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Discovery and SAR study of 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide: A potent inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) for the treatment of cancer.
Bioorg Med Chem. 2015 Oct 15; 23(20):6551-9.BM

Abstract

A series of imidazo[4,5-c]pyridine-7-carboxamide derivatives as poly(ADP-ribose) polymerase (PARP) inhibitors have been developed. All target compounds were evaluated for their PARP-1 inhibitory activity and some were further assessed for cellular potency. These efforts led to identification of a novel PARP-1 inhibitor 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide 11a (XZ-120312). 11a displayed strong inhibition against the PARP-1 enzyme with an IC50 of 8.6±0.6 nM and excellent potentiation of temozolomide cytotoxicity in cancer cell lines SW-620, MDA-MB-468 and A549 by 4.0, 3.0 and 7.7 times, respectively.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Zhu Q
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China.
Wang X
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Hu Y
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China.
He X
School of Engineering, China Pharmaceutical University, Nanjing 21009, China.
Gong G
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Xu Y
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China.

MeSH

Antineoplastic AgentsCell Line, TumorCell ProliferationDose-Response Relationship, DrugDrug DiscoveryDrug Screening Assays, AntitumorHumansImidazolesMolecular StructureNeoplasmsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesPyridinesStructure-Activity Relationship

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26422786

Citation

Zhu, Qihua, et al. "Discovery and SAR Study of 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide: a Potent Inhibitor of poly(ADP-ribose) Polymerase-1 (PARP-1) for the Treatment of Cancer." Bioorganic & Medicinal Chemistry, vol. 23, no. 20, 2015, pp. 6551-9.
Zhu Q, Wang X, Hu Y, et al. Discovery and SAR study of 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide: A potent inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) for the treatment of cancer. Bioorg Med Chem. 2015;23(20):6551-9.
Zhu, Q., Wang, X., Hu, Y., He, X., Gong, G., & Xu, Y. (2015). Discovery and SAR study of 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide: A potent inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) for the treatment of cancer. Bioorganic & Medicinal Chemistry, 23(20), 6551-9. https://doi.org/10.1016/j.bmc.2015.09.026
Zhu Q, et al. Discovery and SAR Study of 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide: a Potent Inhibitor of poly(ADP-ribose) Polymerase-1 (PARP-1) for the Treatment of Cancer. Bioorg Med Chem. 2015 Oct 15;23(20):6551-9. PubMed PMID: 26422786.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discovery and SAR study of 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide: A potent inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) for the treatment of cancer. AU - Zhu,Qihua, AU - Wang,Xueyan, AU - Hu,Yan, AU - He,Xiaorong, AU - Gong,Guoqing, AU - Xu,Yungen, Y1 - 2015/09/16/ PY - 2015/08/07/received PY - 2015/09/14/revised PY - 2015/09/15/accepted PY - 2015/10/1/entrez PY - 2015/10/1/pubmed PY - 2016/4/27/medline KW - Antitumor KW - Imidazo[4,5-c]pyridine-7-carboxamide KW - PARP inhibitor SP - 6551 EP - 9 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 23 IS - 20 N2 - A series of imidazo[4,5-c]pyridine-7-carboxamide derivatives as poly(ADP-ribose) polymerase (PARP) inhibitors have been developed. All target compounds were evaluated for their PARP-1 inhibitory activity and some were further assessed for cellular potency. These efforts led to identification of a novel PARP-1 inhibitor 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide 11a (XZ-120312). 11a displayed strong inhibition against the PARP-1 enzyme with an IC50 of 8.6±0.6 nM and excellent potentiation of temozolomide cytotoxicity in cancer cell lines SW-620, MDA-MB-468 and A549 by 4.0, 3.0 and 7.7 times, respectively. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/26422786/Discovery_and_SAR_study_of_2__1_propylpiperidin_4_yl__3H_imidazo[45_c]pyridine_7_carboxamide:_A_potent_inhibitor_of_poly_ADP_ribose__polymerase_1__PARP_1__for_the_treatment_of_cancer_ DB - PRIME DP - Unbound Medicine ER -
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