Synthesis and Evaluation of Anti-HIV-1 Activities of Novel 7-Hydroxy-1,3- dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-4-carboxylate DerivativesGuan-Nan LIU1,2, Rong-Hua LUO3, Xing-Jie ZHANG3, Yu ZHOU2, Jian LI2, Yong-Tang ZHENG3 and Hong LIU2*
3Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
- *Corresponding Author:
- Hong LIU
State Key Laboratory of Drug Research
Shanghai Institute of Material Medica
Chinese Academy of Sciences
555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park
Shanghai 201203, China
E-mail: [email protected]
Received date: July 03, 2014; Accepted date: July 27, 2014; Published date: July 29, 2014
Citation: LIU GN, LUO RH, ZHANG XJ, ZHOU Y, LI J, et al. (2014) Synthesis and Evaluation of Anti-HIV-1 Activities of Novel 7-Hydroxy-1,3-dioxo-2,3-dihydro- 1H-pyrrolo[3,4-c]pyridine-4-carboxylate Derivatives. Med chem 4:573-580. doi:10.4172/2161-0444.1000196
Copyright: © 2014 LIU GN, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Aim: To design and synthesize a series of novel 7-hydroxy-1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-4- carboxylate derivatives and evaluate their anti-HIV-1 activities. Methods: Holding the same triad of metal-chelating heteroatoms for the catalytic site of IN and introducing a new hydroxyl group into the adjacent position of the amide to form another three-heteroatoms group for metal chelation, a series of novel 7-hydroxy-1,3-dioxo-2,3-dihydro-1Hpyrrolo[ 3,4-c]pyridine-4-carboxylate derivatives were designed and synthesized through multi-step chemical reactions. All the synthesized compounds were evaluated for their inhibitory activities against HIV-1 replication. Results: Thirtyfive new compounds (5–13) have been designed, synthesized and bioassayed. Their structural features were determined by 1H-NMR spectra, and low- and high-resolution mass spectra. Most of the synthesized compounds showed moderate to potent activities against HIV-1. Among the analogs, compounds 7d, 7f, 7i-7j, 8d and 9c exhibited potent anti-HIV-1 activities (EC50<10 μM). In particular, 7d exhibited significant anti-HIV-1 activities with EC50 values of 1.65 μM. Conclusion: This study provides a new template for further development of potent anti-HIV-1 drugs, and the preliminary SAR among the newly synthesized analogs provided useful indications for guiding further rational design of potent anti-HIV-1 agents.