4-(3-bromopropyloxy)benzenesulfonamide | 925418-99-1

• 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: 4-(3-bromopropyloxy)benzenesulfonamide
• 英文别名: 4-(3-bromopropoxy)benzenesulfonamide；4-(3-Bromo-propoxy)-benzenesulfonamide
• CAS: 925418-99-1
• 化学式: C₉H₁₂BrNO₃S
• 分子量: 294.169
• InChiKey: OEXPXOYSXNPEIU-UHFFFAOYSA-N

物化性质

• 沸点：
  446.3±55.0 °C(Predicted)
• 密度：
  1.559±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  77.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(3-bromopropyloxy)benzenesulfonamide 在 sodium hydroxide 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 24.17h， 生成 1-cyclohexyl-3-[4-(3-piperidin-1-ylpropoxy)benzene]sulfonylurea
  参考文献：
  名称：

  Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies

  摘要：

  The combination of antagonism at histamine H-3 receptor and the stimulation of insulin secretion have been proposed as an approach to new dual therapeutic agents for the treatment of type 2 diabetes mellitus associated with obesity. We have designed and synthesized a new series of non-imidazole derivatives, based on a basic amine ring connected through an alkyl spacer of variable length to a phenoxysulfonylurea moiety. These compounds were initially evaluated for histamine H-3 receptor binding affinities, suggesting that a propoxy chain linker between the amine and the core ring could be essential for optimal binding affinity. Compound 56, 1-(naphthalen-1-yl)-3-[(p-(3-pyrrolidin-1-ylpropoxy) benzene)]sulfonylurea exhibited the best H-3 antagonism affinity. However, since all these derivatives failed to block K-ATP channels, the link of these two related moieties should not be considered a good pharmacophore for obtaining new dual H-3 antagonists with insulinotropic activity, suggesting the necessity to propose a new chemical hybrid prototype. (C)2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.02.049
• 作为产物：
  描述：

  3-苯氧基溴丙烷 在 氯磺酸 、 氨 作用下， 以 二氯甲烷 为溶剂， 生成 4-(3-bromopropyloxy)benzenesulfonamide
  参考文献：
  名称：

  用于阿尔茨海默病的新型 Pitolisant 衍生的磺酰化合物

  摘要：

  阿尔茨海默病 （AD） 是一种复杂的多因素神经退行性疾病，其特征是认知能力下降、记忆力减退、行为改变和其他神经系统症状。考虑到对新 AD 疗法的迫切需求，在本研究中，我们设计、合成和评估了受磺脲类药物和 pitolisant 结构启发的多靶点化合物，目的是获得用于 AD 治疗的多靶点配体。由于化学支架的多样性，通过将显示 H3R 拮抗作用和乙酰胆碱酯酶抑制作用的结构部分合并成一个结构部分，采用了一种新的策略。根据它们对 H3R 的结合活性选择的 8 种化合物在体外显示出中等抑制乙酰胆碱酯酶活性的能力，其中两种化合物（衍生物 2 和 7）也能够在体外增加乙酰胆碱的释放。在测试的化合物中，鉴定并选择衍生物 2 进行进一步的体内研究。化合物 2 能够逆转东莨菪碱诱导的认知缺陷，其结果与临床用于治疗 AD 的药物加兰他敏的结果相当。除了疗效外，该化合物在体外还表现出适度的 BBB 渗透性。总而言之，这些结果表明，化合物

  DOI：

  10.3390/ijms25020799

文献信息

• Azole and Thiazole Derivatives and Their Use
  申请人：Ray Nicholas Charles

  公开号：US20100113540A1

  公开（公告）日：2010-05-06

  Compounds of formula (I) are useful in the treatment of diseases where enhanced M3 receptor activation is implicated, such as respiratory tract diseases: wherein (i) R 1 is C 1 -C 6 -alkyl or hydrogen; and R 2 is hydrogen or a group —R 7 , —Z—Y—R 7 , —Z—NR 9 R 10 ; —Z—CO—NR 9 R 10 , —Z—NR 9 — [AE11] C(O)O—R 7 , or —Z—C(O)—R 7 ; and R 3 is a lone pair, or C 1 C 6 -alkyl; or (ii) R 1 and R 3 together with the nitrogen to which they are attached form a heterocycloalkyl ring and R 2 is a lone pair or a group —R 7 , —Z—Y—R 7 , —Z—NR 9 R 10 , —Z—CO—NR 9 R 10 , —Z—NR 9 — [AE12] C(O)O—R 7 ; or; —Z—C(O)—R 7 ; or (iii) R 1 and R 2 together with the nitrogen to which they are attached form a heterocycloalkyl ring, said ring being substituted by a group —Y—R 7 , —Z—Y—R 7 , —Z—NR 9 R 10 ; —Z—CO—NR 9 R 10 ; —Z—NR 9 — [AE13] C(O)O—R 7 ; or; —Z—C(O)—R 7 ; and R 3 is a lone pair, or C 1 -C 6 -alkyl; R 4 and R 5 are independently selected from the group consisting of aryl, ary-tfused-heterocycloalkyl, heteroaryl, C 1 -C 6 -alkyl, cycloalkyl; R 6 is —OH, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, hydroxy-C 1 -C 6 -alkyl, nitrile, a group CONR 8 2 or a hydrogen atom; A is an oxygen or a sulfur atom; X is an alkylene, alkenylene or alkynylene group; R 7 is an C 1 -C 6 -alkyl, aryl, aryl-fused-cycloalkyl, aryl-fused-heterocycloalkyl, heteroaryl, aryl(C 1 -C 8 -alkyl)-, heteroaryl(C 1 -C 8 -alkyl)-, cycloalkyl or heterocycloalkyl group; R 8 is C 1 -C 6 -alkyl or a hydrogen atom; Z is a C 1 -C 16 -alkylene, C 2 -C 16 -alkenylene or C 2 -C 16 -alkynylene group; Y is a bond or oxygen atom; R 9 and R 10 are independently a hydrogen atom, C 1 -C 6 -alkyl, aryl, aryl-fused-heterocycloalkyl, aryl-fused-cycloalkyl, heteroaryl, aryl(C 1 -C 6 -alkyl)-, or heteroaryl(C 1 -C 6 -alkyl)- group; or R 9 and R 10 together with the nitrogen atom to which they are attached form a heterocyclic ring of 48 atoms, optionally containing a further nitrogen or oxygen atom.

  式（I）的化合物在治疗呼吸道疾病等需要增强M3受体激活的疾病中有用，其中（i）R1为C1-C6烷基或氢，R2为氢或基团-R7、-Z-Y-R7、-Z-NR9R10、-Z-CO-NR9R10、-Z-NR9-[AE11]C（O）O-R7或-Z-C（O）-R7，R3为孤对电子或C1-C6烷基；或（ii）R1和R3与它们连接的氮一起形成杂环烷基环，R2为孤对电子或基团-R7、-Z-Y-R7、-Z-NR9R10、-Z-CO-NR9R10、-Z-NR9-[AE12]C（O）O-R7或-Z-C（O）-R7；或（iii）R1和R2与它们连接的氮一起形成杂环烷基环，该环被基团-Y-R7、-Z-Y-R7、-Z-NR9R10、-Z-CO-NR9R10、-Z-NR9-[AE13]C（O）O-R7或-Z-C（O）-R7取代，R3为孤对电子或C1-C6烷基；R4和R5独立地选自芳基、芳基融合的杂环烷基、杂芳基、C1-C6烷基、环烷基；R6为-OH、C1-C6烷基、C1-C6-烷氧基、羟基-C1-C6烷基、腈基、基团CONR82或氢原子；A为氧原子或硫原子；X为烷基、烯基或炔基；R7为C1-C6烷基、芳基、芳基融合的环烷基、芳基融合的杂环烷基、杂芳基、芳基（C1-C8烷基）-、杂芳基（C1-C8烷基）-、环烷基或杂环烷基；R8为C1-C6烷基或氢原子；Z为C1-C16烷基、C2-C16烯基或C2-C16炔基；Y为键或氧原子；R9和R10独立地为氢原子、C1-C6烷基、芳基、芳基融合的杂环烷基、芳基融合的环烷基、杂芳基、芳基（C1-C6烷基）-或杂芳基（C1-C6烷基）-基团；或R9和R10与它们连接的氮原子一起形成48个原子的杂环，可选地含有进一步的氮或氧原子。
• AZOLE AND THIAZOLE DERIVATIVES AND THEIR USE
  申请人：Ray Nicholas Charles

  公开号：US20120277275A1

  公开（公告）日：2012-11-01

  Compounds of formula (I) are useful in the treatment of diseases where enhanced M3 receptor activation is implicated, such as respiratory tract diseases:

  式(I)的化合物在治疗呼吸道疾病等需要增强M3受体激活的疾病中很有用。
• PHARMACEUTICAL COMPOSITION FOR INHALATION COMPRISING AN OXAZOLE OR THIAZOLE M3 MUSCARINIC RECEPTOR ANTAGONIST
  申请人：Pulmagen Therapeutics (Synergy) Limited

  公开号：EP2280006A1

  公开（公告）日：2011-02-02

  Pharmaceutical compositions for inhalation comprising compounds of formula (I) are useful in the treatment of diseases where enhanced M3 receptor activation is implicated, such as respiritory tract diseases: wherein (i) R1 is C1-C6-alkyl or hydrogen; and R2 is hydrogen or a group -R7, -Z-Y-R7, -Z-NR9R10; -Z-CO-NR9R10, -Z-NR9-C(O)O-R7, or -Z-C(O)-R7; and R3 is a lone pair, or C1-C6-alkyl; or (ii) R1 and R3 together with the nitrogen to which they are attached form a heterocycloalkyl ring, and R2 is a lone pair or a group -R7, -Z-Y-R7, -Z-NR9R10, -Z-CO-NR9R10, -Z-NR9-C(O)O-R7; or; -Z-C(O)-R7; or (iii) R1 and R2 together with the nitrogen to which they are attached form a heterocycloalkyl ring, said ring being substituted by a group -Y-R7, -Z-Y-R7, -Z-NR9R10; -Z-CO-NR9R10; -Z-NR9-C(O)OR7; or; -Z-C(O)-R7; and R3 is a lone pair, or C1-C6-alkyl; R4 and R5 are independently selected from the group consisting of aryl, aryl-fused-heterocycloalkyl, heteroaryl, C1-C6-alkyl, cycloalkyl; R6 is -OH, C1-C6-alkyl, C1-C6-alkoxy, hydroxy-C1-C6-alkyl, nitrile, a group CONR82 or a hydrogen atom; A is an oxygen or a sulfur atom; X is an alkylene, alkenylene or alkynylene group; R7 is an C1-C6-alkyl, aryl, aryl-fused-cycloalkyl, aryl-fused-heterocycloalkyl, heteroaryl, aryl(C1-C8-alkyl)-, heteroaryl(C1-C8-alkyl)-, cycloalkyl or heterocycloalkyl group; R8 is C1-C6-alkyl or a hydrogen atom; Z is a C1-C16-alkylene, C2-C16-alkenylene or C2-C16-alkynylene group; Y is a bond or oxygen atom; R9 and R10 are independently a hydrogen atom, C1-C6-alkyl, aryl, aryl-fused-heterocycloalkyl, aryl-fused-cycloalkyl, heteroaryl, aryl(C1-C6-alkyl)-, or heteroaryl(C1-C6-alkyl)- group; or R9 and R10 together with the nitrogen atom to which they are attached form a heterocyclic ring of 4-8 atoms, optionally containing a further nitrogen or oxygen atom.

  由式（I）化合物组成的吸入用药物组合物可用于治疗与 M3 受体激活增强有关的疾病，如呼吸道疾病： 其中 (i) R1 是 C1-C6- 烷基或氢；R2 是氢或基团 -R7、-Z-Y-R7、 -Z-CO-NR9R10，-Z-NR9-C(O)O-R7，或-Z-C(O)-R7；R3 是孤对或 C1-C6-烷基；或 (ii) R1 和 R3 与它们所连接的氮一起形成杂环烷基环，R2 是孤对或基团 -R7，-Z-Y-R7，-Z-NR9R10、 -Z-CO-NR9R10、-Z-NR9-C(O)O-R7；或；-Z-C(O)-R7；或 (iii) R1 和 R2 与它们所连接的氮一起形成杂环烷基环，所述环被基团 -Y-R7、-Z-Y-R7、-Z-NR9R10 取代；-Z-CO-NR9R10；-Z-NR9-C(O)OR7；或；-Z-C(O)-R7；R4 和 R5 独立地选自由芳基、芳基-融合-杂环烷基、杂芳基、C1-C6-烷基、环烷基组成的组；R6 是-OH、C1-C6-烷基、C1-C6-烷氧基、羟基-C1-C6-烷基、腈、基团 CONR82 或氢原子；A 是氧原子或硫原子；X 是亚烷基、烯基或炔基；R7 是 C1-C6 烷基、芳基、芳基-融合环烷基、芳基-融合杂环烷基、杂芳基、芳基（C1-C8-烷基）-、杂芳基（C1-C8-烷基）-、环烷基或杂环烷基；R8 是 C1-C6 烷基或氢原子；Z 是 C1-C16 烯基、C2-C16 烯基或 C2-C16 烯炔基；Y 是键或氧原子；R9 和 R10 独立地为氢原子、C1-C6-烷基、芳基、芳基-熔合杂环烷基、芳基-熔合环烷基、杂芳基、芳基（C1-C6-烷基）- 或杂芳基（C1-C6-烷基）- 基团；或 R9 和 R10 与它们所连接的氮原子一起形成一个 4-8 个原子的杂环，可选地含有另一个氮原子或氧原子。
• WO2007/17669
  申请人：——

  公开号：——

  公开（公告）日：——
• Antifolate and antiproliferative activity of 6,8,10-triazaspiro[4.5]deca-6,8-dienes and 1,3,5-triazaspiro[5.5]undeca-1,3-dienes
  作者：Xiang Ma、Wai-Keung Chui

  DOI：10.1016/j.bmc.2009.11.065

  日期：2010.1

  Two series of triazaspiroalkanedienes, bearing a substituted phenoxy propyloxy side chain, were identified as potent mammalian DHFR inhibitors. One series has a 6,5-spiro bicyclic ring system and the other series has a 6,6-spiro bicyclic system. Both series were synthesized and tested for in vitro mammalian DHFR inhibitory activity and antiproliferative activity against A549 human lung-cancer cells. Compound 3c showed the highest antiproliferative activity against A549 cells with an IC50 value of 27.1 nM. Rescue experiment confirmed its antifolate antiproliferative mechanism. The excellent antifolate and antiproliferative activity of selected analogues presented in this study warrants further investigation as potential leads in the anticancer drug discovery. (C) 2009 Elsevier Ltd. All rights reserved.