tert-butyl (3S)-3-methyl-5-oxo-piperazine-1-carboxylate

• 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: tert-butyl (3S)-3-methyl-5-oxo-piperazine-1-carboxylate
• 英文别名: tert-butyl (S)-3-methyl-5-oxopiperazine-1-carboxylate；tert-butyl (3S)-3-methyl-5-oxopiperazine-1-carboxylate
• 化学式: C₁₀H₁₈N₂O₃
• 分子量: 214.265
• InChiKey: CSDMPDKITXDRDO-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (3S)-3-methyl-5-oxo-piperazine-1-carboxylate 在 劳森试剂 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以2.69 g的产率得到tert-butyl (S)-3-methyl-5-thioxopiperazine-1-carboxylate
  参考文献：
  名称：

  含窒素複素環アミド化合物及びその医薬用途

  摘要：

  具有丙酮酸脱氢酶激酶抑制活性的含氮多环酰胺化合物或其制药上可接受的盐，以及包含它们的药物组合物的提供。化合物的式[I-a]或式[II]，或其制药上可接受的盐。（虚线连接：单键或双键。X₁：C、N、O。X₂：C、N。R₁a：C₁-₄烷基、C₁-₄烷基羰基。R₂：卤素、氰基、C₁-₄烷基。A₁〜A₇：C、N、O。A₈：C、N。R₃、R₄：H、C₁-₄烷基。Cy₁：C₄-₆环烷基等。Cy₂：C₃-₆环烷基等。m、t、w：0、1。n、r、v：0、1、2）【选择图】无

  公开号：

  JP2019131544A
• 作为产物：
  描述：

  ethyl 2-(benzyl(2-oxopropyl)amino)acetate 在 盐酸 、 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 磷酸吡哆醛 、 氢气 、 异丙胺 、 三乙胺 作用下， 以 aq. phosphate buffer 、 乙醇 、 正庚烷 、 二氯甲烷 、 水 为溶剂， 反应 26.0h， 生成 tert-butyl (3S)-3-methyl-5-oxo-piperazine-1-carboxylate
  参考文献：
  名称：

  胺转氨酶介导的光学纯哌嗪酮和 1,4-二氮杂环酮合成

  摘要：

  已经设计了一种生物催化方法，用于在温和条件下在水介质中合成光学活性哌嗪酮和 1,4-二氮杂环酮。本文所述的方法基于易于获得的N- (2-氧代丙基) 氨基酸酯的生物催化转氨作用和随后最初形成的胺的自发环化。合成哌嗪酮的两种对映异构体都可以通过选择具有相反选择性的胺转氨酶来制备。对反应条件进行了优化，并在制备规模上进行了八种选定的工艺。因此，以高分离产率 (70-90%) 合成了 7 种光学活性哌嗪酮，以中等产率 (51%) 合成了 1,4-二氮杂环酮，在所有情况下ee ≥99%。

  DOI：

  10.1002/adsc.202101510

文献信息

• [EN] PYRIMIDONE DERIVATIVES AND THEIR USE IN THE TREATMENT, AMELIORATION OR PREVENTION OF A VIRAL DISEASE<br/>[FR] DÉRIVÉS DE PYRIMIDONE ET LEUR UTILISATION DANS LE TRAITEMENT, LE SOULAGEMENT OU LA PRÉVENTION D'UNE MALADIE VIRALE
  申请人：SAVIRA PHARMACEUTICALS GMBH

  公开号：WO2017158151A1

  公开（公告）日：2017-09-21

  The present invention relates to a compound having the general formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease, in particular influenza.

  本发明涉及具有通式（I）的化合物，可选地为药学上可接受的盐、溶剂合物、多晶形、共药、共晶体、前药、互变异构体、消旋体、对映体或二对映体或其混合物，用于治疗、改善或预防病毒性疾病，特别是流感。
• NITROGENATED HETEROCYCLIC AMIDE COMPOUND, AND USE THEREOF FOR MEDICAL PURPOSES
  申请人：Japan Tobacco Inc.

  公开号：EP3747888A1

  公开（公告）日：2020-12-09

  The present invention provides a compound having a PDHK inhibitory activity and useful for the treatment or prophylaxis of diabetes (type 1 diabetes, type 2 diabetes etc.), insulin resistance syndrome, metabolic syndrome, hyperglycemia, hyperlactacidemia, diabetic complications (diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, cataract etc.), cardiac failure (acute cardiac failure, chronic cardiac failure), cardiomyopathy, myocardial ischemia, myocardial infarction, angina pectoris, dyslipidemia, atherosclerosis, peripheral arterial disease, intermittent claudication, chronic obstructive pulmonary disease, brain ischemia, cerebral apoplexy, mitochondrial disease, mitochondrial encephalomyopathy, cancer, pulmonary hypertension or Alzheimer disease. The present invention relates to a compound of the formula [I-a] or the formula [II], or a pharmaceutically acceptable salt thereof: wherein each symbol means the same as that described in the specification.

  本发明提供了一种具有 PDHK 抑制活性的化合物，可用于治疗或预防糖尿病（1 型糖尿病、2 型糖尿病等）、胰岛素抵抗综合征、代谢综合征、高血糖、高乳酸血症、糖尿病并发症（糖尿病神经病变、糖尿病视网膜病变、糖尿病肾病、白内障等）、心力衰竭（急性心力衰竭、慢性心力衰竭、心肌病、心肌缺血、心肌梗死、心绞痛、血脂异常等）。心肌病、心肌缺血、心肌梗塞、心绞痛、血脂异常、动脉粥样硬化、外周动脉疾病、间歇性跛行、慢性阻塞性肺病、脑缺血、脑中风、线粒体疾病、线粒体脑肌病、癌症、肺动脉高压或阿尔茨海默病。本发明涉及式[I-a]或式[II]化合物或其药学上可接受的盐： 其中各符号的含义与说明书中所述的相同。
• Nitrogen-containing heterocyclic amide compound and pharmaceutical use thereof
  申请人：Japan Tobacco Inc.

  公开号：US10800784B2

  公开（公告）日：2020-10-13

  The present invention provides a compound having a PDHK inhibitory activity and useful for the treatment or prophylaxis of diabetes (type 1 diabetes, type 2 diabetes etc.), insulin resistance syndrome, metabolic syndrome, hyperglycemia, hyperlactacidemia, diabetic complications (diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, cataract etc.), cardiac failure (acute cardiac failure, chronic cardiac failure), cardiomyopathy, myocardial ischemia, myocardial infarction, angina pectoris, dyslipidemia, atherosclerosis, peripheral arterial disease, intermittent claudication, chronic obstructive pulmonary disease, brain ischemia, cerebral apoplexy, mitochondrial disease, mitochondrial encephalomyopathy, cancer, pulmonary hypertension or Alzheimer disease. The present invention relates to a compound of the formula [I-a] or the formula [II], or a pharmaceutically acceptable salt thereof: wherein each symbol means the same as that described in the specification.

  本发明提供了一种具有 PDHK 抑制活性的化合物，可用于治疗或预防糖尿病（1 型糖尿病、2 型糖尿病等）、胰岛素抵抗综合征、代谢综合征、高血糖、高乳酸血症、糖尿病并发症（糖尿病神经病变、糖尿病视网膜病变、糖尿病肾病、白内障等）、心力衰竭（急性心力衰竭、慢性心力衰竭、心肌病、心肌缺血、心肌梗死、心绞痛、血脂异常等）。心肌病、心肌缺血、心肌梗塞、心绞痛、血脂异常、动脉粥样硬化、外周动脉疾病、间歇性跛行、慢性阻塞性肺病、脑缺血、脑中风、线粒体疾病、线粒体脑肌病、癌症、肺动脉高压或阿尔茨海默病。本发明涉及式[I-a]或式[II]化合物或其药学上可接受的盐： 其中各符号的含义与说明书中所述的相同。
• Stereocontrolled Synthesis of DTPA Analogs Branched in the Ethylene Unit
  作者：Christopher W. Grote、Dong Jin Kim、Henry Rapoport

  DOI：10.1021/jo00126a059

  日期：1995.10

  Stereochemically controlled synthesis of diethylenetriaminepentaacetic acid (DTPA) analogues substituted on the ethylene backbones with methyl groups, the chiral center a to the terminal nitrogen being derived from (S)- or (R)-alanine, has been achieved. The key intermediate (S)-propylenediaminetriacetic acid triester was synthesized via selective detosylation of the alkylation product derived from (S)-alanine and tert-butyl glycinate. Attaching the remaining modified alanine (or glycine) fragment through acyl coupling and then selective reduction of the amide followed by hydrolysis of the esters afforded the substituted DTPA analogues. Ester differentiation has been accomplished through alkylation rather than acylation of the (S)-propylenediaminetriacetic acid triester. A byproduct from this alkylation is the oxazoloisoindole formed by internal alkylation of the oxygen of the phthaloyl protecting group. Phthaloyl deprotection followed by dialkylation afforded the ester-differentiated (S,S)-dipropylenetriaminepentaacetic esters. The enantiomeric purity of the chiral intermediates (S)-alaninol and (S)-propylenediamines were determined by HPLC using epimeric standards.
• NITROGEN-CONTAINING HETEROCYCLIC AMIDE COMPOUND AND PHARMACEUTICAL USE THEREOF
  申请人：Japan Tobacco Inc.

  公开号：US20210284644A1

  公开（公告）日：2021-09-16

  The present invention provides a compound having a PDHK inhibitory activity and useful for the treatment or prophylaxis of diabetes (type 1 diabetes, type 2 diabetes etc.), insulin resistance syndrome, metabolic syndrome, hyperglycemia, hyperlactacidemia, diabetic complications (diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, cataract etc.), cardiac failure (acute cardiac failure, chronic cardiac failure), cardiomyopathy, myocardial ischemia, myocardial infarction, angina pectoris, dyslipidemia, atherosclerosis, peripheral arterial disease, intermittent claudication, chronic obstructive pulmonary disease, brain ischemia, cerebral apoplexy, mitochondrial disease, mitochondrial encephalomyopathy, cancer, pulmonary hypertension or Alzheimer disease. The present invention relates to a compound of the formula [I-a] or the formula [II], or a pharmaceutically acceptable salt thereof: wherein each symbol means the same as that described in the specification.