Design, synthesis and biological evaluation of novel inosine 5′-monophosphate dehydrogenase (IMPDH) inhibitors. (June 2014)

• Record Type: Journal Article
• Authors: Dunkern, Torsten; Chavan, Sunil; Bankar, Digambar; Patil, Anuja; Kulkarni, Pritee; Kharkar, Prashant S.; Prabhu, Arati; Goebel, Heike; Rolser, Edith; Burckhard-Boer, Waltraud; Arumugam, Premkumar; Makhija, Mahindra T.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 29:Number 3(2014:Jun.)
• Page Start: 408
• Page End: 419
• Publication Date: 2014-06
• Subjects: Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2013.793184
• Languages: English
• ISSNs: 1475-6366

Abstract

<abstract> <title>Abstract</title> <p>This study is based on our attempts to further explore the structure–activity relationship (SAR) of VX-148 (<bold>3</bold>) in an attempt to identify inosine 5′-mono-phosphate dehydrogenase (IMPDH) inhibitors superior to mycophenolic acid. A five-point pharmacophore developed using structurally diverse, known IMPDH inhibitors guided further design of novel analogs of <bold>3</bold>. Several conventional as well as novel medicinal chemistry strategies were tried. The combined structure- and ligand-based approaches culminated in a few analogs with either retained or slightly higher potency. The compounds which retained the potency were also checked for their ability to inhibit human peripheral blood mononuclear cells proliferation. This study illuminates the stringent structural requirements and strict SAR for IMPDH II inhibition.</p> </abstract>