0-2; q为0-2，但R2和R3不能同时为氢; 或其药学上可接受的盐，其作为避孕剂有用。
• Aryl sulfonic acids and derivatives as FSH antagonists
  申请人：American Home Products Corporation

  公开号：US20020111369A1

  公开（公告）日：2002-08-15

  This invention provides compounds of formula I having the structure 1 wherein Q is hydrogen or —SO 2 R 1 ; X is a bond, O, S(O) n , —CH═CH—, —CH 2 CH 2 —, —C≡C—, or —CH 2 S(O) n CH 2 —; R 1 is OH, NH 2 , C 1 to C 6 alkoxy, C 1 to C 3 perfluoroalkoxy; 2 R 2 and R 4 are each, independently, hydrogen, OR 6 , —S(O) m R 6 , —NHR 6 , —N(R 6 ) 2 , or —CH 2 SO 2 CH 3 ; R 3 and R 5 are each, independently, hydrogen, —NO 2 , —NH 2 , —SO 2 R 9 , or —CH 2 R 9 ; R 6 is hydrogen, C 1 to C 6 alkyl, C 3 to C 6 alkenyl, —CH 2 CH 2 Z, —CH 2 COR 7 , —CH 2 CH═CHCOR 7 3 Y 1 and Y 3 are each, independently, N, or CH; Y 2 and Y 4 are each independently, O, S, or NR 13 ; R 7 is —OR 8 , —NHR 8 , —N(R 8 ) 2 , or —NHCH 2 CH 2 OR 8 ; Z is —OR 8 , —OCH 2 CH 2 OR 8 , —N(R 8 ) 2 , or 4 R 8 is hydrogen, or C 1 to C 3 alkyl; R 9 is C 1 to C 6 alkyl, C 3 to C 6 alkenyl, OH, NHR 10 , N(R 10 ) 2 , CH 2 COR 11 , —CH 2 CH═CHCOR 11 , or 5 R 10 is C 1 to C 3 alkyl, C 3 to C 4 alkenyl, phenyl, —CH 2 CH 2 OCH 3 , or 6 R 11 is —OR 12 , NHR 12 , —N(R 12 ) 2 , or —NHCH 2 CH 2 OR 12 ; R 12 is hydrogen, or C 1 to C 3 alkyl; R 13 is hydrogen, or C 1 to C 3 alkyl; W is a bond, CH 2 , CH 2 CH 2 , O, S(O) q , NCHO, NCOCH 3 , or NR 12 ; m is 0-2; n is 0-2; q is 0-2, with the proviso that R 2 and R 3 are not both hydrogen; or pharmaceutically acceptable salt thereof, which are useful as contraceptive agents.

  本发明提供了式I的化合物，其具有结构1， 其中， Q为氢或—SO2R1； X为键合，O，S(O)n，—CH═CH—，—CH2CH2—，—C≡C—或—CH2S(O)nCH2—； R1为OH，NH2，C1到C6烷氧基，C1到C3全氟烷氧基； R2和R4各自独立地为氢，OR6，—S(O)mR6，—NHR6，—N(R6)2或—CH2SO2CH3； R3和R5各自独立地为氢，—NO2，—NH2，—SO2R9或—CH2R9； R6为氢，C1到C6烷基，C3到C6烯基，—CH2CH2Z，—CH2COR7，—CH2CH═CHCOR73； Y1和Y3各自独立地为N或CH； Y2和Y4各自独立地为O，S或NR13； R7为—OR8，—NHR8，—N(R8)2或—NHCH2CH2OR8； Z为—OR8，—OCH2CH2OR8，—N(R8)2或 4 R8为氢或C1到C3烷基； R9为C1到C6烷基，C3到C6烯基，OH，NHR10，N(R10)2，CH2COR11，—CH2CH═CHCOR11或 5 R10为C1到C3烷基，C3到C4烯基，苯基，—CH2CH2OCH3或 6 R11为—OR12，NHR12，—N(R12)2或—NHCH2CH2OR12； R12为氢或C1到C3烷基； R13为氢或C1到C3烷基； W为键合，CH2，CH2CH2，O，S(O)q，NCHO，NCOCH3或NR12； m为0-2； n为0-2； q为0-2； 但R2和R3不能同时为氢； 或其药学上可接受的盐，其作为避孕剂具有用途。
• Benzamide Compounds and Related Methods of Use
  申请人：Northwestern University

  公开号：US20150025235A1

  公开（公告）日：2015-01-22

  Benzamide compounds and derivatives thereof, as can be used for selective inhibition of the SIRT2 enzyme and/or therapeutic use in the treatment of Huntington's disease.

  苯甲酰胺化合物及其衍生物可用于选择性抑制SIRT2酶和/或治疗亨廷顿病。
• US6355633B1
  申请人：——

  公开号：US6355633B1

  公开（公告）日：2002-03-12