2-氨基-1-哌啶-1-基乙酮盐酸盐 | 5437-48-9

• 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
• 中文名称: 2-氨基-1-哌啶-1-基乙酮盐酸盐
• 中文别名: 2-氨基-1-哌啶-1-乙酮盐酸盐
• 英文名称: 2-amino-1-piperidino-1-ethanone hydrochloride
• 英文别名: 2-amino-1-(piperidin-1-yl)ethanone hydrochloride；2-amino-1-(piperidin-1-yl)ethan-1-one hydrochloride；1-glycyl-piperidine; hydrochloride；2-amino-1-piperidin-1-ylethanone;hydrochloride
• CAS: 5437-48-9
• 化学式: C₇H₁₄N₂O*ClH
• mdl: MFCD07366743
• 分子量: 178.662
• InChiKey: OINZXLOVUKWACU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.66
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.857
• 拓扑面积：
  46.3
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933399090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存放在室温下，干燥且密封。

反应信息

• 作为反应物：
  描述：

  2-氨基-1-哌啶-1-基乙酮盐酸盐 在 2-氟吡啶 、 三氟甲磺酸酐 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 17.83h， 生成 6-bromo-3-(piperidin-1-yl)imidazo[1,2-a]pyrimidine
  参考文献：
  名称：

  三氟甲磺酸酐区域选择性合成3-氨基咪唑并[1,2-a]嘧啶

  摘要：

  摘要 据报道，通过三氟甲磺酸酐介导的酰胺活化和分子内环化的3-氨基咪唑并[1,2- a ]嘧啶的区域选择性合成。添加的吡啶碱的性质允许从简单的普通前体获得两种区域异构体。该方法容许一定范围的官能团，并提供对新型杂环支架的访问。 据报道，通过三氟甲磺酸酐介导的酰胺活化和分子内环化的3-氨基咪唑并[1,2- a ]嘧啶的区域选择性合成。添加的吡啶碱的性质允许从简单的普通前体获得两种区域异构体。该方法容许一定范围的官能团，并提供对新型杂环支架的访问。

  DOI：

  10.1055/s-0036-1588425
• 作为产物：
  描述：

  (2-氧代-2-哌啶-1-基-乙基)-氨基甲酸叔丁酯 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 生成 2-氨基-1-哌啶-1-基乙酮盐酸盐
  参考文献：
  名称：

  环状AMP磷酸二酯酶的抑制剂。4. lixazinone（N-cyclohexyl-N-methyl-4-[（1,2,3,5-tetrahydro-2-oxoimidazo [2,1-b] quinazolin-7-yl）-]的合成和评价氧]丁酰胺，RS-82856）。

  摘要：

  环状AMP磷酸二酯酶（cAMP PDE）抑制剂和强心药lixazinone（N-环己基-N-甲基-4-[（1,2,3,5-四氢-2-氧代咪唑[2,1-b]喹唑啉-7-发现）））氧基]丁酰胺，RS-82856，1）及其酸和碱加成盐在适用于静脉内给药的制剂中溶解性不足。这些结果促使人们对具有提高的水溶性的潜在前药进行了研究，旨在通过三种不同的机制释放1：（1）α-羧酰胺的脱羧；（2）可溶的N-1-（酰氧基）甲基或（N，N-二烷基氨基）甲基部分的水解损失；或（3）胍基酯或酰胺的分子内封闭。通过三个标准对目标化合物作为1的传输系统进行了评估：（1）在生理条件下化学转化率为1；（2）在固定时间点抑制IV型cAMP PDE；（3）通过静脉内和口服给予的麻醉犬体内的变力活性。发现从4a（系列1）释放1太慢，以至于不能作为1的前药使用，因为脱羧只能由强酸诱导，而在强酸条件下发现水解开环剧烈竞争。相反，尽管

  DOI：

  10.1021/jm00119a015

文献信息

• Discovery of Potent and Selective Allosteric Inhibitors of Protein Arginine Methyltransferase 3 (PRMT3)
  作者：H. Ümit Kaniskan、Mohammad S. Eram、Kehao Zhao、Magdalena M. Szewczyk、Xiaobao Yang、Keith Schmidt、Xiao Luo、Sean Xiao、Miao Dai、Feng He、Irene Zang、Ying Lin、Fengling Li、Elena Dobrovetsky、David Smil、Sun-Joon Min、Jennifer Lin-Jones、Matthieu Schapira、Peter Atadja、En Li、Dalia Barsyte-Lovejoy、Cheryl H. Arrowsmith、Peter J. Brown、Feng Liu、Zhengtian Yu、Masoud Vedadi、Jian Jin

  DOI：10.1021/acs.jmedchem.7b01674

  日期：2018.2.8

  disclosed a highly potent, selective, and cell-active allosteric inhibitor of PRMT3, compound 4. Here, we report comprehensive structure-activity relationship studies that target the allosteric binding site of PRMT3. We conducted design, synthesis, and evaluation of novel compounds in biochemical, selectivity, and cellular assays that culminated in the discovery of 4 and other highly potent (IC50 values:

  PRMT3催化各种蛋白质精氨酸残基的不对称二甲基化。它对于核糖体的成熟至关重要，并且与多种疾病有关。我们最近公开了PRMT3化合物4的高效，选择性和细胞活性变构抑制剂。在这里，我们报道了针对PRMT3变构结合位点的全面的构效关系研究。我们在生化，选择性和细胞分析中进行了新化合物的设计，合成和评估，最终发现了4种和其他高效（IC50值：〜10-36 nM），选择性和细胞活性的变构抑制剂。 PRMT3（化合物29、30、36和37）。此外，我们生成了与这些有效抑制剂非常相似的化合物，但它们作为阴性对照的效力却大大降低了（化合物49-51）。这些抑制剂和阴性对照是生物医学界进一步研究PRMT​​3的生物学功能和疾病关联的有价值的化学工具。
• Synthesis of 1,2,3-thiadiazoles
  作者：Norton P. Peet、Shyam Sunder

  DOI：10.1002/jhet.5570120620

  日期：1975.12

  hydroxide yielded hydrazones rather than thiadiazoles. The reaction of α-[(ethoxycarbonyl)hydrazono]benzenepropanoic acid (25) with thionyl chloride yielded 5-phenyl-1,2,3-thiadiazole-4-carbocylic acid (26a), the corresponding acid chloride 26b, and 5-(phenylmethyl)-2H-1,3,4-oxadiazine-2,6(3H)dione (27). The yields of 26a, 26b, and 27 were dependent on the reaction conditions employed. Oxadiazine 27 could also

  探索了几种用于制备某些4,5-二取代-1,2,3-噻二唑的方法。苯氧基乙酰氯与重氮乙酰酰胺的反应产生了α-重氮-β-酮乙酰胺，将其与硫化氢和氢氧化铵环合成4-甲酰胺基-5-苯氧基甲基-1,2,3-噻二唑。然而，用硫化氢和氢氧化铵处理α-重氮-α-苯甲酰基乙酰胺会产生，而不是噻二唑。α-[（乙氧羰基）肼基]苯丙酸（25）与亚硫酰氯反应生成5-苯基-1,2,3-噻二唑-4-碳氢酸（26a），相应的酰氯26b和5-（苯甲基）-2 H -1,3,4-恶二嗪-2,6（3 H）二酮（27）。26a，26b和27的产率取决于所采用的反应条件。恶二嗪27也可以与亚硫酰氯转化为酰氯26b。用乙硼烷还原1-（[5-（4-氯苯氧基）甲基-1,2,3-噻二唑-4-基]-羰基）哌啶（10b），得到硼配合物，产生1-（[5-（（从乙醇中重结晶后得到4-氯苯氧基）甲基）-1，2，3-噻二唑-4-基]甲基）哌啶（31）。
• Aminoalkyl-pyrazinones and-pyridones as thrombin inhibitors
  申请人：Feurer Achim

  公开号：US20070099927A1

  公开（公告）日：2007-05-03

  The invention relates to compounds of formula (I) wherein A, B, X, R 1 , R 2 , G, R 3 , D and E have the meaning as cited in the description and the claims. Said compounds are useful as coagulants. The invention also relates to the production and use thereof as medicament.

  本发明涉及式(I)的化合物，其中A，B，X，R1，R2，G，R3，D和E的含义如描述和权利要求中所述。所述化合物可用作凝血剂。本发明还涉及其制备和用作药物的用途。
• Design, Synthesis, and Structure−Activity Relationships of Macrocyclic Hydroxamic Acids That Inhibit Tumor Necrosis Factor α Release in Vitro and in Vivo
  作者：Chu-Biao Xue、Matthew E. Voss、David J. Nelson、James J.-W. Duan、Robert J. Cherney、Irina C. Jacobson、Xiaohua He、John Roderick、Lihua Chen、Ronald L. Corbett、Li Wang、Dayton T. Meyer、Kenneth Kennedy、William F. DeGrado、Karl D. Hardman、Christopher A. Teleha、Bruce D. Jaffee、Rui-Qin Liu、Robert A. Copeland、Maryanne B. Covington、David D. Christ、James M. Trzaskos、Robert C. Newton、Ronald L. Magolda、Ruth R. Wexler、Carl P. Decicco

  DOI：10.1021/jm010127e

  日期：2001.8.1

  To search for TNF-alpha (tumor necrosis factor alpha) converting enzyme (TACE) inhibitors, we designed a new class of macrocyclic hydroxamic acids by linking the PI and P2 ' residues of acyclic anti-succinate-based hydroxamic acids. A variety of residues including amide, carbamate, alkyl, sulfonamido, Boc-amino, and amino were found to be suitable P1-P2 ' linkers. With an N-methylamide at P3 ', the 13-16-membered macrocycles prepared exhibited low micromolar activities in the inhibition of TNF-alpha release from LPS-stimulated human whole blood. Further elaboration in the P3 ' -P4 ' area using the cyclophane and cyclic carbamate templates led to the identification of a number of potent analogues with IC50 values of less than or equal to 0.2 muM in whole blood assay (WBA). Although the P3 ' area can accommodate a broad array of structurally diversified functional groups including polar residues, hydrophobic residues, and amino and carboxylic acid moieties, in both the cyclophane series and the cyclic carbamate series, a glycine residue at P3 ' was identified as a critical structural component to achieve both good in vitro potency and good oral activity. With a glycine residue at P3 ', an N-methylamide at P4 ' provided the best cyclophane analogue, SL422 (WBA IC50 = 0.22 muM, LPS-mouse ED50 = 15 mg/kg, po), whereas a morpholinylamide at P4 ' afforded the most potent and most orally active cyclic carbamate analogue, SP057 (WBA IC50 = 0.067 muM, LPS-mouse ED50 = 2.3 mg/kg, po). Further profiling for SL422 and SP057 showed that these macrocyclic compounds are potent TACE inhibitors, with K-i values of 12 and 4.2 nM in the porcine TACE assay, and are broad-spectrum MMP inhibitors. Pharmacokinetic studies in beagle dogs revealed that SL422 and SP057 are orally bioavailable, with oral bioavailabilities of 11% and 23%, respectively.
• Carbonic anhydrase inhibitors: Design, synthesis, kinetic, docking and molecular dynamics analysis of novel glycine and phenylalanine sulfonamide derivatives
  作者：İsmail Fidan、Ramin Ekhteiari Salmas、Mehmet Arslan、Murat Şentürk、Serdar Durdagi、Deniz Ekinci、Esra Şentürk、Sedat Coşgun、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2015.10.009

  日期：2015.12

  The inhibition of two human cytosolic carbonic anhydrase isozymes I and II, with some novel glycine and phenylalanine sulfonamide derivatives were investigated. Newly synthesized compounds G1-4 and P1-4 showed effective inhibition profiles with K-I values in the range of 14.66-315 mu M for hCA I and of 18.31-143.8 mu M against hCA II, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico docking studies were applied. Atomistic molecular dynamic simulations were performed for docking poses which utilize to illustrate the inhibition mechanism of used inhibitors into active site of CAII. These sulfonamide containing compounds generally were competitive inhibitors with 4-nitro-phenylacetate as substrate. Some investigated compounds here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide, sulfanilamide or mafenide and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms which have not been yet assayed for their interactions with such agents. (C) 2015 Elsevier Ltd. All rights reserved.