Compound property enhancement by virtual compound synthesis
Compound property enhancement by virtual compound synthesis
复制标题
通过虚拟化合物合成增强化合物性能
DOI：
10.1142/s0219720018400164
复制
发表时间：
2018
影响因子：
1
通讯作者：
Sekijima Masakazu
中科院分区：
文献类型：
--
作者：
Arai Naoki;Yoshikawa Shunsuke;Yasuo Nobuaki;Yoshino Ryunosuke;Sekijima Masakazu
在药物发现过程中，候选药物在开发药物产品的几个步骤中被缩小。这些步骤的理论化学空间估计为。为了覆盖这一空间，已经开发了广泛的虚拟复合库；然而，大量库的编译需要大量的计算成本。因此，为了降低计算成本，研究人员构建了针对目标疾病的定制虚拟化合物库。在本研究中，我们开发了一个从输入化合物生成虚拟化合物库的系统。当用户输入一个化合物时，系统递归地应用虚拟合成反应规则来改善化合物的性能。由于该系统中的反应规则是基于真实的有机合成反应，因此合成途径也可以由用户跟踪。该系统具有有效药物设计的有用功能，例如结构保存，允许维持效力所需的亚结构。为了验证定向反应集的效果，我们将定向反应集应用于100种化合物。此外，为了证实该体系能够再现真实的合成途径，通过输入异丁基苯和7,8-二氟-2,3-二氢-3-甲基- 4h -苯并杂嗪，探索了布洛芬和氧氟沙星的合成途径。此应用程序可通过以下URL获得：http://enh.sekijima-lab.org。
During drug discovery, drug candidates are narrowed down over several steps to develop pharmaceutical products. The theoretical chemical space in such steps is estimated to be. To cover that space, extensive virtual compound libraries have been developed; however, the compilation of extensive libraries comes at large computational cost. Thus, to reduce the computational cost, researchers have constructed custom-made virtual compound libraries that focus on target diseases. In this study, we develop a system that generates virtual compound libraries from input compounds. When a user inputs a compound, the system recursively applies virtual synthetic reaction rules to the compound to improve its properties. The synthetic pathway can also be traced by the user because the reaction rules in this system are based on real organic synthesis reactions. This system has useful functions for effective drug design, such as structural preservation, allowing the substructures necessary for potency to be maintained. In this paper, to confirm the effect of directional reaction sets, we applied the reaction sets to 100 compounds. Moreover, to confirm that the system can reproduce real synthetic pathways, the synthetic pathways of Ibuprofen and Ofloxacin were explored by inputting isobutyl benzene and 7,8-difluoro-2,3-dihydro-3-methyl-4H-benzoxazine. This application is available at the following URL: http://enh.sekijima-lab.org.
DOI：
10.1021/ci9800209
发表时间：
1998-11-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
Cramer, RD;Patterson, DE;Lawless, MS
通讯作者：
Lawless, MS
DOI：
10.1016/j.ddtec.2013.01.004
发表时间：
2013-09-01
期刊：
Drug discovery today. Technologies
影响因子：
--
作者：
Peng, Zhengwei
通讯作者：
Peng, Zhengwei
取代的7-氧代-2,3-二氢-7H-吡啶并[1,2,3-de][1,4]苯并恶嗪-6-羧酸的合成和抗菌活性。
影响因子：
1.7
作者：
I. Hayakawa;T. Hiramitsu;Yoshiaki Tanaka
通讯作者：
Yoshiaki Tanaka