Synthesis of 3-dimensional scaffolds for application in medicinal chemistry

In this thesis the successful synthesis of a novel tricyclic scaffold containing a ring fused triazole and piperidine will be discussed and furthermore its utility as a new potential privileged structure will be evaluated. As starting material for the synthesis of the considered scaffolds the comm...

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Main Author: Schwehm, Carolin Maria
Format: Thesis (University of Nottingham only)
Language:English
Published: 2016
Online Access:https://eprints.nottingham.ac.uk/32362/
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author Schwehm, Carolin Maria
author_facet Schwehm, Carolin Maria
author_sort Schwehm, Carolin Maria
building Nottingham Research Data Repository
collection Online Access
description In this thesis the successful synthesis of a novel tricyclic scaffold containing a ring fused triazole and piperidine will be discussed and furthermore its utility as a new potential privileged structure will be evaluated. As starting material for the synthesis of the considered scaffolds the commercially available ethyl 4-oxopiperidine-1-carboxylate 108 was used. Piperidone 108 was converted into scaffolds 96, 97 and 98 alternating the ring size (n=1, 2, 3) of the fused bicyclic ring. This tricyclic triazole scaffold was incorporated into known biologically active molecules (Sitaglitpin, a DPP-4 inhibitor; Maraviroc, a CCR-5 receptor antagonist and GDC-0941, a pi3K inhibitor) to test its potential to serve as a new possible Privileged Scaffold. Through scaffold hopping, analogues with excellent biological activity against the chosen biological targets were achieved. Additionally, the stereoselective synthesis of one of the four possible isomers of the tricyclic triazole 178 was obtained in 4 steps to give the synthetically access towards the synthesis of all feasible enantiomeric and diastereomeric analogues.
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spelling nottingham-323622025-02-28T13:24:19Z https://eprints.nottingham.ac.uk/32362/ Synthesis of 3-dimensional scaffolds for application in medicinal chemistry Schwehm, Carolin Maria In this thesis the successful synthesis of a novel tricyclic scaffold containing a ring fused triazole and piperidine will be discussed and furthermore its utility as a new potential privileged structure will be evaluated. As starting material for the synthesis of the considered scaffolds the commercially available ethyl 4-oxopiperidine-1-carboxylate 108 was used. Piperidone 108 was converted into scaffolds 96, 97 and 98 alternating the ring size (n=1, 2, 3) of the fused bicyclic ring. This tricyclic triazole scaffold was incorporated into known biologically active molecules (Sitaglitpin, a DPP-4 inhibitor; Maraviroc, a CCR-5 receptor antagonist and GDC-0941, a pi3K inhibitor) to test its potential to serve as a new possible Privileged Scaffold. Through scaffold hopping, analogues with excellent biological activity against the chosen biological targets were achieved. Additionally, the stereoselective synthesis of one of the four possible isomers of the tricyclic triazole 178 was obtained in 4 steps to give the synthetically access towards the synthesis of all feasible enantiomeric and diastereomeric analogues. 2016-07-21 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/32362/1/PhD%20thesis%20Carolin%20Schwehm%20final.pdf Schwehm, Carolin Maria (2016) Synthesis of 3-dimensional scaffolds for application in medicinal chemistry. PhD thesis, University of Nottingham.
spellingShingle Schwehm, Carolin Maria
Synthesis of 3-dimensional scaffolds for application in medicinal chemistry
title Synthesis of 3-dimensional scaffolds for application in medicinal chemistry
title_full Synthesis of 3-dimensional scaffolds for application in medicinal chemistry
title_fullStr Synthesis of 3-dimensional scaffolds for application in medicinal chemistry
title_full_unstemmed Synthesis of 3-dimensional scaffolds for application in medicinal chemistry
title_short Synthesis of 3-dimensional scaffolds for application in medicinal chemistry
title_sort synthesis of 3-dimensional scaffolds for application in medicinal chemistry
url https://eprints.nottingham.ac.uk/32362/