5-fluorothiophene-2-sulfonyl chloride | 1132652-99-3

• 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-fluorothiophene-2-sulfonyl chloride
• CAS: 1132652-99-3
• 化学式: C₄H₂ClFO₂S₂
• mdl: MFCD11215408
• 分子量: 200.642
• InChiKey: CSUVXKJWOIMNOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-fluorothiophene-2-sulfonyl chloride 、 L-异亮氨醇 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 5-fluoro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]-2-thiophenesulfonamide
  参考文献：
  名称：

  (S)-N-(5-Chlorothiophene-2-sulfonyl)-β,β-diethylalaninol a Notch-1-sparing γ-secretase inhibitor

  摘要：

  Accumulation of beta-amyloid (A beta), produced by the proteolytic cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase, is widely believed to be associated with Alzheimer's disease (AD). Research around the high-throughput screening hit (S)-4-chlorophenylsulfonyl isoleucinol led to the identification of the Notch-1-sparing (9.5-fold) gamma-secretase inhibitor (S)-N-(5-chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol 7.b.2 (A beta (40/42) EC50 = 28 nM), which is efficacious in reduction of A beta production in vivo. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.116

文献信息

• [EN] 1 -OXO-1,2-DIHYDROISOQUINOLIN-7-YL-(5-SUBSTITUTED-THIOPHEN-2-YL)-SULFONAMIDE COMPOUNDS, FORMULATIONS CONTAINING THOSE COMPOUNDS, AND THEIR USE AS AICARFT INHIBITORS IN THE TREATMENT OF CANCERS<br/>[FR] COMPOSÉS 1-OXO-1,2-DIHYDROISOQUINOLÉINE-7-YL-(5-SUBSTITUÉ-THIOPHÉN-2-YL)-SULFONAMIDE, FORMULATIONS CONTENANT CES COMPOSÉS ET LEUR UTILISATION COMME INHIBITEURS D'AICARFT DANS LE TRAITEMENT DE CANCERS
  申请人：LILLY CO ELI

  公开号：WO2016089670A1

  公开（公告）日：2016-06-09

  1-Oxo-1,2-dihydroisoquinolin-7-yl-(5-substituted-thiophen-2-yl)-sulfonamide compounds, formulations containing those compounds, and their use as AICARFT inhibitors.

  1-Oxo-1,2-二氢异喹啉-7-基-(5-取代噻吩-2-基)-磺酰胺化合物，含有这些化合物的配方，以及它们作为AICARFT抑制剂的用途。
• Discovery of <i>N</i>-(6-Fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-[(3<i>R</i>)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), a Potent and Selective Nonclassical Antifolate Aminoimidazole-4-carboxamide Ribonucleotide Formyltransferase (AICARFT) Inhibitor Effective at Tumor Suppression in a Cancer Xenograft Model
  作者：Kevin R. Fales、F. George Njoroge、Harold B. Brooks、Stefan Thibodeaux、Alicia Torrado、Chong Si、James L. Toth、Jefferson R. Mc Cowan、Kenneth D. Roth、Kenneth J. Thrasher、Kwame Frimpong、Matthew R. Lee、Robert D. Dally、Timothy A. Shepherd、Timothy B. Durham、Brandon J. Margolis、Zhipei Wu、Yong Wang、Shane Atwell、Jing Wang、Yu-Hua Hui、Timothy I. Meier、Susan A. Konicek、Sandaruwan Geeganage

  DOI：10.1021/acs.jmedchem.7b01046

  日期：2017.12.14

  novo synthesis of purine and pyrimidine bases required for DNA and RNA biosynthesis. These synthetic pathways are frequently upregulated in cancer and involve various folate-dependent enzymes. Antifolates have a proven record as clinically used oncolytic agents. Our recent research efforts have produced LSN 3213128 (compound 28a), a novel, selective, nonclassical, orally bioavailable antifolate with

  癌症的标志是不受限制的增殖，这可能导致对DNA和RNA生物合成所需的嘌呤和嘧啶碱基从头合成的需求增加。这些合成途径在癌症中经常被上调，并涉及各种叶酸依赖性酶。抗叶酸药已作为临床上使用的溶瘤剂得到了证明。我们最近的研究工作已经产生了LSN 3213128（化合物28a），这是一种新颖的，选择性的，非经典的，口服可生物利用的抗叶酸药物，对嘌呤生物合成途径中的一种酶氨基咪唑-4-羧酰胺核糖核苷酸甲酰基转移酶（AICARFT）具有有效的抑制作用。用化合物28a抑制AICARFT结果导致NCI-H460和MDA-MB-231met2癌细胞系中5-氨基咪唑4-羧酰胺核糖核苷酸（ZMP）急剧升高并抑制了生长。在基于小鼠的三阴性乳腺癌（TNBC）的异种移植模型中使用这种抑制剂进行治疗会导致肿瘤生长受到抑制。
• [EN] SPIROCYCLIC CAV2.3 ANTAGONISTS<br/>[FR] ANTAGONISTES DE CAV2.3 SPIROCYCLIQUES
  申请人：[en]LARIO THERAPEUTICS LIMITED

  公开号：WO2023094827A1

  公开（公告）日：2023-06-01

  Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof wherein X1, R3, R4, a, b, p, q, r, L, and Ring A are as defined herein. The compounds are antagonists of the resistant (R-type) voltage-gated calcium ion channel Cav 2.3. Also disclosed are pharmaceutical compositions comprising the compounds; and the compounds for use in the treatment of diseases modulated Cav 2.3, including neurodegenerative conditions such as Parkinson's disease, focal, drug-resistant forms of epilepsy, and other neurological disorders such as developmental and epileptic encephalopathies and Fragile X syndrome.
• WO2023/94830
  申请人：——

  公开号：——

  公开（公告）日：——
• (S)-N-(5-Chlorothiophene-2-sulfonyl)-β,β-diethylalaninol a Notch-1-sparing γ-secretase inhibitor
  作者：Derek C. Cole、Joseph R. Stock、Anthony F. Kreft、Madelene Antane、Suzan H. Aschmies、Kevin P. Atchison、David S. Casebier、Thomas A. Comery、George Diamantidis、John W. Ellingboe、Boyd L. Harrison、Yun Hu、Mei Jin、Dennis M. Kubrak、Peimin Lu、Charles W. Mann、Robert L. Martone、William J. Moore、Aram Oganesian、David R. Riddell、June Sonnenberg-Reines、Shaiu-Ching Sun、Erik Wagner、Zheng Wang、Kevin R. Woller、Zheng Xu、Hua Zhou、J. Steven Jacobsen

  DOI：10.1016/j.bmcl.2008.11.116

  日期：2009.2

  Accumulation of beta-amyloid (A beta), produced by the proteolytic cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase, is widely believed to be associated with Alzheimer's disease (AD). Research around the high-throughput screening hit (S)-4-chlorophenylsulfonyl isoleucinol led to the identification of the Notch-1-sparing (9.5-fold) gamma-secretase inhibitor (S)-N-(5-chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol 7.b.2 (A beta (40/42) EC50 = 28 nM), which is efficacious in reduction of A beta production in vivo. (C) 2008 Elsevier Ltd. All rights reserved.