sitagliptin sulfate | 1169707-31-6

• 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: sitagliptin sulfate
• 英文别名: (3R)-3-amino-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one;sulfuric acid
• CAS: 1169707-31-6
• 化学式: C₁₆H₁₅F₆N₅O*H₂O₄S
• 分子量: 505.398
• InChiKey: WSJSNSFEWVZILC-SBSPUUFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.36
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  160
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  sitagliptin sulfate 以 水 为溶剂， 以92%的产率得到西他列汀
  参考文献：
  名称：

  Sitagliptin inhibit human lymphocytes proliferation and Th1/Th17 differentiation in vitro

  摘要：

  Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein, CD26, and plays an important role in T-cell immunity. Recent studies suggest that DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1 diabetic mouse models. To investigate the direct effect of DPP4 in immune response, human peripheral blood mononuclear cells (PBMC) from healthy volunteers were obtained by Ficoll gradient and cultivated in the absence (control) or presence of phytohemagglutinin (PHA), or stimulated with PHA and treated with sitagliptin. The immune modulation mechanisms analyzed were: cell proliferation, by MIT assay; cytokine quantification by ELISA or cytometric bead array (CBA), Thl/ Th2/Th17 phenotyping by flow cytometric analysis and CD26 gene expression by real time PCR. The results showed that sitagliptin treatment inhibited the proliferation of PBMC-PHA stimulated cells in a dose dependent manner and decreased CD26 expression by these cells, suggesting that sitagliptin may interfere in CD26 expression, dimerization and cell signaling. Sitagliptin treatment not only inhibited IL-10 (p < 0.05) and IFN-gamma (p = 0.07) cytokines, but also completely abolish IL-6 expression by PBMCs (p < 0.001). On the other hand, IL 4 were secreted in culture supernatants from sitagliptin treated cells. A statistically significant increase (p < 0.05) in the ratio of TGF-beta/proliferation index after sitagliptin treatment (2627.97 +/- 1351.65), when comparing to untreated cells (646.28 +/- 376.94), was also demonstrated, indicating higher TGF-betal production by viable cells in cultures. Sitagliptin treatment induced a significantly (p < 0.05) decrease in IL-17 and IFN-gamma intracellular expression compared with PHA alone. Also, the percentage of T CD4(+) IL-17(+), T CD4(+)IFNgamma(+) and T CD4(+)11.-4(+) cells were significantly reduced (p < 0.05) by sitagliptin. Our data demonstrated an immunosuppressive effect of sitagliptin on Th1, Th17 and Th2 lymphocytes differentiation that leads to the generation of regulatory TGF-betal secreting cells with low CD26 gene expression that may influence the state of pancreatic beta-cells and controlling DM1 patients. (C) 2017 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2016.12.040
• 作为产物：
  描述：

  西他列汀 在 硫酸 作用下， 以 乙腈 为溶剂， 生成 sitagliptin sulfate
  参考文献：
  名称：

  SOLID STATE FORMS OF SITAGLIPTIN SALTS

  摘要：

  本发明提供了西格列汀盐的晶体形式、制备西格列汀盐晶体形式的工艺以及西格列汀盐的制药组合物。

  公开号：

  US20110245498A1

文献信息

• Novel salts of sitagliptin
  申请人：LEK Pharmaceuticals d.d.

  公开号：EP2218721A1

  公开（公告）日：2010-08-18

  The present invention relates to novel pharmaceutically acceptable salts of sitagliptin, to processes for their preparation and to pharmaceutical compositions containing them.

  本发明涉及西格列汀的新型药用可接受盐，以及其制备过程和含有它们的药物组合物。
• [EN] PROCESSES FOR THE PREPARATION OF SITAGLIPTIN AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF<br/>[FR] PROCÉDÉS DE PRÉPARATION DE SITAGLIPTINE ET SELS PHARMACEUTIQUEMENT ACCEPTABLES DE CELLE-CI
  申请人：REDDYS LAB LTD DR

  公开号：WO2009085990A3

  公开（公告）日：2009-09-03
• [EN] CRYSTALLINE SALTS OF SITAGLIPTIN<br/>[FR] SELS CRISTALLINS DE SITAGLIPTINE
  申请人：RATIOPHARM GMBH

  公开号：WO2010000469A3

  公开（公告）日：2010-11-18
• SOLID STATE FORMS OF SITAGLIPTIN SALTS
  申请人：PILARSKI Gideon

  公开号：US20100249140A1

  公开（公告）日：2010-09-30

  Solid state forms of Sitagliptin salts, processes for preparing the solid state forms, and pharmaceutical compositions thereof, are provided.

  提供了西他列汀盐的固态形式、制备固态形式的方法以及其药物组合物。
• Sitagliptin inhibit human lymphocytes proliferation and Th1/Th17 differentiation in vitro
  作者：Marcelo Maia Pinheiro、Caroline Lais Stoppa、Claudete Justina Valduga、Cristina Eunice Okuyama、Renata Gorjão、Regina Mara Silva Pereira、Susana Nogueira Diniz

  DOI：10.1016/j.ejps.2016.12.040

  日期：2017.3

  Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein, CD26, and plays an important role in T-cell immunity. Recent studies suggest that DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1 diabetic mouse models. To investigate the direct effect of DPP4 in immune response, human peripheral blood mononuclear cells (PBMC) from healthy volunteers were obtained by Ficoll gradient and cultivated in the absence (control) or presence of phytohemagglutinin (PHA), or stimulated with PHA and treated with sitagliptin. The immune modulation mechanisms analyzed were: cell proliferation, by MIT assay; cytokine quantification by ELISA or cytometric bead array (CBA), Thl/ Th2/Th17 phenotyping by flow cytometric analysis and CD26 gene expression by real time PCR. The results showed that sitagliptin treatment inhibited the proliferation of PBMC-PHA stimulated cells in a dose dependent manner and decreased CD26 expression by these cells, suggesting that sitagliptin may interfere in CD26 expression, dimerization and cell signaling. Sitagliptin treatment not only inhibited IL-10 (p < 0.05) and IFN-gamma (p = 0.07) cytokines, but also completely abolish IL-6 expression by PBMCs (p < 0.001). On the other hand, IL 4 were secreted in culture supernatants from sitagliptin treated cells. A statistically significant increase (p < 0.05) in the ratio of TGF-beta/proliferation index after sitagliptin treatment (2627.97 +/- 1351.65), when comparing to untreated cells (646.28 +/- 376.94), was also demonstrated, indicating higher TGF-betal production by viable cells in cultures. Sitagliptin treatment induced a significantly (p < 0.05) decrease in IL-17 and IFN-gamma intracellular expression compared with PHA alone. Also, the percentage of T CD4(+) IL-17(+), T CD4(+)IFNgamma(+) and T CD4(+)11.-4(+) cells were significantly reduced (p < 0.05) by sitagliptin. Our data demonstrated an immunosuppressive effect of sitagliptin on Th1, Th17 and Th2 lymphocytes differentiation that leads to the generation of regulatory TGF-betal secreting cells with low CD26 gene expression that may influence the state of pancreatic beta-cells and controlling DM1 patients. (C) 2017 Elsevier B.V. All rights reserved.