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Synthetic Design

Claire Littler edited this page Aug 2, 2017 · 3 revisions

Synthetic Design

The approach to the synthesis of Series 4 up has mainly involved the functionalization of a pyrazine core, followed by a cyclization reaction to give the triazolopyrazine which may then be subsequently functionalized. The two main series, ether- and amide-linked compounds are shown below along with a specific example of a potent compound in each series.

Examples of ether and amide target molecules.

Background

What is OSM Series 4?

Aims, Concerns and Current Interest in Series 4

Sources of Data

Structure-Activity Relationships

Modification of Core Triazolopyrazine

Modification of Pyrazine Substitution Pattern

Modification of the Triazole Substitution

Pyrazine Side Chain Modifications - Ethers

Pyrazine Side Chain Modifications - Amides

Pyrazine Side Chain Modifications - Reversed Amides

Pyrazine Side Chain Modifications - Others

Metabolites

Biological Data Currently not Incorporated into the Main Wiki Sections

Physicochemical/Metabolic Parameters

Physicochem/metabolism/PK

Metabolism ID

Aldehyde Oxidase Assay

Stages and Efficacy

Liver Stage

Gametocyte Stage

In Vivo Efficacy

Potency vs. Resistant Strains

Other Observations

Mechanism of Action, Activity and Toxicity

Mechanism of Action: Possible PfATP4 Activity Deduced from Parasite Ion Regulation Assays

hERG Activity

Toxicity

Synthetic Chemistry

Synthetic Design

Synthesis of the Ether-Linked Series

Synthesis of the Amide-Linked Series

Synthesis of the Reverse Amide- Linked Series

Synthesis of Benzylic Functionalised Ether-Linked Series

Alternative Routes to the Triazolopyrazine Core

Triazolopyrazine telesubstitution

Biofunctionalisation

Late Stage Functionalisation

Fluoroalkene Isostere

Spectroscopy

Chirality, Relevant and Desirable Compounds

Chirality/Stereogenic Centres in This Series

Other Sources of Compounds Relevant to this Series

Desirable Compounds Not Yet Synthesised

Other Evaluations

Evaluations vs Other Organisms

Strings

Strings for Google

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