Bicyclo[2.2.2]octyltriazole inhibitors of 11β-hydoxysteroid dehydrogenase type 1. Pharmacological agents for the treatment of metabolic syndrome

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 8, 2011, Pages 2568-2572

  Maletic, Milana ^a   Leeman, Aaron ^a   Szymonifka, Michael ^a   Mundt, Steven S ^a   Zokian, Hratch J ^a   Shah, Kashmira ^a   Dragovic, Jasminka ^a   Lyons, Kathy ^a   Thieringer, Rolf ^a   Vosatka, Anne H ^a   Balkovec, James ^a   Waddell, Sherman T ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

11 HSD1 inhibitor; Metabolic Syndrome; Sulfone

Indexed keywords

11BETA HYDROXYSTEROID DEHYDROGENASE 1; BICYCLO[2.2.2]OCTYLTRIAZOLE; OXIDOREDUCTASE INHIBITOR; UNCLASSIFIED DRUG;

AEROBIC METABOLISM; AREA UNDER THE CURVE; ARTICLE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; HUMAN; IC 50; METABOLIC SYNDROME X; MOUSE; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 2; ANIMALS; BICYCLO COMPOUNDS; ENZYME INHIBITORS; HUMANS; METABOLIC SYNDROME X; MICE; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZOLES;

EID: 79953283569     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.01.018     Document Type: Article

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18. While mouse PK was not obtained on all the compounds described in this communication, plasma levels of compound were determined in mice following the PD studies. There was generally a good correlation between efficacy and compound levels in plasma for the compounds in Tables 4 and 5 ; compounds with decreased plasma exposures showed lowered efficacy in extended PD.
19. Unpublished results; (a) Maletic, M.; Leeman, A.; Mundt, S.; Zokian, H.; Shah, K.; Dragovic, J.; Lyons, K.; Tan, E.; Thieringer, R.; Vosatka, A.; Springer, M.; Balkovec, J.; Waddell, S. T. 'Bicyclo[2.2.2]octyltriazole inhibitors of 11β-HSD type 1: Pharmacological agents for the treatment of metabolic syndrome' Metabolic Syndrome and Cardiovascular Risk Keystone Symposium, Steamboat Springs, CO, Mar 28-Apr 1, 2007; Poster 224; (b) Maletic, M.; Leeman, A.; Waddell, S. T.; Balkovec, J. 'Bicyclo[2.2.2]octyltriazole inhibitors of 11β-HSD type 1: Pharmacological agents for the treatment of metabolic syndrome' 231st ACS National Meeting, Atlanta, GA, Mar 26-30, 2006; MEDI-196.