Design and Synthesis of Hepatitis C Virus NS3 Protease Inhibitors Incorporating a P2 Cyclopentane-Derived Scaffold

• This thesis describes the design, synthesis and structure-activity relationships analysis of potential inhibitors targeting the hepatitis C virus (HCV) NS3 protease. Also discussed is the disease caused by HCV infection and the class of enzymes known as proteases. Furthermore are explained why such enzymes can be considered to be suitable targets for developing drugs to combat diseases in general and in particular HCV, focusing on the NS3 protease. Moreover, some strategies used to design protease inhibitors and the desired properties of potential drug candidates are briefly examined. Synthesis of linear and macrocyclic NS3 protease inhibitors comprising a designed trisubstituted cyclopentane moiety as an N-acyl-(4R)-hydroxyproline bioisostere is also addressed, and several very potent and promising compounds are evaluated.

Subject headings

NATURVETENSKAP  -- Kemi -- Organisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Organic Chemistry (hsv//eng)

Keyword

HCV

NS3 protease

Proline mimic

Cyclopentane-derived scaffold

Linear inhibitors

Macrocyclic inhibitors

Organic synthesis

Organisk syntes

Publication and Content Type

vet (subject category)

lic (subject category)