期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

一种用SMILES码构建虚拟组合化学库的新方法 被引量：1

A new method for constructing virtual combinatorial chemical library by SMILES
原文传递
导出
摘要 提出了一种利用SMILES码构建虚拟组合化学库的新方法。该方法用SMILES码代表骨架和侧链,通过对其进行排列组合生成虚拟组合化学库。用户可设定ADME筛选条件对生成的库进行初筛,以舍弃在理论上药代动力学行为不好的分子。该法通过构建一个抗2型糖尿病药物虚拟组合化学库(A2DDVCL)而得到了验证。A2DDVCL建立在过氧化物酶增殖体活化受体(PPAR)配体的基础上,拟从其中发现治疗慢性代谢疾病特别是2型糖尿病的药物。 This article brings forward a new method for constructing virtual combinatorial library by SMILES. Backbone and sidechains were denoted by SMILES, and they were permutated and combinated to form virtual combinatorial library. The users could set ADME filters to discard molecules which may have bad pharmacokinetics behaviors. This method was verified by constructing an Anti Type 2 Diabetic Drug Virtual Combinatorial Library (A2DDVCL) which based on the ligands of Peroxisome Proliferator-Activated Receptors (PPAR) , a nuclear receptor.
作者 廖晨钟 石乐明 周家驹 鲁先平
机构地区 深圳微芯生物科技有限公司 中国科学院过程工程研究所
出处 《计算机与应用化学》 CAS CSCD 北大核心 2005年第4期247-252,共6页 Computers and Applied Chemistry
基金 国家十五重大科技专项"创新药物与中药现代化"资助项目(2002AA223146)3项国家863资助项目(2002AA234041 2002AA234021 2002AAl04270)广东省2002年重大项目招标中标项目(2002-108)
关键词 SMILES码 虚拟组合化学库 PPAR 2型糖尿病 药物发现 SMILES, virtual combinatorial library, PPAR, type 2 diabetes, drug discovery
分类号 R914.2 [医药卫生—药物化学]
  • 相关文献

参考文献15

  • 1Agrafiotis DK, Lobanov VS and Salemme FR. Combinatorial informatics in the post-genomics ERA. Nature Reviews, Drug Discovery,2002,1:337-346.
  • 2Huc I and Lean JM. Virtual combinatorial libraries: Dynamic generation of molecular and supramolecular diversity by self-assembly.Proc Natl Acad Sci USA, 1997, 94:2106 - 2110.
  • 3Weininger D. SMILES 1. Introduction and encoding rules. J Chem Inf Comput Sci. 1988. 28:31-36.
  • 4Willson TM, Brown PJ and Sternbach DD, et al. The PPARs:From orphan receptors to drug discovery. J Med Chem, 2000, 43:527 -550.
  • 5Wang YX, Lee CH and Tiep S, et al. Peroxisome-Proliferator-Activated receptor B activates fat metabolism to prevent obesity. Cell,2003, 113:159 - 170.
  • 6Mogensen JP, Jeppesen L and Bury PS, et al. Desigan and synthesis of novel PPAR α/γ/δ triple activators using a known PPAR α/γ dual activator as structural template. Bioorg Med Chem Lett, 2003,13:257 - 260.
  • 7Sauerberg P, Bury PS and Mogensen JP, et al. Large dimeric ligands with favorable pharmacokinetic properties and peroxisome proliferator-activated receptor agonist activity in vitro and in vivo. J Med Chem, 2003, 46:4883 -4894.
  • 8Lipinski CA, Lombardo F and Dominy BW, et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev,1997,23:3-25.
  • 9Xu J. Drug-like Index:A new approach to measure drug - like compounds and their diveristy. J Chem Inf Comput Sci, 2000, 40 : 1177- 1187.
  • 10Wang RX, Fu Y and Lai LH. A new atom-Additive method for calculating partition coefficients. J Chem Inf Comput Sci,1997,37:615 -621.

共引文献8

同被引文献17

  • 1舒祝明.血管紧张素Ⅱ受体拮抗剂的临床应用[J].中国药物与临床,2005,5(1):43-45. 被引量：5
  • 2苏青,周鲁.基于构效关系的非肽类血管紧张素Ⅱ受体阻滞剂分子设计[J].中国新药杂志,2006,15(7):537-541. 被引量：1
  • 3Agrafiotis DK, Lobanov VS, Salemme FR. Combinatorial informatics in the post - genomics ERA. Nat Rev Drug Discov. 2002, 1 ( 2 ) : 337 - 346
  • 4Drewry DH,Yong SS. Approaches to the design of combinatorial libraries. Chemometr Intell Lab. 1999,48( 1 ) :1
  • 5Huc I, Lean JM. Virtual combinatorial libraries: Dynamic generation of molecular and supramolecular diversity by self - assembly. Pro Natl Acad Sci. 1997,94(22) :2106
  • 6Kick EK. Structure - based design and combinatorial chemistry yield low nanomolar inhibitors of cathepsin D. Chem Biol. 1997,4(2) : 297
  • 7Tasir SH. , Skillman AG, Christima EL, et al. Potent, low molecular weight non - peptide inhibitors of malarial aspartyl protease plasmepsin Ⅱ. J Chem lnf Comput. Sci , 1999,42 (8) :1428
  • 8Lipinski CA,Lombardo F,Domlny BW,et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 1997,23(1):3
  • 9Matsoukas J M, Bigam G, Zhou N. ^1 H - NMR studies of [ Sar^1 ] angiotensin Ⅱ conformation by nuclear Over- hause effect spectroscopy in the rotating frame (ROESY) :Clustering of the aromatic rings in dimethylsulfoxide. Peptides. 1990,11 (2) :359
  • 10Matsoukas J M, Polevaya L,Ancans J,et al. The design and synthesis of a potent angiotensin Ⅱ cyclic analogue confirms the ring cluster receptor conformation of the hormone angiotensin Ⅱ. Bioorg Med Chem. 2000,8 ( 1 ) :1

引证文献1

计算机与应用化学
2005年 第4期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部