((R)-1-formyl-2-phenylsulfanylethyl)carbamic acid tert-butyl ester | 406233-60-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: ((R)-1-formyl-2-phenylsulfanylethyl)carbamic acid tert-butyl ester
• 英文别名: tert-butyl (1R)-1-formyl-2-(phenylthio)ethylcarbamate；tert-butyl N-[(2R)-1-oxo-3-phenylsulfanylpropan-2-yl]carbamate
• CAS: 406233-60-1
• 化学式: C₁₄H₁₉NO₃S
• 分子量: 281.376
• InChiKey: ZBBFNJJUPNVBBK-LLVKDONJSA-N

物化性质

• 沸点：
  407.0±40.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ((R)-1-formyl-2-phenylsulfanylethyl)carbamic acid tert-butyl ester 在 盐酸 、 4-二甲氨基吡啶 、 叔丁基二甲硅基三氟甲磺酸酯 、 水 、 双(三甲基硅烷基)氨基钾 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 丙酮 、 乙腈 为溶剂， 反应 35.0h， 生成 (R)-3-(1-(3-(4-(N-(4-(4-(3-(2-(4-chlorophenyl)-1-isopropyl-5-methyl-4-(methylsulfonyl)-1H-pyrrol-3-yl)-5-fluorophenyl)piperazin-1-yl)phenyl)sulfamoyl)-2-(trifluoromethylsulfonyl)phenylamino)-4-(phenylthio)butyl)piperidine-4-carbonyloxy)propylphosphonic acid
  参考文献：
  名称：

  一种制备磺胺类化合物的工艺

  摘要：

  本发明涉及一种制备磺胺类化合物的工艺，所述磺胺类化合物是Bcl‑2/Bcl‑xL的抑制剂，包括化合物(3R)‑1‑(3‑(4‑(4‑(4‑(3‑(2‑(4‑氯苯基)‑1‑异丙基‑4‑甲磺酰基‑5‑甲基‑1H‑吡咯‑3‑基)‑5‑氟苯基)哌嗪‑1‑基)‑苯氨基磺酰)‑2‑三氟甲磺酰基‑苯胺基)‑4‑苯硫基‑丁基)‑哌啶‑4‑羧酸3‑膦酸基丙酯。本发明还涉及用于制备所述磺胺类化合物的中间体及其制备方法。

  公开号：

  CN111410666B
• 作为产物：
  描述：

  Boc-L-丝氨酸甲酯 在 二异丁基氢化铝 、 二异丙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.83h， 生成 ((R)-1-formyl-2-phenylsulfanylethyl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  Discovery and Structure−Activity Relationship of Antagonists of B-Cell Lymphoma 2 Family Proteins with Chemopotentiation Activity in Vitro and in Vivo

  摘要：

  Development of a rationally designed potentiator of cancer chemotherapy, via inhibition of Bcl-X-L function, is described. Lead compounds generated by NMR screening and directed parallel synthesis displayed sub mu M binding but were strongly deactivated in the presence of serum. The dominant component of serum deactivation was identified as domain III of human serum albumin (HSA); NMR solution structures of inhibitors bound to both Bcl-X-L and HSA domain III indicated two potential optimization sites for separation of affinities. Modifications at both sites resulted in compounds with improved Bcl-X-L binding and greatly increased activity in the presence of human serum, culminating in 73R, which bound to Bcl-X-L with a K-i of 0.8 nM. In a cellular assay 73R reversed the protection afforded by Bcl-X-L overexpression against cytokine deprivation in FL5.12 cells with an EC50 of 0.47 mu M. 73R showed little effect on the viability of the human non small cell lung cancer cell line A549. However, consistent with the proposed mechanism, 73R potentiated the activity of paclitaxel and UV irradiation in vitro and potentiated the antitumor efficacy of paclitaxel in a mouse xenograft model.

  DOI：

  10.1021/jm050754u

文献信息

• N-acylsulfonamide apoptosis promoters
  申请人：——

  公开号：US20020055631A1

  公开（公告）日：2002-05-09

  N-Benzoyl arylsulfonamides having the formula 1 are BCL-Xl inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-Xl inhibiting compositions and methods of promoting apoptosis in a mammal.

  N-苯甲酰芳基磺胺酰胺具有以下化学式，是BCL-Xl抑制剂，有助于促进细胞凋亡。还公开了BCL-Xl抑制组合物和在哺乳动物中促进细胞凋亡的方法。
• N-Acylsulfonamide apoptosis promoters
  申请人：——

  公开号：US20020086887A1

  公开（公告）日：2002-07-04

  N-Benzoyl arylsulfonamides having the formula 1 Are BCL-X1 inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-X1 inhibiting compositions and methods of promoting apoptosis in a mammal.

  N-苯甲酰芳基磺胺酰胺具有以下化学式，是BCL-X1抑制剂，有助于促进细胞凋亡。还公开了BCL-X1抑制组合物和在哺乳动物中促进细胞凋亡的方法。
• [EN] PROCESS FOR PREPARING SULFONAMIDE COMPOUNDS<br/>[FR] PROCÉDÉ DE PRÉPARATION DE COMPOSÉS DE SULFONAMIDE
  申请人：ASCENTAGE PHARMA SUZHOU CO LTD

  公开号：WO2020140956A1

  公开（公告）日：2020-07-09

  Provided are a process for preparing a sulfonamide compound which is an inhibitor of Bcl-2/Bcl-xL, including the compound (3R) -1- (3- (4- (4- (4- (3- (2- (4-chlorophenyl) -1-isopropyl-4-methylsulfonyl-5-methyl-1H-pyrrol-3-yl) -5-fluorophenyl) piperazine -1-yl) -phenylaminosulfonyl) -2-trifluoromethanesulfonyl-anilino) -4-ph enylthio-butyl) -piperidine-4-carboxylic acid 3-phosphonopropyl ester, an intermediate for preparing the sulfonamide compound and a preparation process thereof.

  提供了一种制备硫酰胺化合物的过程，该化合物是Bcl-2/Bcl-xL的抑制剂，包括化合物(3R)-1-(3-(4-(4-(4-(3-(2-(4-氯苯基)-1-异丙基-4-甲基磺酰基-5-甲基-1H-吡咯-3-基)-5-氟苯基)哌嗪-1-基)-苯胺磺酰基)-2-三氟甲磺酰基苯胺基)-4-苯硫基-丁基)-哌啶-4-羧酸3-磷酸丙基酯，用于制备硫酰胺化合物的中间体及其制备过程。
• N-ACYLSULFONAMIDE APOPTOSIS PROMOTERS
  申请人：Augeri David J.

  公开号：US20090137585A1

  公开（公告）日：2009-05-28

  N-Benzoyl arylsulfonamides having the formula are BCL-Xl inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-Xl inhibiting compositions and methods of promoting apoptosis in a mammal.

  具有以下式子的N-苯甲酰基芳基磺酰胺是BCL-Xl抑制剂，有助于促进细胞凋亡。本文还披露了BCL-Xl抑制剂组合物和在哺乳动物中促进细胞凋亡的方法。
• Process for preparing sulfonamide compounds
  申请人：Ascentage Pharma (Suzhou) Co., Ltd.

  公开号：US11370807B2

  公开（公告）日：2022-06-28

  The present invention relates to a process for preparing a sulfonamide compound which is an inhibitor of Bcl-2/Bcl-xL, including the compound (3R)-1-(3-(4-(4-(4-(3-(2-(4-chlorophenyl)-1-isopropyl-4-methylsulfonyl-5-methyl-1H-pyrrol-3-yl)-5-fluorophenyl)piperazine-1-yl)-phenylaminosulfonyl)-2-trifluoromethanesulfonyl-anilino)-4-phenylthio-butyl)-piperidine-4-carboxylic acid 3-phosphonopropyl ester. The present invention also relates to an intermediate for preparing the sulfonamide compound and a preparation process thereof.

  本发明涉及一种磺酰胺化合物的制备方法，该化合物是 Bcl-2/Bcl-xL 的抑制剂、包括化合物(3R)-1-(3-(4-(4-(3-(2-(4-氯苯基)-1-异丙基-4-甲基磺酰基-5-甲基-1H-吡咯-3-基)-5-氟苯基)哌嗪-1-基)-苯氨基磺酰基)-2-三氟甲磺酰基-苯胺基)-4-苯硫基丁基)-哌啶-4-羧酸 3-膦酰丙酯。本发明还涉及一种制备磺酰胺化合物的中间体及其制备工艺。