Synthesis and SAR of tetracyclic pyrroloquinolones as phosphodiesterase 5 inhibitors.
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.
Jiang
Weiqin
W
Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, LLC, 1000 Route 202 South; PO Box 300, Raritan, NJ 08869, USA. wijiang1@prdus.jnj.com
Alford
Vernon C
VC
Qiu
Yuhong
Y
Bhattacharjee
Sheela
S
John
T Matthew
TM
Haynes-Johnson
Donna
D
Kraft
Patricia J
PJ
Lundeen
Scott G
SG
Sui
Zhihua
Z
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
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