Design and synthesis of novel phthalazinone derivatives as potent poly(ADP-ribose)polymerase 1 inhibitors-Reference-Cited by-同舟云学术

Design and synthesis of novel phthalazinone derivatives as potent poly(ADP-ribose)polymerase 1 inhibitors

Published:2020-10 Issue:19 Volume:12 Page:1691-1707
ISSN:1756-8919
Container-title:Future Medicinal Chemistry
language:en
Short-container-title:Future Medicinal Chemistry

Author:

Xin Minhang¹,Sun Jiajia¹,Huang Wei²^ORCID,Tang Feng³,Liu Zhaoyu³,Jin Qiu³,Wang Jia³

Affiliation:

1. Department of Medicinal Chemistry, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No 76, Yanta West Road, Xi'an, 710061, PR China

2. Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology & Health, College of Chemistry, Central China Normal University, Wuhan, 430079, PR China

3. Jiangsu Simcere Pharmaceutical Co. Ltd., No 699-18, Xuan Wu District, Nanjing, 210042, PR China

Abstract

Aim: The development of effective PARP-1 inhibitors has received great enthusiasm in medicinal chemistry communities. Results: A new series of novel phthalazinone derivatives were designed and synthesized. Among these, B1 and B16 displayed more potent PARP-1 inhibitory activities than olaparib. B16 gave an IC50 value of 7.8 nM against PARP-1, and a PF50 value of 3.4 in the sensitizing effect assay. The in vivo pharmacokinetic properties evaluation showed B16 displayed insufficient oral exposure, and it was also not stable in rat blood. Conclusion: The results indicated that our design phthalazinone derivatives were potent PARP-1 inhibitors, and compound B16 was a valuable lead compound with significant in vitro efficacy, deserving further optimization to develop anticancer drug candidate.

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

Link

https://www.future-science.com/doi/pdf/10.4155/fmc-2020-0009

Reference22 articles.

1. PARP inhibitors: Synthetic lethality in the clinic

2. The diverse roles and clinical relevance of PARPs in DNA damage repair: Current state of the art

3. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy

4. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase

5. The Story of Rucaparib (Rubraca)

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