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

Autor: Viveki AB; Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Mansfield TM; Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, USA., Tran KA; Center for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Lenkeit E; Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, USA., 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., 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., Chamakuri S; Center for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2023 Oct 02; Vol. 29 (55), pp. e202301888. Date of Electronic Publication: 2023 Aug 29.
DOI: 10.1002/chem.202301888
Abstrakt: 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.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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