Structure-Activity Relationship Studies of EP2 Antagonists for Aqueous Solubility Enhancement Restricted; Files Only

Abstract

Over the past decade, EP2 antagonism has emerged as a promising treatment for neuroinflammation and neurodegenerative diseases including Alzheimer’s, Parkinson’s, epilepsy, and traumatic brain injury. Following the discovery of selective antagonists, proof of concept in animals supports the continued pursuit of a clinical candidate with improved solubility, brain permeability, and half-life. Following structure-activity relations of previous successful compounds, derivatives were developed with varying middle and final rings in an attempt to optimize the candidates. Two scaffolds were followed resulting in the synthesis of two novel antagonists and partial synthesis of multiple others. Of these compounds, one had moderate potency and low solubility, while the other had improved potency and selectivity against the DP1 receptor. 

Table of Contents

Abstract 1

Introduction 2

Goals 8

Results 9

Discussion 14

Experimental Methods 19

Characterization 23

References 33

About this Honors Thesis

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School	Emory College
Department	Chemistry
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Chemistry, Biochemistry Chemistry, Organic
Keyword	Neurodegenerative Disease EP2 antagonist
Committee Chair / Thesis Advisor	Thota Ganesh, Emory University
Committee Members	David Lynn, Emory University Antonio Brathwaite, Emory University

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