Design and discovery of a selective small molecule &#954; opioid antagonist (2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242).

Verhoest, Patrick R; Basak, Aarti Sawant; Parikh, Vinod; Hayward, Matthew; Kauffman, Gregory W; Paradis, Vanessa; McHardy, Stanton F; McLean, Stafford; Grimwood, Sarah; Schmidt, Anne W; Vanase-Frawley, Michelle; Freeman, Jodi; Van Deusen, Jeffrey; Cox, Loretta; Wong, Diane; Liras, Spiros

Design and discovery of a selective small molecule κ opioid antagonist (2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242).

Verhoest, Patrick R; Basak, Aarti Sawant; Parikh, Vinod; Hayward, Matthew; Kauffman, Gregory W; Paradis, Vanessa; McHardy, Stanton F; McLean, Stafford; Grimwood, Sarah; Schmidt, Anne W; Vanase-Frawley, Michelle; Freeman, Jodi; Van Deusen, Jeffrey; Cox, Loretta; Wong, Diane; Liras, Spiros.

Affiliation

Verhoest PR; Neuroscience Medicinal Chemistry, Pfizer PharmaTherapeutics Research and Development, Groton, Connecticut, USA. patrick.r.verhoest@pfizer.com

J Med Chem ; 54(16): 5868-77, 2011 Aug 25.

Article in En | MEDLINE | ID: mdl-21744827

Subject(s)

Biphenyl Compounds/pharmacology; Drug Design; Drug Discovery; Narcotic Antagonists/pharmacology; Receptors, Opioid, kappa/antagonists & inhibitors; Sulfonamides/pharmacology; 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/pharmacology; Analgesics/chemistry; Analgesics/pharmacokinetics; Analgesics/pharmacology; Animals; Area Under Curve; Biphenyl Compounds/chemistry; Biphenyl Compounds/pharmacokinetics; Brain/metabolism; Disease Models, Animal; Dogs; Haplorhini; Humans; Metabolic Clearance Rate; Mice; Microsomes, Liver/metabolism; Models, Chemical; Molecular Structure; Morphine/pharmacology; Narcotic Antagonists/chemistry; Narcotic Antagonists/pharmacokinetics; Pain/metabolism; Pain/prevention & control; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa/agonists; Receptors, Opioid, kappa/metabolism; Receptors, Opioid, mu/agonists; Structure-Activity Relationship; Sulfonamides/chemistry; Sulfonamides/pharmacokinetics

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Full text: 1 Database: MEDLINE Main subject: Sulfonamides / Biphenyl Compounds / Drug Design / Receptors, Opioid, kappa / Drug Discovery / Narcotic Antagonists Type of study: Prognostic_studies Language: En Year: 2011 Type: Article

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