Bioorganic and Medicinal Chemistry Letters

, volume 31 , pages 127710

Identification of 2-substituted pyrrolo[1,2-b]pyridazine derivatives as new PARP-1 inhibitors

Haoyue Xiang, ^{1, 2}

Jianyang Chen ³

Xia-Juan Huan ³

Yi Chen ⁴

Zhaobing Gao ⁵

Jian-qing Ding ³

Ze-Hong Miao ³

Chunhao Yang ³

Hide authors affiliations Show authors affiliations: 5 affiliations

College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, PR China |

State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China. |

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China. |

⁴

Division of Anti-tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China |

⁵

Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China |

Publication type: Journal Article

Publication date: 2021-01-01

Elsevier

Bioorganic and Medicinal Chemistry Letters

scimago Q2

wos Q2

SJR: 0.472

CiteScore: 5.1

Impact factor: 2.2

ISSN: 0960894X, 14643405

DOI: 10.1016/j.bmcl.2020.127710

Copy DOI

PubMed ID: 33246105

Organic Chemistry

Drug Discovery

Biochemistry

Molecular Biology

Pharmaceutical Science

Clinical Biochemistry

Molecular Medicine

Abstract

A library of new 2-substituted pyrrolo[1,2-b]pyridazine derivatives were rapidly assembled and identified as PARP inhibitors. Structure-activity relationship for this class of inhibitor resulted in the discovery of most potent compounds 15a and 15b that exhibited about 29- and 5- fold selective activity against PARP-1 over PARP-2 respectively. The antiproliferative activity of the as-prepared compounds were demonstrated by further celluar assay in BRCA2-deficient V-C8 and BRCA1-deficient MDA-MB-436 cell lines, displaying that compound 15b could robustly reduce the corresponding cell proliferation and growth with CC50s of 340 and 106 nM respectively. The PK property of 15b was also investigated here.

Found

1 citation

Ivanov Andrey

56 publications, 557 citations

h-index: 13

A.E. Favorsky Irkutsk Institute of Chemistry of the Siberian Branch of the Russian Academy of Sciences

1 citation

Gyrgenova Elena

7 publications, 5 citations

h-index: 1

A.E. Favorsky Irkutsk Institute of Chemistry of the Siberian Branch of the Russian Academy of Sciences

Research interests

Organic Chemistry

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GOST |

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GOST Copy

Xiang, H. et al. Identification of 2-substituted pyrrolo[1,2-b]pyridazine derivatives as new PARP-1 inhibitors // Bioorganic and Medicinal Chemistry Letters. 2021. Vol. 31. p. 127710.

GOST all authors (up to 50) Copy

Xiang, H., Chen J., Huan X., Chen Y., Gao Z., Ding J., Miao Z., Yang C. Identification of 2-substituted pyrrolo[1,2-b]pyridazine derivatives as new PARP-1 inhibitors // Bioorganic and Medicinal Chemistry Letters. 2021. Vol. 31. p. 127710.

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1016/j.bmcl.2020.127710

UR - https://doi.org/10.1016/j.bmcl.2020.127710

TI - Identification of 2-substituted pyrrolo[1,2-b]pyridazine derivatives as new PARP-1 inhibitors

T2 - Bioorganic and Medicinal Chemistry Letters

AU - Xiang,, Haoyue

AU - Chen, Jianyang

AU - Huan, Xia-Juan

AU - Chen, Yi

AU - Gao, Zhaobing

AU - Ding, Jian-qing

AU - Miao, Ze-Hong

AU - Yang, Chunhao

PY - 2021

DA - 2021/01/01

PB - Elsevier

SP - 127710

VL - 31

PMID - 33246105

SN - 0960-894X

SN - 1464-3405

ER -

BibTex

Cite this

BibTex (up to 50 authors) Copy

@article{2021_Xiang,,

author = {Haoyue Xiang, and Jianyang Chen and Xia-Juan Huan and Yi Chen and Zhaobing Gao and Jian-qing Ding and Ze-Hong Miao and Chunhao Yang},

title = {Identification of 2-substituted pyrrolo[1,2-b]pyridazine derivatives as new PARP-1 inhibitors},

journal = {Bioorganic and Medicinal Chemistry Letters},

year = {2021},

volume = {31},

publisher = {Elsevier},

month = {jan},

url = {https://doi.org/10.1016/j.bmcl.2020.127710},

pages = {127710},

doi = {10.1016/j.bmcl.2020.127710}

}

Publisher

Elsevier

Journal

Bioorganic and Medicinal Chemistry Letters

scimago Q2

wos Q2

SJR

0.472

CiteScore

5.1

Impact factor

2.2

ISSN

0960894X (Print)

14643405 (Electronic)