1-[2-(2,2-Dimethylpropoxy)phenyl]piperazine | 186387-00-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-[2-(2,2-Dimethylpropoxy)phenyl]piperazine
• CAS: 186387-00-8
• 化学式: C₁₅H₂₄N₂O
• 分子量: 248.368
• InChiKey: BYAQYSSJWRCBRM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[2-(2,2-Dimethylpropoxy)phenyl]piperazine 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 3-[4-[2-(2,2-Dimethylpropoxy)phenyl]piperazin-1-yl]propan-1-amine
  参考文献：
  名称：

  N-Arylpiperazinyl-N‘-propylamino Derivatives of Heteroaryl Amides as Functional Uroselective α₁-Adrenoceptor Antagonists

  摘要：

  Novel arylpiperazines were identified as alpha(1)-adrenoceptor(BR) subtype-selective antagonists by functional in vitro screening. 3-[4-(ortho-Substituted phenyl)piperazin-1-yl]propylamines were derivatized with N,N-dimethyl anthranilamides, nicotinamides,;as well as carboxamides of quinoline, I,8-naphthyridine, pyrazolo[3,4-b]pyridine, isoxazolo[3,4-b]pyridine, imidazo[4,5-b]pyridine, and pyrazolo[1,5-a]pyrimidines. Strips of rabbit bladder neck were employed as a predictive assay for antagonism in the human lower tract. Rings of rat aorta;a were used as a ''negative screen'' for the test antagonists. Binding to alpha(1)-ARs was relatively sensitive to size and electronic features of the arylpiperazine portion of the antagonists and permissive to these features on the heteroaryl carboxamide side. These structure-affinity findings were exploited to produce nicotinamides (e.g, 13ii and 25x) and pyrazolo[3,4-b]pyridines (e.g. 37f and 37y) ligands with nanomolar affinity at the alpha(1)-AR subtype prevalent in the human lower urinary tract (pA(2) values: 8.8, 10.7, 9.3, and 9.9, respectively) and displaying 2-3 orders of magnitude selectivity over the alpha(1D)-AR.

  DOI：

  10.1021/jm970166j
• 作为产物：
  描述：

  硝苯酚 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 三苯基膦 、 sodium iodide 、 偶氮二甲酸二乙酯 作用下， 以 乙醇 、 二乙二醇二甲醚 为溶剂， 反应 19.5h， 生成 1-[2-(2,2-Dimethylpropoxy)phenyl]piperazine
  参考文献：
  名称：

  N-Arylpiperazinyl-N‘-propylamino Derivatives of Heteroaryl Amides as Functional Uroselective α₁-Adrenoceptor Antagonists

  摘要：

  Novel arylpiperazines were identified as alpha(1)-adrenoceptor(BR) subtype-selective antagonists by functional in vitro screening. 3-[4-(ortho-Substituted phenyl)piperazin-1-yl]propylamines were derivatized with N,N-dimethyl anthranilamides, nicotinamides,;as well as carboxamides of quinoline, I,8-naphthyridine, pyrazolo[3,4-b]pyridine, isoxazolo[3,4-b]pyridine, imidazo[4,5-b]pyridine, and pyrazolo[1,5-a]pyrimidines. Strips of rabbit bladder neck were employed as a predictive assay for antagonism in the human lower tract. Rings of rat aorta;a were used as a ''negative screen'' for the test antagonists. Binding to alpha(1)-ARs was relatively sensitive to size and electronic features of the arylpiperazine portion of the antagonists and permissive to these features on the heteroaryl carboxamide side. These structure-affinity findings were exploited to produce nicotinamides (e.g, 13ii and 25x) and pyrazolo[3,4-b]pyridines (e.g. 37f and 37y) ligands with nanomolar affinity at the alpha(1)-AR subtype prevalent in the human lower urinary tract (pA(2) values: 8.8, 10.7, 9.3, and 9.9, respectively) and displaying 2-3 orders of magnitude selectivity over the alpha(1D)-AR.

  DOI：

  10.1021/jm970166j

文献信息

• 3-(4-phenylpiperazin-1-yl)propyl-amino, thio and oxy -pyridine, pyrimidine and benzene derivatives as alpha1-adrenoceptor antagonists
  申请人：F. Hoffmann-La Roche AG

  公开号：EP0711757A1

  公开（公告）日：1996-05-15

  The present invention relates to novel α₁-adrenoceptor antagonists of Formula I: in which: p is 0 or 1; t is 0, 1 or 2; X is O, S or NR⁶ (in which R⁶ is hydro or (C₁₋₆)alkyl); Y and Z are independently CH or N; R¹ is hydro, hydroxy, halo, nitro, amino, cyano, (C₁₋₄)alkylthio, acetylamino, trifluoroacetylamino, methylsulfonylamino, (C₁₋₆)alkyl, (C₃₋₆)cycloalkyl, (C₃₋₆)cycloalkyl(C₁₋₄)alkyl, oxazol-2-yl, aryl, heteroaryl, aryl(C₁₋₄)alkyl, heteroaryl(C₁₋₄)alkyl, (C₁₋₆)alkyloxy, (C₃₋₆)cycloalkyloxy, (C₃₋₆)cycloalkyl(C₁₋₄)alkyloxy, 2-propynyloxy, aryloxy, heteroaryloxy, aryl(C₁₋₄)alkyloxy or heteroaryl(C₁₋₄)alkyloxy (wherein alkyl is optionally substituted with one to three halo atoms and aryl or heteroaryl is optionally substituted with one to two substituents independently selected from halo and cyano); R² is hydro, hydroxy, halo, cyano, (C₁₋₆)alkyl or (C₁₋₆)alkyloxy (wherein alkyl is optionally substituted with one to three halo atoms); R³ is -C(O)R⁷ (wherein R⁷ is (C₁₋₆)alkyl, (C₃₋₆)cycloalkyl, di(C₁₋₄)alkylamino, N-(C₁₋₄)alkyl-N-(C₁₋₄)alkyloxyamino, (C₁₋₄)alkyl((C₁₋₄)alkyloxy)amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl or piperazin-1-yl); R⁴ is halo, hydroxy, cyano, (C₁₋₆)alkyl or (C₁₋₆)alkyloxy; and R⁵ is (C₁₋₆)alkyl; and the pharmaceutically acceptable salts and N-oxides thereof.

  本发明涉及式 I 的新型 α₁-肾上腺素受体拮抗剂： 其中 p 是 0 或 1； t 是 0、1 或 2 X 是 O、S 或 NR⁶（其中 R⁶ 是氢或 (C₁₋₆)烷基）； Y 和 Z 独立地为 CH 或 N； R¹是氢、羟基、卤代、硝基、氨基、氰基、(C₁₋₄)烷硫基、乙酰氨基、三氟乙酰氨基、甲磺酰氨基、(C₁₋₆)烷基、(C₃₋₆)环烷基、(C₃₋₆)环烷基(C₁₋₄)烷基、噁唑-2-基、芳基、杂芳基、芳基(C₁₋₄)烷基、杂芳基(C₁₋₄)烷基、(C₁₋₆)烷氧基、(C₃₋₆)环烷氧基、(C₃₋₆)环烷基(C₁₋₄)烷氧基，2-丙炔氧基，芳基氧基，杂芳基氧基、芳基（C₁₋₄）烷氧基或杂芳基（C₁₋₄）烷氧基（其中烷基任选被一至三个卤原子取代，芳基或杂芳基任选被一至两个独立选自卤素和氰基的取代基取代）； R² 是氢、羟基、卤代、氰基、(C₁₋₆)烷基或(C₁₋₆)烷氧基（其中烷基任选被一至三个卤原子取代）； R³ 是 -C(O)R⁷（其中 R⁷ 是 (C₁₋₆)烷基、(C₃₋₆)环烷基、二(C₁₋₄)烷基氨基、N-(C₁₋₄)烷基-N-(C₁₋₄)烷氧基氨基、(C₁₋₄)烷基((C₁₋₄烷氧基)氨基、吡咯烷-1-基、哌啶-1-基、吗啉-4-基或哌嗪-1-基)； R⁴ 是卤素、羟基、氰基、(C₁₋₆)烷基或 (C₁₋₆)烷氧基；和 R⁵ 是 (C₁₋₆)烷基；及其药学上可接受的盐和 N-氧化物。
• Pyrimidinedione, pyrimidinetrione, triazinedione, tetrahydroquinazolinedione derivatives as alpha-1-adrenergic receptor antagonists
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0748800A2

  公开（公告）日：1996-12-18

  The present invention relates to novel α1-adrenoceptor antagonists of the formula I in which: R1 is acetylamino, amino, cyano, trifluoroacetylamino, halo, hydro, hydroxy, nitro, methylsulfonylamino, 2-propynyloxy, a group selected from (C1-6)alkyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-4)alkyl, (C1-6)alkyloxy, (C3-6)cycloalkyloxy, (C3-6)cycloalkyl(C1-4)alkyloxy and (C1-4)alkylthio (which group is optionally further substituted with one to three halo atoms) or a group selected from aryl, aryl(C1-4)alkyl, heteroaryl, heteroaryl(C1-4)alkyl, aryloxy, aryl(C1-4)alkyloxy, heteroaryloxy and heteroaryl(C1-4)alkyloxy (which aryl and heteroaryl are optionally further substituted with one to two radicals independently selected from halo and cyano); R2 is cyano, halo, hydro, hydroxy or a group selected from (C1-6)alkyl and (C1-6)alkyloxy (which group is optionally further substituted with one to three halogen atoms); R3 and R4 are both hydro or methyl or together are ethylene; and R5 is a group selected from Formulae (a), (b), (c) and (d): in which: X is C(O), CH2 or CH(OH); Y is CH2 or CH(OH); Z is N or C(R9), wherein R9 is hydro, (C1-6)alkyl or hydroxy; R6 is hydro, a group selected from (C1-6)alkyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-4)alkyl (which group is optionally further substituted with one to three halo atoms) or a group selected from aryl, heteroaryl, aryl(C1-4)alkyl and heteroaryl(C1-4)alkyl (which aryl and heteroaryl are optionally further substituted with one to three radicals selected from halo, cyano, (C1-6)alkyloxy, (C1-6)alkyl and aryl); R7 is (C1-6)alkanoyl, carbamoyl, cyano, di(C1-6)alkylamino, halo, hydro, hydroxy, hydroxyiminomethyl, (C1-6)alkylsulfonyl, (C1-6)alkylthio, a group selected from (C1-6)alkyl, (C3-6)cycloalkyl, (C1-6)alkyloxy and (C1-6)alkyloxy(C1-4)alkyl (which group is optionally further substituted with one to three radicals selected from halo, hydroxy or (C1-6)alkyloxy) or a group selected from aryl, heteroaryl, aryl(C1-4)alkyl and heteroaryl(C1-4)alkyl (which aryl and heteroaryl are optionally further substituted with one to three radicals selected from halo, cyano, (C1-6)alkyloxy, (C1-6)alkyl and aryl) or R7 and R9 together are tetramethylene; and each R8 is independently hydro, hydroxy, methyl or ethyl; and the pharmaceutically acceptable salts and N-oxides thereof.

  本发明涉及式 I 的新型 α1 肾上腺素受体拮抗剂 其中 R1为乙酰氨基、氨基、氰基、三氟乙酰氨基、卤代、氢、羟基、硝基、甲磺酰氨基、2-丙炔氧基、选自(C1-6)烷基、(C3-6)环烷基、(C3-6)环烷基(C1-4)烷基、(C1-6)烷氧基、(C3-6)环烷氧基的基团、(C1-6)烷氧基、(C3-6)环烷氧基、(C3-6)环烷基(C1-4)烷氧基和(C1-4)烷硫基（该基团可选择进一步被一至三个卤原子取代）或选自芳基的基团、芳基、芳基（C1-4）烷基、杂芳基、杂芳基（C1-4）烷基、芳氧基、芳基（C1-4）烷氧基、杂芳氧基和杂芳基（C1-4）烷氧基（其中芳基和杂芳基可任选地被一至两个独立选自卤原子和氰基的基团进一步取代）； R2 是氰基、卤代、氢基、羟基或选自 (C1-6) 烷基和 (C1-6) 烷氧基的基团（该基团可任选进一步被一至三个卤素原子取代）； R3 和 R4 都是羟基或甲基，或一起是乙烯；以及 R5 是选自式(a)、(b)、(c)和(d)的基团： 其中 X 是 C(O)、CH2 或 CH(OH)； Y 是 CH2 或 CH(OH)； Z 是 N 或 C(R9)，其中 R9 是氢、(C1-6)烷基或羟基； R6 是氢、选自(C1-6)烷基、(C3-6)环烷基、(C3-6)环烷基(C1-4)烷基（该基团可任选进一步被一至三个卤原子取代）或选自芳基、杂芳基、芳基(C1-4)烷基和杂芳基(C1-4)烷基（该芳基和杂芳基可任选进一步被一至三个选自卤素、氰基、(C1-6)烷氧基、(C1-6)烷基和芳基的基团取代）的基团； R7 是(C1-6)烷酰基、氨基甲酰基、氰基、二(C1-6)烷基氨基、卤素、氢、羟基、羟基亚氨基甲基、(C1-6)烷基磺酰基、(C1-6)烷硫基、选自(C1-6)烷基、(C3-6)环烷基、(C1-6)烷氧基和(C1-6)烷氧基(C1-4)烷基的基团（该基团可选择进一步被选自卤素、羟基或(C1-6)烷氧基的一至三个基团取代）、羟基或(C1-6)烷氧基)或选自芳基、杂芳基、芳基(C1-4)烷基和杂芳基(C1-4)烷基的基团(其中芳基和杂芳基可选择进一步被一至三个选自卤代、氰基、(C1-6)烷氧基、(C1-6)烷基和芳基的基团取代)或 R7 和 R9 一起为四亚甲基；每个 R8 独立地是氢、羟基、甲基或乙基；以及它们的药学上可接受的盐和 N-氧化物。
• Synthesis and SAR of highly potent dual 5-HT1A and 5-HT1B antagonists as potential antidepressant drugs
  作者：Andreas Kling、Udo E.W. Lange、Helmut Mack、Margot H.M. Bakker、Karla U. Drescher、Wilfried Hornberger、Charles W. Hutchins、Achim Möller、Reinhold Müller、Martin Schmidt、Liliane Unger、Karsten Wicke、Kurt Schellhaas、Gerd Steiner

  DOI：10.1016/j.bmcl.2005.04.077

  日期：2005.12

  Novel 5-HT1 autoreceptor ligands based on the N-4-aryl-piperazinyl-N'-ethyl-5,6,7,8-tetrahydropyrido[4', 3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one core are described. Aiming at antidepressants with a novel mode of action our objective was to identify potent antagonists showing balanced affinities and high selectivity for the 5-HT1A and 5-HT1B receptors. Strategies for the development of dual 5-HT1A and 5-HT1B antagonists based on 1 and 2 as leads and the corresponding results are discussed. Isoquinoline analogue 33 displayed high affinity and an antagonistic mode of action for the 5-HT1A and the 5-HT1B receptors and was characterized further with respect to selectivity, electrically stimulated [H-3]5-HT release and in vivo efficacy. (c) 2005 Published by Elsevier Ltd.
• Pyrimidinedione, pyrimidinetrione, triazinedione derivatives as alpha-1-adrenergic receptor antagonists
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0748800B1

  公开（公告）日：2001-05-09
• US5688795A
  申请人：——

  公开号：US5688795A

  公开（公告）日：1997-11-18