{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:10:34Z","timestamp":1791169834662,"version":"4.1.0"},"reference-count":53,"publisher":"American Chemical Society (ACS)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Med. Chem."],"published-print":{"date-parts":[[2008,2,1]]},"DOI":"10.1021\/jm061475p","type":"journal-article","created":{"date-parts":[[2008,1,19]],"date-time":"2008-01-19T06:00:29Z","timestamp":1200722429000},"page":"449-469","source":"Crossref","is-referenced-by-count":88,"title":["Synthesis and Biological Evaluation of Novel 2,4-Diaminoquinazoline Derivatives as <i>SMN2<\/i> Promoter Activators for the Potential Treatment of Spinal Muscular Atrophy"],"prefix":"10.1021","volume":"51","author":[{"given":"John","family":"Thurmond","sequence":"first","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew E. R.","family":"Butchbach","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marty","family":"Palomo","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Pease","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munagala","family":"Rao","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Bedell","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Keyvan","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Pai","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rama","family":"Mishra","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Haraldsson","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorkell","family":"Andresson","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisli","family":"Bragason","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margret","family":"Thosteinsdottir","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon Mar","family":"Bjornsson","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Coovert","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur H. M.","family":"Burghes","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Gurney","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasbir","family":"Singh","sequence":"additional","affiliation":[{"name":"deCODE chemistry, Inc., 2501 Davey Road, Woodridge, Illinois 60517, deCODE genetics, Inc., Sturlugata 8, IS-101, Reykjavik, Iceland, Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2008,1,19]]},"reference":[{"key":"ref1\/cit1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1136\/jmg.15.6.409","volume":"15","author":"Pears J.","year":"1978","journal-title":"J. Med. Genet."},{"key":"ref2\/cit2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1136\/adc.45.239.33","volume":"45","author":"Roberts D. F.","year":"1970","journal-title":"Arch. Dis. Child."},{"key":"ref3\/cit3","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1086\/515465","volume":"60","author":"McAndrew P. E.","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref4\/cit4","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","volume":"80","author":"Lefebvre S.","year":"1995","journal-title":"Cell"},{"key":"ref5\/cit5","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","volume":"96","author":"Lorson C. L.","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"ref6\/cit6","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1093\/hmg\/8.7.1177","volume":"8","author":"Monani U. R.","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref7\/cit7","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/ng854","volume":"30","author":"Cartegni L.","year":"2002","journal-title":"Nat. Genet."},{"key":"ref8\/cit8","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1006\/bbrc.1995.2135","volume":"213","author":"Gennarelli M.","year":"1995","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref9\/cit9","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/ng0598-63","volume":"19","author":"Lorson C. L.","year":"1998","journal-title":"Nat. Genet."},{"key":"ref10\/cit10","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/hmg\/9.2.259","volume":"9","author":"Lorson C. L.","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref11\/cit11","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1093\/hmg\/6.8.1205","volume":"6","author":"Coovert D. D.","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref12\/cit12","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/ng0797-265","volume":"16","author":"Lefebvre S.","year":"1997","journal-title":"Nat. Genet."},{"key":"ref13\/cit13","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1093\/hmg\/8.13.2525","volume":"8","author":"Vitali T.","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref14\/cit14","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1086\/513886","volume":"61","author":"Campbell L.","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref15\/cit15","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1086\/338627","volume":"70","author":"Feldkotter M.","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref16\/cit16","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.nmd.2006.08.011","volume":"16","author":"Arkblad E. L.","year":"2006","journal-title":"Neuromuscular Disord."},{"key":"ref17\/cit17","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1101\/gr.7.4.339","volume":"7","author":"DiDonato C. J.","year":"1997","journal-title":"Genome Res."},{"key":"ref18\/cit18","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1006\/geno.1996.4551","volume":"40","author":"Viollet L.","year":"1997","journal-title":"Genomics"},{"key":"ref19\/cit19","doi-asserted-by":"crossref","first-page":"9920","DOI":"10.1073\/pnas.94.18.9920","volume":"94","author":"Schrank B.","year":"1997","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"ref20\/cit20","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1016\/S0002-9440(10)63428-1","volume":"165","author":"Vitte J. M.","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref21\/cit21","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1083\/jcb.152.5.1107","volume":"152","author":"Cifuentes-Diaz C.","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref22\/cit22","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1093\/hmg\/9.5.849","volume":"9","author":"Frugier T.","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref23\/cit23","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/71709","volume":"24","author":"Hsieh-Li H. M.","year":"2000","journal-title":"Nat. Genet."},{"key":"ref24\/cit24","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/hmg\/9.3.333","volume":"9","author":"Monani U. R.","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref25\/cit25","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ddmec.2004.09.011","volume":"1","author":"Butchbach M. E. R.","year":"2004","journal-title":"Drug Discovery Today: Dis. Models"},{"key":"ref26\/cit26","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/hmg\/ddi078","volume":"14","author":"Le T. T.","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref27\/cit27","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1083\/jcb.200208079","volume":"160","author":"Monani U. R.","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref28\/cit28","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/sj.ejhg.5201102","volume":"12","author":"Andreassi C.","year":"2004","journal-title":"Eur. J. Hum. Genet,."},{"key":"ref29\/cit29","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1093\/hmg\/10.24.2841","volume":"10","author":"Andreassi C.","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref30\/cit30","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1093\/hmg\/ddg256","volume":"12","author":"Brichta L.","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref31\/cit31","doi-asserted-by":"crossref","first-page":"9808","DOI":"10.1073\/pnas.171105098","volume":"98","author":"Chang J. G.","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"ref32\/cit32","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/ana.10743","volume":"54","author":"Sumner C. J.","year":"2003","journal-title":"Ann. Neurol."},{"key":"ref33\/cit33","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1093\/hmg\/ddi205","volume":"14","author":"Jarecki J.","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref34\/cit34","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1021\/jm00163a067","volume":"33","author":"Harris N. V.","year":"1990","journal-title":"J. Med. Chem."},{"key":"ref35\/cit35","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1002\/jhet.5570280530","volume":"28","author":"Hynes J. H.","year":"1991","journal-title":"J. Heterocycl. Chem."},{"key":"ref36\/cit36","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.1021\/jo016257c","volume":"67","author":"Nettles S. M.","year":"2002","journal-title":"J. Org. Chem."},{"key":"ref37\/cit37","unstructured":"A similar trend was also observed with couple of other sulphides and sulphones. In addition, in vitro metabolic stability studies using rat and human liver mircosomal preparation revealed that the thioethers disappeared rapidly, most likely because of oxidation at sulfur to provide sulfoxide and\/or sulphone."},{"key":"ref38\/cit38","unstructured":"For conformational analysis the (S)-enantiomer of analogues7a,9aand9bwere used using Systematic Search sub-routine of SYBYL."},{"key":"ref39\/cit39","volume-title":"SYBYL Molecular Modeling Systems","edition":"6"},{"issue":"1","key":"ref40\/cit40a","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1080\/01926230252824644","volume":"30","author":"Cockerell G. L","year":"2002","journal-title":"Toxicol. Pathol."},{"key":"ref40\/cit40b","first-page":"30","volume":"1","author":"McKim J. M.","year":"2005","journal-title":"Pharm. Discovery"},{"issue":"31","key":"ref41\/cit41a","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.2174\/1381612033453712","volume":"9","author":"McGuir J. J.","year":"2003","journal-title":"Curr. Pharm. Des."},{"issue":"1","key":"ref41\/cit41b","first-page":"1","volume":"39","author":"Moffatt B. A.","year":"2002","journal-title":"Arabidopsis Book"},{"key":"ref42\/cit42","first-page":"646","volume":"60","author":"Cody V.","year":"2004","journal-title":"Acta Crystallogr."},{"key":"ref43\/cit43","unstructured":"Analogues representing this approach will be reported in a future communication elsewhere."},{"key":"ref44\/cit44","unstructured":"It is worth pointing out that during the docking studies for some selected analogues corresponding to the reverse benzyl ether series (10) using the DHFR active site (using coordinates of1s3u.pdb), an intramolecular hydrogen bond was observed between the benzyl ether oxygen and HN of the 4-amino group instead of the typical H-bond of N4\u2212H with Val115 carbonyl. However, this in silico observation has not been confirmed with experimental data."},{"key":"ref45\/cit45","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1021\/jm00269a005","volume":"16","author":"Ashton W. T.","year":"1973","journal-title":"J. Med Chem."},{"key":"ref46\/cit46a","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0076-6879(00)26057-6","volume":"326","author":"Zlokarnik G.","year":"2000","journal-title":"Methods Enzymol."},{"key":"ref46\/cit46b","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.279.5347.84","volume":"279","author":"Zlokarnik G.","year":"1998","journal-title":"Science"},{"key":"ref47\/cit47","doi-asserted-by":"crossref","first-page":"9187","DOI":"10.1016\/S0021-9258(19)76524-7","volume":"263","author":"Appleman J. R.","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref48\/cit48","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1093\/hmg\/6.8.1205","volume":"6","author":"Coovert D. D.","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref49\/cit49","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1006\/excr.2000.4858","volume":"25","author":"Young P. J.","year":"2000","journal-title":"Exp. Cell Res."},{"key":"ref50\/cit50","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1046\/j.1471-4159.2003.01588.x","volume":"84","author":"Butchbach M. E. R.","year":"2003","journal-title":"J. Neurochem."}],"container-title":["Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jm061475p","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:51:59Z","timestamp":1678063919000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/doi\/10.1021\/jm061475p"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,19]]},"references-count":53,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2008,2,1]]}},"alternative-id":["10.1021\/jm061475p"],"URL":"https:\/\/doi.org\/10.1021\/jm061475p","relation":{},"ISSN":["0022-2623","1520-4804"],"issn-type":[{"value":"0022-2623","type":"print"},{"value":"1520-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,19]]}}}