{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T23:14:18Z","timestamp":1774566858135,"version":"3.50.1"},"reference-count":34,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2002,7,1]],"date-time":"2002-07-01T00:00:00Z","timestamp":1025481600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2002,7,1]],"date-time":"2002-07-01T00:00:00Z","timestamp":1025481600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2002,7]]},"DOI":"10.1124\/jpet.302.1.127","type":"journal-article","created":{"date-parts":[[2003,1,10]],"date-time":"2003-01-10T18:42:35Z","timestamp":1042224155000},"page":"127-137","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":34,"title":["Pharmacology of N-(3,5-Dichloro-1-oxido-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline Carboxamide (SCH 351591), a Novel, Orally Active Phosphodiesterase 4 Inhibitor"],"prefix":"10.1016","volume":"302","author":[{"given":"M. Motasim","family":"Billah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Minnicozzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Warneck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Hey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Kreutner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles A.","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidney R.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Young","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard W.","family":"Chapman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hazel","family":"Dyke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nang-Yang","family":"Shih","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.","family":"Piwinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis M.","family":"Cuss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Montana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashit K.","family":"Ganguly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert W.","family":"Egan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1124\/jpet.302.1.127_bib1","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S0022-3565(24)37221-0","article-title":"SB207499 (Ariflo), a potent and selective second generation phosphodiesterase 4 inhibitor: in vitro antiinflammatory actions.","volume":"284","author":"Barnette","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.302.1.127_bib2","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1097\/00063198-200003000-00014","article-title":"New phosphodiesterase inhibitors as therapeutics for the treatment of chronic lung diseases.","volume":"6","author":"Barnette","year":"2000","journal-title":"Curr Opin Pulmon Med"},{"key":"10.1124\/jpet.302.1.127_bib3","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/S1367-5931(00)00108-3","article-title":"Asthma: where beyond steroids.","volume":"4","author":"Bertrand","year":"2000","journal-title":"Curr Opin Chem Biol"},{"key":"10.1124\/jpet.302.1.127_bib4","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/S0022-3565(24)29538-0","article-title":"In vivo efficacy in airway disease models of Roflumilast, a novel orally active PDE4 inhibitor.","volume":"297","author":"Bundschuh","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.302.1.127_bib5","first-page":"A522","article-title":"Ariflo improves pulmonary function in patients with asthma: results of a study in patients taking inhaled corticosteroids.","volume":"159","author":"Compton","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1124\/jpet.302.1.127_bib6","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0140-6736(01)05481-2","article-title":"Cilomilast, a selective phosphodiesterase-4 inhibitor for treatment of patients with chronic obstructive pulmonary disease: a randomized, dose-ranging study.","volume":"358","author":"Compton","year":"2001","journal-title":"Lancet"},{"key":"10.1124\/jpet.302.1.127_bib7","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/S0091-6749(95)70128-1","article-title":"Prominent neutrophilic inflammation in sputum from subjects with acute asthma exacerbation.","volume":"95","author":"Fahy","year":"1995","journal-title":"J Allergy Clin Immunol"},{"key":"10.1124\/jpet.302.1.127_bib8","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1164\/ajrccm.150.5.7952568","article-title":"Potentiation of nonadrenergic noncholinergic relaxation of human isolated bronchus by selective inhibitors of phosphodiesterase isozymes.","volume":"150","author":"Fernandes","year":"1994","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1124\/jpet.302.1.127_bib9","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1378\/chest.119.5.1329","article-title":"Heterogeneity of airway inflammation in persistent asthma: evidence of neutrophilic inflammation and increased sputum interleukin-8.","volume":"119","author":"Gibson","year":"2001","journal-title":"Chest"},{"key":"10.1124\/jpet.302.1.127_bib10","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2165\/00003495-200059020-00004","article-title":"Phosphodiesterase 4 Inhibitors and the treatment of asthma: where are we now and where do we go from here.","volume":"59","author":"Giembycz","year":"2000","journal-title":"Drugs"},{"key":"10.1124\/jpet.302.1.127_bib11","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0022-3565(24)29537-9","article-title":"Anti-inflammatory and immunoregulatory potential of the novel PDE4 inhibitor Roflumilast in vitro.","volume":"297","author":"Hatzelmann","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.302.1.127_bib12","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/S1367-5931(00)00105-8","article-title":"Chronic obstructive pulmonary disease: emerging therapies.","volume":"4","author":"Hay","year":"2000","journal-title":"Curr Opin Chem Biol"},{"key":"10.1124\/jpet.302.1.127_bib13","first-page":"A859","article-title":"Effects of selective phosphodiesterase inhibitors on antigen-induced leukotriene release and leukotriene-dependent tracheal muscle contraction.","volume":"145","author":"Heaslip","year":"1992","journal-title":"Am Rev Respir Dis"},{"key":"10.1124\/jpet.302.1.127_bib14","doi-asserted-by":"crossref","first-page":"4909","DOI":"10.4049\/jimmunol.155.10.4909","article-title":"Cyclic nucleotide phosphodiesterase type IV participates in the regulation of IL-10 and in the subsequent inhibition of TNF\u03b1 and IL-6 by endotoxin-stimulated macrophages.","volume":"155","author":"Kambayashi","year":"1995","journal-title":"J Immunol"},{"key":"10.1124\/jpet.302.1.127_bib15","first-page":"312","article-title":"PDE4 inhibitors\u2014a review of the recent patent literature.","volume":"4","author":"Martin","year":"2001","journal-title":"Drugs"},{"key":"10.1124\/jpet.302.1.127_bib16","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s000110050488","article-title":"Recent insights into pathogenesis and control of asthma and atopic diseases.","volume":"48","author":"Mayer","year":"1999","journal-title":"Inflamm Res"},{"key":"10.1124\/jpet.302.1.127_bib17","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1164\/ajrccm.161.3.9809071","article-title":"Interleukin-8 secretion and neutrophil recruitment accompanies induced sputum eosinophil activation in children with acute asthma.","volume":"161","author":"Norzila","year":"2000","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1124\/jpet.302.1.127_bib18","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1164\/ajrccm.155.3.9117016","article-title":"Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with FEV1.","volume":"156","author":"O\u2019Shaughnessy","year":"1997","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1124\/jpet.302.1.127_bib19","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1152\/jappl.1989.66.3.1108","article-title":"Tachykinins mediate bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs.","volume":"66","author":"Ray","year":"1989","journal-title":"J Appl Physiol"},{"key":"10.1124\/jpet.302.1.127_bib20","doi-asserted-by":"crossref","first-page":"S191","DOI":"10.1164\/ajrccm.157.5.rsaa-5","article-title":"Inflammatory and structural changes in the small airways in bronchial asthma.","volume":"157","author":"Roche","year":"1998","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1124\/jpet.302.1.127_bib21","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1067\/mai.2001.118596","article-title":"The phosphodiesterase 4 inhibitor roflumilast is effective in the treatment of allergic rhinitis.","volume":"108","author":"Schmidt","year":"2001","journal-title":"J Allergy Clin Immunol"},{"key":"10.1124\/jpet.302.1.127_bib22","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1038\/sj.bjp.0703725","article-title":"The effects of selective and non-selective phosphodiesterase inhibitors on allergen- and leukotriene C4-induced contractions in passively sensitized airways.","volume":"131","author":"Schmidt","year":"2000","journal-title":"Br J Pharmacol"},{"key":"10.1124\/jpet.302.1.127_bib23","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1177\/00912700222011328","article-title":"The new phosphodiesterase 4 inhibitor roflumilast is efficacious in exercise-induced asthma and leads to suppression of LPS-stimulated TNF-\u03b1 ex vivo.","volume":"42","author":"Timmer","year":"2002","journal-title":"J Clin Pharmacol"},{"key":"10.1124\/jpet.302.1.127_bib24","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1164\/ajrccm.157.2.9708012","article-title":"Phosphodiesterase isozymes: molecular targets for novel antiasthma agents.","volume":"157","author":"Torphy","year":"1998","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1124\/jpet.302.1.127_bib25","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1006\/pupt.1999.0181","article-title":"Airflo (SB207499), a second generation phosphodiesterase 4 inhibitor in the treatment of asthma and COPD: from concept to clinic.","volume":"12","author":"Torphy","year":"1999","journal-title":"Pul Pharmacol Ther"},{"key":"10.1124\/jpet.302.1.127_bib26","first-page":"313a","article-title":"Molecular basis for an improved therapeutic index of SB207499, a second generation phosphodiesterase 4 inhibitor.","volume":"10","author":"Torphy","year":"1997","journal-title":"Eur Respir J"},{"key":"10.1124\/jpet.302.1.127_bib27","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1016\/S0021-9258(18)46016-4","article-title":"Coexpression of human cAMP-specific phosphodiesterase activity and high affinity rolipram binding in yeast.","volume":"267","author":"Torphy","year":"1992","journal-title":"J Biol Chem"},{"key":"10.1124\/jpet.302.1.127_bib28","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/S0022-3565(25)23837-X","article-title":"Inhibition of neurally mediated nonadrenergic noncholinergic relaxation of human isolated bronchus by isozyme selective phosphodiesterase inhibitors.","volume":"271","author":"Undem","year":"1994","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.302.1.127_bib29","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/S0022-3565(24)37892-9","article-title":"Antiasthma activity of the second generation phosphodiesterase (PDE4) inhibitor SB207499 (Ariflo) in the guinea pig.","volume":"287","author":"Underwood","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.302.1.127_bib30","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1159\/000237251","article-title":"Catecholamine and \u03b2-adrenoreceptor influences on airway reactivity to antigen in the guinea pig.","volume":"109","author":"Underwood","year":"1996","journal-title":"Int Arch Allergy Immunol"},{"key":"10.1124\/jpet.302.1.127_bib31","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/S0022-3565(25)38342-4","article-title":"Inhibition of antigen-induced bronchoconstriction and eosinophil infiltration in the guinea pig by the cyclic AMP-specific phosphodiesterase inhibitor, rolipram.","volume":"266","author":"Underwood","year":"1993","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.302.1.127_bib32","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1136\/thx.45.3.161","article-title":"What is the role of the eosinophil.","volume":"45","author":"Venge","year":"1990","journal-title":"Thorax"},{"key":"10.1124\/jpet.302.1.127_bib33","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1006\/bbrc.1997.6636","article-title":"Expression, purification, and characterization of human cAMP-specific phosphodiesterase (PDE4) subtypes A, B, C and D.","volume":"234","author":"Wang","year":"1997","journal-title":"Biochem Boiphys Res Commun"},{"key":"10.1124\/jpet.302.1.127_bib34","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1164\/ajrccm.160.3.9812110","article-title":"Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics.","volume":"160","author":"Wenzel","year":"1999","journal-title":"Am J Respir Crit Care Med"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002235652435743X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002235652435743X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.302.1.127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T23:22:10Z","timestamp":1740007330000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002235652435743X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,7]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,7]]}},"alternative-id":["S002235652435743X"],"URL":"https:\/\/doi.org\/10.1124\/jpet.302.1.127","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2002,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pharmacology of N-(3,5-Dichloro-1-oxido-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline Carboxamide (SCH 351591), a Novel, Orally Active Phosphodiesterase 4 Inhibitor","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.302.1.127","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2002 The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}