Construction of Diversified Penta-Spiro-Heterocyclic and Fused-Heterocyclic Frameworks with Potent Antitumor Activity.

C−H activation/ [4+1] and [4+2] annulation antitumor indazolone spiro/fused-heterocyclic frameworks substrate- and pH- controlled strategies

Journal

Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783

Informations de publication

Date de publication:
26 Sep 2023
Historique:
received: 20 05 2023
medline: 28 9 2023
pubmed: 28 6 2023
entrez: 27 6 2023
Statut: ppublish

Résumé

Multiple-spiro/fused-heterocyclic frameworks containing indazolone are structurally unique and represent a class of potentially dominant skeletons. In this work, we successfully fulfilled Rh(III)-catalyst mediated substrate- and pH- controlled strategies to construct four novel types of complicated penta-spiro/fused-heterocyclic frameworks via C-H activation/[4+1] and [4+2] annulation cascades. This method had mild reaction conditions, a broad scope of substrates, moderate to good yields, and valuable applications, which could realize for the first time the generation of the novel di-spiro-heterocyclic and multiple fused-heterocyclic products with unique structures. More importantly, novel spiro[cyclohexane-indazolo[1,2-a]indazole] scaffold constructed by this method exhibited potent antitumor activity against a variety of refractory solid tumors and hematological malignancies in vitro. Overall, our work provided new insights into the construction of complex and diverse multiple spiro/fused-heterocyclic systems and offered novel valuable lead compounds for the discovery of antitumor drugs.

Identifiants

pubmed: 37370192
doi: 10.1002/chem.202301553
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202301553

Subventions

Organisme : National Natural Science Foundation of China
ID : 21907102, 82130105, 82173656
Organisme : Lingang Laboratory
ID : LG202103-02-07, LG-QS-202205-09

Informations de copyright

© 2023 Wiley-VCH GmbH.

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Auteurs

Qi Liu (Q)

State Key Laboratory of Drug Research Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China.
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China.

Xuyi Liu (X)

State Key Laboratory of Drug Research Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China.

Yazhou Li (Y)

State Key Laboratory of Drug Research Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China.

Yu Zhou (Y)

State Key Laboratory of Drug Research Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China.

Linxiang Zhao (L)

School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China.

Xuewu Liang (X)

State Key Laboratory of Drug Research Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China.

Hong Liu (H)

State Key Laboratory of Drug Research Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China.
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China.

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