Tento výsledek nelze pro nepřihlášené uživatele zobrazit.
K zobrazení výsledku je třeba se přihlásit.

Optimizing the Benefit/Risk of Acetyl-CoA Carboxylase Inhibitors through Liver Targeting.

Autor: Huard K; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., Smith AC; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Cappon G; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Dow RL; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., Edmonds DJ; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., El-Kattan A; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., Esler WP; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., Fernando DP; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Griffith DA; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., Kalgutkar AS; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., Ross TT; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., Bagley SW; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Beebe D; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., Bi YA; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Cabral S; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Crowley C; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., Doran SD; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Dowling MS; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Liras S; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., Mascitti V; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Niosi M; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Pfefferkorn JA; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., Polivkova J; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Préville C; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Price DA; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., Shavnya A; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Shirai N; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Smith AH; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Southers JR; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Tess DA; Pfizer Worldwide Research and Development, 1 Portland Street, Cambridge, Massachusetts 02139, United States., Thuma BA; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Varma MV; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States., Yang X; Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2020 Oct 08; Vol. 63 (19), pp. 10879-10896. Date of Electronic Publication: 2020 Sep 18.

Discovery and in Vitro Optimization of 3-Sulfamoylbenzamides as ROMK Inhibitors.

Autor: Sammons MF; Pfizer Worldwide Research & Development, 610 Main Street, Cambridge, Massachusetts 02139, United States., Kharade SV; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States., Filipski KJ; Pfizer Worldwide Research & Development, 610 Main Street, Cambridge, Massachusetts 02139, United States., Boehm M; Pfizer Worldwide Research & Development, 610 Main Street, Cambridge, Massachusetts 02139, United States., Smith AC; Pfizer Worldwide Research & Development, Eastern Point Road, Groton, Connecticut 06340, United States., Shavnya A; Pfizer Worldwide Research & Development, Eastern Point Road, Groton, Connecticut 06340, United States., Fernando DP; Pfizer Worldwide Research & Development, Eastern Point Road, Groton, Connecticut 06340, United States., Dowling MS; Pfizer Worldwide Research & Development, Eastern Point Road, Groton, Connecticut 06340, United States., Carpino PA; Pfizer Worldwide Research & Development, 610 Main Street, Cambridge, Massachusetts 02139, United States., Castle NA; Neusentis, Pfizer Worldwide Research & Development, Durham, North Carolina 27703, United States., Zellmer SG; Neusentis, Pfizer Worldwide Research & Development, Durham, North Carolina 27703, United States., Antonio BM; Neusentis, Pfizer Worldwide Research & Development, Durham, North Carolina 27703, United States., Gosset JR; Pfizer Worldwide Research & Development, 610 Main Street, Cambridge, Massachusetts 02139, United States., Carlo A; Pfizer Worldwide Research & Development, Eastern Point Road, Groton, Connecticut 06340, United States., Denton JS; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.

Publikováno v: ACS medicinal chemistry letters [ACS Med Chem Lett] 2018 Jan 19; Vol. 9 (2), pp. 125-130. Date of Electronic Publication: 2018 Jan 19 (Print Publication: 2018).

Discovery and Preclinical Characterization of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic Acid (PF-06409577), a Direct Activator of Adenosine Monophosphate-activated Protein Kinase (AMPK), for the Potential Treatment of Diabetic Nephropathy.

Autor: Cameron KO; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Kung DW; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Kalgutkar AS; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Kurumbail RG; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Miller R; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Salatto CT; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Ward J; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Withka JM; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Bhattacharya SK; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Boehm M; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Borzilleri KA; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Brown JA; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Calabrese M; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Caspers NL; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Cokorinos E; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Conn EL; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Dowling MS; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Edmonds DJ; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Eng H; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Fernando DP; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Frisbie R; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Hepworth D; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Landro J; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Mao Y; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Rajamohan F; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Reyes AR; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Rose CR; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Ryder T; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Shavnya A; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Smith AC; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Tu M; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Wolford AC; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States., Xiao J; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ‡Cardiovascular, Metabolic and Endocrine Diseases Research Unit, and §Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research & Development , 610 Main Street, Cambridge, Massachusetts 02139, United States.; Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, ⊥Cardiovascular, Metabolic and Endocrine Diseases Research Unit, #Worldwide Medicinal Chemistry, ∇Pharmacokinetics, Dynamics and Metabolism, ○Pharmaceutical Sciences, Pfizer Worldwide Research & Development , Groton, Connecticut 06340, United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2016 Sep 08; Vol. 59 (17), pp. 8068-81. Date of Electronic Publication: 2016 Aug 20.

Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.

Autor: Ruggeri RB; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Buckbinder L; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Bagley SW; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Carpino PA; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Conn EL; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Dowling MS; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Fernando DP; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Jiao W; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Kung DW; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Orr ST; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Qi Y; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Rocke BN; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Smith A; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Warmus JS; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Zhang Y; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Bowles D; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Widlicka DW; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Eng H; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Ryder T; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Sharma R; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Wolford A; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Okerberg C; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Walters K; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Maurer TS; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Zhang Y; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Bonin PD; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Spath SN; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Xing G; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Hepworth D; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Ahn K; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States., Kalgutkar AS; Worldwide Research and Development, Pfizer, Inc., Groton, Connecticut 06340, United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2015 Nov 12; Vol. 58 (21), pp. 8513-28. Date of Electronic Publication: 2015 Oct 28.