BIOMAT Database Logo BIOMAT Database Logo

The discovery of novel, potent and selective PDE5 inhibitors. 2001

Y Bi, and P Stoy, and L Adam, and B He, and J Krupinski, and D Normandin, and R Pongrac, and L Seliger, and A Watson, and J E Macor
Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. yingzhi.bi@bms.com

The design and synthesis of a novel scaffold for potent and selective PDE5 inhibitors are described. Compound 3a was more potent (PDE5 IC50=0.31 nM) and selective (>10,000-fold vs PDE1 and 160-fold selective vs PDE6) PDE5 inhibitor than sildenafil.

UI MeSH Term Description Entries
D010726 Phosphodiesterase Inhibitors Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. Phosphodiesterase Antagonists,Phosphodiesterase Inhibitor,Phosphoric Diester Hydrolase Inhibitors,Antiphosphodiesterases,Inhibitor, Phosphodiesterase
D010727 Phosphoric Diester Hydrolases A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4. Phosphodiesterase,Phosphodiesterases,Hydrolases, Phosphoric Diester
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011687 Purines A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D000068677 Sildenafil Citrate A PHOSPHODIESTERASE TYPE-5 INHIBITOR; VASODILATOR AGENT and UROLOGICAL AGENT that is used in the treatment of ERECTILE DYSFUNCTION and PRIMARY PULMONARY HYPERTENSION. 1-((3-(6,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine citrate,Acetildenafil,Desmethyl Sildenafil,Desmethylsildenafil,Homosildenafil,Hydroxyhomosildenafil,NCX-911,Revatio,Sildenafil,Sildenafil Lactate,Sildenafil Nitrate,UK 92480-10,UK-92,480-10,Viagra,Citrate, Sildenafil,Lactate, Sildenafil,NCX 911,NCX911,Nitrate, Sildenafil,Sildenafil, Desmethyl,UK 92,480 10,UK 92480 10,UK 9248010
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013450 Sulfones Sulfone
D015106 3',5'-Cyclic-GMP Phosphodiesterases Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate. 3',5'-Cyclic GMP 5'-Nucleotidohydrolase,3',5'-Cyclic GMP Phosphodiesterase,3',5'-Cyclic-GMP Phosphodiesterase,3,5-Cyclic GMP 5-Nucleotidohydrolase,3,5-Cyclic GMP Phosphodiesterase,3',5' Cyclic GMP 5' Nucleotidohydrolase,3',5' Cyclic GMP Phosphodiesterase,3',5' Cyclic GMP Phosphodiesterases,3,5 Cyclic GMP 5 Nucleotidohydrolase,3,5 Cyclic GMP Phosphodiesterase,5'-Nucleotidohydrolase, 3',5'-Cyclic GMP,5-Nucleotidohydrolase, 3,5-Cyclic GMP,GMP 5'-Nucleotidohydrolase, 3',5'-Cyclic,GMP 5-Nucleotidohydrolase, 3,5-Cyclic,GMP Phosphodiesterase, 3',5'-Cyclic,GMP Phosphodiesterase, 3,5-Cyclic,Phosphodiesterase, 3',5'-Cyclic GMP,Phosphodiesterase, 3',5'-Cyclic-GMP,Phosphodiesterase, 3,5-Cyclic GMP,Phosphodiesterases, 3',5'-Cyclic-GMP
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs

Related Publications

Y Bi, and P Stoy, and L Adam, and B He, and J Krupinski, and D Normandin, and R Pongrac, and L Seliger, and A Watson, and J E Macor
Discovery of furyl/thienyl β-carboline derivatives as potent and selective PDE5 inhibitors with excellent vasorelaxant effect.
October 2018, European journal of medicinal chemistry,
Y Bi, and P Stoy, and L Adam, and B He, and J Krupinski, and D Normandin, and R Pongrac, and L Seliger, and A Watson, and J E Macor
Discovery of novel N-acylpyrazoles as potent and selective thrombin inhibitors.
January 2023, European journal of medicinal chemistry,
Y Bi, and P Stoy, and L Adam, and B He, and J Krupinski, and D Normandin, and R Pongrac, and L Seliger, and A Watson, and J E Macor
Discovery of Potent and Selective PI3Kγ Inhibitors.
October 2020, Journal of medicinal chemistry,
Y Bi, and P Stoy, and L Adam, and B He, and J Krupinski, and D Normandin, and R Pongrac, and L Seliger, and A Watson, and J E Macor
Design and synthesis of xanthine analogues as potent and selective PDE5 inhibitors.
November 2002, Bioorganic & medicinal chemistry letters,
Y Bi, and P Stoy, and L Adam, and B He, and J Krupinski, and D Normandin, and R Pongrac, and L Seliger, and A Watson, and J E Macor
Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors.
January 2013, Drug metabolism and disposition: the biological fate of chemicals,
Y Bi, and P Stoy, and L Adam, and B He, and J Krupinski, and D Normandin, and R Pongrac, and L Seliger, and A Watson, and J E Macor
Discovery of novel tetrahydroisoquinoline derivatives as potent and selective factor Xa inhibitors.
January 2005, Bioorganic & medicinal chemistry letters,
Y Bi, and P Stoy, and L Adam, and B He, and J Krupinski, and D Normandin, and R Pongrac, and L Seliger, and A Watson, and J E Macor
Discovery of potent and selective PKC-theta inhibitors.
January 2007, Bioorganic & medicinal chemistry letters,
Y Bi, and P Stoy, and L Adam, and B He, and J Krupinski, and D Normandin, and R Pongrac, and L Seliger, and A Watson, and J E Macor
Highly potent and selective chiral inhibitors of PDE5: an illustration of Pfeiffer's rule.
December 2008, Bioorganic & medicinal chemistry letters,
Y Bi, and P Stoy, and L Adam, and B He, and J Krupinski, and D Normandin, and R Pongrac, and L Seliger, and A Watson, and J E Macor
Discovery and SAR of novel, potent and selective protein tyrosine phosphatase 1B inhibitors.
October 2003, Bioorganic & medicinal chemistry letters,
Y Bi, and P Stoy, and L Adam, and B He, and J Krupinski, and D Normandin, and R Pongrac, and L Seliger, and A Watson, and J E Macor
A novel series of potent and selective PDE5 inhibitors with potential for high and dose-independent oral bioavailability.
June 2006, Journal of medicinal chemistry,
Copied contents to your clipboard!