2-amino-3-methylbutyric acid 3-{[3-(biphenyl-4-sulfonyl)thiazolidine-2-carbonyl]amino}-3-(4-fluorophenyl)propyl ester | 2005486-31-5

• 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: 2-amino-3-methylbutyric acid 3-{[3-(biphenyl-4-sulfonyl)thiazolidine-2-carbonyl]amino}-3-(4-fluorophenyl)propyl ester
• 英文别名: (3S)-3-({[(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yI]carbonyl}amino)-3-(4-fluorophenyl)propyl L-valinate；OBE002；Ebopiprant；[(3S)-3-(4-fluorophenyl)-3-[[(2S)-3-(4-phenylphenyl)sulfonyl-1,3-thiazolidine-2-carbonyl]amino]propyl] (2S)-2-amino-3-methylbutanoate
• CAS: 2005486-31-5
• 化学式: C₃₀H₃₄FN₃O₅S₂
• 分子量: 599.747
• InChiKey: UUIBKACUTXYSAK-YCVJPRETSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  153
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-amino-3-methylbutyric acid 3-{[3-(biphenyl-4-sulfonyl)thiazolidine-2-carbonyl]amino}-3-(4-fluorophenyl)propyl ester 在 Endogenous esterases 作用下， 生成 (S)-3-(biphenyl-4-sulfonyl)-thiazolidine-2-carboxylic acid [(S)-1-(4-fluoro-phenyl)-3-hydroxypropyl]amide
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR THE TREATMENT OR PREVENTION OF PRETERM LABOR
  [FR] COMPOSITIONS ET PROCÉDÉS DE TRAITEMENT OU DE PRÉVENTION DE TRAVAIL PRÉMATURÉ

  摘要：

  The disclosure provides compositions and methods for delaying the onset of delivery in a pregnant subject, such as a pregnant human subject, that is undergoing or at risk of undergoing preterm labor at a gestational age of from about 24 weeks to about 34 weeks. Using the compositions and methods described herein, such subjects may be administered atosiban in combination with a prostaglandin F2α (PGF2α) antagonist. Exemplary PGF2α receptor antagonists that may be used for the treatment or prevention of preterm labor as described herein include 1,3-thiazolidine-2-carboxamide compounds, such as (3S)-3-({[(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate or a pharmaceutically acceptable salt thereof (e.g., (3S)-3-({[(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate hydrochloride). The compositions and methods described herein provide various clinical benefits. Delivery at an early gestational age is a leading cause of perinatal mortality. By delaying labor in pregnant human patients at an early gestational age, the compositions and methods of the disclosure provide unborn infants with additional time to develop vital organs and tissue systems, thereby significantly improving the likelihood of survival following delivery. The compositions and methods described herein may be used to delay the onset of delivery by one or more hours, days, or weeks, for example, so as to enable pregnant subjects to reach a gestational age at which parturition is substantially safer.

  公开号：

  WO2022101495A1
• 作为产物：
  描述：

  (S)-3-(biphenyl-4-sulfonyl)-thiazolidine-2-carboxylic acid [(S)-1-(4-fluoro-phenyl)-3-hydroxypropyl]amide 在 4-二甲氨基吡啶 、 碳酸氢钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-amino-3-methylbutyric acid 3-{[3-(biphenyl-4-sulfonyl)thiazolidine-2-carbonyl]amino}-3-(4-fluorophenyl)propyl ester
  参考文献：
  名称：

  α-amino esters of hydroxypropylthiazolidine carboxamide derivative and salt form, crystal polymorph thereof

  摘要：

  本发明提供了一种羟丙基噻唑啉羧酰胺衍生物的α-氨基酯，即(2S)-3-([1,1'-联苯]-4-基磺酰基)-N-[(1S)-3-羟基-1-苯基丙基]-1,3-噻唑啉-2-羧酰胺，以及其盐和晶体多态体，可用于抑制前列腺素F受体。本发明还涵盖了通过向需要治疗的患者投药这些物质来治疗早产等疾病的方法。

  公开号：

  US09447055B1

文献信息

• Alpha-amino esters of hydroxypropylthiazolidine carboxamide derivative and salt form, crystal polymorph thereof
  申请人：Merck Serono S.A.

  公开号：US10259795B2

  公开（公告）日：2019-04-16

  The invention provides α-amino esters of a hydroxypropylthiazolidine carboxamide derivative, (2S)-3-([1,1′-biphenyl]-4-ylsulfonyl)-N-[(1S)-3-hydroxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide, as well as salts and crystal polymorphs thereof, that can be used to inhibit prostaglandin F receptor. The invention further encompasses methods of treating disorders such as pre-term labor at the early gestational stage by the administration of these substances to a patient in need of treatment.

  本发明提供了可用于抑制前列腺素F受体的羟丙基噻唑烷甲酰胺衍生物(2S)-3-([1,1′-联苯]-4-基磺酰基)-N-[(1S)-3-羟基-1-苯基丙基]-1,3-噻唑烷-2-甲酰胺的α-氨基酯及其盐类和晶体多晶型物。本发明还包括通过向需要治疗的患者施用这些物质来治疗妊娠早期早产等疾病的方法。
• Compositions and methods for delaying the incidence of labor
  申请人：ObsEva S.A.

  公开号：US11534428B1

  公开（公告）日：2022-12-27

  The invention provides compositions and methods for delaying the onset of delivery in a pregnant subject, such as a pregnant human subject, that is undergoing or at risk of undergoing preterm labor at a gestational age of from about 24 weeks to about 34 weeks. Using the compositions and methods described herein, such subjects may be administered nifedipine in combination with a prostaglandin F2α (PGF2α) antagonist. Exemplary PGF2α receptor antagonists that may be used for the treatment or prevention of preterm labor as described herein include 1,3-thiazolidine-2-carboxamide compounds, such as (3S)-3-([(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate or a pharmaceutically acceptable salt thereof (e.g., (3S)-3-([(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate hydrochloride. Using the compositions and methods described herein, a subject may be dosed with a PGF2α receptor antagonist and a reduced amount or frequency of nifedipine relative to the amount or frequency of nifedipine that would otherwise be used if the nifedipine were given in the absence of the PGF2α receptor antagonist.

  本发明提供了用于延缓妊娠受试者（如怀孕的人类受试者）在孕龄约24周至约34周时发生早产或有发生早产风险的组合物和方法。使用本文所述的组合物和方法，可将硝苯地平与前列腺素 F2α (PGF2α)拮抗剂联合给药。可用于治疗或预防本文所述早产的示例性 PGF2α 受体拮抗剂包括 1,3-噻唑烷-2-甲酰胺化合物，如 (3S)-3-([(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate 或其药学上可接受的盐（例如：(3S)-3-([(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-噻唑烷-2-基]羰基}-氨基}-3-(4-氟苯基)丙基）、(3S)-3-([(2S)-3-(联苯-4-基磺酰基)-1,3-噻唑烷-2-基]羰基}-氨基)-3-(4-氟苯基)丙基 L-缬氨酸盐酸盐。使用本文所述的组合物和方法，可向受试者施用 PGF2α 受体拮抗剂和硝苯地平，相对于在没有 PGF2α 受体拮抗剂的情况下施用硝苯地平的用量或次数而言，可减少硝苯地平的用量或次数。
• ALPHA-AMINO ESTERS OF HYDROXYPROPYLTHIAZOLIDINE CARBOXAMIDE DERIVATIVE AND SALT FORM, CRYSTAL POLYMORPH THEREOF
  申请人：ObsEva S.A.

  公开号：EP3397622A1

  公开（公告）日：2018-11-07
• CO-ADMINISTRATION OF ALPHA-AMINO ESTER OF HYDROXYPROPYLTHIAZOLIDINE CARBOXAMIDE DERIVATIVE AND A TOCOLYTIC AGENT
  申请人：ObsEva S.A.

  公开号：EP3397622B1

  公开（公告）日：2022-03-09
• L-VALINATE OF HYDROXYPROPYLTHIAZOLIDINE CARBOXAMIDE DERIVATIVE AND SALT FORM, CRYSTAL POLYMORPH THEREOF
  申请人：Merck Serono S.A.

  公开号：EP3400217A1

  公开（公告）日：2018-11-14