Heterocyclic Merging of Stereochemically Diverse Chiral Piperazines and Morpholines with Indazoles.

chiral morpholines chiral piperazines fused heterocycles indazoles scaffold merging

Journal

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

Informations de publication

Date de publication:
02 Oct 2023
Historique:
received: 13 06 2023
medline: 18 7 2023
pubmed: 18 7 2023
entrez: 18 7 2023
Statut: ppublish

Résumé

We report a heterocyclic merging approach to construct novel indazolo-piperazines and indazolo-morpholines. Starting from chiral diamines and amino alcohols, novel regiochemically (1,3 and 1,4) and stereochemically diverse (relative and absolute) cohorts of indazolo-piperazines and indazolo-morpholines were obtained within six or seven steps. The key transformations involved are a Smiles rearrangement to generate the indazole core structure and a late-stage Michael addition to build the piperazine and morpholine heterocycles. We further explored additional vector diversity by incorporating substitutions on the indazole aromatic ring, generating a total of 20 unique, enantiomerically pure heterocyclic scaffolds.

Identifiants

pubmed: 37462979
doi: 10.1002/chem.202301888
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202301888

Subventions

Organisme : NIGMS NIH HHS
ID : R01GM139295
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01GM139295
Pays : United States
Organisme : Bill & Melinda Gates Foundation
ID : INV-001902
Pays : United States

Informations de copyright

© 2023 Wiley-VCH GmbH.

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Auteurs

Amol B Viveki (AB)

Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Timothy M Mansfield (TM)

Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, USA.

Kevin A Tran (KA)

Center for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Evan Lenkeit (E)

Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, USA.

Kevin R MacKenzie (KR)

Center for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Damian W Young (DW)

Center for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, USA.

Srinivas Chamakuri (S)

Center for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Classifications MeSH