Pyridine-Fused 2-Pyridones via Povarov and A3 Reactions: Rapid Generation of Highly Functionalized Tricyclic Heterocycles Capable of Amyloid Fibril Binding

Pardeep Singh; Dan E. Adolfsson; Jörgen Ådén; Andrew G. Cairns; Christian Bartens; Kristoffer Brännström; Anders Olofsson; Fredrik Almqvist

doi:10.1021/acs.joc.8b03015

Pyridine-Fused 2-Pyridones via Povarov and A³ Reactions: Rapid Generation of Highly Functionalized Tricyclic Heterocycles Capable of Amyloid Fibril Binding

Pardeep Singh
, Dan E. Adolfsson
, Jörgen Ådén
, Andrew G. Cairns
, Christian Bartens
, Kristoffer Brännström
, Anders Olofsson
, Fredrik Almqvist (Lead / Corresponding author)

Drug Discovery Unit

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

We here describe the use of three-component reactions to synthesize tricyclic pyridine ring-fused 2-pyridones. The developed protocols have a wide substrate scope and allow for the installation of diverse chemical functionalities on the tricyclic central fragment. Several of these pyridine-fused rigid polyheterocycles are shown to bind to Aβ and α-synuclein fibrils, which are associated with neurodegenerative diseases.

Original language	English
Pages (from-to)	3887-3903
Number of pages	17
Journal	Journal of Organic Chemistry
Volume	84
Issue number	7
Early online date	13 Mar 2019
DOIs	https://doi.org/10.1021/acs.joc.8b03015
Publication status	Published - 5 Apr 2019

Keywords

Functionalization
Nanofibers
Peptides and proteins
Scaffolds
Substituents

ASJC Scopus subject areas

Organic Chemistry

Access to Document

10.1021/acs.joc.8b03015

Cite this

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title = "Pyridine-Fused 2-Pyridones via Povarov and A3 Reactions: Rapid Generation of Highly Functionalized Tricyclic Heterocycles Capable of Amyloid Fibril Binding",

abstract = "We here describe the use of three-component reactions to synthesize tricyclic pyridine ring-fused 2-pyridones. The developed protocols have a wide substrate scope and allow for the installation of diverse chemical functionalities on the tricyclic central fragment. Several of these pyridine-fused rigid polyheterocycles are shown to bind to Aβ and α-synuclein fibrils, which are associated with neurodegenerative diseases.",

keywords = "Functionalization, Nanofibers, Peptides and proteins, Scaffolds, Substituents",

author = "Pardeep Singh and Adolfsson, \{Dan E.\} and J{\"o}rgen {\AA}d{\'e}n and Cairns, \{Andrew G.\} and Christian Bartens and Kristoffer Br{\"a}nnstr{\"o}m and Anders Olofsson and Fredrik Almqvist",

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doi = "10.1021/acs.joc.8b03015",

language = "English",

volume = "84",

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journal = "Journal of Organic Chemistry",

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T2 - Rapid Generation of Highly Functionalized Tricyclic Heterocycles Capable of Amyloid Fibril Binding

AU - Singh, Pardeep

AU - Adolfsson, Dan E.

AU - Ådén, Jörgen

AU - Cairns, Andrew G.

AU - Bartens, Christian

AU - Brännström, Kristoffer

AU - Olofsson, Anders

AU - Almqvist, Fredrik

PY - 2019/4/5

Y1 - 2019/4/5

N2 - We here describe the use of three-component reactions to synthesize tricyclic pyridine ring-fused 2-pyridones. The developed protocols have a wide substrate scope and allow for the installation of diverse chemical functionalities on the tricyclic central fragment. Several of these pyridine-fused rigid polyheterocycles are shown to bind to Aβ and α-synuclein fibrils, which are associated with neurodegenerative diseases.

AB - We here describe the use of three-component reactions to synthesize tricyclic pyridine ring-fused 2-pyridones. The developed protocols have a wide substrate scope and allow for the installation of diverse chemical functionalities on the tricyclic central fragment. Several of these pyridine-fused rigid polyheterocycles are shown to bind to Aβ and α-synuclein fibrils, which are associated with neurodegenerative diseases.

KW - Functionalization

KW - Nanofibers

KW - Peptides and proteins

KW - Scaffolds

KW - Substituents

UR - https://www.scopus.com/pages/publications/85063365828

U2 - 10.1021/acs.joc.8b03015

DO - 10.1021/acs.joc.8b03015

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SN - 0022-3263

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SP - 3887

EP - 3903

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 7

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