N,N-双(4-甲氧基苄基)-4-溴苯磺酰胺 | 192767-23-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N,N-双(4-甲氧基苄基)-4-溴苯磺酰胺
• 中文别名: 4-溴-N，N-双(4-甲氧基苄基)苯磺酰胺
• 英文名称: 4-bromo-N,N-bis(4-methoxybenzyl)benzenesulfonamide
• 英文别名: Benzenesulfonamide, 4-bromo-N,N-bis[(4-methoxyphenyl)methyl]-；4-bromo-N,N-bis[(4-methoxyphenyl)methyl]benzenesulfonamide
• CAS: 192767-23-0
• 化学式: C₂₂H₂₂BrNO₄S
• 分子量: 476.391
• InChiKey: YYLDNQJUMNGLLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  64.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-N¹,N¹-dimethyl-4-(phenylthio)butane-1,3-diamine 、 N,N-双(4-甲氧基苄基)-4-溴苯磺酰胺 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 甲苯 为溶剂， 反应 15.0h， 以60%的产率得到4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-N,N-bis[(4-methoxyphenyl)methyl]benzenesulfonamide
  参考文献：
  名称：

  Discovery of an Orally Bioavailable Small Molecule Inhibitor of Prosurvival B-Cell Lymphoma 2 Proteins

  摘要：

  Overexpression of prosurvival proteins such as Bcl-2 and Bcl-X-L has been correlated with tumorigenesis and resistance to chemotherapy, and thus, the development of antagonists of these proteins may provide a novel means for the treatment of cancer. We recently described the discovery of 1 (ABT-737), which binds Bcl-2, Bcl-X-L, and Bcl-w with high affinity, shows robust antitumor activity in murine tumor xenograft models, but is not orally bioavailable. Herein, we report that targeted modifications at three key positions of 1 resulted in a 20-fold improvement in the pharmacokinetic/pharmacodynamic relationship (PK/PD) between oral exposure (AUC) and in vitro efficacy in human tumor cell lines (EC50). The resulting compound, 2 (ABT-263), is orally efficacious in an established xenograft model of human small cell lung cancer, inducing complete tumor regressions in all animals. Compound 2 is currently in multiple phase 1 clinical trials in patients with small cell lung cancer and hematological malignancies.

  DOI：

  10.1021/jm800669s
• 作为产物：
  描述：

  bis(p-methoxybenzyl)ammonium tosylate 、 4-溴苯磺酰氯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以89%的产率得到N,N-双(4-甲氧基苄基)-4-溴苯磺酰胺
  参考文献：
  名称：

  Discovery of an Orally Bioavailable Small Molecule Inhibitor of Prosurvival B-Cell Lymphoma 2 Proteins

  摘要：

  Overexpression of prosurvival proteins such as Bcl-2 and Bcl-X-L has been correlated with tumorigenesis and resistance to chemotherapy, and thus, the development of antagonists of these proteins may provide a novel means for the treatment of cancer. We recently described the discovery of 1 (ABT-737), which binds Bcl-2, Bcl-X-L, and Bcl-w with high affinity, shows robust antitumor activity in murine tumor xenograft models, but is not orally bioavailable. Herein, we report that targeted modifications at three key positions of 1 resulted in a 20-fold improvement in the pharmacokinetic/pharmacodynamic relationship (PK/PD) between oral exposure (AUC) and in vitro efficacy in human tumor cell lines (EC50). The resulting compound, 2 (ABT-263), is orally efficacious in an established xenograft model of human small cell lung cancer, inducing complete tumor regressions in all animals. Compound 2 is currently in multiple phase 1 clinical trials in patients with small cell lung cancer and hematological malignancies.

  DOI：

  10.1021/jm800669s

文献信息

• [EN] SSTR5 ANTAGONISTS<br/>[FR] ANTAGONISTES DE SSTR5
  申请人：KALLYOPE INC

  公开号：WO2021113368A1

  公开（公告）日：2021-06-10

  This disclosure is directed, at least in part, to SSTR5 antagonists useful for the treatment of conditions or disorders involving the gut-brain axis. In some embodiments, the SSTR5 antagonists are gut-restricted compounds. In some embodiments, the condition or disorder is a metabolic disorder, such as diabetes, obesity, nonalcoholic steatohepatitis (NASH), or a nutritional disorder such as short bowel syndrome.

  这项披露至少部分针对SSTR5拮抗剂，用于治疗涉及肠脑轴的疾病或疾病。在某些实施例中，SSTR5拮抗剂是肠限制性化合物。在某些实施例中，该疾病或疾病是代谢性疾病，如糖尿病、肥胖症、非酒精性脂肪肝炎（NASH）或营养紊乱，如短肠综合征。
• [EN] TRI-ARYL ETHANE DERIVATIVES AS PDE IV INHIBITORS<br/>[FR] DERIVES D'ETHANE TRI-ARYLE UTILISES COMME INHIBITEURS DE PDE IV
  申请人：MERCK FROSST CANADA INC.

  公开号：WO1997022586A1

  公开（公告）日：1997-06-26

  (EN) The invention encompasses the novel compound of formula (I), useful in the treatment of diseases, including asthma, by raising the level of cyclic adenosine-3',5'-monophosphate (cAMP) through the inhibition of phosphodiesterase IV (PDE IV). The invention also encompasses certain pharmaceutical compositions and methods for treatment of diseases by inhibition of PDE IV, resulting in an elevation of cAMP, comprising the use of compounds of Formula (I).(FR) Nouveau composé de formule (I) utilisé pour traiter des maladies, y compris l'asthme, par augmentation du niveau d'adénosine-3',5'-monophosphate cyclique (cAMP), cette augmentation étant obtenue par l'inhibition de la phosphodiestérase IV (PDE IV). L'invention se rapporte également à certaines compositions pharmaceutiques et à des méthodes de traitement des maladies par inhibition de la PDE IV, entraînant une augmentation de cAMP, ces méthodes consistant à utiliser des composés de la formule (I).

  该发明涵盖了化合物(I)的新颖结构，通过抑制磷酸二酯酶IV（PDE IV）提高环磷酸腺苷-3'，5'-单磷酸（cAMP）水平，用于治疗包括哮喘在内的疾病。该发明还涵盖了某些药物组合物和通过抑制PDE IV治疗疾病的方法，导致cAMP升高，包括使用化合物(I)的方法。
• Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof
  申请人：ENANTA PHARMACEUTICALS, INC.

  公开号：US10457703B2

  公开（公告）日：2019-10-29

  The present invention provides compounds represented by Formula I, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates or combination thereof, The invention also provides pharmaceutical compositions comprising these compounds and methods of using this compounds for treating FXR-mediated or TGR5-mediated diseases or conditions.

  本发明提供了式 I 所代表的化合物或其药学上可接受的盐、立体异构体、溶液剂、水合物或其组合、 本发明还提供了包含这些化合物的药物组合物以及使用这些化合物治疗 FXR 介导或 TGR5 介导的疾病或病症的方法。
• TRI-ARYL ETHANE DERIVATIVES AS PDE IV INHIBITORS
  申请人：MERCK FROSST CANADA INC.

  公开号：EP0873311A1

  公开（公告）日：1998-10-28
• BILE ACID DERIVATIVES AS FXR/TGR5 AGONISTS AND METHODS OF USE THEREOF
  申请人：Enanta Pharmaceuticals, Inc.

  公开号：EP3277286A1

  公开（公告）日：2018-02-07