2,2-二甲基-1,2,5,6-四氢吡嗪 | 153627-83-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 2,2-二甲基-1,2,5,6-四氢吡嗪
• 英文名称: 2,2-dimethyl-1,2,5,6-tetrahydropyrazine
• 英文别名: 6,6-dimethyl-1,2,3,6-tetrahydropyrazine；1,2,5,6,-tetrahydro-2,2-dimethylpyrazine；6,6-dimethyl-2,3-dihydro-1H-pyrazine
• CAS: 153627-83-9
• 化学式: C₆H₁₂N₂
• mdl: MFCD09030637
• 分子量: 112.175
• InChiKey: CTZVYIJJRBEMRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.833
• 拓扑面积：
  24.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,2-二甲基-1,2,5,6-四氢吡嗪 在 palladium on activated charcoal 甲酸 、 氢气 、 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 20.0h， 生成 齐洛那平
  参考文献：
  名称：

  Enhanced D1 Affinity in a Series of Piperazine Ring Substituted 1-Piperazino-3-Arylindans with Potential Atypical Antipsychotic Activity

  摘要：

  A study of the effect of aromatic substitution on D-1 and D-2 affinity in a series of previously reported trans-1-piperazino-3-phenylindans shows similar structure-activity relationships for the two receptor sites. 6-Substituted derivatives have affinity for both receptors, and 6-chloro- or B-fluoro-substituted derivatives show preference for D-1 receptors. D-1 affinity and selectivity are significantly increased in a series of new piperazine ring substituted derivatives. Potent D-1 and D-2 antagonism in vivo are confined to derivatives with relatively small substituents in the 2-position of the piperazine ring (e.g. 2-methyl, 2,2-dimethyl, 2-spirocyclobutyl or 2-spirocyclopentyl). Consequently, the effect of aromatic substitution is examined in a series of 1-(2,2-dimethylpiperazino)-3-arylindans. All these compounds except the 4-, 5-, 7- and 4'-chlorosubstituted derivatives have potent D-1 affinity (IC50's below 10 nM) and the majority of the compounds antagonize SK&F 38393-induced circling in 6-OHDA-lesioned rats with ED(50) values about 1 mu mol/kg. In vitro all compounds show preference for D-1 receptors, but in vivo they are equally effective as D-1 and D-2 antagonists. The compounds have high affinity for 5-HT2 receptors and selected compounds show high affinity for alpha(1) adrenoceptors. Furthermore, a subgroup consisting of (-)-38, (-)-39, (-)-41, and (-)-54 does not induce catalepsy in rats. These compounds have the potential of being ''atypical'' antipsychotics and have consequently been selected for further studies. The non-receptor-blocking enantiomers are shown to be inhibitors of DA and NE uptake in accordance with previous observations in compounds unsubstituted in the piperazine ring. Two compounds, (+)-38 and (+)-40, block DA uptake with IC50 values below 10 nM. Finally, the observed structure-activity relationships are discussed in relation to previously published pharmacophore models for D-2 and 5-HT2 receptors. It is concluded that the piperazine substituents might induce a different binding mode at the dopamine receptor sites, perhaps only at the D-1 receptor site.

  DOI：

  10.1021/jm00022a004
• 作为产物：
  描述：

  2-溴-2-甲基丙醛 生成 2,2-二甲基-1,2,5,6-四氢吡嗪
  参考文献：
  名称：

  1-piperazino-1,2-dihydroindene derivatives

  摘要：

  具有公式（I）的1-哌嗪基-1,2-二氢吲哚化合物的反式异构体，其中X和Y是氢，卤素，三氟甲基，烷基，烷基硫，三氟甲基硫，烷氧基，羟基，烷基磺酰基，氨基，烷基氨基，硝基或氰基；Ar是苯基，噻吩基或呋喃基，每个基团均可选择性地被取代；R1是氢，或可选地羟基取代的烷基，烯基，环烷基或环烷基烷基；R2是烷基，烯基，环烷基或环烷基烷基；或R1和R2共同形成与哌嗪环融合的5至7成员杂环，该环可以被羟基取代；R3是氢，烷基，烯基，环烷基或环烷基烷基；或R2和R3共同形成与哌嗪环螺合的3至7成员碳环，该环与哌嗪环融合；R4是氢或烷基。该发明的化合物在多巴胺D1受体上具有强大的拮抗作用，并且在治疗中枢神经系统疾病，如精神病，精神分裂症（正性和负性症状），焦虑，抑郁，睡眠障碍，偏头痛，帕金森病或可卡因滥用方面具有用处。

  公开号：

  US05807855A1

文献信息

• Pharmaceutical compounds
  申请人：Folkes Adrian

  公开号：US20080076758A1

  公开（公告）日：2008-03-27

  Compounds of Formulae Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia and Ib for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  化合物Ia和Ib的结构，以及它们的立体异构体、几何异构体、互变异构体、溶剂合物、代谢产物和药学上可接受的盐，可用于抑制包括PI3K在内的脂质激酶，并用于治疗由脂质激酶介导的癌症等疾病。公开了使用化合物Ia和Ib进行体外、体内和体内诊断、预防或治疗哺乳动物细胞中的这类疾病，或相关的病理状况的方法。
• [EN] PROCESS FOR THE PREPARATION OF 2,2-DIMETHYLPIPERAZINE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE 2,2-DIMÉTHYLPIPÉRAZINE
  申请人：H LUNDBECK AS

  公开号：WO2019193134A1

  公开（公告）日：2019-10-10

  This invention relates to a novel chemical process for the synthesis of 2,2-dimethylpiperazine and the further transformation of 2,2-dimethylpiperazine into ferf-butyl-3,3-dimethylpiperazine-l- carboxylate-hemi-DL-tartrate.

  本发明涉及一种新型化学合成2,2-二甲基哌嗪的过程，并将2,2-二甲基哌嗪进一步转化为反式-叔丁基-3,3-二甲基哌嗪-1-羧酸半-DL-酒石酸盐。
• [EN] 1-PIPERAZINO-1,2-DIHYDROINDENE DERIVATIVES<br/>[FR] DERIVES DE 1-PIPERAZINO-1,2-DIHYDROINDENE
  申请人：H. LUNDBECK A/S

  公开号：WO1993022293A1

  公开（公告）日：1993-11-11

  (EN) Trans isomers of 1-piperazino-1,2-dihydroindene compounds having general formula (I), wherein X and Y are hydrogen, halogen, trifluoromethyl, alkyl, alkylthio, trifluoromethylthio, alkoxy, hydroxy, alkylsulfonyl, amino, alkylamino, nitro or cyano; Ar is a phenyl, thienyl or furyl group, each optionally substituted; R1 is hydrogen, or optionally hydroxy substituted alkyl, alkenyl, cycloalkyl or cycloalkylalkyl; R2 is alkyl, alkenyl, cycloalkyl, or cycloalkylalkyl; or R1 and R2 together form a 5 to 7-membered heterocyclic ring fused with the piperazine ring, which ring may be substituted with hydroxy; R3 is hydrogen, alkyl, r alkenyl, cycloalkyl or cycloalkylalkyl; or R2 and R3 together form a 3 to 7-membered carbocyclic ring which is spirofused to the piperazine ring; and R4 is hydrogen or alkyl; have potent antagonistic action on dopamine D1 receptors. The compounds are useful in the treatment of diseases in the central nervous system, in particular psychoses, schizophrenia (positive as well as negative symptoms), anxiety, depression, sleep disturbances, migraine, Parkinson's disease or cocaine abuse.(FR) Trans-isomères de composés de 1-pipérazine-1,2-dihydroindène répondant à la formule générale (I) dans laquelle X et Y représentent hydrogène, halogène, trifluorométhyle, alkyle, alkylthio, trifluorométhylthio, alcoxy, hydroxy, alkylsulfonyle, amino, alkylamino, nitro ou cyano; Ar représente un groupe phényle, thiényle ou furyle, chacun éventuellement substitué; R1 représente hydrogène ou alkyle, alcényle, cycloalkyle ou cycloalkylalkyle éventuellement substitué par hydroxy; R2 représente alkyle, alcényle, cycloalkyle ou cycloalkylalkyle; ou R1 et R2 forment ensemble un noyau hétérocyclique comprenant 5 à 7 éléments, fusionné avec le noyau pipérazine, ce noyau pouvant être substitué par hydroxy; R3 représente hydrogène, alkyle, alcényle, cycloalkyle ou cycloalkylalkyle; ou R2 et R3 forment ensemble un noyau carbocyclique comprenant 3 à 7 éléments qui est spiro-fusionné au noyau pipérazine; et R4 représente hydrogène ou alkyle. Ces composés présentent une activité antagoniste puissante par rapport aux récepteurs de dopamine D1. Ces composés peuvent être utilisés dans le traitement de maladies du système nerveux central, en particulier les psychoses, la schizophénie (symptômes positifs aussi bien que négatifs), l'anxiété, la dépression, les troubles du sommeil, la migraine, la maladie de Parkinson ou l'abus de cocaïne.

  (I)式中的1-哌嗪基-1,2-二氢茚化合物的顺式异构体，其中X和Y为氢、卤素、三氟甲基、烷基、烷硫基、三氟甲基硫基、烷氧基、羟基、烷基磺酰基、氨基、烷基氨基、硝基或氰基；Ar为苯基、噻吩基或呋喃基，每个基团均可选地被取代；R1为氢或可选地被羟基取代的烷基、烯基、环烷基或环烷基烷基；R2为烷基、烯基、环烷基或环烷基烷基；或R1和R2共同形成与哌嗪环融合的5到7元杂环，该环可能被羟基取代；R3为氢、烷基、烯基、环烷基或环烷基烷基；或R2和R3共同形成与哌嗪环融合的3到7元碳环，该环与哌嗪环螺合；R4为氢或烷基。这些化合物对多巴胺D1受体具有强烈的拮抗作用。这些化合物在治疗中枢神经系统疾病，特别是精神病、精神分裂症（正向和负向症状）、焦虑、抑郁、睡眠障碍、偏头痛、帕金森病或可卡因滥用方面有用。
• PHARMACEUTICAL COMPOUNDS
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：US20140309216A1

  公开（公告）日：2014-10-16

  Compounds of Formulae Ia, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  Ia式化合物及其立体异构体、几何异构体、互变异构体、溶剂化物、代谢物和药学上可接受的盐，可用于抑制脂质激酶，包括PI3K，并用于治疗由脂质激酶介导的癌症等疾病。公开了使用Ia式化合物的方法，用于哺乳动物细胞中的体外、原位和体内诊断、预防或治疗此类疾病或相关病理条件。
• WO2008/134035
  申请人：——

  公开号：——

  公开（公告）日：——