Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/136060
Title: DISCOVERY AND DEVELOPMENT OF BICYCLIC HETEROCYCLES AS INHIBITORS OF CHIKUNGUNYA VIRUS
Authors: CHING KUAN CHIEH
Keywords: Thieno[3,2-b]pyrroles, Pyrrolo[2,3-d]thiazoles, Alphavirus, Pharmacokinetics, Structure-activity relationship, Structure-metabolism relationship
Issue Date: 20-Jan-2017
Source: CHING KUAN CHIEH (2017-01-20). DISCOVERY AND DEVELOPMENT OF BICYCLIC HETEROCYCLES AS INHIBITORS OF CHIKUNGUNYA VIRUS. ScholarBank@NUS Repository.
Abstract: Chikungunya virus (CHIKV) is a re-emerging vector-borne alphavirus, and there is no approved effective antiviral treatment currently available for CHIKV. In our quest for small molecules as potent inhibitors of CHIKV, structure-activity relationship studies of a series of thieno[3,2-b]pyrrole derivatives were performed. The investigations identified a tri-substituted thieno[3,2-b]pyrrole 5-carboxamide which displayed antiviral potency and low cytotoxicity. Unfortunately, this lead compound exhibited poor metabolic stability in human liver microsomes. Two approaches, namely scaffold hopping and replacement of potential metabolically labile sites with groups that may hinder metabolism, were utilized in order to study the structure-metabolism relationship of this lead compound and related analogues. The investigations afforded two metabolically stable compounds, a thieno[3,2-b]pyrrole and a pyrrolo[2,3-d]thiazole which also displayed reasonably good in vivo pharmacokinetic properties. All in all, these studies have identified at least one compound that have the potential for further development as antiviral drugs against CHIKV infection.
URI: http://scholarbank.nus.edu.sg/handle/10635/136060
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