盐酸曲唑酮杂质 | 32229-98-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 盐酸曲唑酮杂质
• 中文别名: 3-[4-(3-氯苯基)哌嗪-1-基]丙-1-醇；曲唑酮相关物质5；曲唑酮杂质12；曲唑酮杂质7；盐酸曲唑酮杂质G(BP)
• 英文名称: 4-(3-chlorophenyl)-1-piperazinopropanol
• 英文别名: 1-(3-hydroxy-n-propyl)-4-(3-chlorophenyl)-piperazine；3-[4-(3-chloro-phenyl)-1-piperazinyl]propanol；3-[4-(3-Chlorophenyl)piperazin-1-yl]propan-1-ol
• CAS: 32229-98-4
• 化学式: C₁₃H₁₉ClN₂O
• mdl: MFCD11613839
• 分子量: 254.76
• InChiKey: MHOVZUZZHTZBSV-UHFFFAOYSA-N

物化性质

• 熔点：
  88-90°C
• 溶解度：
  可溶于DMSO（轻微）、乙酸乙酯（轻微、加热）、甲醇（轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.538
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  盐酸曲唑酮杂质 在 三苯基膦 作用下， 以 四氯化碳 为溶剂， 以70%的产率得到1-(3-氯苯基-4-氯丙基)哌嗪盐酦盐
  参考文献：
  名称：

  Synthesis of 2-phenylthiazolidine derivatives as cardiotonic agents. II. 2-(Phenylpiperazinoalkoxyphenyl)thiazolidine-3-thiocarboxamides and the corresponding carboxamides.

  摘要：

  大量2-（苯基哌嗪基烷氧苯基）噻唑烷-3-硫代羧酰胺及其相应羧酰胺（II）被合成并在麻醉犬中测试其强心活性。化合物II通过羟基苯甲醛（III）及其中间体（IV、V和X）制备。通过改变结构参数来研究结构-活性关系（SAR）。将哌嗪基烷氧基团从邻位位置移至间位或对位导致活性显著下降。将硫代羧酰胺转变为羧酰胺基团导致活性显著增加。这种趋势在这一系列化合物中普遍存在，并构成与简单2-苯基噻唑烷系列SAR的主要偏离。关于氨基烷氧链长度的影响，乙氧基衍生物通常比更高级的类似物更有效。在（硫代）羧酰胺基团中延长N-烷基通常导致活性下降。在合成的各种衍生物中，II15被发现其效力约为氨力农的一百倍，且作用时间较长。

  DOI：

  10.1248/cpb.35.2394
• 作为产物：
  描述：

  Ethyl-3-<4-(3-chlorphenyl)-1-piperazinyl>-propionat 以 四氢呋喃 为溶剂， 以91%的产率得到盐酸曲唑酮杂质
  参考文献：
  名称：

  N-Aryl-N-phenoxy-alkyl-piperazine compounds useful in decreasing

  摘要：

  一种化学式为：##STR1##的哌嗪衍生物，其中R.sup.1为氢、烷基（C.sub.1-8）、烷基（C.sub.1-4）-磺酰基或化学式为R.sup.3 CO-的酰基（其中R.sup.3为氢、烷基（C.sub.1-7）、卤代烷基（C.sub.1-4）、烷氧基（C.sub.1-4）-羰基-烷基（C.sub.1-4）、环烷基（C.sub.3-6）、烯基（C.sub.2-5）、烷氧基（C.sub.1-4）、氨基、烷基（C.sub.1-4）-氨基或苯胺基），R.sup.2为氢、烷基（C.sub.1-4）、烷氧基（C.sub.1-4）-羰基-烷基（C.sub.1-4）、羧基-烷基（C.sub.1-4）、烯基（C.sub.2-5）或烷基（C.sub.1-4）-磺酰基，或R.sup.1和R.sup.2结合形成琥珀酰基，环A为苯基、烷基（C.sub.1-4）-苯基或卤代苯基，n为2至6的整数，或其药学上可接受的酸盐。该哌嗪衍生物（I）具有降低颅内压的活性。该衍生物还对中枢神经系统具有抑制作用。

  公开号：

  US04413006A1

文献信息

• Piperazinyl derivatives and methods of treating central nervous system
  申请人：Novo Nordisk A/S

  公开号：US05246935A1

  公开（公告）日：1993-09-21

  Piperazinyl derivatives of the general formula I ##STR1## wherein R.sup.1 represents substituted phenyl, 1- or 2-diazanaphthyl, azadiazanaphtyl or diazanaphtyl groups; n is 1, 2, 3 or 4; X is --O-- or ##STR2## wherein R.sup.2 is hydrogen, C.sub.1-6 -alkyl or C.sub.3-8 -cycloalkyl; Y is .dbd.O or .dbd.S or .dbd.NZ wherein Z is hydrogen, C.sub.1-6 -alkyl or --CN and R.sup.3 is selected from a group consisting of various structures have been found to exhibit high affinity for various receptor subtypes including the 5-HT.sub.2 receptor, the 5-HT.sub.1A receptor, the alpha.sub.1 receptor the dopamine receptor or a combination of these and may therefore be useful for treating CNS system, cardiovascular system and gastrointestinal disorders.

  通式I的吡哌啉衍生物 其中R.sup.1代表取代苯基，1-或2-二氮杂萘基，氮杂萘基或二氮杂萘基；n为1、2、3或4；X为--O--或 其中R.sup.2为氢、C.sub.1-6-烷基或C.sub.3-8-环烷基；Y为.dbd.O、.dbd.S或.dbd.NZ，其中Z为氢、C.sub.1-6-烷基或--CN，R.sup.3从一组中选择，该组包括各种结构已被发现对各种受体亚型表现出高亲和力，包括5-HT.sub.2受体，5-HT.sub.1A受体，alpha.sub.1受体，多巴胺受体或这些受体的组合，因此可能对治疗中枢神经系统，心血管系统和胃肠道疾病有用。
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF TRAZODONE AND HYDROCHLORIDE SALT THEREOF<br/>[FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE TRAZODONE ET SON SEL DE CHLORHYDRATE
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2015110883A1

  公开（公告）日：2015-07-30

  The present invention provides an improved process for preparation of the substantially pure trazodone and its hydrochloride salt. The process comprises reaction of the compound- Π (as described) with the compound-Ill (as described) optionally in the presence of an inorganic base, and a catalyst; wherein in the said process the trazodone free base and/or its hydrochloride salt are isolated by precipitation at lower temperature. The improved process for the preparation of trazodone hydrochloride (the compound I) provides the product with total amount of alkylating substances (as described herein) as impurity in less than 10 ppm. The improved process for the preparation of trazodone hydrochloride (the compound I) provides the product with total amount of l-(3-chlorophenyl)-4-(3-chloropropyl) piperazine as an impurity in less than 2.5 ppm.

  本发明提供了一种改进的制备几乎纯曲唑酮及其盐酸盐的过程。该过程包括将化合物-Π（如所述）与化合物-III（如所述）在无机碱和催化剂的存在下反应；在该过程中，曲唑酮游离碱和/或其盐酸盐通过在较低温度下沉淀而得到。制备曲唑酮盐酸盐（化合物I）的改进过程将烷基化物（如本文所述）的总量作为杂质控制在不到10ppm。制备曲唑酮盐酸盐（化合物I）的改进过程将1-(3-氯苯基)-4-(3-氯丙基)哌嗪的总量作为杂质控制在不到2.5ppm。
• Piperazinylalkoxyindanes and acid addition salts thereof
  申请人：MITSUBISHI KASEI CORPORATION

  公开号：EP0021368A1

  公开（公告）日：1981-01-07

  Piperazinylalkoxyindanes having the general formula wherein n is an integer of 3 or 4; R1 is hydrogen, halogen, alkyl, alkoxy, hydroxy, phenyl or nitro; and R2 is phenyl or pyridyl optionally having at least one substituent selected from the group consisting of halogen, trifluoromethyl, alkoxy and alkylcarbonyl, and acid addition salts thereof are disclosed, which have anti-anxiety activity and are effective as sedatives.

  通式如下的哌嗪基烷氧基茚满酮 其中 n 是 3 或 4 的整数；R1 是氢、卤素、烷基、烷氧基、羟基、苯基或硝基；R2 是苯基或吡啶基，可选择具有至少一个从卤素、三氟甲基、烷氧基和烷基羰基组成的组中选出的取代基，本发明公开了这些化合物及其酸加成盐，它们具有抗焦虑活性，可有效用作镇静剂。
• Crystalline nefazodone hydrochloride dihydrate and process for the preparation thereof
  申请人：Finaf 92, S.A.

  公开号：EP1000944A1

  公开（公告）日：2000-05-17

  A crystalline form of nefazodone and a process for the preparation thereof are disclosed. The crystalline form, or crystalline nefazodone hydrochloride dihydrate, has the chemical name of 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-ethyl-2,4-dihydro-4-(2-phenoxyethyl)-3H-1,2,4-triazol-3-one hydrochloride dihydrate and formula The process comprises preparing the crystalline nefazodone hydrochloride dihydrate by crystallising nefazodone hydrochloride dihydrate from an organic solvent/water mixture comprising at least 0.2 parts by volume of an organic solvent for each part by volume of water.

  本文公开了一种奈法佐酮的结晶形式及其制备方法。该结晶形式或结晶盐酸奈法佐酮二水合物的化学名称为 2-[3-[4-(3-氯苯基)-1-哌嗪基]丙基]-5-乙基-2,4-二氢-4-(2-苯氧乙基)-3H-1,2,4-三唑-3-酮盐酸盐二水合物，其化学式为 该工艺包括通过从有机溶剂/水混合物中结晶盐酸奈法佐酮二水合物来制备结晶盐酸奈法佐酮二水合物，有机溶剂/水混合物的体积比为每份水至少 0.2 份有机溶剂。
• New 8-aminoalkyl derivatives of purine-2,6-dione with arylalkyl, allyl or propynyl substituents in position 7, their 5-HT1A, 5-HT2A, and 5-HT7 receptor affinity and pharmacological evaluation
  作者：Grażyna Chłoń-Rzepa、Paweł Żmudzki、Grzegorz Satała、Beata Duszyńska、Anna Partyka、Dagmara Wróbel、Magdalena Jastrzębska-Więsek、Anna Wesołowska、Andrzej J. Bojarski、Maciej Pawłowski、Paweł Zajdel

  DOI：10.1016/s1734-1140(13)70960-5

  日期：2013.1

  Background: Our previous studies in a group of arylpiperazine derivatives of 1,3-dimethyl-3,7-dihydro-purine-2,6-diones, aimed at chemical diversification of the purine-2,6-dione by introduction of hydrophobic substituent in a 7- or 8- position or elongation of the linker length between arylpiperazine and purine core, allowed a selection of potent 5-HT1A, 5-HT2A and 5-HT7 receptor ligands displaying anxiolytic and antidepressant properties. Continuing our research in this field, in the present studies we designed a new series of 8-aminoalkylamino (15-35) and 8-arylpiperazinylpropoxy (36-42) derivatives of 7-substituted 1,3-dimethyl-3,7-dihydropurine-2,6-dione as potential 5-HT1A, 5-HT2A and 5-HT7 receptor ligands with potential psychotropic activity. Methods: Radioligand binding assays were employed for determining the affinity and the selectivity profile of the synthesized compounds for native 5-HT1A, 5-HT2A, and cloned 5-HT6 and 5-HT7 receptors. The functional activity of the selected compounds at 5-HT1A and 5-HT2A receptors was tested in the commonly used in vivo models. Antidepressant and anxiolytic properties were evaluated in the forced swim (FST) and the four-plate test (FPT) in mice, respectively. Results: Among the evaluated series, selected 7-benzyl-8-((4-(4-(3-chlorophenyl)piperazin-1-yl)butyl)amino)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione (21), a mixed 5-HT1A/5-HT2A/5-HT7 receptor ligand, produced an antidepressant-like effect in FST, and exerted anxiolytic-like activity in FPT. Another pharmacologically evaluated compound 42 (a mixed 5-HT1A/5-HT7 ligand) slightly, but non-significantly attenuated the immobility time of mice in FST and was devoid of activity in FPT. Conclusions: Study revealed advantage of mixed 5-HT1A/5-HT2A/5-HT7 receptor ligands over 5-HT1A/5-HT7 agents to display antidepressant- and anxiolytic-like activity. Modification of arylalkyl/allyl substituent in position 7 of purine-2,6-dione opens possibility for designing new 5-HT ligands with preserved p electron system and lower molecular weight.