(S)-3-(2-nitro-4-sulfamoylphenylamino)-4-phenylsulfanylbutyric acid | 872866-37-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-3-(2-nitro-4-sulfamoylphenylamino)-4-phenylsulfanylbutyric acid
• 英文别名: (3S)-3-((4-(aminosulfonyl)-2-nitrophenyl)amino)-4-(phenylthio)butanoic acid；(3S)-3-(2-nitro-4-sulfamoylanilino)-4-phenylsulfanylbutanoic acid
• CAS: 872866-37-0
• 化学式: C₁₆H₁₇N₃O₆S₂
• 分子量: 411.459
• InChiKey: GMEUXIDJEIPOKO-NSHDSACASA-N

物化性质

• 沸点：
  708.7±70.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  189
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (S)-3-(2-nitro-4-sulfamoylphenylamino)-4-phenylsulfanylbutyric acid 在 4-二甲氨基吡啶 、 硼烷 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 4-((S)-3-(morpholin-4-yl)-1-phenylsulfanylmethylpropylamino)-3-nitrobenzenesulfonamide
  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
• 作为产物：
  描述：

  4-氟-3-硝基苯磺酰胺 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 (S)-3-(2-nitro-4-sulfamoylphenylamino)-4-phenylsulfanylbutyric acid
  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。
• 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。
• US6720338B2
  申请人：——

  公开号：US6720338B2

  公开（公告）日：2004-04-13
• US7504512B2
  申请人：——

  公开号：US7504512B2

  公开（公告）日：2009-03-17