The design and synthesis of novel SGLT2 inhibitors: C-glycosides with benzyltriazolopyridinone and phenylhydantoin as the aglycone moieties

Guo, Cheng; Hu, Min; DeOrazio, Russell J.; Usyatinsky, Alexander; Fitzpatrick, Kevin; Zhang, Zhenjun; Maeng, Jun‐Ho; Kitchen, Douglas B.; Tom, S; Luche, Michele; Khmelnitsky, Yuri L.; Mhyre, Andrew J.; Guzzo, Peter R.; Liu, Shuang

doi:10.1016/j.bmc.2014.04.036

Cited by 35 publications

(22 citation statements)

References 17 publications

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“…[1] For instance, in the design of SGLT2 inhibitors, replacement of an O-glycoside with a C-glycoside can dramatically improve the pharmacokinetic profiles and drug-like properties. [2] Glycoamino acids, as mimic moieties of protein glycosylation, are an important scaffold and building block for regulating carbohydrate-mediated biological events. [3] Over the past few decades, the synthesis of complex C-glycosides has seen significant progress.…”

mentioning

confidence: 99%

Palladium‐Catalysed C(sp³)−H Glycosylation for the Synthesis of C‐Alkyl Glycoamino Acids

Liu,

Wang,

Dai

et al. 2020

Angew Chem Int Ed

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We have developed a highly efficient and practical approach for palladium‐catalyzed trifluoroacetate‐promoted N‐quinolylcarboxamide‐directed glycosylation of inert β‐C(sp3)−H bonds of N‐phthaloyl α‐amino acids with glycals under mild conditions. For the first time, C(sp3)−H activation for glycosylation was achieved to build C‐alkyl glycosides. This method facilitates the synthesis of various β‐substituted C‐alkyl glycoamino acids and offers a tool for glycopeptide synthesis.

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confidence: 99%

Palladium‐Catalysed C(sp³)−H Glycosylation for the Synthesis of C‐Alkyl Glycoamino Acids

Liu,

Wang,

Dai

et al. 2020

Angew Chem Int Ed

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“…Substrates with a heteroatom at the α-C were also effective although the yields dropped, probably because of the inductive effect of the heteroatom (30)(31)(32)(33)(34). The tertiary carboxylic acids such as simple alkyl substituted (35)(36)(37), deuterated (38), fluorinated (39), and cyclic systems (41)(42)(43)(44) were demonstrated effective as well. It is worth to mention that these tertiary substituted triazolopyridinone derivatives had never been reported before, and they cannot be prepared by the conventional nucleophilic substitution from the corresponding 1,2,4-triazolo[4,3-a]pyridin-3(2H)-one and alkyl halides (see Supplementary methods).…”

Section: Resultsmentioning

confidence: 99%

Enantiospecific electrochemical rearrangement for the synthesis of hindered triazolopyridinone derivatives

Chen

et al. 2020

Nat Commun

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Triazolopyridinone derivatives are of high value in both medicinal and material chemistry. However, the chiral or hindered triazolopyridinone derivatives remain an underexplored area of chemical space because they are difficult to prepare via conventional methods. Here we report an electrochemical rearrangement for the efficient synthesis of otherwise inaccessible triazolopyridinones with diverse alkyl carboxylic acids as starting materials. This enables the efficient preparation of more than 60 functionalized triazolopyridinones under mild conditions in a sustainable manner. This method is evaluated for the late stage modification of bioactive natural products, amino acids and pharmaceuticals, and it is further applied to the decagram scale preparation of enantiopure triazolopyridinones. The control experiments support a mechanism involving an oxidative cyclization and 1,2-carbon migration. This facile and scalable rearrangement demonstrates the power of electrochemical synthesis to access otherwise-inaccessible triazolopyridinones and may find wide application in organic, material and medicinal chemistry.

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“…Inicialmente o pâncreas produz uma maior quantidade do hormônio visando garantir o controle da glicemia, porém, progressivamente, as células  ficam sobrecarregadas e vão sendo gradativamente danificadas, reduzindo a capacidade de produção de insulina. 3 Cerca de 90-95% dos casos de diabetes são do tipo II, 4 em decorrência do aumento exponencial na prevalência da obesidade, maus hábitos alimentares, estilo de vida sedentário e envelhecimento populacional, havendo uma maior pré-disposição em indivíduos acima dos 40 anos. 1,2 Nestes indivíduos, diversos mecanismos estão conhecidamente associados ao estabelecimento da resistência à insulina, incluindo a predisposição genética, a glicotoxicidade, a lipotoxicidade, o estresse oxidativo e o estabelecimento de um quadro inflamatório generalizado, caracterizando o diabetes tipo II como um distúrbio endócrino, metabólico e inflamatório crônico e sistêmico, de natureza complexa e multifatorial.…”

Section: Diabetes Mellitusunclassified

Drugs for the Treatment of Type II Diabetes: A Visit to the Past and a Look to the Future

2017

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ResumoO diabetes mellitus consiste em uma síndrome metabólica caracterizada por níveis elevados de glicose sanguínea (hiperglicemia). Atualmente, cerca de 90-95% dos casos de diabetes são do tipo II, o qual se desenvolve a partir de um quadro inicial de resistência periférica à insulina. Em decorrência do avanço exponencial dos principais fatores de risco para o estabelecimento da doença, incluindo a obesidade, maus hábitos alimentares, estilo de vida sedentário e envelhecimento populacional, as estatísticas apontam para a existência de uma epidemia global de diabetes tipo II, com estimativas assustadoras para o futuro. Tratando-se de uma doença crônica sistêmica de progressão lenta, há uma demanda imediata por medicamentos eficazes e com um perfil de segurança adequado ao uso contínuo. Esta revisão detalha a evolução dos fármacos antidiabéticos atualmente disponíveis no mercado farmacêutico, demonstrando os avanços realizados até então e os desafios para o futuro.

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The design and synthesis of novel SGLT2 inhibitors: C-glycosides with benzyltriazolopyridinone and phenylhydantoin as the aglycone moieties

Cited by 35 publications

References 17 publications

Palladium‐Catalysed C(sp³)−H Glycosylation for the Synthesis of C‐Alkyl Glycoamino Acids

Palladium‐Catalysed C(sp³)−H Glycosylation for the Synthesis of C‐Alkyl Glycoamino Acids

Enantiospecific electrochemical rearrangement for the synthesis of hindered triazolopyridinone derivatives

Drugs for the Treatment of Type II Diabetes: A Visit to the Past and a Look to the Future

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The design and synthesis of novel SGLT2 inhibitors: C-glycosides with benzyltriazolopyridinone and phenylhydantoin as the aglycone moieties

Cited by 35 publications

References 17 publications

Palladium‐Catalysed C(sp3)−H Glycosylation for the Synthesis of C‐Alkyl Glycoamino Acids

Palladium‐Catalysed C(sp3)−H Glycosylation for the Synthesis of C‐Alkyl Glycoamino Acids

Enantiospecific electrochemical rearrangement for the synthesis of hindered triazolopyridinone derivatives

Drugs for the Treatment of Type II Diabetes: A Visit to the Past and a Look to the Future

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Palladium‐Catalysed C(sp³)−H Glycosylation for the Synthesis of C‐Alkyl Glycoamino Acids

Palladium‐Catalysed C(sp³)−H Glycosylation for the Synthesis of C‐Alkyl Glycoamino Acids