title: Synthesis and SAR of tetracyclic pyrroloquinolones as phosphodiesterase 5 inhibitors.
abstract: The synthesis of the fused tetracyclic pyrroloquinolones 9a-i in four steps is described. The PDE5 inhibitory activities of these compounds, their selectivities against PDE1, PDE2, PDE3, PDE4 and PDE6, the preclinical pharmacokinetic assessments and the in vivo efficacy in increasing intracavernosal pressure are presented and discussed.
authors.affiliation: Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, LLC, 1000 Route 202 South; PO Box 300, Raritan, NJ 08869, USA. wijiang1@prdus.jnj.com
authors.forename: Weiqin
authors.initials: W
authors.lastname: Jiang
authors.forename: Vernon C
authors.initials: VC
authors.lastname: Alford
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Qiu
authors.forename: Sheela
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: T Matthew
authors.initials: TM
authors.lastname: John
authors.forename: Donna
authors.initials: D
authors.lastname: Haynes-Johnson
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Kraft
authors.forename: Scott G
authors.initials: SG
authors.lastname: Lundeen
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Sui
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004285:Dogs; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry*; D010879:Piperazines / Q000008:administration & dosage; D011687:Purines; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013329:Structure-Activity Relationship; D013450:Sulfones
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D015363:Quinolones; D013450:Sulfones; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human