[1]熊照明.如何提高新药研发的成功率:化合物的物理化学性质的优化及其对类药性质的影响[J].常州大学学报(自然科学版),2014,(03):64-68.[doi:10.3969/j.issn.2095-0411.2014.03.013]
 XIONG Zhao-ming.How to Improve R&D Success Rate:Optimization of Physicochemical Properties and Their Impact on DrugLike Properties[J].Journal of Changzhou University(Natural Science Edition),2014,(03):64-68.[doi:10.3969/j.issn.2095-0411.2014.03.013]
点击复制

如何提高新药研发的成功率:化合物的物理化学性质的优化及其对类药性质的影响()
分享到:

常州大学学报(自然科学版)[ISSN:2095-0411/CN:32-1822/N]

卷:
期数:
2014年03期
页码:
64-68
栏目:
生物医学工程
出版日期:
2014-06-30

文章信息/Info

Title:
How to Improve R&D Success Rate:Optimization of Physicochemical Properties and Their Impact on DrugLike Properties
作者:
熊照明
美国Boehringer Ingelheim 制药公司,康乃狄克州 瑞吉费尔德 06877
Author(s):
XIONG Zhao-ming
Boehringer Ingelheim Pharmaceuticals Inc.,Ridgefield,CT 06877,USA
关键词:
理化性质 新药研发 类药性质
Keywords:
physicochemical properties new drug R&D druglike properties
分类号:
R91
DOI:
10.3969/j.issn.2095-0411.2014.03.013
文献标志码:
A
摘要:
近年来,为提高新药研发的成功率,通过对实验药物的物理化学性质进行统计分析,并和成功药物进行比较对照,试图找出化合物的物理化学性质与它们的类药性质的关系,从而可以指导新药的设计,加快新药研发的成功率和研发速度。
Abstract:
In order to improve pharmaceutical industry R&D success rate, studies have been reported on the analysis of physicochemical properties of experimental and approved drugs.Some general trends have been found from these studies on how physicochemical properties impact compounds'druglike properties.

参考文献/References:

[1]DiMasi J A,Hansen R W,Grabowski H G.The price of innovation:new estimates of drug development costs[J].J Health Econ,2003,22:151-185.
[2]Kola I,Landis J.Can the pharmaceutical industry reduce attrition rates [J].Nature Rev Drug Discov,2004,3:711-716.
[3]Abou-Gharbia M,Childers W E.Discovery of innovative therapeutics:Today's realities and tomorrow's vision.2. pharma's challenges and their commitment to innovation[J].J Med Chem,2014,doi:10.1021/jm401564r.
[4]Hornberg J J, Laursen M, Brenden N, et al. Exploratory toxicology as an integrated part of drug discovery[J].Drug Discovery Today, 2014, doi: 10.1016/j.drudis.2013.12.008.
[5]Leeson P D,Springthorpe B.The influence of drug-like concepts on decision-making in medicinal chemistry[J].Nature Rev Drug Discov,2007,6:881.
[6]Wenlock M C,Austin R P,Barton P,et al.A comparison of physiochemical property profiles of development and marketed oral drugs[J].J Med Chem,2003,46:1250.
[7]Perola E.An analysis of the binding efficiencies of drugs and their leads in successful drug discovery programs[J].J Med Chem,2010,53:2986-2997.
[8]Shultz M D.The thermodynamic basis for the use of lipophilic efficiency(LipE)in enthalpic optimizations[J].Bioorg Med Chem Lett,2013,23:5992-6000.
[9]Hopkins A L,Keseru G M,Leeson P D,et al.The role of ligand efficiency metrics in drug discovery[J].Nature Rev Drug Discov,2014,13:105-121.
[10]Lipinski C A,Lombardo F,Dominy B W,et al.Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings[J].Drug Del Rev,1997,23:3-25.
[11]Veber D F,Johnson S R,Cheng H Y,et al.Molecular properties that influencethe oral bioavailability of drug candidates[J].J Med Chem,2002,45:2615-2623.
[12]Timothy J R,Simon J F M.The impact of aromatic ring count on compound developability are too many aromatic rings a liability in drug design[J].Drug Discovery Today,2009,14:1011-1020.
[13]Lovering F,Bikker J,Humblet C.Escape from flatland:Increasing saturation as an approach to improving clinical success[J].J Med Chem,2009,52:6752-6756.
[14]Jain N,Yalkowsky S H.Estimation of the aqueous solubility Ⅰ:Appliacationto organic nonelectrolytes[J].J Pharm Sci,2001,90:234-252.
[15]Hughes J D,Blaqq J,Price D A,et al.Physiochemical drug properties associated with in vivo toxicological outcomes[J].Bioorg Med Chem Lett,2008,18:4872-4875.

备注/Memo

备注/Memo:
作者简介:熊照明(1971-),男,安徽马鞍山人,研究员,博士,主要从事新药的设计和合成研究工作。Email:zhaoming_xiong@yahoo.com
更新日期/Last Update: 2014-06-30