4-(2-aminophenyl)piperazine-1-carbaldehyde | 91337-66-5

• 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: 4-(2-aminophenyl)piperazine-1-carbaldehyde
• CAS: 91337-66-5
• 化学式: C₁₁H₁₅N₃O
• 分子量: 205.26
• InChiKey: FOXQGUQJESLPCG-UHFFFAOYSA-N

物化性质

• 沸点：
  425.5±40.0 °C(Predicted)
• 密度：
  1.270±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  49.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-aminophenyl)piperazine-1-carbaldehyde 在 盐酸 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 N-methyl-N-[2-(1-piperazinyl)phenyl]methanesulfonamide dihydrochloride
  参考文献：
  名称：

  Novel potent neuropeptide Y Y5 receptor antagonists: Synthesis and structure–activity relationships of phenylpiperazine derivatives

  摘要：

  A series of phenylpiperazine derivatives were synthesized and evaluated for their neuropeptide Y (NPY) Y5 receptor antagonistic activities. The benzindane portion of 2 was replaced by I-phenylpiperazine, resulting in novel urea derivative X Subsequent optimization of the phenylpiperazine template by substitution of the phenyl moiety resulted in a series of (2-methanesulfonamidephenyl)piperazine derivatives that showed potent binding affinity and antagonistic activity for the Y5 receptor. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.07.023
• 作为产物：
  描述：

  1-(2-硝基苯基)哌嗪 在 乙醇 、 15% palladium on carbon 、 氢气 、 sodium 作用下， 以 甲醇 为溶剂， 20.0~50.0 ℃ 、344.75 kPa 条件下， 反应 25.0h， 生成 4-(2-aminophenyl)piperazine-1-carbaldehyde
  参考文献：
  名称：

  具有抗疟原虫活性的新型2-苯氧基苯甲酰胺的合成及构效关系

  摘要：

  来自疟疾风险药物盒项目的 2-苯氧基苯甲酰胺1已显示出针对不同恶性疟原虫菌株的多阶段活性。它是通过逆合成方法成功合成的。随后，制备了 21 种新衍生物并测试了它们对恶性疟原虫NF54 菌株血液阶段的体外活性. 揭示了对结构-活性关系的一些见解。化合物的抗疟原虫活性和细胞毒性在很大程度上取决于苯胺基部分结构的取代模式以及取代基的大小。二芳基醚部分结构对活性有进一步影响。此外，计算了几个物理化学和药代动力学参数（log P、log D 7 . 4和配体效率）或通过实验确定（被动渗透性和 CYP3A4 抑制）。的叔丁基-4- {4- [2-（4-氟苯氧基）-3-（三氟甲基）苯甲酰氨基]苯基}哌嗪-1-羧酸叔丁酯具有针对高抗疟原虫活性的恶性疟原虫NF54（Pf的NF54 IC 50= 0.2690 µM) 和非常低的细胞毒性（L-6 细胞 IC 50 = 124.0 µM），从而获得了 460 的

  DOI：

  10.3390/ph14111109

文献信息

• Pyrimidinedione, pyrimidinetrione, triazinedione and
  申请人：Syntex (U.S.A.) Inc.

  公开号：US05859014A1

  公开（公告）日：1999-01-12

  Compounds of Formula I: ##STR1## where R.sup.5 is a group selected from Formulae (a), (b), (c) and (d): ##STR2## and the pharmaceutically acceptable salts and N-oxides thereof, are .alpha..sub.1 -adrenergic receptor antagonists useful for the treatment of diseases involving directly or indirectly an obstruction of the lower urinary tract, such as benign prostatic hyperplasia.

  化合物的化学式I：##STR1##其中R.sup.5是从式(a)、(b)、(c)和(d)中选择的基团：##STR2##以及其药用可接受的盐和N-氧化物，是用于治疗涉及直接或间接阻塞下尿道的疾病，如良性前列腺增生的α1-肾上腺素受体拮抗剂。
• 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。
• NEW VORTIOXETINE INTERMEDIATE AND SYNTHESIS PROCESS THEREOF
  申请人：Shanghai Syncores Technologies, Inc.

  公开号：EP3141543A1

  公开（公告）日：2017-03-15

  The present invention provides a new intermediate II and a method for synthesizing the same. The method comprises: (a) firstly diazotizing a compound of formula I as a raw material, and then halogenating to obtain an intermediate II; and (b) reacting the intermediate II with a compound III to obtain a compound IV, hydrolyzing the obtained compound IV directly without being separated to obtain Vortioxetine represented by compound V. The intermediate II can be used for synthesizing Vortioxetine.

  本发明提供了一种新的中间体 II 及其合成方法。该方法包括：(a) 首先将式 I 的化合物作为原料重氮化，然后卤化，得到中间体 II；(b) 将中间体 II 与化合物 III 反应，得到化合物 IV，将得到的化合物 IV 直接水解而不分离，得到以化合物 V 为代表的伏替西汀。
• 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
• US5859014A
  申请人：——

  公开号：US5859014A

  公开（公告）日：1999-01-12