Journal article
Synthesis and biological evaluation of benzocyclobutane-C-glycosides as potent and orally active SGLT1/SGLT2 dual inhibitors
Bioorganic & medicinal chemistry letters, v 28(7), pp 1182-1187
15 Apr 2018
PMID: 29523385
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Synthesis and biological evaluation of benzocyclobutane-C-glycosides as potent and orally active SGLT1/SGLT2 dual inhibitors are described. Compound 19 showed high inhibitory potency at SGLT1 (IC
= 45 nM), and excellent potency at SGLT2 (IC
= 1 nM). It also displayed excellent PK profiles in mice, rats, dogs and monkeys (F = 78-107%). In SD rats, compound 19 treatments significantly reduced blood glucose levels in a dose-dependent manner. In ZDF rats, compound 19 displayed anti-hyperglycemic effect up to 24 h. Therefore, compound 19 may serve as valuable pharmacological tool, and potential use as a treatment for metabolic syndrome.
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Details
- Title
- Synthesis and biological evaluation of benzocyclobutane-C-glycosides as potent and orally active SGLT1/SGLT2 dual inhibitors
- Creators
- Gee-Hong Kuo - Cardiovascular and Metabolism Research, Janssen Research and Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA. Electronic address: gkuo@its.jnj.comMicheal D Gaul - Janssen (United States)Yin Liang - Janssen (United States)June Z Xu - Janssen (United States)Fuyong Du - Janssen (United States)Pamela Hornby - Janssen (United States)Guozhang Xu - Janssen (United States)Jenson Qi - Janssen (United States)Nathaniel Wallace - Janssen (United States)Seunghun Lee - Cardiovascular and Metabolism Research, Janssen Research and Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USAEugene Grant - Janssen (United States)William V Murray - Janssen (United States)Keith Demarest - Janssen (United States)
- Publication Details
- Bioorganic & medicinal chemistry letters, v 28(7), pp 1182-1187
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000428092400006
- Scopus ID
- 2-s2.0-85042854737
- Other Identifier
- 991021931907304721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Chemistry, Medicinal
- Chemistry, Organic