5'-chloro-N-[3,3,3-trifluoro-2-(trifluoromethyl)-1-R-(hydroxymethyl)propyl]thiophene-2'-sulfonamide | 1092559-85-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 5'-chloro-N-[3,3,3-trifluoro-2-(trifluoromethyl)-1-R-(hydroxymethyl)propyl]thiophene-2'-sulfonamide
• 英文别名: (R)-5-chloro-N-(4,4,4-trifluoro-1-hydroxy-3-(trifluoromethyl)butan-2-yl)thiophene-2-sulfonamide；PF-5212362；begacestat；GSI-953；(2R)-N-(5-chlorothiophen-2-yl)-4,4,4-trifluoro-1-hydroxy-3-(trifluoromethyl)butane-2-sulfonamido；5-chloro-N-[(2R)-4,4,4-trifluoro-1-hydroxy-3-(trifluoromethyl)butan-2-yl]thiophene-2-sulfonamide
• CAS: 1092559-85-7
• 化学式: C₉H₈ClF₆NO₃S₂
• 分子量: 391.743
• InChiKey: PSXOKXJMVRSARX-BYPYZUCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  5-氯噻唑-2-磺酰氯 、 (2R)-2-amino-4,4,4-trifluoro-3-(trifluoromethyl)butan-1-ol hydrochloride 在 三乙胺 、 N,N-二(三甲基硅基)乙酰胺 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 5'-chloro-N-[3,3,3-trifluoro-2-(trifluoromethyl)-1-R-(hydroxymethyl)propyl]thiophene-2'-sulfonamide
  参考文献：
  名称：

  Discovery of Begacestat, a Notch-1-Sparing γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease

  摘要：

  SAR on HTS hits I and 2 led to the potent, Notch-l-sparing GSI 9, which lowered brain A beta in Tg2576 mice at 100 mg/kg po. Converting the metabolically labile methyl groups in 9 to trifluoromethyl groups afforded the more stable analogue 10, which had improved in vivo potency. Further side chain modification afforded the potent Notch-1-sparing GSI begacestat (5). which was selected for development for the treatment of Alzheimer's disease.

  DOI：

  10.1021/jm801252w

文献信息

• CELLS EXPRESSING A BCMA-TARGETING CHIMERIC ANTIGEN RECEPTOR, AND COMBINATION THERAPY WITH A GAMMA SECRETASE INHIBITOR
  申请人：Novartis AG

  公开号：US20200055948A1

  公开（公告）日：2020-02-20

  The invention relates to the treatment of diseases associated with expression of BCMA, in particular myelomas. The invention relates to combination therapies of a BCMA CAR-expressing cell and a gamma secretase inhibitor.
• BCMA-TARGETING AGENT, AND COMBINATION THERAPY WITH A GAMMA SECRETASE INHIBITOR
  申请人：Daley Michael

  公开号：US20200179511A1

  公开（公告）日：2020-06-11

  The invention provides compositions and methods for treating diseases associated with expression of BCMA. The invention also relates to a method of administering a BCMA-targeting agent which is an anti-BCMA antibody molecule or a recombinant non-antibody protein that binds to BCMA, and a gamma secretase inhibitor.
• TRISPECIFIC BINDING MOLECULES AGAINST CANCERS AND USES THEREOF
  申请人：GRANDA Brian

  公开号：US20210163620A1

  公开（公告）日：2021-06-03

  The present disclosure provides multispecific binding molecules that specifically bind to a first tumor-associated antigen that is expressed on cancerous B cells, a second tumor-associated antigen that is expressed on cancerous B cells, and a component of a human T-cell receptor complex, conjugates comprising the trispecific binding molecules, and pharmaceutical compositions comprising the multispecific binding molecules and the conjugates. The disclosure further provides methods of using the multispecific binding molecules to treat cancers that express the tumor-associated antigens. The disclosure yet further provides recombinant host cells engineered to express the multispecific binding molecules and methods of producing the multispecific binding molecules by culturing the host cells under conditions in which the multispecific binding molecules are expressed.
• DOSING REGIMEN AND COMBINATION THERAPIES FOR MULTISPECIFIC ANTIBODIES TARGETING B-CELL MATURATION ANTIGEN
  申请人：NOVARTIS AG

  公开号：US20220332821A1

  公开（公告）日：2022-10-20

  The present disclosure relates to dosing regimens, formulations, and combinations comprising a multispecific antibody having at least binding specificity towards B cell maturation antigen (BCMA) and a T-cell engaging arm; and methods of using such multispecific antibodies in the treatment or prevention of disease, such as, cancer.
• TRISPECIFIC BINDING MOLECULES AGAINST BCMA AND USES THEREOF
  申请人：HUANG Lu

  公开号：US20220396631A1

  公开（公告）日：2022-12-15

  The present disclosure provides multispecific binding molecules that specifically bind to BCMA, a component of a human T-cell receptor complex and either CD2 or a tumor associated antigen, conjugates comprising the multispecific binding molecules, and pharmaceutical compositions comprising the multispecific binding molecules and the conjugates The disclosure further provides methods of using the multispecific binding molecules to treat disease and disorders associated with expression of BCMA. The disclosure yet further provides recombinant host cells engineered to express the multispecific binding molecules and methods of producing the multispecific binding molecules by culturing the host cells under conditions in which the multispecific binding molecules are expressed.