7-[4-(phenylsulfonyl)butoxy]-1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one | 112859-12-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-[4-(phenylsulfonyl)butoxy]-1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one
• 英文别名: 7-(4-(Phenylsulfonyl)butoxy)-1,3-dihydro-2H-imidazo(4,5-b)quinolin-2-one；7-[4-(benzenesulfonyl)butoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one
• CAS: 112859-12-8
• 化学式: C₂₀H₁₉N₃O₄S
• 分子量: 397.455
• InChiKey: PSFRCKHLCWZSJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4-nitrophenyl carbonate 、 7-[4-(phenylsulfonyl)butoxy]-1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以82%的产率得到Ethyl 2,3-dihydro-2-oxo-7-<<4-(phenylsulfonyl)butyl>oxy>-1H-imidazo<4,5-b>quinoline-1-carboxylate
  参考文献：
  名称：

  Regiospecific Functionalization of 1,3-Dihydro-2H-benzimidazol-2-one and Structurally Related Cyclic Urea Derivatives

  摘要：

  Methods for selectively protecting one of the degenerate nitrogen atoms of the cyclic urea derivatives 1,3-dihydro-2H-benzimidazol-2-one (6a), 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (11), 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-ones (20), 1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (22), and 1,3-dihydro-4-phenyl-2H-imidazol-2-one (27) were developed. Heating these cyclic ureas with ethyl 2-pyridyl carbonate in the presence of a base in CH3CN at reflux or DMF at 100 degrees C cleanly provided the monoethoxycarbonyl derivatives 7a, 12, 21, 23, and 28, respectively. Alternatively, treatment of 6a with an excess of diethyl pyrocarbonate or di-tert-butyl dicarbonate afforded the bis-alkoxycarbonyl derivatives 8a and 8b, respectively, which underwent disproportionation to 7a and 7b upon heating with 1 mol equiv of 6a and K2CO3 in CH3CN at reflux. The regiochemistry of the introduction of alkoxycarbonyl groups to benzimidazol-2-one derivatives was not significantly influenced by an electron-withdrawing (CF3, 6b) or an electron-donating (OCH3, 6c) substituent at C-5 of the heterocyclic ring. However, the reaction was found to be sensitive to steric factors since a chlorine substituent ortho to one of the urea N atoms (6e) completely directed the alkoxycarbonyl moiety to the less sterically encumbered N atom, affording a single product (7f, 7g). Alkylation of 7a-g proceeded efficiently to provide products 10a-10ag after removal of the protecting group. Halogenation of monoprotected benzimidazol-2-one 7a occurred regiospecifically to give the monohalo derivatives 7h, 7i, and 7k, the identity of which were readily established from the characteristic chemical shift and spin coupling pattern in their 1H NMR spectra. A protecting group interchange strategy that took advantage of the distinctive chemical reactivities of the EtO(2)C and t-BuO(2)C protecting groups toward isopropylamine was developed that provided access to the isomerically substituted series of monohalo, mono-N-alkylated benzimidazol-2-ones 71 and 7m. The efficient derivatization of the unprotected N atom of these monoprotected cyclic urea derivatives was accomplished by treating with activated and unactivated halides in the. presence of K2CO3 or exposure to alcohols under Mitsunobu conditions. In several cases, mixtures of O- and N-alkylated products were produced which were readily separated by chromatography. Alkylation of 7h with activated halides, using K2CO3 in CH3CN at reflux, occurred without protecting group equilibration; however, a mixture of isomeric alkylated products was obtained when 7h was heated at 110 degrees C in DMF with cyclohexylmethyl bromide in the presence of K2CO3 as the base. Derivatization of 7h under Mitsunobu reaction conditions proceeded with retention of the topological substituent relationships. Subsequent removal of the alkoxycarbonyl moiety afforded monoalkylated cyclic urea derivatives.

  DOI：

  10.1021/jo00111a014
• 作为产物：
  描述：

  (4-氯-丁烷-1-磺酰基)-苯 在 palladium on activated charcoal 氢气 、 碘 、 sodium ethanolate 、 potassium carbonate 、 potassium iodide 作用下， 以 甲醇 、 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.33h， 生成 7-[4-(phenylsulfonyl)butoxy]-1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one
  参考文献：
  名称：

  血小板cAMP磷酸二酯酶抑制剂。2.与被官能化侧链取代的1，3-二氢-2H-咪唑并[4，5-b]喹啉-2-酮相关的结构活性关系。

  摘要：

  合成了一系列在7位被官能化侧链取代的1,3-二氢-2H-咪唑并[4,5-b]喹啉-2-酮衍生物，并将其评估为人血小板cAMP磷酸二酯酶的抑制剂（ PDE）以及ADP和胶原蛋白诱导的血小板聚集。结构修饰集中于侧链末端，侧链长度和侧链连接原子的变化。在侧链末端结合的官能团包括羧酸，酯和酰胺，醇，乙酸酯，腈，四唑和苯基砜部分。cAMP PDE抑制能力各不相同，并取决于侧链末端及其与杂环核的关系。杂环的N-1或N-3处的甲基化降低了cAMP PDE抑制能力。该结构类别的几个代表证明了对ADP和胶原蛋白诱导的血小板凝集的有效抑制作用，并且在低纳摩尔浓度下最大程度地发挥了最大作用。酰胺13d，13f，13h，13k，13m和13w比相对简单取代的化合物具有更大的效力。但是，血小板抑制特性在整个系列中并不总是与cAMP PDE抑制相关，这可能是由于膜通透性的变化所致。口服给予大鼠后，离体测量的几种化合物

  DOI：

  10.1021/jm00092a019

文献信息

• Imidazoquinolinylether derivatives useful as phosphodiesterase and blood
  申请人：Bristol-Myers Company

  公开号：US04775674A1

  公开（公告）日：1988-10-04

  Novel series of 2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolinyl ether derivatives of formula ##STR1## wherein R.sub.1 is hydrogen, lower alkly, benzyl; R.sub.2 is hydrogen, halogen, lower alkyl, lower alkoxy; Alk is alkylene; Y is hydroxy and alkanoic or aralkanoic esters thereof, oxo ketone, dialkylamino, carboxylic acid and esters, carboxamides, alkoxy, ethanolamines and cyclic carbamates thereof, tetrazolyl, and optionally substituted phenylsulfonyl. The compounds are cyclic AMP phosphodiesterase inhibitors and are particularly useful as inhibitors of blood platelet aggregation and/or as cardiotonic agents.

  2,3-二氢-2-氧基-1H-咪唑并[4,5-b]喹啉基醚衍生物的小说系列，其化学式为##STR1##其中R.sub.1为氢、低烷基、苄基；R.sub.2为氢、卤素、低烷基、低烷氧基；Alk为烷基；Y为羟基和羧酸酯、酮基、二烷基胺、羧酸和酯、羧酰胺、烷氧基、乙醇胺和环状碳酸酯、四唑基，以及可选择地取代的苯磺酰基。这些化合物是环磷酸腺苷磷酸二酯酶抑制剂，特别适用于抑制血小板聚集和/或作为心力衰竭药物。
• US4775674A
  申请人：——

  公开号：US4775674A

  公开（公告）日：1988-10-04
• US5158958A
  申请人：——

  公开号：US5158958A

  公开（公告）日：1992-10-27
• US5196428A
  申请人：——

  公开号：US5196428A

  公开（公告）日：1993-03-23
• US5208237A
  申请人：——

  公开号：US5208237A

  公开（公告）日：1993-05-04