title: Design and synthesis of xanthine analogues as potent and selective PDE5 inhibitors.
abstract: We have discovered potent and selective xanthine PDE5 inhibitors. Compound 25 (PDE5 IC(50)=0.6 nM, PDE6/PDE5=101) demonstrated similar functional efficacy and PK profile to Sildenafil (PDE5 IC(50)=3.5 nM, PDE6/PDE5=7).
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. yuguang.wang@spcorp.com
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Wang
authors.forename: Samuel
authors.initials: S
authors.lastname: Chackalamannil
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Hu
authors.forename: Craig D
authors.initials: CD
authors.lastname: Boyle
authors.forename: Claire M
authors.initials: CM
authors.lastname: Lankin
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.forename: Ruo
authors.initials: R
authors.lastname: Xu
authors.forename: Theodros
authors.initials: T
authors.lastname: Asberom
authors.forename: Dmitri
authors.initials: D
authors.lastname: Pissarnitski
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Stamford
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Skell
authors.forename: Stanley
authors.initials: S
authors.lastname: Kurowski
authors.forename: Subbarao
authors.initials: S
authors.lastname: Vemulapalli
authors.forename: Jairam
authors.initials: J
authors.lastname: Palamanda
authors.forename: Madhu
authors.initials: M
authors.lastname: Chintala
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Joyce
authors.initials: J
authors.lastname: Myers
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000478:Alkylation; D000818:Animals; D019540:Area Under Curve; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D015195:Drug Design; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D010413:Penis / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011687:Purines; D011817:Rabbits; D000068677:Sildenafil Citrate; D013329:Structure-Activity Relationship; D013450:Sulfones; D014970:Xanthines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014970:Xanthines; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5