1-(2-cyclopropylphenyl)piperazine | 136605-78-2

• 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-cyclopropylphenyl)piperazine
• CAS: 136605-78-2
• 化学式: C₁₃H₁₈N₂
• 分子量: 202.299
• InChiKey: HDQVZCLSESHBHG-UHFFFAOYSA-N

物化性质

• 沸点：
  330.6±30.0 °C(Predicted)
• 密度：
  1.089±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(2-cyclopropylphenyl)piperazine 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 xylene 为溶剂， 反应 29.0h， 生成 2-{3-[4-(2-Cyclopropyl-phenyl)-piperazin-1-yl]-propylamino}-N,N-dimethyl-nicotinamide
  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：

  1-环丙基-2-硝基苯 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 sodium iodide 作用下， 以 乙醇 、 二乙二醇二甲醚 为溶剂， 反应 19.5h， 生成 1-(2-cyclopropylphenyl)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

• 2-Aminopyrimidine-4-carboxamide derivatives, their preparation and their
  申请人：Synthelabo

  公开号：US05164397A1

  公开（公告）日：1992-11-17

  A compound of formula (I) ##STR1## in which n denotes 2, 3, 4, or 5, p denotes 0 or 1, m denotes 0, 1, 2, 3, 4, or 5, and R.sub.1 denotes a hydrogen atom or a methyl group, each X, which may be identical or different to any other X if m is greater than 1, denotes fluorine, chlorine, methoxy, isopropyl or cyclopropyl, in the form of a free base or an acid addition salt.

  在公式（I）##STR1##中，n代表2、3、4或5，p代表0或1，m代表0、1、2、3、4或5，R.sub.1代表氢原子或甲基基团，每个X（如果m大于1，可能与任何其他X相同或不同）代表氟、氯、甲氧基、异丙基或环丙基，以自由碱或酸盐的形式。
• 2-aminopyrazine-5-carboxamide derivatives, their preparation and their
  申请人：Synthelabo

  公开号：US05420130A1

  公开（公告）日：1995-05-30

  Compounds corresponding to the general formula (I) ##STR1## in which n represents 0 or 1, R.sub.1 represents a methyl group, in which case R.sub.2 represents a phenoxy(C.sub.1 -C.sub.4)alkyl group (in which the phenoxy group is optionally substituted), or else R.sub.1 and R.sub.2 together form, and with the nitrogen atom which carries them, a 4-(phenoxymethyl)piperid-1-yl group (in which the phenoxy group is optionally substituted) or a 4-phenylpiperazin-1-yl group (in which the phenyl group is optionally substituted), R.sub.3 represents a hydrogen atom or a methyl group, R.sub.4 represents a hydrogen atom and R.sub.5 represents a hydrogen atom or a group of general formula -CH.sub.2 -CH.sub.2 -NH-R.sub.6, R.sub.6 being a hydrogen atom or a tert-butyloxycarbonyl, 4-carbamoylpyrimidin-2-yl or 5-carbamoylpyrazin-2-yl group, are useful in the treatment of diseases and complaints involving hyperactivity of the .alpha.-adrenergic system at the level of the lower urinary apparatus.

  通式（I）对应的化合物为##STR1##其中n代表0或1，R.sub.1代表甲基基团，此时R.sub.2代表苯氧基（C.sub.1-C.sub.4）烷基基团（其中苯氧基可选地被取代），或者R.sub.1和R.sub.2共同形成，并与携带它们的氮原子一起形成4-（苯氧甲基）哌啶-1-基基团（其中苯氧基可选地被取代）或4-苯基哌嗪-1-基基团（其中苯基可选地被取代），R.sub.3代表氢原子或甲基基团，R.sub.4代表氢原子，R.sub.5代表氢原子或一般式-CH.sub.2-CH.sub.2-NH-R.sub.6的基团，其中R.sub.6是氢原子或叔丁氧羰基、4-氨基甲酰基嘧啶-2-基或5-氨基甲酰基吡嗪-2-基基团，可用于治疗涉及下部尿道α-肾上腺素能系统过度活跃的疾病和不适。
• Dérivés de 2-aminopyrimidine-4-carboxamide, leur préparation et leur application en thérapeutique
  申请人：SYNTHELABO

  公开号：EP0435749A1

  公开（公告）日：1991-07-03

  Composés de formule générale (I) dans laquelle n représente le nombre 2, 3, 4 ou 5, p représente le nombre 0 ou 1, R1 représente un atome d'hydrogène ou un groupe méthyle, Xm représente un ou plusieurs atomes ou groupes choisis parmi les suivants : hydrogène, fluor, chlore, méthoxy, isopropyle, cydopropyle, à l'état de bases libres ou de sels d'addition à des acides. Application en thérapeutique.

  通式 (I) 的化合物 其中 n 代表数字 2、3、4 或 5，p 代表数字 0 或 1，R1 代表氢原子或甲基，Xm 代表一个或多个原子或基团，这些原子或基团选自下 列原子或基团：氢、氟、氯、甲氧基、异丙基、二丙基，以游离碱或与酸的加成盐的形式存在。 治疗应用。
• Dérivés de 2-aminopyrazine-5-carboxamide, leur préparation et leur application en thérapeutique
  申请人：SYNTHELABO

  公开号：EP0625514A1

  公开（公告）日：1994-11-23

  Composés répondant à la formule générale (I) dans laquelle n représente 0 ou 1, R₁ représente un groupe méthyle, auquel cas R₂ représente un groupe phénoxy(C₁-C₄)alkyle (dont le groupe phénoxy est éventuellement substitué), ou bien R₁ et R₂ forment ensemble, et avec l'atome d'azote qui les porte, un groupe 4-(phénoxyméthyl)pipéridin-1-yle (dont le groupe phénoxy est éventuellement substitué), ou un groupe 4-phénylpipérazin-1-yle (dont le groupe phényle est éventuellement substitué), R₃ représente un atome d'hydrogène ou un groupe méthyle, R₄ représente un atome d'hydrogène, R₅ représente un atome d'hydrogène ou un groupe de formule générale -CH₂-CH₂-NH-R₆, R₆ étant un atome d'hydrogène, ou un groupe tertiobutyloxycarbonyle, 4-carbamoylpyrimidin-2-yle, ou 5-carbamoylpyrazin-2-yle. Application en thérapeutique.

  通式(I)对应的化合物 其中 n 代表 0 或 1，R₁ 代表甲基，在这种情况下，R₂ 代表苯氧基（C₁-C₄）烷基（其中苯氧基任选被取代），或 R₁ 和 R₂ 一起，并与携带它们的氮原子一起，形成 4-(苯氧基甲基)哌啶-1-基团（其中苯氧基任选被取代）、R₃ 代表氢原子或甲基，R₄ 代表氢原子、R₅代表氢原子或通式-CH₂-CH₂-NH-R₆的基团，R₆为氢原子或叔丁氧羰基、4-氨基甲酰基嘧啶-2-基或 5-氨基甲酰基吡嗪-2-基。 治疗应用。
• 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。