2-甲基-D-脯氨酸甲酯盐酸盐 | 1286768-32-8

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 脯氨酸类衍生物
• 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-甲基-D-脯氨酸甲酯盐酸盐
• 中文别名: (R)-2-甲基吡咯烷-2-甲酸甲酯盐酸盐
• 英文名称: (R)-methyl 2-methylpyrrolidine-2-carboxylate hydrochloride
• 英文别名: (R)-2-methylpyrrolidine-2-carboxylic acid methyl ester hydrochloride；Methyl (2R)-2-methylpyrrolidine-2-carboxylate hydrochloride；methyl (2R)-2-methylpyrrolidine-2-carboxylate;hydrochloride
• CAS: 1286768-32-8
• 化学式: C₇H₁₃NO₂*ClH
• 分子量: 179.647
• InChiKey: YCYWAVUCBMJUPK-OGFXRTJISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.72
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  38.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-甲基-D-脯氨酸甲酯盐酸盐 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 二异丁基氢化铝 、 sodium carbonate 、 potassium carbonate 、 zinc dibromide 、 四甲基胍 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 33.5h， 生成 methyl (R)-6-fluoro-2-(2-methyl-1-(2,2,2-trifluoroacetyl)pyrrolidin-2-yl)-1H-indole-4-carboxylate
  参考文献：
  名称：

  Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development

  摘要：

  Poly (ADP-ribose) polymerase (PARP) plays a significant role in DNA repair responses; therefore, this enzyme is targeted by PARP inhibitors in cancer therapy. Here we have developed a number of fused tetra- or pentacyclic dihydrodiazepinoindolone derivatives with excellent PARP enzymatic and cellular PARylation inhibition activities. These efforts led to the identification of pamiparib (BGB-290, 139), which displays excellent PARP-1 and PARP-2 inhibition with IC₅₀ of 1.3 and 0.9 nM, respectively. In a cellular PARylation assay, this compound inhibits PARP activity with IC₅₀ = 0.2 nM. Cocrystal of pamiparib shows similar binding sites with PARP with other PARP inhibitors, but pamiparib is not a P-gp substrate and shows excellent drug metabolism and pharmacokinetics (DMPK) properties with significant brain penetration (17-19%, mice). The compound is currently being investigated in phase III clinical trials as a maintenance therapy in platinum-sensitive ovarian cancer and gastric cancer.

  DOI：

  10.1021/acs.jmedchem.0c01346
• 作为产物：
  描述：

  D-脯氨酸 在 盐酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 正庚烷 、 乙腈 为溶剂， 反应 9.0h， 生成 2-甲基-D-脯氨酸甲酯盐酸盐
  参考文献：
  名称：

  CYCLIC AMINE DERIVATIVES AS EP4 RECEPTOR ANTAGONISTS

  摘要：

  本发明描述了一组新型的环胺衍生物化合物，具有EP4受体拮抗活性，特别是用于治疗或缓解前列腺素E介导的疾病的药物化合物。因此，本发明涉及的是新型化合物，它们是PGE2受体的EP4亚型的选择性拮抗剂，具有镇痛和抗炎活性，其制备过程，包含它们的药物组合物以及它们作为药物的使用，例如用于治疗或缓解急性疼痛、慢性疼痛、骨关节炎、与炎症相关的疾病如关节炎、类风湿性关节炎、癌症、偏头痛和子宫内膜异位症的前列腺素E介导的疾病。

  公开号：

  US20150087626A1

文献信息

• DIHYDROPYRIDAZINE-3,5-DIONE DERIVATIVE AND PHARMACEUTICALS CONTAINING THE SAME
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：US20160002251A1

  公开（公告）日：2016-01-07

  The present invention provides a dihydropyridazine-3,5-dione derivative or a salt thereof, or a solvate of the compound or the salt, a pharmaceutical drug, a pharmaceutical composition, a sodium-dependent phosphate transporter inhibitor, and a preventive and/or therapeutic agent for hyperphosphatemia, secondary hyperparathyroidism, chronic renal failure, chronic kidney disease, and arteriosclerosis associated with vascular calcification comprising the compound as an active ingredient, and a method for prevention and/or treatment.

  本发明提供了一种二氢吡啶嗪-3,5-二酮衍生物或其盐，或化合物或盐的溶剂化合物，一种药物，一种药物组合物，一种钠依赖性磷酸盐转运体抑制剂，以及作为活性成分的化合物的高磷血症、继发性甲状旁腺功能亢进症、慢性肾功能衰竭、慢性肾病和与血管钙化相关的动脉硬化的预防和/或治疗剂，以及预防和/或治疗的方法。
• [EN] CYCLIC AMINE DERIVATIVES AS EP4 RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS AMINÉS CYCLIQUES EN TANT QU'ANTAGONISTES DU RÉCEPTEUR EP4
  申请人：ROTTAPHARM SPA

  公开号：WO2013004290A1

  公开（公告）日：2013-01-10

  There is described a novel group of cyclic amine derivative compounds, having an EP4 receptor antagonistic activity and specifically pharmaceutical compounds which are useful for the treatment or alleviation of Prostaglandin E mediated diseases. The present invention therefore relates to novel compounds which are selective antagonists of the EP4 subtype of PGE2 receptors with analgesic and antinflammatory activity, processes for their preparation, pharmaceutical compositions containing them and their use as medicaments, inter alia for the treatment or alleviation of Prostaglandin E mediated diseases such as acute and chronic pain, osteoarthritis, inflammation-associated disorder as arthritis, rheumatoid arthritis, cancer, migraine and endometriosis.

  本发明描述了一组新型的环状胺衍生物化合物，具有EP4受体拮抗活性，特别是用于治疗或减轻前列腺素E介导的疾病的药物化合物。因此，本发明涉及的是新型化合物，它们是PGE2受体的EP4亚型的选择性拮抗剂，具有镇痛和抗炎活性，其制备过程，包含它们的药物组合物以及它们作为药物的使用，包括用于治疗或减轻前列腺素E介导的疾病，如急性疼痛、慢性疼痛、骨关节炎、与炎症相关的疾病如关节炎、类风湿性关节炎、癌症、偏头痛和子宫内膜异位症。
• Discovery of 2-Alkyl-1-arylsulfonylprolinamides as 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors
  作者：Jianxin Yu、Haiyan Liu、Guangxin Xia、Lin Liu、Zhenmin Xu、Qian Chen、Chen Ma、Xing Sun、Jiajun Xu、Hua Li、Ping Li、Yufang Shi、Bing Xiong、Xuejun Liu、Jingkang Shen

  DOI：10.1021/ml300144n

  日期：2012.10.11

  On the basis of scaffold hopping, a novel series of 2-alkyl-1-arylsulfonylprolinamides was discovered as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) inhibitors. A representative compound 4ek, obtained through SAR and structure optimization studies, demonstrates excellent in vitro potency against 11β-HSD-1 and dose-dependent in vivo inhibition of 11β-HSD-1 in a prednisone/prednisolone transformation

  在支架跳跃的基础上，发现了一系列新型 2-烷基-1-芳基磺酰基脯氨酰胺作为 11β-羟基类固醇脱氢酶 1 (11β-HSD-1) 抑制剂。通过 SAR 和结构优化研究获得的代表性化合物4ek在小鼠的泼尼松/泼尼松龙转化生物标志物研究中显示出对 11β-HSD-1 的出色体外效力和对 11β-HSD-1 的剂量依赖性体内抑制。
• [EN] CYCLIC AMINE DERIVATIVES AS EP4 RECEPTOR AGONISTS<br/>[FR] DÉRIVÉS AMINÉS CYCLIQUES EN TANT QU'AGONISTES DU RÉCEPTEUR EP4
  申请人：ROTTAPHARM SPA

  公开号：WO2013004291A1

  公开（公告）日：2013-01-10

  There is described a group of novel cyclic amine derivative compounds having an EP4 receptor agonistic activity. Specifically, the compounds according to the invention are provided with analgesic, antiinflammatory, antiglaucoma activity, and also with anti-osteoporosis and antiulcerative activity. The present invention therefore relates to novel cyclic amine derivative compounds, processes for their preparation, pharmaceutical compositions containing them and their use as medicaments, inter alia for the treatment or alleviation of Prostaglandin E mediated diseases such as pain, glaucoma, ulcerative colitis and osteoporosis.

  本发明涉及一组具有EP4受体激动活性的新型环胺衍生物化合物。具体地，根据本发明的化合物具有镇痛、抗炎、抗青光眼活性，同时还具有抗骨质疏松和抗溃疡活性。因此，本发明涉及新型环胺衍生物化合物，其制备方法、含有它们的药物组合物以及它们作为药物的用途，包括用于治疗或缓解前列腺素E介导的疾病，如疼痛、青光眼、溃疡性结肠炎和骨质疏松症。
• CYCLIC AMINE DERIVATIVES AS EP4 RECEPTOR AGONISTS
  申请人：Borriello Manuela

  公开号：US20140243373A1

  公开（公告）日：2014-08-28

  There is described a group of novel cyclic amine derivative compounds having an EP 4 receptor agonistic activity. Specifically, the compounds according to the invention are provided with analgesic, antinflammatory, antiglaucoma activity, and also with anti-osteoporosis and antiulcerative activity. The present invention therefore relates to novel cyclic amine derivative compounds, processes for their preparation, pharmaceutical compositions containing them and their use as medicaments, inter alia for the treatment or alleviation of Prostaglandin E mediated diseases such as pain, glaucoma, ulcerative colitis and osteoporosis.

  本文描述了一组新型环胺衍生物化合物，具有EP4受体激动活性。具体来说，根据本发明的化合物具有镇痛、抗炎、抗青光眼活性，以及抗骨质疏松和抗溃疡活性。因此，本发明涉及新型环胺衍生物化合物、其制备方法、含有它们的药物组合物以及它们作为药物的用途，其中包括用于治疗或缓解前列腺素E介导的疾病，如疼痛、青光眼、溃疡性结肠炎和骨质疏松症。