N-hydroxy-3-{1-[3-(4-isopropyl-phenyl)-propyl]-2-oxo-2,5-dihydro-1H-pyrrol-3-yl}-propionamide | 798543-27-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-hydroxy-3-{1-[3-(4-isopropyl-phenyl)-propyl]-2-oxo-2,5-dihydro-1H-pyrrol-3-yl}-propionamide
• 英文别名: N-hydroxy-3-[5-oxo-1-[3-(4-propan-2-ylphenyl)propyl]-2H-pyrrol-4-yl]propanamide
• CAS: 798543-27-8
• 化学式: C₁₉H₂₆N₂O₃
• 分子量: 330.427
• InChiKey: YCBDRHADLNRBCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-methoxy-2-methylene-5-oxopentanoic acid 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 4-二甲氨基吡啶 、 羟胺钾盐 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N-hydroxy-3-{1-[3-(4-isopropyl-phenyl)-propyl]-2-oxo-2,5-dihydro-1H-pyrrol-3-yl}-propionamide
  参考文献：
  名称：

  基于内酰胺的HDAC抑制剂用于抗癌化学疗法：通过翻译后修饰和表观遗传控制恢复RUNX3

  摘要：

  肿瘤抑制子相关转录因子3（RUNX3）的表达和稳定性受组蛋白脱乙酰基酶（HDAC）调节。HDAC抑制会改变RUNX3的表观遗传和翻译后稳定性，从而导致肿瘤抑制。但是，HDAC抑制剂可以通过染色质重塑非选择性地改变全局基因的表达。因此，筛选了基于内酰胺的HDAC抑制剂以鉴定有效的蛋白质稳定剂，该稳定剂可通过乙酰化保持RUNX3的稳定性。通过基于细胞的RUNX激活和HDAC抑制测定法确定了111种基于内酰胺的类似物的RUNX活性和HDAC抑制作用。3- [1-（4-溴苄基）-2-氧代-2,5-二氢-1 H-吡咯-3-基] -N-羟基丙酰胺（11-8）可显着提高RUNX3的乙酰化和稳定性，并具有相对较低的RUNX3 mRNA表达和HDAC抑制活性。在MKN28异种移植模型中，该化合物显示出显着的抗肿瘤作用，比SAHA强。因此，我们提出了一种新的策略，其中HDAC抑制剂用作选择性靶向RUNX3的表

  DOI：

  10.1002/cmdc.201300393

文献信息

• [EN] NOVEL 2-OXO-HETEROCYCLIC COMPOUNDS AND THE PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME<br/>[FR] NOUVEAUX COMPOSES 2-OXO-HETEROCYCLIQUES ET COMPOSITIONS PHARMACEUTIQUES CONTENANT CES COMPOSES
  申请人：KOREA RES INST OF BIOSCIENCE

  公开号：WO2004101523A1

  公开（公告）日：2004-11-25

  The present invention is related to new 2-oxo-cyclic compound the process for preparing them and a pharmaceutical composition comprising the same. The present invention provides a pharmaceutical composition for preventing and treating the inflammatory disease comprising the pain or inflammation caused by rheumatic disease, for example, rheumatoid arthritis, spondyloarthopathies, gout, osteoarthritis, systemic lupus erythematosus and juvenile arthritis, and inflammatory syndrome for example, from myositis, gingivitis, synovitis, ankylosing spondylitis, burstitis, burns and scar, inflammatory Crohn's disease, Types I diabetes. therefore, it can be used as the therapeutics for treating and preventing inflammatory diseases.

  本发明涉及新的2-氧代环化合物及其制备方法和包含其的药物组合物。本发明提供了一种用于预防和治疗炎症性疾病的药物组合物，包括由风湿性疾病引起的疼痛或炎症，例如类风湿性关节炎、脊柱关节病、痛风、骨关节炎、全身性红斑狼疮和儿童关节炎，以及炎症综合征，例如肌炎、牙龈炎、滑囊炎、强直性脊柱炎、滑囊炎、烧伤和疤痕、炎症性克罗恩病、I型糖尿病等。因此，它可以用作治疗和预防炎症性疾病的治疗药物。
• Use of novel 2-oxo-heterocyclic compounds and the pharmaceutical compositions comprising the same
  申请人：Han Hee Gyoon

  公开号：US20060173043A1

  公开（公告）日：2006-08-03

  The present invention is related to novel use of 2-oxo-heterocyclic compounds having anticancer activity and the process for preparing them and a pharmaceutical composition comprising the same. The present invention provides a pharmaceutical composition for preventing and treating the cancer disease comprising lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head and neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer or cancer of the anal region, stomach cancer, colon cancer, breast cancer, gynecologic tumors, Hodgkin's disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, sarcomas of soft tissues, cancer of the urethra, cancer of the penis, prostate cancer, chronic or acute leukemia, solid tumors of childhood, lymphocytic lymphonas, cancer of the bladder, cancer of the kidney or ureter, or neoplasms of the central nervous system, therefore, it can be used as the therapeutics for treating and preventing cancer diseases.

  本发明涉及具有抗癌活性的2-氧代杂环化合物的新用途及其制备过程，以及包含它们的药物组合物。本发明提供了一种用于预防和治疗肺癌、骨癌、胰腺癌、皮肤癌、头颈部癌症、皮肤或眼内黑色素瘤、子宫癌、卵巢癌、直肠癌或肛门区癌症、胃癌、结肠癌、乳腺癌、妇科肿瘤、霍奇金病、食管癌、小肠癌、内分泌系统癌症、软组织肉瘤、尿道癌、阴茎癌、前列腺癌、慢性或急性白血病、儿童实体瘤、淋巴细胞性淋巴瘤、膀胱癌、肾或输尿管癌或中枢神经系统肿瘤的药物组合物，因此，它可以用作治疗和预防癌症疾病的治疗药物。
• Novel 2-oxo-heterocyclic compounds and the pharmaceutical compositions comprising the same
  申请人：Kho Hee Yung

  公开号：US20070167486A1

  公开（公告）日：2007-07-19

  The present invention is related to new 2-oxo-cyclic compound the process for preparing them and a pharmaceutical composition comprising the same. The present invention provides a pharmaceutical composition for preventing and treating the inflammatory disease comprising the pain or inflammation caused by rheumatic disease, for example, rheumatoid arthritis, spondyloarthopathies, gout, osteoarthritis, systemic lupus erythematosus and juvenile arthritis, and inflammatory syndrome for example, from myositis, gingivitis, synovitis, ankylosing spondylitis, burstitis, burns and scar, inflammatory Crohn's disease, Types I diabetes. therefore, it can be used as the therapeutics for treating and preventing inflammatory diseases.

  本发明涉及新的2-氧代环状化合物及其制备方法和包含它们的药物组合物。本发明提供了一种用于预防和治疗炎症性疾病的药物组合物，包括由风湿性疾病引起的疼痛或炎症，例如风湿性关节炎、脊柱关节病、痛风、骨关节炎、全身性红斑狼疮和儿童关节炎，以及炎症综合征，例如肌炎、牙龈炎、滑膜炎、强直性脊柱炎、滑囊炎、烧伤和疤痕、炎性克罗恩病、1型糖尿病等。因此，它可以用作治疗和预防炎症性疾病的治疗剂。
• Novel 2-Oxo-Heterocyclic Compounds And The Pharmaceutical Compositions Comprising The Same
  申请人：KHO Yung Hee

  公开号：US20100286207A1

  公开（公告）日：2010-11-11

  The present invention is related to new 2-oxo-cyclic compound, the process for preparing them and a pharmaceutical composition comprising the same. The present invention provides a pharmaceutical composition for preventing and treating the inflammatory disease comprising the pain or inflammation caused by rheumatic disease, for example, rheumatoid arthritis, spondyloarthopathies, gout, osteoarthritis, systemic lupus erythematosus and juvenile arthritis, and inflammatory syndrome for example, from myositis, gingivitis, synovitis, ankylosing spondylitis, burstitis, burns and scar, inflammatory Crohn's disease, Types I diabetes. therefore, it can be used as the therapeutics for treating and preventing inflammatory diseases.

  本发明涉及一种新的2-氧代环状化合物、其制备方法以及包含其的药物组合物。本发明提供了一种预防和治疗炎症性疾病的药物组合物，包括由风湿性疾病引起的疼痛或炎症，例如风湿性关节炎、脊柱关节病、痛风、骨关节炎、系统性红斑狼疮和少年关节炎，以及由肌炎、牙龈炎、滑膜炎、强直性脊柱炎、滑囊炎、烧伤和瘢痕、炎症性克罗恩病、1型糖尿病等引起的炎症综合征。因此，它可以用作治疗和预防炎症性疾病的治疗药物。
• Property-Based Optimization of Hydroxamate-Based γ-Lactam HDAC Inhibitors to Improve Their Metabolic Stability and Pharmacokinetic Profiles
  作者：Eunhyun Choi、Chulho Lee、Misun Cho、Jeong Jea Seo、Jee Sun Yang、Soo Jin Oh、Kiho Lee、Song-Kyu Park、Hwan Mook Kim、Ho Jeong Kwon、Gyoonhee Han

  DOI：10.1021/jm3009376

  日期：2012.12.13

  Hydroxamate-based HDAC inhibitors have promising anticancer activities but metabolic instability and poor pharmacokinetics leading to poor in vivo results. QSAR and PK studies of HDAC inhibitors showed that a gamma-lactam core and a modified cap group, including halo, alkyl, and alkoxy groups with various carbon chain linkers, improved HDAC inhibition and metabolic stability. The biological properties of the gamma-lactam HDAC inhibitors were evaluated; the compound designated 8f had potent anticancer activity and high oral bioavailability.