Optimization of triazoles as novel and potent nonphlorizin SGLT2 inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 12, 2011, Pages 3774-3779

  Du, Xiaohui ^a   Lizarzaburu, Mike ^a   Turcotte, Simon ^a   Lee, Taeweon ^a   Greenberg, Joanne ^a   Shan, Bei ^a   Fan, Peter ^a   Ling, Yun ^a   Medina, Julio C ^a   Houze, Jonathan ^a  

^a AMGEN INC   (United States)

Author keywords

Benzooxazinone head groups; Indane tail group; Noncompetitive SGLT2 inhibitors; SAR; Solubility; Triazoles

Indexed keywords

SODIUM GLUCOSE COTRANSPORTER 2; TRIAZOLE DERIVATIVE;

ANIMAL CELL; ARTICLE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG MEGADOSE; DRUG SOLUBILITY; DRUG STABILITY; HUMAN; HUMAN CELL; LIVER MICROSOME; MOUSE; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

DRUG STABILITY; MOLECULAR STRUCTURE; PHLORHIZIN; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZOLES;

EID: 79957842977     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.04.053     Document Type: Article

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24. 14C] AMG, 10 uCi/ml, Moravek) was added and incubated at 37 °C incubator for 60 min. Assay plate was briefly washed with the buffer before air drying, and counted in Microbeta plate counter (PerkinElmer Biosciences).
25. Microsome stability were measured in a high throughput format by incubating inhibitors at 1 μM concentration with rat (r) or human (h) microsomes and the percentage of the parent compounds remaining were measured after 30 min. of incubation by liquid chromatography/mass spectrometry analysis. Only selective compounds were measured of its mouse liver microsomal stability manually.