C-Aryl glycoside inhibitors of SGLT2: Exploration of sugar modifications including C-5 spirocyclization

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 5, 2010, Pages 1569-1572

  Robinson, Ralph P ^a   Mascitti, Vincent ^a   Boustany Kari, Carine M ^a   Carr, Christopher L ^a   Foley, Patrick M ^a   Kimoto, Emi ^a   Leininger, Michael T ^a   Lowe, Andre ^a   Klenotic, Michelle K ^a   MacDonald, James I ^a   Maguire, Robert J ^a   Masterson, Victoria M ^a   Maurer, Tristan S ^a   Miao, Zhuang ^a   Patel, Jigna D ^a   Préville, Cathy ^a   Reese, Matthew R ^a   She, Li ^a   Steppan, Claire M ^a   Thuma, Benjamin A ^a   Zhu, Tong ^a   more..

^a PFIZER INC   (United States)

Author keywords

C Aryl glycoside; Diabetes; Glucose; Inhibitor; SGLT; SGLT2; Transporter

Indexed keywords

1,3 DIOXOLANE DERIVATIVE; ARYL GLYCOSIDE SODIUM GLUCOSE TRANSPORTER 2 INHIBITOR; AZETIDINE DERIVATIVE; DIOXOTHIETANE; GLUCOSE; GLYCOSIDE; HYDROXYL GROUP; LACTONE DERIVATIVE; OXETANE DERIVATIVE; PROTEIN INHIBITOR; SODIUM GLUCOSE COTRANSPORTER 2; SPIRO COMPOUND; SUGAR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CHEMICAL MODIFICATION; CONTROLLED STUDY; CYCLIZATION; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG HALF LIFE; DRUG MEGADOSE; DRUG POTENCY; GLUCOSE URINE LEVEL; HUMAN; HUMAN CELL; NONHUMAN; PHARMACOLOGICAL PARAMETERS; RAT; SPIROCYCLIZATION; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

ANIMALS; CYCLIZATION; GLYCOSIDES; HUMANS; HYPOGLYCEMIC AGENTS; MALE; MICROSOMES, LIVER; RATS; RATS, SPRAGUE-DAWLEY; SODIUM-GLUCOSE TRANSPORTER 2; SPIRO COMPOUNDS;

RATTUS;

EID: 76649110175     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.01.075     Document Type: Article

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20. Rat PK studies were carried out in Sprague-Dawley rats. Allometric scaling of rat clearance for 2 provided an estimate of human clearance in good agreement with the value derived from published PK data for 2.
21. Although we determined a half-life in rats for 2 similar to that reported in Ref. 3 (4.6 h), our measurements of Cl and Vdss in differ from those reported (4.8 mL/min/kg and 1.7 L/h, respectively).
22. Additional support for this conclusion is provided by the C-5 modifications reported in Ref. 13.