title: Microwave accelerated synthesis of isoxazole hydrazide inhibitors of the system xc- transporter: Initial homology model.
abstract: Microwave accelerated reaction system (MARS) technology provided a good method to obtain selective and open isoxazole ligands that bind to and inhibit the Sxc- antiporter. The MARS provided numerous advantages, including: shorter time, better yield and higher purity of the product. Of the newly synthesized series of isoxazoles the salicyl hydrazide 6 exhibited the highest level of inhibitory activity in the transport assay. A homology model has been developed to summarize the SAR results to date, and provide a working hypothesis for future studies.
authors.affiliation: Department of Biomedical & Pharmaceutical Sciences, Center for Structural & Functional Neuroscience, The University of Montana, Missoula, MT 59812, United States; Medicinal Chemistry Graduate Program, The University of Montana, Missoula, MT 59812, United States.
authors.forename: Afnan A
authors.initials: AA
authors.lastname: Matti
authors.forename: Joseph
authors.initials: J
authors.lastname: Mirzaei
authors.forename: John
authors.initials: J
authors.lastname: Rudolph
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Smith
authors.forename: Jayme L
authors.initials: JL
authors.lastname: Newell
authors.forename: Sarjubhai A
authors.initials: SA
authors.lastname: Patel
authors.forename: Michael R
authors.initials: MR
authors.lastname: Braden
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bridges
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Natale
mesh_terms: D027182:Amino Acid Transport System y+ / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D003553:Cystine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008872:Microwaves; D062105:Molecular Docking Simulation; D040681:Structural Homology, Protein
chemical_list: D027182:Amino Acid Transport System y+; D007555:Isoxazoles; C118895:SLC7A11 protein, human; D018698:Glutamic Acid; D003553:Cystine
keywords: Cystine; Glutamate; Isoxazole; Microwave; Transporter
references.citation: J Phys Chem A. 2007 Dec 27;111(51):13506-14
references.pmid: 18052263
references.citation: Clin Cancer Res. 2011 Sep 15;17(18):6000-11
references.pmid: 21750203
references.citation: J Pharm Sci. 1991 Apr;80(4):341-8
references.pmid: 1865334
references.citation: Curr Top Med Chem. 2006;6(8):823-47
references.pmid: 16719820
references.citation: J Med Chem. 2001 Nov 22;44(24):4292-5
references.pmid: 11708931
references.citation: Bioorg Med Chem. 2010 Jan 1;18(1):202-13
references.pmid: 19932968
references.citation: J Biol Chem. 2004 Jul 23;279(30):31228-36
references.pmid: 15151999
references.citation: ACS Comb Sci. 2011 Jan 10;13(1):2-6
references.pmid: 21247117
references.citation: J Med Chem. 1997 May 9;40(10):1417-21
references.pmid: 9154964
references.citation: Bioinformatics. 2007 Nov 1;23(21):2947-8
references.pmid: 17846036
references.citation: Acta Crystallogr Sect E Struct Rep Online. 2008 Dec 17;65(Pt 1):o144-5
references.pmid: 21581603
references.citation: Tetrahedron Lett. 2011 Oct 26;52(43):5656-5658
references.pmid: 21966033
references.citation: Br J Pharmacol. 2012 Jan;165(1):20-34
references.pmid: 21564084
references.citation: J Mol Biol. 1993 Dec 5;234(3):779-815
references.pmid: 8254673
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):3935-40
references.pmid: 21368142
references.citation: Science. 2009 Aug 21;325(5943):1010-4
references.pmid: 19608859
references.citation: J Med Chem. 2001 Jul 19;44(15):2403-10
references.pmid: 11448222
references.citation: Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444-8
references.pmid: 3162770
references.citation: Farmaco. 2002 Feb;57(2):89-96
references.pmid: 11902661
references.citation: Bioorg Med Chem Lett. 2010 Apr 15;20(8):2680-3
references.pmid: 20303751
references.citation: Proteins. 2003 Sep 1;52(4):609-23
references.pmid: 12910460
references.citation: Bioorg Med Chem. 1998 Jul;6(7):925-35
references.pmid: 9730228
references.citation: Magn Reson Chem. 2005 Mar;43(3):240-5
references.pmid: 15609372
references.citation: J Org Chem. 2007 Mar 2;72(5):1566-9
references.pmid: 17288479
references.citation: J Med Chem. 2009 Dec 10;52(23):7397-409
references.pmid: 19788200
references.citation: Farmaco Sci. 1969 Oct;24(10):885-92
references.pmid: 5361903
references.citation: Bioorg Med Chem Lett. 2011 Oct 15;21(20):6184-7
references.pmid: 21889337
references.citation: J Med Chem. 2007 Aug 9;50(16):3945-53
references.pmid: 17629262
references.citation: Pharmacol Rev. 2012 Jul;64(3):780-802
references.pmid: 22759795
references.citation: J Chem Inf Model. 2012 Sep 24;52(9):2387-97
references.pmid: 22853713
references.citation: J Comb Chem. 2010 Mar 8;12(2):245-7
references.pmid: 20050700
references.citation: J Med Chem. 2008 Mar 13;51(5):1333-43
references.pmid: 18278859
references.citation: J Med Chem. 1999 Jun 3;42(11):1894-900
references.pmid: 10354397