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",

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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

VL - 84

SP - 3887

EP - 3903

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 7

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