Design and Synthesis of HIV 1 Integrase Inhibitors

In recent years, HIV-1 integrase (IN) has emerged as an attractive target for the treatment of human immunodeficiency virus type 1 (HIV-1), the causative pathogen of acquired immuno-deficiency syndrome (AIDS).

Design and Synthesis of HIV 1 Integrase Inhibitors

Design and Synthesis of HIV 1 Integrase Inhibitors

In recent years, HIV-1 integrase (IN) has emerged as an attractive target for the treatment of human immunodeficiency virus type 1 (HIV-1), the causative pathogen of acquired immuno-deficiency syndrome (AIDS). Several classes of IN inhibitors are known but many of these compounds are toxic, do not show antiviral activity or display decreased potency. Therefore, new classes of potent IN inhibitors are desperately needed. The b-diketo (b-DK) class of compounds has emerged as one of the most successful classes of IN inhibitors. Although several b-DK inhibitors with potent antiviral activity are known, compounds containing b-DK motifs have limitations in drug development. The overall objective of this dissertation was to design and synthesize a novel series of IN inhibitors that retain the favorable characteristics of the b-DK scaffolds but are devoid of the "undruggable" properties. The design of the target molecules was established from crystal structure-based correlation and structure-activity relationship studies, which led to scaffolds containing three specific functional groups. Each molecule was designed to contain the core functional motif (a,b-diketoamide), optimal aryl groups (3-benzylphenyl or substituted 3-benzylphenyl) and a terminal group (proton donor or acceptor or amphoteric functional groups) in a planar or near planar configuration. Several oxalamate containing compounds were successfully designed and synthesized; and many of these synthetic analogs were sent to be screened for inhibitory activity against HIV-1 IN. The synthetic analogs described herein may elicit alluring antiviral activity, serve as potential lead molecules for future optimizations and ultimately elucidate mechanistic insight into HIV-1 IN inhibition.

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Design and Synthesis of HIV-1 Integrase Inhibitors
Language: en
Pages: 414
Authors: Sarah Chajkowski Scarry, University of Mississippi. Department of Medicinal Chemistry, University of Mississippi. School of Pharmacy
Categories:
Type: BOOK - Published: 2012 - Publisher:

In recent years, HIV-1 integrase (IN) has emerged as an attractive target for the treatment of human immunodeficiency virus type 1 (HIV-1), the causative pathogen of acquired immuno-deficiency syndrome (AIDS). Several classes of IN inhibitors are known but many of these compounds are toxic, do not show antiviral activity or
AIDS Bibliography
Language: en
Pages:
Authors: Sarah Chajkowski Scarry, University of Mississippi. Department of Medicinal Chemistry, University of Mississippi. School of Pharmacy
Categories: AIDS (Disease)
Type: BOOK - Published: 1995 - Publisher:

Books about AIDS Bibliography
Investigating the Functional Interaction Between Human Immunodeficiency Virus Type 1 Integrase and Reverse Transcripts and the Mechanism by which Integrase Influences the Early Events of Reverse Transcription
Language: en
Pages: 372
Authors: Charles Warren Dobard
Categories: AIDS (Disease)
Type: BOOK - Published: 2007 - Publisher:

Books about Investigating the Functional Interaction Between Human Immunodeficiency Virus Type 1 Integrase and Reverse Transcripts and the Mechanism by which Integrase Influences the Early Events of Reverse Transcription
Development of HIV-1 Integrase Inhibitors: Recent Molecular Modeling Perspectives
Language: en
Pages:
Authors: Charles Warren Dobard
Categories: AIDS (Disease)
Type: BOOK - Published: 2015 - Publisher:

Highlights: Latest advances of HIV-1 integrase inhibitors focusing on molecular modeling. Features and functionalities of these computational approaches. Practices dealing with the ambiguities in drug discovery. A general workflow of the discovery of novel inhibitors using virtual screening. Abstract : Of the three viral enzymes essential to HIV replication, HIV-1
Cumulated Index Medicus
Language: en
Pages:
Authors: Charles Warren Dobard
Categories: Medicine
Type: BOOK - Published: 1991 - Publisher:

Books about Cumulated Index Medicus

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