4-(2-formyl-4-methyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester | 851753-68-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(2-formyl-4-methyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 4-(2-formyl-4-methylphenyl)piperazine-1-carboxylate
• CAS: 851753-68-9
• 化学式: C₁₇H₂₄N₂O₃
• 分子量: 304.389
• InChiKey: ZOLFIDPRXAGRKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-formyl-4-methyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester 在 titanium(IV) tetraethanolate 、 三甲基铝 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 乙醇 、 正庚烷 、 二氯甲烷 、 正戊烷 为溶剂， 反应 17.75h， 生成 4-{4-methyl-2-[(S)-2-methyl-1-(2-methyl-propane-2-sulfonylamino)-propyl]-phenyl}-piperazine-1-carboxylic aicd tert-butyl ester
  参考文献：
  名称：

  Practical Asymmetric Synthesis of α-Branched 2-Piperazinylbenzylamines by 1,2-Additions of Organometallic Reagents to N-tert-Butanesulfinyl Imines

  摘要：

  2-[4-(tert-Butoxycarbonyl)piperazinyl]benzylidene-tert-butanesulfinamides underwent nucleophilic 1,2-addition with different organometallic reagents to give highly diastereomerically enriched adducts. X-ray crystallography of the resulting alpha-branched N-Boc-2-piperazinylbenzyl-tert-butanesulfinamides confirms different mechanisms depending on the organometallic reagent used. Differential deprotection of the N-Boc and the tert-butanesulfinamides was investigated, and the dehydration byproducts have been identified and characterized. To avoid the formation of byproducts in the acidic deprotection step, the N-tert-butanesulfinamide group was converted to the corresponding N-tert-butanesulfonamide (Bus), which allowed for clean orthogonal deprotection. The efficient synthesis and deprotection of the N-Boc-2-piperazinylbenzyl-tert-butanesulfinamides herein described constitutes an attractive method for extensive structure-activity studies in the search for novel ligands of the human melanocortin 4 receptor.

  DOI：

  10.1021/jo051514p
• 作为产物：
  描述：

  5-Methyl-2-(piperazin-1-YL)benzaldehyde 、 二碳酸二叔丁酯 在 碳酸氢钠 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 4-(2-formyl-4-methyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Design, Synthesis, In Vitro, and In Vivo Characterization of Phenylpiperazines and Pyridinylpiperazines as Potent and Selective Antagonists of the Melanocortin-4 Receptor

  摘要：

  Benzylamine and pyridinemethylamine derivatives were synthesized and characterized as potent and selective antagonists of the melanocortin-4 receptor (MC4R). These compounds were also profiled in rodents for their pharmacokinetic properties. Two compounds with diversified profiles in chemical structure, pharmacological activities, and pharmacokinetics, 10 and 12b, showed efficacy in an established murine cachexia model. For example, 12b had a K-i value of 3.4 nM at MC4R, was more than 200-fold selective over MC3R, and had a good pharmacokinetic profile in mice, including high brain penetration. Moreover, 12b was able to stimulate food intake in the tumor-bearing mice and reverse their lean body mass loss. Our results provided further evidence that a potent and selective MC4R antagonist with appropriate pharmacokinetic properties might potentially be useful for the treatment of cancer cachexia.

  DOI：

  10.1021/jm701137s

文献信息

• Novel, Versatile Three-Step Synthesis of 1,2,3,4,10,10a-Hexahydro­pyrazino[1,2-a]indoles by Intramolecular Carbene-Mediated C-H Insertion
  作者：Jan Kehler、Niels Krogsgaard-Larsen、Mikael Begtrup、Matthias Herth

  DOI：10.1055/s-0030-1258967

  日期：2010.12

  A new convenient three-step synthesis of the privileged CNS scaffold 1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoles has been developed. The method makes use of an intramolecular carbene-mediated C-H insertion in phenylpiperazine-derived tosyl­hydrazones made from 2-fluorobenzaldehydes. Notably, the piperazine can be replaced with other cyclic nitrogen bases and the methodology is successfully extended to pyrrolidine, piperidine, azepane, morpholine, and homopiperazine.

  开发了一种新的便捷三步合成特权中枢神经系统骨架1,2,3,4,10,10a-六氢吡嗪并[1,2-a]吲哚的方法。该方法利用了由2-氟苯醛制得的苯基哌嗪衍生的托磺酰肼中发生的分子内碳烯介导的C-H插入。值得注意的是，哌嗪可以被其他环状氮碱替代，该方法成功扩展到了吡咯烷、哌啶、七元环胺、吗啉和同哌嗪。
• CHEMICAL COMPOUNDS 251
  申请人：Dakin Leslie

  公开号：US20110218182A1

  公开（公告）日：2011-09-08

  The invention relates to chemical compounds of formula (I), and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of PIM-1 and/or PIM-2, and/or PIM-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of PIM kinase related conditions and diseases, preferably cancer.

  该发明涉及化学式(I)的化合物及其盐。在某些实施例中，该发明涉及PIM-1和/或PIM-2以及/或PIM-3蛋白激酶活性或酶功能的抑制剂或调节剂。在更进一步的实施例中，该发明涉及包含本文披露的化合物的药物组合物，以及它们在预防和治疗PIM激酶相关疾病和疾病，特别是癌症中的用途。
• Ligands of melanocortin receptors and compositions and methods related thereto
  申请人：Tucci C. Fabio

  公开号：US20050119252A1

  公开（公告）日：2005-06-02

  Compounds which function as melanocortin receptor ligands and having utility in the treatment of melanocortin receptor-based disorders. The compounds have the following structure (I): including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein m, n, q, s, R 1 , R 1a , R 1b , R 2 , R 3 , R 4a , R 4b , R 5a , R 5b , X 1 , X 2 , X 3 , X 4 and Ar are as defined herein. Pharmaceutical compositions containing a compound of structure (I), as well as methods relating to the use thereof, are also disclosed.

  这是一种功能为黑素皮质素受体配体的化合物，可用于治疗基于黑素皮质素受体的疾病。该化合物具有以下结构（I）：包括立体异构体，前药和其药学上可接受的盐，其中m，n，q，s，R1，R1a，R1b，R2，R3，R4a，R4b，R5a，R5b，X1，X2，X3，X4和Ar的定义如本文所述。还公开了含有结构（I）化合物的药物组成物，以及与其使用相关的方法。
• Chemical Compounds 251
  申请人：AstraZeneca AB

  公开号：US20150051185A1

  公开（公告）日：2015-02-19

  The invention relates to chemical compounds of formula I, and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of PIM-1 and/or PIM-2, and/or PIM-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of PIM kinase related conditions and diseases, preferably cancer.

  本发明涉及公式I的化合物及其盐。在某些实施例中，本发明涉及PIM-1和/或PIM-2，以及/或PIM-3蛋白激酶活性或酶功能的抑制剂或调节剂。在更进一步的实施例中，本发明涉及包含本文所披露的化合物的制药组合物，以及它们在预防和治疗PIM激酶相关的疾病和状况，尤其是癌症方面的应用。
• [EN] LIGANDS OF MELANOCORTIN RECEPTORS AND COMPOSITIONS AND METHODS RELATED THERETO<br/>[FR] LIGANDS DE RECEPTEURS DE LA MELANOCORTINE, COMPOSITIONS ET PROCEDES ASSOCIES
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2005042516A3

  公开（公告）日：2005-12-01