6-氯-N-(6-甲基吡啶-2-基)烟酰胺 | 1016408-05-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 6-氯-N-(6-甲基吡啶-2-基)烟酰胺
• 英文名称: 6-chloro-N-(6-methylpyridin-2-yl)nicotinamide
• 英文别名: 6-chloro-N-(6-methylpyridine-2-yl)nicotinamide；6-chloro-N-(6-methylpyridin-2-yl)pyridine-3-carboxamide
• CAS: 1016408-05-1
• 化学式: C₁₂H₁₀ClN₃O
• mdl: MFCD10449091
• 分子量: 247.684
• InChiKey: ZZRIRLOTVWEOQO-UHFFFAOYSA-N

物化性质

• 沸点：
  333.5±42.0 °C(Predicted)
• 密度：
  1.353±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)
• 溶解度：
  >37.2 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.083
• 拓扑面积：
  54.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-氯-N-(6-甲基吡啶-2-基)烟酰胺 、 6-benzyloxy-1,2,3,4-tetrahydro-isoquinoline 以 异丙醇 为溶剂， 反应 48.0h， 以55%的产率得到N-(6-methylpyridin-2-yl)-6-(6-phenylmethoxy-3,4-dihydro-1H-isoquinolin-2-yl)pyridine-3-carboxamide
  参考文献：
  名称：

  SAR Based Design of Nicotinamides as a Novel Class of Androgen Receptor Antagonists for Prostate Cancer

  摘要：

  Molecular knowledge of pure antagonism and systematic SAR study offered a direction for structural optimization of DIMN to provide nicotinamides as a novel series of AR antagonists. Nicotinamides with extended linear scaffold bearing sterically bulky alkoxy groups on isoquinoline end were synthesized for H12 displacement AR binding affinity and molecular basis of antiandrogenic effect establish the optimized derivatives, 7au and 7bb, as promising candidates of second generation AR antagonists for advanced prostate cancer.

  DOI：

  10.1021/jm3014103
• 作为产物：
  描述：

  6-氯烟酸 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 6-氯-N-(6-甲基吡啶-2-基)烟酰胺
  参考文献：
  名称：

  SAR Based Design of Nicotinamides as a Novel Class of Androgen Receptor Antagonists for Prostate Cancer

  摘要：

  Molecular knowledge of pure antagonism and systematic SAR study offered a direction for structural optimization of DIMN to provide nicotinamides as a novel series of AR antagonists. Nicotinamides with extended linear scaffold bearing sterically bulky alkoxy groups on isoquinoline end were synthesized for H12 displacement AR binding affinity and molecular basis of antiandrogenic effect establish the optimized derivatives, 7au and 7bb, as promising candidates of second generation AR antagonists for advanced prostate cancer.

  DOI：

  10.1021/jm3014103

文献信息

• Design and synthesis of novel androgen receptor antagonists via molecular modeling
  作者：Chao Zhao、You Hee Choi、Daulat Bikram Khadka、Yifeng Jin、Kwang-Youl Lee、Won-Jea Cho

  DOI：10.1016/j.bmc.2015.12.047

  日期：2016.2

  Several androgen receptor (AR) antagonists are clinically prescribed to treat prostate cancer. Unfortunately, many patients become resistant to the existing AR antagonists. To overcome this, a novel AR antagonist candidate called DIMN was discovered by our research group in 2013. In order to develop compounds with improved potency, we designed novel DIMN derivatives based on a docking study and substituted carbons with heteroatom moieties. Encouraging in vitro results for compounds 1b, 1c, 1e, 3c, and 4c proved that the new design was successful. Among the newly synthesized compounds, 1e exhibited the strongest inhibitory effect on LNCaP cell growth (IC50 = 0.35 mu M) and also acted as a competitive AR antagonist with selectivity over the estrogen receptor (ER) and the glucocorticoid receptor (GR). A docking study of compound 1e fully supported these biological results. Compound 1e is considered to be a novel, potent and AR-specific antagonist for treating prostate cancer. Thus, our study successfully applied molecular modeling and bioisosteric replacement for hit optimization. The methods here provide a guide for future development of drug candidates through structure-based drug discovery and chemical modifications. (c) 2015 Elsevier Ltd. All rights reserved.
• [EN] NEW NICOTINAMIDE DERIVATIVES WITH ANTI-ANDROGEN EFFECTS, PROCESSES OF PREPARING, AND ANTIANDROGENS COMPRISING THE SAME<br/>[FR] NOUVEAUX DÉRIVÉS DE NICOTINAMIDE AYANT DES EFFETS ANTI-ANDROGÉNIQUES, PROCÉDÉS DE PRÉPARATION, ET ANTI-ANDROGÈNES LES COMPRENANT
  申请人：UNIV NAT CHONNAM IND FOUND

  公开号：WO2010143803A3

  公开（公告）日：2011-01-27
• SAR Based Design of Nicotinamides as a Novel Class of Androgen Receptor Antagonists for Prostate Cancer
  作者：Su Hui Yang、Chin-Hee Song、Hue Thi My Van、Eunsook Park、Daulat Bikram Khadka、Eun-Yeung Gong、Keesook Lee、Won-Jea Cho

  DOI：10.1021/jm3014103

  日期：2013.4.25

  Molecular knowledge of pure antagonism and systematic SAR study offered a direction for structural optimization of DIMN to provide nicotinamides as a novel series of AR antagonists. Nicotinamides with extended linear scaffold bearing sterically bulky alkoxy groups on isoquinoline end were synthesized for H12 displacement AR binding affinity and molecular basis of antiandrogenic effect establish the optimized derivatives, 7au and 7bb, as promising candidates of second generation AR antagonists for advanced prostate cancer.