{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:27:39Z","timestamp":1790958459123,"version":"4.1.0"},"reference-count":78,"publisher":"American Chemical Society (ACS)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Med. Chem."],"published-print":{"date-parts":[[1996,1,1]]},"DOI":"10.1021\/jm9505122","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T06:00:31Z","timestamp":1027663231000},"page":"892-903","source":"Crossref","is-referenced-by-count":101,"title":["High-Affinity Inhibitors of Dihydrofolate Reductase:\u2009 Antimicrobial and Anticancer Activities of 7,8-Dialkyl-1,3-diaminopyrrolo[3,2-<i>f<\/i>]quinazolines with Small Molecular Size"],"prefix":"10.1021","volume":"39","author":[{"given":"Lee F.","family":"Kuyper","sequence":"first","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Baccanari","sequence":"additional","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Jones","sequence":"additional","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert N.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Tansik","sequence":"additional","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne S.","family":"Joyner","sequence":"additional","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Boytos","sequence":"additional","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon K.","family":"Rudolph","sequence":"additional","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vince","family":"Knick","sequence":"additional","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Robert","family":"Wilson","sequence":"additional","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Marc","family":"Caddell","sequence":"additional","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry S.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C. W.","family":"Comley","sequence":"additional","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy N.","family":"Stables","sequence":"additional","affiliation":[{"name":"Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, U.K., and Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[1996,2,16]]},"reference":[{"key":"jm9505122b00001\/jm9505122b00001_1","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1096\/fasebj.4.8.2185970","volume":"4","author":"Schweitzer B. I.","year":"1990","journal-title":"FASEB J."},{"key":"jm9505122b00002\/jm9505122b00002_1","first-page":"369","volume-title":"Computer-Aided Drug Design","author":"Kuyper L. F.","year":"1989"},{"key":"jm9505122b00003\/jm9505122b00003_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1200\/JCO.1993.11.1.5","volume":"11","author":"Bertino J. R","year":"1993","journal-title":"J. Clin. Oncol."},{"key":"jm9505122b00004\/jm9505122b00004_1","first-page":"719","volume":"19","author":"Fleming G. F.","year":"1992","journal-title":"Semin. Oncol."},{"key":"jm9505122b00005\/jm9505122b00005_1","volume-title":"Folate Antagonists as Therapeutic Agents","author":"Sirotnak F. M.","year":"1984"},{"key":"jm9505122b00006\/jm9505122b00006_1","first-page":"331","volume-title":"Progress in Medicinal Chemistry","volume":"19","author":"Roth B.","year":"1982"},{"key":"jm9505122b00007\/jm9505122b00007_1","first-page":"236","volume":"4","author":"Salter A. J.","year":"1982","journal-title":"Rev. Infect. Dis."},{"key":"jm9505122b00008\/jm9505122b00008_1","first-page":"98","volume-title":"Tropical Medicine from Romance to Reality","author":"Hitchings G. H.","year":"1978"},{"key":"jm9505122b00009\/jm9505122b00009_1","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1056\/NEJM198710153171602","volume":"317","author":"Allegra C. J.","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"jm9505122b00010\/jm9505122b00010_1","first-page":"361A","volume":"38","author":"Falloon J.","year":"1990","journal-title":"Clin. Res."},{"key":"jm9505122b00011\/jm9505122b00011_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1128\/AAC.39.1.79","volume":"39","author":"Rosowsky A.","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"jm9505122b00012\/jm9505122b00012_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/0014-4894(90)90008-Z","volume":"71","author":"Kovacs J. A.","year":"1990","journal-title":"Exp. Parasitol."},{"key":"jm9505122b00013\/jm9505122b00013_1","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1128\/AAC.33.10.1753","volume":"33","author":"Derouin F.","year":"1989","journal-title":"Antimicrob. Agents Chemother."},{"key":"jm9505122b00014\/jm9505122b00014_1","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/S0021-9258(19)85059-7","volume":"264","author":"Baccanari D. P.","year":"1989","journal-title":"J. Biol. Chem."},{"key":"jm9505122b00015\/jm9505122b00015_1","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1056\/NEJM199104113241511","volume":"324","author":"Edwards J. E","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"jm9505122b00016\/jm9505122b00016_1","volume-title":"Opportunistic Infections in Patients with the Acquired Immunodeficiency Syndrome","author":"Leoung G.","year":"1989"},{"key":"jm9505122b00017\/jm9505122b00017_1","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1126\/science.7992040","volume":"266","author":"Sternberg S","year":"1994","journal-title":"Science"},{"key":"jm9505122b00018\/jm9505122b00018_1","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1056\/NEJM198311033091805","volume":"309","author":"Jolivet J.","year":"1983","journal-title":"N. Engl. J. Med."},{"key":"jm9505122b00019\/jm9505122b00019_1","first-page":"217","volume-title":"Folate Antagonists as Therapeutic Agents","volume":"1","author":"Dembo M.","year":"1984"},{"key":"jm9505122b00020\/jm9505122b00020_1","first-page":"250","volume-title":"Nutritional, Pharmacologic and Physiologic Aspects of Folates and Pterins","author":"Henderson G. B.","year":"1986"},{"key":"jm9505122b00021\/jm9505122b00021_1","first-page":"35","volume":"5","author":"Sirotnak F. M","year":"1987","journal-title":"Natl. Cancer Inst. Monogr."},{"key":"jm9505122b00022\/jm9505122b00022_1","first-page":"337","volume":"6","author":"Cavallito J. C.","year":"1978","journal-title":"Drug Metab. Dispos."},{"key":"jm9505122b00023\/jm9505122b00023_1","first-page":"120","volume":"5","author":"Sigel C. W.","year":"1987","journal-title":"Natl. Cancer Instit. Monogr."},{"key":"jm9505122b00024\/jm9505122b00024_1","first-page":"172","volume":"9","author":"Lin J. T.","year":"1991","journal-title":"Cancer Invest."},{"key":"jm9505122b00025\/jm9505122b00025_1","first-page":"576","volume":"49","author":"Fulton B.","year":"1995","journal-title":"Drugs"},{"key":"jm9505122b00026\/jm9505122b00026_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1128\/AAC.32.4.430","volume":"32","author":"Kovacs J. A.","year":"1988","journal-title":"Antimicrob. Agents Chemother."},{"key":"jm9505122b00027\/jm9505122b00027_1","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1128\/AAC.31.9.1323","volume":"31","author":"Queener S. F.","year":"1987","journal-title":"Antimicrob. Agents Chemother."},{"key":"jm9505122b00028\/jm9505122b00028_1","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/infdis\/161.1.91","volume":"161","author":"Sattler F. R.","year":"1990","journal-title":"J. Infect. Dis."},{"key":"jm9505122b00029\/jm9505122b00029_1","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1021\/jm00145a002","volume":"28","author":"Goodford P. J","year":"1985","journal-title":"J. Med. Chem."},{"key":"jm9505122b00030\/jm9505122b00030_1","volume-title":"Patent 4,118,561","author":"Ledig K. W.","year":"1978"},{"key":"jm9505122b00031\/jm9505122b00031_1","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1002\/jhet.5570310668","volume":"31","author":"Jones M. L.","year":"1994","journal-title":"J. Heterocycl. Chem."},{"key":"jm9505122b00032\/jm9505122b00032_1","first-page":"3007","volume":"3002","author":"Parr W. J. E","year":"1981","journal-title":"J. Chem. Soc., Perkin Trans. I"},{"key":"jm9505122b00033\/jm9505122b00033_1","first-page":"125","volume":"121","author":"Verardo G.","year":"1993","journal-title":"Synthesis"},{"key":"jm9505122b00034\/jm9505122b00034_1","first-page":"1148","volume":"1147","author":"Kotsuki H.","year":"1990","journal-title":"Synthesis"},{"key":"jm9505122b00035\/jm9505122b00035_1","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1002\/jlac.19656870116","volume":"687","author":"Suhr H","year":"1965","journal-title":"Justus Liebigs Ann. Chem."},{"key":"jm9505122b00036\/jm9505122b00036_1","first-page":"491","volume":"104","author":"Peters A. T.","year":"1988","journal-title":"J. Soc. Dyers Colour."},{"key":"jm9505122b00037\/jm9505122b00037_1","first-page":"339","volume":"16","author":"Bui N. M.","year":"1965","journal-title":"Int. J. Appl. Radiat. Isot."},{"key":"jm9505122b00038\/jm9505122b00038_1","volume-title":"Palladium Reagents in Organic Syntheses","author":"Heck R. F.","year":"1985"},{"key":"jm9505122b00039\/jm9505122b00039_1","first-page":"1308","volume":"36","author":"Sakamoto T.","year":"1988","journal-title":"Chem. Pharm. Bull."},{"key":"jm9505122b00040\/jm9505122b00040_1","first-page":"2584","volume":"30","author":"Arcadi A.","year":"1989","journal-title":"Tetrahedron Lett."},{"key":"jm9505122b00041\/jm9505122b00041_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1021\/cr00062a002","volume":"84","author":"Blaney J. M.","year":"1984","journal-title":"Chem. Rev."},{"key":"jm9505122b00042\/jm9505122b00042_1","first-page":"362","volume-title":"Topics in Molecular Pharmacology","volume":"3","author":"Champness J. N.","year":"1986"},{"key":"jm9505122b00043\/jm9505122b00043_1","first-page":"71","volume-title":"Biological Macromolecules and Assemblies","volume":"3","author":"Kraut J.","year":"1987"},{"key":"jm9505122b00044\/jm9505122b00044_1","first-page":"131","volume-title":"Folate Antagonists as Therapeutic Agents","volume":"1","author":"Freisheim J. H.","year":"1984"},{"key":"jm9505122b00045\/jm9505122b00045_1","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/S0969-2126(94)00093-X","volume":"2","author":"Champness J. N.","year":"1994","journal-title":"Structure"},{"key":"jm9505122b00046\/jm9505122b00046_1","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1016\/0006-2952(79)90066-2","volume":"28","author":"McCormack J. J.","year":"1979","journal-title":"Biochem. Pharmacol."},{"key":"jm9505122b00047\/jm9505122b00047_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1128\/AAC.15.1.81","volume":"15","author":"Castaldo R. A.","year":"1979","journal-title":"Antimicrob. Agents Chemother."},{"key":"jm9505122b00049\/jm9505122b00049_1","first-page":"203","volume":"52","author":"van der Bliek A. M.","year":"1989","journal-title":"Adv. Cancer Res."},{"key":"jm9505122b00050\/jm9505122b00050_1","doi-asserted-by":"crossref","first-page":"12166","DOI":"10.1016\/S0021-9258(18)37730-5","volume":"263","author":"Gottesman M. M.","year":"1988","journal-title":"J. Biol. Chem."},{"key":"jm9505122b00051\/jm9505122b00051_1","first-page":"462","volume":"33","author":"Zamora J. M.","year":"1988","journal-title":"Mol. Pharmacol."},{"key":"jm9505122b00052\/jm9505122b00052_1","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/0304-3835(86)90145-X","volume":"31","author":"Klohs W. D.","year":"1986","journal-title":"Cancer Lett."},{"key":"jm9505122b00053\/jm9505122b00053_1","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1093\/jnci\/81.4.290","volume":"81","author":"Assaraf Y. G.","year":"1989","journal-title":"J. Natl. Cancer Inst."},{"key":"jm9505122b00054\/jm9505122b00054_1","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1021\/jm00169a014","volume":"33","author":"Selassie C. D.","year":"1990","journal-title":"J. Med. Chem."},{"key":"jm9505122b00055\/jm9505122b00055_1","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/340400a0","volume":"340","author":"McGrath J. P.","year":"1989","journal-title":"Nature"},{"key":"jm9505122b00056\/jm9505122b00056_1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1126\/science.1348873","volume":"256","author":"Raymond M.","year":"1992","journal-title":"Science"},{"key":"jm9505122b00057\/jm9505122b00057_1","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1073\/pnas.86.2.695","volume":"86","author":"Cordon-Cardo C.","year":"1989","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"jm9505122b00058\/jm9505122b00058_1","first-page":"339","volume":"31","author":"Baccanari D. P.","year":"1990","journal-title":"Proc. Am. Assoc. Cancer Res."},{"key":"jm9505122b00059\/jm9505122b00059_1","first-page":"112","volume":"7","author":"Hill B. T.","year":"1980","journal-title":"Cancer Treat. Rev."},{"key":"jm9505122b00060\/jm9505122b00060_1","first-page":"104","volume":"18","author":"Duch D. S.","year":"1980","journal-title":"Mol. Pharmacol."},{"key":"jm9505122b00061\/jm9505122b00061_1","first-page":"6","volume":"157","author":"Luft B. J.","year":"1988","journal-title":"J. Infect. Dis."},{"key":"jm9505122b00062\/jm9505122b00062_1","first-page":"638","volume":"7","author":"Frenkel J. K.","year":"1957","journal-title":"Antibiot. Chemother."},{"key":"jm9505122b00063\/jm9505122b00063_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1006\/prep.1993.1003","volume":"4","author":"Delves C. J.","year":"1993","journal-title":"Protein Express. Purif."},{"key":"jm9505122b00064\/jm9505122b00064_1","first-page":"625","volume":"32","author":"Hughes W. T","year":"1988","journal-title":"Antimicrob. Agents Chemother."},{"key":"jm9505122b00065\/jm9505122b00065_1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/0140-6736(91)93402-U","volume":"337","author":"Ruskin J.","year":"1991","journal-title":"Lancet"},{"key":"jm9505122b00066\/jm9505122b00066_1","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1021\/jo01256a011","volume":"34","author":"Roth B.","year":"1969","journal-title":"J. Org. Chem."},{"key":"jm9505122b00067\/jm9505122b00067_1","first-page":"2185","volume":"24","author":"Cha S.","year":"1975","journal-title":"Biochem. Pharmacol."},{"key":"jm9505122b00068\/jm9505122b00068_1","first-page":"323","volume":"127","author":"Henderson P. J. F","year":"1972","journal-title":"Biochemistry"},{"key":"jm9505122b00069\/jm9505122b00069_1","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1021\/bi00510a002","volume":"20","author":"Baccanari D. B.","year":"1981","journal-title":"Biochemistry"},{"key":"jm9505122b00070\/jm9505122b00070_1","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1021\/bi00272a017","volume":"22","author":"Delcamp T. J.","year":"1983","journal-title":"Biochemistry"},{"key":"jm9505122b00071\/jm9505122b00071_1","first-page":"10607","volume":"264","author":"Krug E. C.","year":"1989","journal-title":"J. Biol. Chem."},{"key":"jm9505122b00072\/jm9505122b00072_1","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/bjc.1988.125","volume":"57","author":"Carmichael J.","year":"1988","journal-title":"Br. J. Cancer"},{"key":"jm9505122b00073\/jm9505122b00073_1","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1093\/jnci\/82.13.1107","volume":"82","author":"Skehan P.","year":"1990","journal-title":"J. Natl. Cancer Inst."},{"key":"jm9505122b00074\/jm9505122b00074_1","first-page":"1965","volume":"34","author":"Ou-Yang K.","year":"1990","journal-title":"Antimicrob. Agents Chemother."},{"key":"jm9505122b00075\/jm9505122b00075_1","first-page":"2886","volume":"48","author":"McLemore T. L.","year":"1988","journal-title":"Cancer Res."},{"key":"jm9505122b00076\/jm9505122b00076_1","first-page":"284","volume":"27","author":"Wang A. M.","year":"1991","journal-title":"Cancer Chemother. Pharmacol."},{"key":"jm9505122b00077\/jm9505122b00077_1","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/j.1550-7408.1994.tb01515.x","volume":"41","author":"Comley J. C. W.","year":"1994","journal-title":"J. Eukaryot. Microbiol."},{"key":"jm9505122b00078\/jm9505122b00078_1","first-page":"811","volume":"39","author":"Comley J. C. W.","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"jm9505122b00079\/jm9505122b00079_1","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1002\/jps.2600711027","volume":"71","author":"Foss R. G.","year":"1982","journal-title":"J. Pharm. Sci."}],"container-title":["Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jm9505122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T07:03:56Z","timestamp":1634454236000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/doi\/10.1021\/jm9505122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,1,1]]},"references-count":78,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1996,1,1]]}},"alternative-id":["10.1021\/jm9505122"],"URL":"https:\/\/doi.org\/10.1021\/jm9505122","relation":{},"ISSN":["0022-2623","1520-4804"],"issn-type":[{"value":"0022-2623","type":"print"},{"value":"1520-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,1,1]]}}}