Antifolate agents: a patent review (2006 - 2010).
Antifolate agents: a patent review (2006 - 2010).
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DOI：
10.1517/13543776.2011.587804
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发表时间：
2011-09
影响因子：
6.6
通讯作者：
Anderson AC
中科院分区：
文献类型：
--
作者：
Wright DL;Anderson AC
50多年来，靶向叶酸途径的药物作为抗癌、抗微生物和免疫调节剂对疾病治疗产生了重大影响。在学术界和制药工业中，发现具有改进的性质和上级活性的新型抗叶酸剂仍然是一个有吸引力的策略。本文综述了2006-2010年叶酸生物合成途径中酶靶点的小分子抑制剂的专利文献。抗叶酸剂作为抗癌剂和抗微生物剂的研究仍然是一个活跃的研究领域。新的专利披露揭示了新型抗叶酸剂支架，具有改进的药物样特性的抗叶酸剂和有效靶向癌细胞的新策略。高分辨率结构信息的持续使用指导了几种化合物的发现。由于需要高水平的效力和选择性，特别是在靶向致病物种中，使用高分辨率晶体结构仍然是指导新型抗叶酸剂设计的重要工具。有趣的是，披露新型化合物的专利是X射线晶体学是设计过程中不可或缺的组成部分。最后，已经报道了各种新的结构，可能在未来的治疗性抗叶酸剂的开发中发挥重要作用。
For over 50 years, drugs targeting the folate pathway have significantly impacted disease treatment as anticancer, antimicrobial and immunomodulatory agents. The discovery of novel antifolate agents with improved properties and superior activities remains an attractive strategy, both in academia and the pharmaceutical industry. This review surveys the patent literature from 2006–2010 for small molecule inhibitors of enzymatic targets in the folate biosynthetic pathway. The pursuit of antifolates as anticancer and antimicrobial agents continues to be an active area of research. New patent disclosures reveal novel antifolate scaffolds, antifolates with improved drug-like properties and new strategies to effectively target cancer cells. The continued use of high resolution structural information has guided the discovery of several compounds. Owing to the need for high levels of potency and selectivity, especially in targeting pathogenic species, the use of high resolution crystal structures remains an important tool to guide the design of novel antifolates. Interestingly, the patents disclosing novel compounds were ones where X-ray crystallography was an integral component of the design process. Finally, a variety of new structures have been reported that may play an important role in the future development of therapeutic antifolates.
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影响因子：
7.3
作者：
Gangjee A;Li W;Kisliuk RL;Cody V;Pace J;Piraino J;Makin J
通讯作者：
Makin J
影响因子：
7.3
作者：
Beierlein JM;Frey KM;Bolstad DB;Pelphrey PM;Joska TM;Smith AE;Priestley ND;Wright DL;Anderson AC
通讯作者：
Anderson AC
影响因子：
7.3
作者：
Costi, PM;Rinaldi, M;La Colla, P
通讯作者：
La Colla, P
影响因子：
2.9
作者：
Cody, V;Galitsky, N;Queener, SF
通讯作者：
Queener, SF
DOI：
10.1107/s1744309109041979
发表时间：
2009-11-01
影响因子：
0.9
作者：
Chitnumsub, Penchit;Yuvaniyama, Jirundon;Yuthavong, Yongyuth
通讯作者：
Yuthavong, Yongyuth