title: An investigation of phenylthiazole antiflaviviral agents.
abstract: Flaviviruses are one of the most clinically important pathogens and their infection rates are increasing steadily. The phenylthiazole ring system has provided a template for the design and synthesis of antiviral agents that inhibit the flaviviruses by targeting their E-protein. Unfortunately, there is a correlation between phenylthiazole antiflaviviral activity and the presence of the reactive and therefore potentially toxic mono- or dibromomethyl moieties at thiazole-C4. Adding a linear hydrophobic tail para to the phenyl ring led to a new class of phenylthiazole antiflaviviral compounds that lack the toxic dibromomethyl moiety. This led to development of a drug-like phenylthiazole 12 that had high antiflaviviral selectivity (TI=147).
authors: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy and The Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
authors: Abdelrahman S
authors: AS
authors: Mayhoub
authors: Mansoora
authors: M
authors: Khaliq
authors: Carolyn
authors: C
authors: Botting
authors: Ze
authors: Z
authors: Li
authors: Richard J
authors: RJ
authors: Kuhn
authors: Mark
authors: M
authors: Cushman
references: Org Biomol Chem. 2003 Jan 7;1(1):140-4
references: 12929401
references: Bioorg Med Chem. 2007 Dec 15;15(24):7795-802
references: 17888664
references: Mol Cell. 2004 Jan 16;13(1):77-89
references: 14731396
references: Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):6986-91
references: 12759475
references: Antiviral Res. 2009 Dec;84(3):260-6
references: 19800368
references: Structure. 2004 Sep;12(9):1607-18
references: 15341726
references: Antimicrob Agents Chemother. 2006 Apr;50(4):1320-9
references: 16569847
references: Virology. 2005 Jan 20;331(2):247-59
references: 15629769
references: ACS Chem Biol. 2008 Dec 19;3(12):765-75
references: 19053243
references: Int J Biochem Cell Biol. 2007;39(3):606-14
references: 17188926
references: JAMA. 2003 Jul 23;290(4):524-8
references: 12876096
references: Antiviral Res. 2009 Jan;81(1):6-15
references: 18796313
references: JAMA. 2003 Jul 23;290(4):511-5
references: 12876094
references: Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):105-10
references: 16373502
references: Rev Environ Contam Toxicol. 1995;142:65-85
references: 7652197
references: Antimicrob Agents Chemother. 2008 Sep;52(9):3385-93
references: 18606844
references: Nat Struct Biol. 2003 Nov;10(11):907-12
references: 14528291
references: Curr Opin Microbiol. 2008 Aug;11(4):369-77
references: 18644250
references: Neurol India. 2010 Jul-Aug;58(4):585-91
references: 20739797
references: J Med Chem. 2011 Mar 24;54(6):1704-14
references: 21355607
references: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14333-8
references: 14612562
references: Antimicrob Agents Chemother. 2009 May;53(5):1823-31
references: 19223625
references: J Med Chem. 2008 Aug 14;51(15):4660-71
references: 18610998
references: Antimicrob Agents Chemother. 2002 May;46(5):1231-9
references: 11959550
references: Trop Med Int Health. 2007 Sep;12(9):1087-95
references: 17875019
references: J Med Chem. 2003 Oct 23;46(22):4776-89
references: 14561097