1-(cyclopropylsulfonyl)piperazine | 1043529-57-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(cyclopropylsulfonyl)piperazine
• 英文别名: cyclopropylsulfonyl-piperazine；1-cyclopropylsulfonylpiperazine
• CAS: 1043529-57-2
• 化学式: C₇H₁₄N₂O₂S
• 分子量: 190.266
• InChiKey: ZLBFRRMSHIALOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  57.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(cyclopropylsulfonyl)piperazine 、 4-(4-cyano-4-methylpiperidin-1-yl)-6-fluoroquinoline-3-carboxylic acid 在 盐酸 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 1-(3-(4-(cyclopropylsulfonyl)piperazine-1-carbonyl)-6-fluoroquinolin-4-yl)-4-methylpiperidine-4-carbonitrile
  参考文献：
  名称：

  Discovery of Orally Bioavailable, Quinoline-Based Aldehyde Dehydrogenase 1A1 (ALDH1A1) Inhibitors with Potent Cellular Activity

  摘要：

  Aldehyde dehydrogenases (ALDHs) are responsible for the metabolism of aldehydes (exogenous and endogenous) and possess vital physiological and toxicological functions in areas such as CNS, inflammation, metabolic disorders, and cancers. Overexpression of certain ALDHs (e.g., ALDHIAI) is an important biomarker in cancers and cancer stem cells (CSCs) indicating the potential need for the identification and development of small molecule ALDH inhibitors. Herein, a newly designed series of quinoline-based analogs of ALDH1A1 inhibitors is described. Extensive medicinal chemistry optimization and biological characterization led to the identification of analogs with significantly improved enzymatic and cellular ALDH inhibition. Selected analogs, e.g., 86 (NCT-505) and 91 (NCT-506), demonstrated target engagement in a cellular thermal shift assay (CETSA), inhibited the formation of 3D spheroid cultures of OV-90 cancer cells, and potentiated the cytotoxicity of paclitaxel in SKOV-3-TR, a paclitaxel resistant ovarian cancer cell line. Lead compounds also exhibit high specificity over other ALDH isozymes and unrelated dehydrogenases. The in vitro ADME profiles and pharmacokinetic evaluation of selected analogs are also highlighted.

  DOI：

  10.1021/acs.jmedchem.8b00270
• 作为产物：
  描述：

  tert-butyl 4-(cyclopropylsulfonyl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 1-(cyclopropylsulfonyl)piperazine
  参考文献：
  名称：

  新型磺胺类药物通过肿瘤丙酮酸激酶 M2 激活成为有效的抗肺癌药物

  摘要：

  这种理性的追求导致一种新型磺酰胺衍生物被鉴定为一种有效的抗肺癌（LC）化合物。考虑到这些结果，我们合成了 38 种具有不同骨架结构的新型磺酰胺衍生物。在评估一组癌细胞系后，体外细胞毒性测定揭示了对 A549 细胞的有效且选择性的抗增殖作用。化合物9b已成为肿瘤丙酮酸激酶 M2 (PKM2) 的有效激活剂，这是一种已知在 LC 中发挥关键作用的蛋白质。细胞凋亡测定和细胞周期分析表明早期细胞​​凋亡和 G2 期停滞。计算机模拟研究证明了化合物9b与 PKM2 激活剂结合位点之间的相互作用。表面等离子共振 (SPR) 实验强烈表明9b对 PKM2 具有高亲和力（ K d为 1.378 nM）。此外，活性氧的增加和乳酸浓度的降低表明化合物9b具有显着的抗癌作用。值得注意的是， 9b处理后粒径的增加表明 PKM2 发生四聚化。这项工作提供的见解可能会推动开发有效的非铂类抗癌药物的努力。

  DOI：

  10.1039/d4md00367e

文献信息

• INDOL-2-YL-PIPERAZIN-1-YL-METHANONE DERIVATIVES
  申请人：Nettekoven Matthias

  公开号：US20080188484A1

  公开（公告）日：2008-08-07

  The present invention relates to compounds of formula I wherein A and R 1 to R 4 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.

  本发明涉及公式I的化合物，其中A和R1至R4如描述和声明中所定义，并且其药学上可接受的盐。这些化合物可用于治疗和/或预防与H3受体调节相关的疾病。
• [EN] CYCLOBUTYL SUBSTITUTED PYRROLOPYRIDINE AND PYRROLOPYRIMIDINE DERIVATIVES AS JAK INHIBITORS<br/>[FR] DÉRIVÉS PYRROLOPYRIDINE ET PYRROLOPYRIMIDINE À SUBSTITUTION CYCLOBUTYLE UTILISÉS COMME INHIBITEURS DES JAK
  申请人：INCYTE CORP

  公开号：WO2012068450A1

  公开（公告）日：2012-05-24

  The present invention provides cyclobutyl substituted pyrrolopyrimidines and pyrrolopyridines of Formula I: wherein X, Y, Z, L, A, R5, n and m are defined above, as well as their compositions and methods of use, that modulate the activity of Janus kinases (JAKs) and are useful in the treatment of diseases related to the activity of JAKs including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.

  本发明提供了式I的环丁基取代的吡咯并嘧啶和吡咯并吡啶：其中X、Y、Z、L、A、R5、n和m如上定义，以及它们的组合物和使用方法，用于调节Janus激酶（JAKs）的活性，并且在治疗与JAKs活性相关的疾病中是有用的，例如炎症性疾病、自身免疫疾病、癌症和其他疾病。
• [EN] BENZOPYRANE AND IMIDAZOLE DERIVATIVES USEFUL FOR THE STABILIZATION OF AMYLOIDOGENIC IMMUNOGLOBULIN LIGHT CHAINS<br/>[FR] DÉRIVÉS DE STABILISATION DE BENZOPYRANE ET D'IMIDAZOLE UTILISÉS POUR LA STABILISATION DE CHAÎNES LÉGÈRES D'IMMUNOGLOBULINES AMYLOÏDOGÉNIQUES
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2020205683A1

  公开（公告）日：2020-10-08

  In immunoglobulin light chain amyloidosis (AL), the unique antibody light chain (LC) protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. For treating AL patients, such as those with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, provided herein are small molecule compounds of Formula Ia, Formula Ib, and Formula II that are kinetic stabilizers of the native dimeric structure of full-length LCs, which compounds can slow or stop the amyloidogenicity cascade at its origin.

  在免疫球蛋白轻链淀粉样变性（AL）中，每位患者体内由单克隆浆细胞分泌的独特抗体轻链（LC）蛋白会错误折叠和/或聚集，导致器官退化的过程。为了治疗AL患者，例如那些存在严重心脏受累且难以耐受现有化疗方案的患者，本文提供了化学式Ia、化学式Ib和化学式II的小分子化合物，这些化合物是全长LC的动力学稳定剂，可以减缓或停止淀粉样生成性级联反应的起源。
• [EN] FUSED DIHYDROPYRANS AS GPR119 MODULATORS FOR THE TREATMENT OF DIABETES, OBESITY AND RELATED DISEASES<br/>[FR] DIHYDROPYRANNES FONDUS UTILISÉS COMME MODULATEURS DE GPR119 POUR TRAITER LE DIABÈTE, L'OBÉSITÉ ET LES MALADIES ASSOCIÉES
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012080476A1

  公开（公告）日：2012-06-21

  The present invention relates to compounds of general formula (I), wherein the groups R1, LP, LQ, X1, X2, X3, Ar and n are as defined in the application, which have valuable pharmacological properties, and in particular bind to the GPR119 receptor and modulate its activity.

  本发明涉及一般式（I）的化合物，其中基团R1、LP、LQ、X1、X2、X3、Ar和n如申请中所定义，具有有价值的药理特性，特别是结合到GPR119受体并调节其活性。
• Compounds, pharmaceutical compositions and uses thereof
  申请人：HIMMELSBACH Frank

  公开号：US20120322784A1

  公开（公告）日：2012-12-20

  The present invention relates to compounds of formula I, wherein the groups R 1 , L P , L Q , X 1 , X 2 , X 3 , Ar and n are as defined in the application, which have valuable pharmacological properties, and in particular bind to the GPR119 receptor and modulate its activity.

  本发明涉及公式I的化合物， 其中R 1 ，LP，LQ，X 1 ，X 2 ，X 3 ，Ar和n的定义如申请中所述，具有有价值的药理特性，特别是结合GPR119受体并调节其活性。