Concise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition

Abstract Carbasugar sodium-glucose cotransporter 2 (SGLT2) inhibitors are highly promising drug candidates for the treatment of Type 2 diabetes mellitus (T2DM). However, the clinical usage of carbasugar SGLT2 inhibitors has been underexplored, due to the lengthy synthetic routes and the lack of stru...

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Autores principales:	Wai-Lung Ng, Ho-Chuen Li, Kit-Man Lau, Anthony K. N. Chan, Clara Bik-San Lau, Tony K. M. Shing
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/83f1c652d862439b94d28fde317fcb02
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spelling	oai:doaj.org-article:83f1c652d862439b94d28fde317fcb022021-12-02T12:32:32ZConcise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition10.1038/s41598-017-05895-92045-2322https://doaj.org/article/83f1c652d862439b94d28fde317fcb022017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05895-9https://doaj.org/toc/2045-2322Abstract Carbasugar sodium-glucose cotransporter 2 (SGLT2) inhibitors are highly promising drug candidates for the treatment of Type 2 diabetes mellitus (T2DM). However, the clinical usage of carbasugar SGLT2 inhibitors has been underexplored, due to the lengthy synthetic routes and the lack of structure-activity relationship (SAR) studies of these compounds. Herein, we report a concise and stereodivergent synthetic route towards some novel carbasugar SGLT2 inhibitors, featuring an underexploited, regioselective, and stereospecific palladium-catalyzed allyl-aryl coupling reaction. This synthetic strategy, together with computational modeling, revealed the unexpected SAR of these carbasugar SGLT2 inhibitors, and enabled the discovery of a highly selective and potent SGLT2 inhibitor.Wai-Lung NgHo-Chuen LiKit-Man LauAnthony K. N. ChanClara Bik-San LauTony K. M. ShingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wai-Lung Ng Ho-Chuen Li Kit-Man Lau Anthony K. N. Chan Clara Bik-San Lau Tony K. M. Shing Concise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition
description	Abstract Carbasugar sodium-glucose cotransporter 2 (SGLT2) inhibitors are highly promising drug candidates for the treatment of Type 2 diabetes mellitus (T2DM). However, the clinical usage of carbasugar SGLT2 inhibitors has been underexplored, due to the lengthy synthetic routes and the lack of structure-activity relationship (SAR) studies of these compounds. Herein, we report a concise and stereodivergent synthetic route towards some novel carbasugar SGLT2 inhibitors, featuring an underexploited, regioselective, and stereospecific palladium-catalyzed allyl-aryl coupling reaction. This synthetic strategy, together with computational modeling, revealed the unexpected SAR of these carbasugar SGLT2 inhibitors, and enabled the discovery of a highly selective and potent SGLT2 inhibitor.
format	article
author	Wai-Lung Ng Ho-Chuen Li Kit-Man Lau Anthony K. N. Chan Clara Bik-San Lau Tony K. M. Shing
author_facet	Wai-Lung Ng Ho-Chuen Li Kit-Man Lau Anthony K. N. Chan Clara Bik-San Lau Tony K. M. Shing
author_sort	Wai-Lung Ng
title	Concise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition
title_short	Concise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition
title_full	Concise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition
title_fullStr	Concise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition
title_full_unstemmed	Concise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition
title_sort	concise and stereodivergent synthesis of carbasugars reveals unexpected structure-activity relationship (sar) of sglt2 inhibition
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/83f1c652d862439b94d28fde317fcb02
work_keys_str_mv	AT wailungng conciseandstereodivergentsynthesisofcarbasugarsrevealsunexpectedstructureactivityrelationshipsarofsglt2inhibition AT hochuenli conciseandstereodivergentsynthesisofcarbasugarsrevealsunexpectedstructureactivityrelationshipsarofsglt2inhibition AT kitmanlau conciseandstereodivergentsynthesisofcarbasugarsrevealsunexpectedstructureactivityrelationshipsarofsglt2inhibition AT anthonyknchan conciseandstereodivergentsynthesisofcarbasugarsrevealsunexpectedstructureactivityrelationshipsarofsglt2inhibition AT clarabiksanlau conciseandstereodivergentsynthesisofcarbasugarsrevealsunexpectedstructureactivityrelationshipsarofsglt2inhibition AT tonykmshing conciseandstereodivergentsynthesisofcarbasugarsrevealsunexpectedstructureactivityrelationshipsarofsglt2inhibition
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Concise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition

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