(2S,4S)-1-((2R)-2-amino-3-[(4-methoxybenzyl)sulfonyl]-3-methyl-butanoyl)-4-fluoropyrrolidine-2-carbonitrile hydrochloride | 483367-72-2

• 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: (2S,4S)-1-((2R)-2-amino-3-[(4-methoxybenzyl)sulfonyl]-3-methyl-butanoyl)-4-fluoropyrrolidine-2-carbonitrile hydrochloride
• 英文别名: (2S,4S)-1-[(2R)-2-amino-3-[(4-methoxyphenyl)methylsulfonyl]-3-methylbutanoyl]-4-fluoropyrrolidine-2-carbonitrile;hydrochloride
• CAS: 483367-72-2
• 化学式: C₁₈H₂₄FN₃O₄S*ClH
• 分子量: 433.932
• InChiKey: AXBAPGQMEIHAJE-ZPQOTBKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  122
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  tert-butyl (1R)-1-{[(2S,4S)-2-cyano-4-fluoropyrrolidin-1-yl]carbonyl}-2-[(4-methoxybenzyl)sulfonyl]-2-methylpropylcarbamate 在 三氟乙酸 、 水 、 碳酸氢钠 、 盐酸 作用下， 以 二氯甲烷 、 乙醚 为溶剂， 反应 2.0h， 生成 (2S,4S)-1-((2R)-2-amino-3-[(4-methoxybenzyl)sulfonyl]-3-methyl-butanoyl)-4-fluoropyrrolidine-2-carbonitrile hydrochloride
  参考文献：
  名称：

  [EN] ANHYDROUS CRYSTALLINE FORMS OF (2S, 4S)-1-{(2R)-2-AMINO-3-'4-METHOXYBENZYL)SULFONYL!-3-METHYLBUTANOYL}-4-FLUOROPYRROLINDINE-2-CARBONITRILE
  [FR] FORMES CRISTALLINES ANHYDRES DE (2S, 4S)-1-{(2R)-2-AMINO-3-'4-METHOXYBENZYL)SULFONYL!-3-METHYLBUTANOYL}-4-FLUOROPYRROLINDINE-2-CARBONITRILE

  摘要：

  本发明涉及(2S,4S)-1-{(2R)-2-氨基-3-[(4-甲氧基苯基)磺酰基]-3-甲基丁酰}-4-氟吡咯烷-2-碳腈的无水晶形式。化学式(I)。

  公开号：

  WO2004092128A1

文献信息

• Fluoropyrrolidines as dipeptidyl peptidase inhibitors
  申请人：——

  公开号：US20040171848A1

  公开（公告）日：2004-09-02

  The present invention relates to novel compounds, their use for inhibiting serine proteases, such as dipeptidyl peptidases, such as dipeptidyl peptidase IV (DPP-IV) and to methods for their production and their therapeutic utility.

  本发明涉及新型化合物，其用于抑制丝氨酸蛋白酶，例如二肽基肽酶，例如二肽基肽酶IV（DPP-IV），以及其生产方法和治疗效用。
• (2S,4s)-4-fluoro-1-[4-fluoro-beta-(4-fluorophenyl)-I-phenylalanyl]-2-pyrrolidinecarbonitrile p-toluenesulfonic acid salt and anhydrous crystalline forms thereof
  申请人：Igo H David

  公开号：US20070066677A1

  公开（公告）日：2007-03-22

  The present invention includes anhydrous crystalline forms of (2S,4S)-4-fluoro-1-[4-fluoro-β-(4-fluorophenyl)-L-phenylalanyl]-2-pyrrolidinecarbonitrile p-toluenesulfonic acid salt.

  本发明涉及(2S,4S)-4-氟-1-[4-氟-β-(4-氟苯基)-L-苯丙氨基]-2-吡咯烷基氰酸盐的无水晶型态，其为对甲苯磺酸盐。
• Use of dipeptidyl peptidase IV inhibitors
  申请人：Novartis AG

  公开号：EP2839832A2

  公开（公告）日：2015-02-25

  Use of a Dipeptidyl peptidase IV inhibitor (DPP-IV inhibitor), preferably (S)-1-[(3-hydroxy-1-adamantyl)amino] acetyl-2-cyano-pyrrolidine or a pharmaceutically acceptable salt thereof for the prevention, delay of progression or treatment of cardiovascular diseases or damages, renal diseases or damages, Heart Failure, or Heart Failure associated diseases.

  二肽基肽酶 IV 抑制剂（DPP-IV 抑制剂），优选 (S)-1-[(3-hydroxy-1-adamantyl)amino] 乙酰基-2-氰基吡咯烷或其药学上可接受的盐，用于预防、延缓进展或治疗心血管疾病或损害、肾脏疾病或损害、心力衰竭或心力衰竭相关疾病。
• DIRECT COMPRESSION FORMULATION AND PROCESS
  申请人：NOVARTIS AG

  公开号：EP3738585A1

  公开（公告）日：2020-11-18

  Dipeptidylpeptidase IV inhibitor (herein referred to as DPP-IV) that may be 98.5-100% pure is a high-dose drug capable of being directly compressed with specific excipients into sold form dosage forms, such as tablets and capsules having desired, hardness, disintegrating ability and acceptable dissolution characteristics. DPP-IV is not inherently compressible and thus presents formulation problems. Excipients used in the formulation enhance the flow and compaction properties of the drug and tableting mix. Optimal flow contributes to uniform die fill and weight control. The binder used ensures sufficient cohesive properties that allow DPP-IV to be compressed using the direct compression method. The tablets produced provide an acceptable in vitro dissolution profile.

  纯度为 98.5%-100%的二肽基肽酶 IV 抑制剂（以下简称 DPP-IV）是一种高剂量药物，可与特定辅料一起直接压缩成片剂和胶囊等销售剂型，并具有所需的硬度、崩解能力和可接受的溶出特性。DPP-IV 本身不可压缩，因此存在制剂问题。配方中使用的辅料可增强药物和制片混合物的流动性和压实性。最佳的流动性有助于实现均匀的模具填充和重量控制。所使用的粘合剂可确保 DPP-IV 具有足够的内聚性，从而可采用直接压片法进行压片。生产出的片剂具有可接受的体外溶出度曲线。
• Direct compression formulation and process
  申请人：Pfeffer Sabine

  公开号：US20060210627A1

  公开（公告）日：2006-09-21

  This invention relates to tablets especially tablets formed by direct compression of a dipeptidylpeptidase IV (DPP-IV) inhibitor compound, a process for the preparation thereof, to new pharmaceutical formulations, and new tableting powders comprising DPP-IV inhibitor formulations capable of being directly compressed into tablets. The invention relates further to a process for preparing the tablets by blending the active ingredient and specific excipients into the new formulations and then directly compressing the formulations into the direct compression tablets. The invention also relates to vildagliptin particle size distribution and a new crystal form of vildagliptin particularly adapted for the preparation of improved tablets and other pharmaceutical compositions.

  本发明涉及片剂，特别是通过直接压制二肽基肽酶 IV（DPP-IV）抑制剂化合物而形成的片剂、其制备工艺、新的药物制剂以及包含可直接压制成片剂的 DPP-IV 抑制剂制剂的新片剂粉末。本发明还涉及一种通过将活性成分和特定辅料混合到新制剂中，然后直接将制剂压制成直接压片的片剂制备工艺。本发明还涉及维达列汀的粒度分布以及特别适用于制备改良片剂和其他药物组合物的维达列汀新晶形。