ethyl piperazine-2-carboxylate dihydrochloride

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl piperazine-2-carboxylate dihydrochloride
• 英文别名: 2-ethyloxycarbonylpiperazine dihydrochloride；piperazin-2-yl-carboxylic acid ethyl ester dihydrochloride；ethyl 2-piperazinecarboxylate dihydrochloride；2-piperazinecarboxylic acid ethyl ester dihydrochloride；Ethyl piperazine-2-carboxylate hydrochloride；ethyl piperazine-2-carboxylate;hydrochloride
• 化学式: C₇H₁₄N₂O₂*2ClH
• 分子量: 231.122
• InChiKey: WQIUHSNASYOALY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.47
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  50.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl piperazine-2-carboxylate dihydrochloride 在 盐酸 、 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 18.0h， 生成 1-(2-chlorobenzyl)-2-ethoxycarbonylpiperazine
  参考文献：
  名称：

  Design and Synthesis of Imidazoline Derivatives Active on Glucose Homeostasis in a Rat Model of Type II Diabetes. 1. Synthesis and Biological Activities of N-Benzyl-N ‘-(arylalkyl)-2-(4‘,5‘-dihydro-1‘H-imidazol-2‘-yl)piperazines

  摘要：

  The physiopathology of non-insulin-dependent diabetes mellitus is associated with a dysfunction in the regulation of insulin secretion. The alpha(2)-adrenoceptors have been reported to be involved in this alteration, although at-antagonists containing an imidazoline ring may stimulate insulin secretion independently of alpha(2)-adrenoceptor blockage. Recently, a new ''imidazoline-binding site'' involved in the control of K+-ATP channels in the B cell has been proposed. In the course of searching for new antidiabetic agents, 1-alkyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazines, 1-benzyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl) and 1-benzyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)-4-benzylpiperazines have been designed and evaluated as potential adrenoceptor antagonists. Pharmacological evaluation was performed in vivo using glucose tolerance tests performed on a rat model of type II diabetes obtained by injection of a low dose (35 mg/kg) of streptozotocin (STZ). For some compounds, binding experiments were performed on alpha(2) adrenoceptors and I-1 and I-2 imidazoline-binding sites. The biological and physicochemical data have been combined with molecular modeling studies to establish structure-activity relationships. The most active compound was 1-(2',4'-dichlorobenzyl)-2 (4',5'-dihydro-1'H-imidazol-2'-yl)-4-methylpiperazine (7f); intraperitoneal administration (100 mu mol/kg) of 7f strongly improved glucose tolerance in STZ diabetic rats. This effect seemed at least partly mediated by a significant increase of insulin secretion. Other compounds of the same family (7b, 16f, 23b) have also shown potent activity. We found no correlation between in vivo antihyperglycemic properties and in vitro affinities for alpha(2)-adrenoceptors or I-1 and I-2 binding sites. These compounds can be considered as antihyperglycemic agents potentially useful for treatment of type II diabetes and are currently under complementary investigation.

  DOI：

  10.1021/jm9608624
• 作为产物：
  描述：

  1,4-二苄基哌嗪-2-羧酸乙酯 在 盐酸 、 palladium on activated charcoal 、 氢气 作用下， 以 乙醇 、 水 为溶剂， 反应 12.0h， 以97%的产率得到ethyl piperazine-2-carboxylate dihydrochloride
  参考文献：
  名称：

  一种2-羧基哌嗪连接的他克林-8-氨基(羟基)喹啉衍生物及制备与应用

  摘要：

  本发明涉及化学合成技术领域，具体涉及一种2‑羧基哌嗪连接的他克林‑8‑氨基(羟基)喹啉衍生物及制备与应用。所述的2‑羧基哌嗪连接的他克林‑8‑氨基(羟基)喹啉衍生物，为式I化合物或其药学上可接受的盐，以及所述的式I化合物或其药学上可接受的盐的溶剂化合物、对映异构体、非对映异构体、互变异构体或其任意比例的混合物，包括外消旋混合物。经药理试验证实该类化合物对乙酰胆碱酯酶和丁酰胆碱酯酶活性具有抑制作用，属于胆碱酯酶抑制剂；并且还能对β‑淀粉样蛋白的自聚集产生抑制作用，对乙酰胆碱的水解和β‑淀粉样蛋白的自聚集起到延缓作用，进而提高了乙酰胆碱在突触的作用，最终实现有效治疗阿茨海默症的目的。

  公开号：

  CN110041309B
• 作为试剂：
  描述：

  盐酸 、 N,N'-di-tert-butyloxycarbonylpiperazine-2-carboxylic acid ethyl ester 在 ice 、 三乙胺 、 2-(叔丁氧羰基氧亚氨基)-2-苯乙腈 、 ethyl piperazine-2-carboxylate dihydrochloride 、 四氢呋喃 、 二氯甲烷 、 magnesium sulfate 、 silica gel 、 methanol-dichloromethane 作用下， 以 乙醇 为溶剂， 反应 88.0h， 以to thereby give the title compound as an oily product (3.14 g, 49%)的产率得到1-N-Boc-3-哌嗪羧酸乙酯
  参考文献：
  名称：

  Pyrazole derivatives having a pyridazine and pyridine functionality

  摘要：

  本发明是关于一种强的血小板聚集抑制剂，该抑制剂不会抑制COX-1或COX-2。此外，本发明提供了由式（I）表示的化合物，该化合物的盐，以及该化合物或其盐的溶剂或水合物。还提供了含有任何一种化合物、盐或溶剂的药物，以及预防和/或治疗缺血性疾病的药物，其中包含任何一种化合物、盐或溶剂或水合物。

  公开号：

  US07622471B2

文献信息

• Sulfonamide derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06359134B1

  公开（公告）日：2002-03-19

  The present invention provides compounds which specifically inhibit FXa, which are effective when orally administered and which are useful as a safe medicine for the prevention or treatment of diseases caused by thrombus or infarction. Compounds of this invention are piperazinones of the formula: wherein R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; the ring A is an optionally substituted divalent nitrogen-containing heterocyclic group, in addition to being substituted by the group of the formula: and the group of the formula: Y is an optionally substituted divalent hydrocarbon group or an optionally substituted divalent heterocyclic group; X is a direct bond or an optionally substituted alkylene chain; Z is (1) an amino group substituted with an optionally substituted hydrocarbon group, (2) an optionally substituted imino group or (3) an optionally substituted nitrogen-containing heterocyclic group; provided that when X is a direct bond and Z is an optionally substituted 6-membered nitrogen-containing aromatic heterocyclic group, Y is an optionally substituted divalent hydrocarbon group or an optionally substituted divalent unsaturated heterocyclic group; or a salt thereof.

  本发明提供了一种化合物，该化合物特异性地抑制FXa，口服给药有效，并且用作预防或治疗由血栓或梗死引起的疾病的药物是安全的。本发明的化合物是哌嗪酮的公式： 其中R1是可选地取代的烃基或可选地取代的杂环基；环A是除了被公式：的基团取代的之外的可选地取代的二价含氮杂环基： 和公式的基团： Y是可选地取代的二价烃基或可选地取代的二价杂环基；X是直接键或可选地取代的亚烷基链；Z是（1）与可选地取代的烃基取代的氨基，（2）可选地取代的亚氨基或（3）可选地取代的含氮杂环基；当X是直接键并且Z是可选地取代的6-成员含氮芳香杂环基时，Y是可选地取代的二价烃基或可选地取代的二价不饱和杂环基；或其盐。
• Trisubstituted piperazine compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04997836A1

  公开（公告）日：1991-03-05

  Novel trisubstituted piperazine compounds of the formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are lower alkyl groups; A is a phenyl group, a hydrocarbon group formed by condensation of two or three 5- to 8-membered rings, a monocyclic 5- to 8-membered heterocyclic group containing 1 to 3 hetero-atoms selected from the class consisting of nitrogen, oxygen and sulfur, a dicyclic heterocyclic group formed by condensation of a benzene ring with a 5- to 8-membered hetero-ring containing 1 to 3 hetero-atoms selected from the class consisting of nitrogen, oxygen and sulfur, a tricyclic heterocyclic group formed by condensation of (i) a 5- to 8-membered hetero-ring containing 1 to 3 hetero-atoms selected from the class consisting of nitrogen, oxygen and sulfur, and (ii) a benzene ring, and (iii) a benzene ring or a 5- to 8-membered hetero-ring containing 1 to 3 hetero-atoms selected from the class consisting of nitrogen, oxygen and sulfur, or a styryl group of the formula: Ar--CR.sup.4 .dbd.CR.sup.5 -- wherein Ar is a phenyl group, and R.sup.4 and R.sup.5 are independently hydrogen or a lower alkyl group, the phenyl group represented by A or Ar, the hydrocarbon group represented by A, the monocyclic 5- to 8-membered heterocyclic group represented by A, the dicyclic heterocyclic group represented by A and the tricyclic heterocyclic group represented by A being unsubstituted or substituted by one or more substituents selected from the class consisting of a lower alkyl group, a halo lower alkyl group, a hydroxy lower alkyl group, an acyloxy lower alkyl group, a lower alkoxy lower alkyl group, a lower alkoxy group, a halo lower alkoxy group, a lower alkoxycarbonyl lower alkoxy group, a lower alkenyloxy group, aralkyloxy group, a lower alkoxy lower alkoxy group, a lower alkoxycarbonyl group, carboxyl group, carbamoyl group, an N,N-di-lower alkylcarbamoyl group, an N-lower alkylcarbamoyl group, halo group, cyano group, nitro group, hydroxy group, acyloxy group, amino group, a lower alkylsulfonylamino group, acylamino group, a lower alkoxycarbonylamino group, acyl group, mercapto group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group and oxo group; X is methylene group, carbonyl group or thiocarbonyl group and G is a group of the formula: --CH.sub.2 --.sub.n Z--R.sup.6 wherein n is an integer of 0 to 2, Z is a chemical bond, O, S, SO, SO.sub.2, CO, COO, OCO, OCONR.sup.7, CONR.sup.7 or NR.sup.7 (wherein R.sup.7 is hydrogen, a lower alkyl group, a lower haloalkyl group, a lower alkenyl group or a lower alkoxycarbonyl group), and R.sup.6 is hydrogen, a lower alkyl group, a lower haloalkyl group or a lower alkenyl group, provided that, when n is O and Z is chemical bond, R.sup.6 is not hydrogen or a lower alkyl group are useful as a platelet activating factor antagonist.

  新型三取代哌嗪化合物的化学式（I）及其药用盐：##STR1## 其中R.sup.1、R.sup.2和R.sup.3为较低的烷基基团；A为苯基、由两个或三个5至8成员环缩合形成的烃基团、含有1至3个异原子（选自氮、氧和硫）的单环5至8成员杂环基团、由苯环与含有1至3个异原子（选自氮、氧和硫）的5至8成员杂环环缩合形成的二环杂环基团、由（i）含有1至3个异原子（选自氮、氧和硫）的5至8成员杂环环和（ii）苯环缩合形成的三环杂环基团，以及（iii）苯环或含有1至3个异原子（选自氮、氧和硫）的5至8成员杂环环或化学式为Ar--CR.sup.4 .dbd.CR.sup.5--的苯乙烯基团：其中Ar为苯基，R.sup.4和R.sup.5独立地为氢或较低的烷基基团，由A或Ar表示的苯基，由A表示的烃基团，由A表示的单环5至8成员杂环基团，由A表示的二环杂环基团以及由A表示的三环杂环基团未被取代或被选自较低烷基基团、卤代较低烷基基团、羟基较低烷基基团、酰氧基较低烷基基团、较低烷氧基较低烷基基团、较低烷氧基、卤代较低烷氧基、较低烷氧羰基较低烷氧基、较低烯氧基、芳基氧基、较低烷氧较低烷氧基、较低烷氧羰基基团、羧基、氨基、较低烷基磺酰氨基、酰胺基、较低烷氧羰胺基、酰基、巯基、较低烷硫基、较低烷硫氧基、较低烷磺基和氧代基所选的一个或多个取代基所取代；X为亚甲基基团、羰基或硫代羰基，G为化学式：--CH.sub.2--.sub.n Z--R.sup.6，其中n为0至2的整数，Z为化学键、O、S、SO、SO.sub.2、CO、COO、OCO、OCONR.sup.7、CONR.sup.7或NR.sup.7（其中R.sup.7为氢、较低烷基基团、较低卤代烷基基团、较低烯基基团或较低烷氧羰基基团），R.sup.6为氢、较低烷基基团、较低卤代烷基基团或较低烯基基团，但当n为O且Z为化学键时，R.sup.6不为氢或较低烷基基团，可用作血小板活化因子拮抗剂。
• Diamide compound and drugs containing the same
  申请人：Kowa Co., Ltd.

  公开号：US06340682B1

  公开（公告）日：2002-01-22

  The present invention provides diamide derivatives represented by the following general formula (1): wherein A is a phenyl group or the like, which may be substituted, B is —CH═CH—, —C═C—, —(CH═CH)2—, —C≡C—CH═CH—, —CH═CH—C≡C—, phenylene or the like, and W is or and medicines comprising such a compound. These compounds have an excellent inhibitory effect on the production of an IgE antibody and are hence useful as antiallergic agents and the like.

  本发明提供了以下一般式（1）所代表的二酰胺衍生物： 其中A是苯基或类似物，可以被取代，B是—CH═CH—，—C═C—，—(CH═CH)2—，—C≡C—CH═CH—，—CH═CH—C≡C—，苯基或类似物，W是 或 以及包含这种化合物的药物。这些化合物对IgE抗体的产生具有出色的抑制作用，因此可用作抗过敏药物等。
• [EN] COMPOUNDS, THEIR PHARMACEUTICAL COMPOSITIONS AND THEIR USES AS IDH1 MUTANTS INHIBITORS FOR TREATING CANCERS<br/>[FR] COMPOSÉS, COMPOSITIONS PHARMACEUTIQUES DE CEUX-CI ET UTILISATION DE CES COMPOSÉS COMME INHIBITEURS MUTANTS D'IDH1 DANS LE TRAITEMENT DE CANCERS
  申请人：AGIOS PHARMACEUTICALS INC

  公开号：WO2012171506A1

  公开（公告）日：2012-12-20

  Provided are compounds of formula (I), wherein X, Y, Z, W, V, R2, R3 and m are defined as in the description. Their pharmaceutical compositions and their uses as IDH1 mutants inhibitors for treating cancers are also provided.

  提供了公式（I）的化合物，其中X、Y、Z、W、V、R2、R3和m的定义如描述中所述。还提供了它们的药物组合物以及它们作为IDH1突变体抑制剂用于治疗癌症的用途。
• Structure−Activity Relationships in Platelet-Activating Factor. 12. Synthesis and Biological Evaluation of Platelet-Activating Factor Antagonists with Anti-HIV-1 Activity
  作者：Nawal Serradji、Marc Martin、Okkacha Bensaid、Salvatore Cisternino、Christophe Rousselle、Nathalie Dereuddre-Bosquet、Jack Huet、Catherine Redeuilh、Aazdine Lamouri、Chang-Zhi Dong、Pascal Clayette、Jean-Michel Scherrmann、Dominique Dormont、Françoise Heymans

  DOI：10.1021/jm040860g

  日期：2004.12.1

  The HIV-1 central nervous system infection leads to the onset of neurological impairments called AIDS dementia complex (ADC). PAF plays an important role in this pathology, as it is an HIV-1-induced neurotoxin produced by infected or activated macrophages and microglia, in the brain. We previously reported that PAF-antagonists bearing a trisubstituted piperazine presented in vitro anti-HIV-1 activity

  HIV-1中枢神经系统感染导致称为AIDS痴呆综合症（ADC）的神经功能障碍的发作。PAF在这种病理学中起着重要作用，因为它是由HIV-1诱导的神经毒素，它是由感染或激活的巨噬细胞和小胶质细胞在大脑中产生的。我们以前报道过，带有三取代哌嗪的PAF拮抗剂在人巨噬细胞中具有体外抗HIV-1活性。为了改善我们的先导化合物1a的药理活性，我们修改了其氨基甲酸酯功能并评估了其抗逆转录病毒和抗PAF活性。一种氨基甲酸酯衍生物（10c）具有相似的抗病毒活性，但具有更高的抗PAF效力，而具有酰脲功能的4a具有增强的抗病毒活性，可以视为纯的抗逆转录病毒药物，因为它不表现出PAF拮抗作用。此外，我们使用原位小鼠脑灌注方法及其静脉内和口服给药后的血浆浓度，测量了1a穿过血脑屏障的能力。测得的转运参数（K（in））证明1a能够穿越该生物屏障，但是药代动力学研究表明其在大鼠体内的生物利用度较弱。