title: Pyrazolopyrimidine-2,4-dione sulfonamides: novel and selective calcitonin inducers.
abstract: A series of pyrazolo[4,3-d]pyrimidine sulfonamides and pyrazolo[3,4-d]pyrimidine sulfonamides have been synthesized. These compounds increase transcription of a calcitonin-luciferase promoter and production of cellular calcitonin in a calcitonin-secretion/RIA assay with minimized phosphodiesterase type 4 inhibitory activity at 30 microM as compared to structurally related xanthine methylene ketones such as denbufyllene. These two series are notable examples of small molecules that act as CT-inducers, a method to potentially treat bone loss diseases.
authors.affiliation: Chemical Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965-1299, and Bone Metabolism and Osteoporosis Research, Wyeth Research, 145 King of Prussia Road, Radnor, Pennsylvania 19087-4588.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Gilbert
authors.forename: Stephen
authors.initials: S
authors.lastname: Caltabiano
authors.forename: Frank E
authors.initials: FE
authors.lastname: Koehn
authors.forename: Zhen-jia
authors.initials: ZJ
authors.lastname: Chen
authors.forename: Gerardo D
authors.initials: GD
authors.lastname: Francisco
authors.forename: John W
authors.initials: JW
authors.lastname: Ellingboe
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Kharode
authors.forename: AnnaMarie
authors.initials: A
authors.lastname: Mangine
authors.forename: Rita
authors.initials: R
authors.lastname: Francis
authors.forename: Mark
authors.initials: M
authors.lastname: TrailSmith
authors.forename: David
authors.initials: D
authors.lastname: Gralnick
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D002116:Calcitonin / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011863:Radioimmunoassay; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015533:Transcriptional Activation; D014970:Xanthines / Q000737:chemistry / Q000494:pharmacology
chemical_list: D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D014970:Xanthines; C043898:denbufylline; D002116:Calcitonin; D008156:Luciferases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4