Diversity-oriented synthesis-facilitated medicinal chemistry: toward the development of novel antimalarial agents.
Diversity-oriented synthesis-facilitated medicinal chemistry: toward the development of novel antimalarial agents.
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DOI：
10.1021/jm500994n
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发表时间：
2014-10-23
影响因子：
7.3
通讯作者：
Schreiber SL
中科院分区：
文献类型：
--
作者：
Comer E;Beaudoin JA;Kato N;Fitzgerald ME;Heidebrecht RW;Lee Md 4th;Masi D;Mercier M;Mulrooney C;Muncipinto G;Rowley A;Crespo-Llado K;Serrano AE;Lukens AK;Wiegand RC;Wirth DF;Palmer MA;Foley MA;Munoz B;Scherer CA;Duvall JR;Schreiber SL
在这里，我们描述了通过多样性导向的合成（DOS）途径加速的药物化学，以及我们之前报道的源自该合成途径的大环抗疟药的体内研究。关注附肢和骨骼特征的结构-活性关系产生了一种恶性疟原虫无性血液阶段生长的纳摩尔抑制剂，具有改善的溶解度和微粒体稳定性并减少了 hERG 结合。用于制备原始筛选文库的构建/偶联/配对 (B/C/P) 合成策略促进了抗疟先导化合物的药物化学优化。
Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic pathway. Structure–activity relationships that focused on both appendage and skeletal features yielded a nanomolar inhibitor of P. falciparum asexual blood-stage growth with improved solubility and microsomal stability and reduced hERG binding. The build/couple/pair (B/C/P) synthetic strategy, used in the preparation of the original screening library, facilitated medicinal chemistry optimization of the antimalarial lead.
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影响因子：
4.2
作者：
Heidebrecht, Richard W., Jr.;Mulrooney, Carol;Austin, Christopher P.;Barker, Robert H., Jr.;Beaudoin, Jennifer A.;Cheng, Ken Chih-Chien;Comer, Eamon;Dandapani, Sivaraman;Dick, Justin;Duvall, Jeremy R.;Ekland, Eric H.;Fidock, David A.;Fitzgerald, Mark E.;Foley, Michael;Guha, Rajarshi;Hinkson, Paul;Kramer, Martin;Lukens, Amanda K.;Masi, Daniela;Marcaurelle, Lisa A.;Su, Xin-Zhuan;Thomas, Craig J.;Weiwer, Michel;Wiegand, Roger C.;Wirth, Dyann;Xia, Menghang;Yuan, Jing;Zhao, Jinghua;Palmer, Michelle;Munoz, Benito;Schreiber, Stuart
通讯作者：
Schreiber, Stuart
影响因子：
17.1
作者：
Nilsen A;LaCrue AN;White KL;Forquer IP;Cross RM;Marfurt J;Mather MW;Delves MJ;Shackleford DM;Saenz FE;Morrisey JM;Steuten J;Mutka T;Li Y;Wirjanata G;Ryan E;Duffy S;Kelly JX;Sebayang BF;Zeeman AM;Noviyanti R;Sinden RE;Kocken CHM;Price RN;Avery VM;Angulo-Barturen I;Jiménez-Díaz MB;Ferrer S;Herreros E;Sanz LM;Gamo FJ;Bathurst I;Burrows JN;Siegl P;Guy RK;Winter RW;Vaidya AB;Charman SA;Kyle DE;Manetsch R;Riscoe MK
通讯作者：
Riscoe MK
影响因子：
15
作者：
Marcaurelle, Lisa A.;Comer, Eamon;Dandapani, Sivaraman;Duvall, Jeremy R.;Gerard, Baudouin;Kesavan, Sarathy;Lee, Maurice D.;Liu, Haibo;Lowe, Jason T.;Marie, Jean-Charles;Mulrooney, Carol A.;Pandya, Bhaumik A.;Rowley, Ann;Ryba, Troy D.;Suh, Byung-Chul;Wei, Jingqiang;Young, Damian W.;Akella, Lakshmi B.;Ross, Nathan T.;Zhang, Yan-Ling;Fass, Daniel M.;Reis, Surya A.;Zhao, Wen-Ning;Haggarty, Stephen J.;Palmer, Michelle;Foley, Michael A.
通讯作者：
Foley, Michael A.
影响因子：
3.6
作者：
Lowe, Jason T.;Lee, Maurice D.;Marcaurelle, Lisa A.
通讯作者：
Marcaurelle, Lisa A.