Novel C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents: 1,3,4-Thiadiazolylmethylphenyl glucoside congeners

Lee, Jun–Won; Lee, Sung-Han; Seo, Hee Jeong; Son, Eunjung; Lee, Suk Ho; Jung, Myung Eun; Lee, Minwoo; Han, Ho-Kyun; Kim, Jeongmin; Kang, Jahyo; Lee, Jinhwa

doi:10.1016/j.bmc.2010.01.073

Cited by 70 publications

(16 citation statements)

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“…A set of 110 different SGLT2 inhibitors and 44 different SGLT1 inhibitors has been collected from different references [1,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. Of those compounds, 25 SGLT2 inhibitors and 23 SGLT1 inhibitors, which achieve satisfactory diversity in both structural and activity ranges, were selected as the training set for pharmacophore models, respectively.…”

Section: Selection Of Moleculesmentioning

confidence: 99%

A specific pharmacophore model of sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors

et al. 2011

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Sodium-dependent glucose co-transporter 2 (SGLT2) plays a pivotal role in maintaining glucose equilibrium in the human body, emerging as one of the most promising targets for the treatment of diabetes mellitus type 2. Pharmacophore models of SGLT2 inhibitors have been generated with a training set of 25 SGLT2 inhibitors using Discovery Studio V2.1. The best hypothesis (Hypo1(SGLT2)) contains one hydrogen bond donor, five excluded volumes, one ring aromatic and three hydrophobic features, and has a correlation coefficient of 0.955, cost difference of 68.76, RMSD of 0.85. This model was validated by test set, Fischer randomization test and decoy set methods. The specificity of Hypo1(SGLT2) was evaluated. The pharmacophore features of Hypo1(SGLT2) were different from the best pharmacophore model (Hypo1(SGLT1)) of SGLT1 inhibitors we developed. Moreover, Hypo1(SGLT2) could effectively distinguish selective inhibitors of SGLT2 from those of SGLT1. These results indicate that a highly predictive and specific pharmacophore model of SGLT2 inhibitors has been successfully obtained. Then Hypo1(SGLT2) was used as a 3D query to screen databases including NCI and Maybridge for identifying new inhibitors of SGLT2. The hit compounds were subsequently subjected to filtering by Lipinski's rule of five. And several compounds selected from the top ranked hits have been suggested for further experimental assay studies.

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Section: Selection Of Moleculesmentioning

confidence: 99%

A specific pharmacophore model of sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors

et al. 2011

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“…12Lee. J. et al 58 has designed and synthesized novel C-aryl glucoside SGLT2 inhibitors containing 1,3,4-thiadiazole moieties. Among all the synthesized compounds, biaryl-type compounds containing pyrazine 9, 2-furan, and 3-thiophene were found to be most potent.…”

Section: Ppar Gamma Agonistsmentioning

confidence: 99%

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2015

IJPSR

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Diabetes is the most common lifestyle disease associated with many serious worries including diabetic ketoacidosis, cardiac problems, kidney failure, non ketotic hyperosmolar coma, foot ulcers, eye damage etc. All these complications develops due to abnormalities in carbohydrate metabolism and insulin synthesis resulting in high blood sugar with symptoms such as elevated hunger and thirst, polyuria, glycosuria, lethargy etc. The article is focused on different targets of diabetes. INTRODUCTION: Type 2 diabetes mellitus or non-insulin-dependent diabetes mellitus (NIDDM) or adult onset diabetes is a chronic metabolic disorder characterised by hyperglycaemia (fasting and post-prandial). Due to its increasing incidence across the globe, it affects nearly about 5% of the total population in the urbanizednations. 1, 2 and accounts for about 90% of all the diagnosed cases, thereby becoming one of the biggest challenges in 21st century 3-5 leading to hyperglycaemia, insulin resistance and obesity, etc. 6-8. According to the International Diabetes Federation (IDF), the global prevalence of diabetes is predicted to grow from 366 million in 2011to 552 million by 2030 9. The major incidence of diabetes mellitus will occur in Asia, mainly China and India (57 million in India).

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“…Modification of dapagliflozin by replacing the distal aryl ring by heterocycles led to the discovery of canagliflozin (Entry 6) which obtained the second highest interest in clinical developments . Recently, along this line, the structure of dapagliflozin was modified by other heterocycles such as thiazole (Song et al, 2011), 1,3,4-thiadiazole (Lee et al, 2010b), pyridazine (Kim et al, 2010), and pyrimidine (Lee et al, 2010a) (Song et al, 2011) 6.7 (Xu et al, 2010) 1.4 (Robinson et al, 2010) 1.3* (Nomura, 2010) 0.3 4. 5.…”

Section: (Handlon 2005)mentioning

confidence: 99%

Carbohydrate Derivatives and Glycomimetic Compounds in Established and Investigational Therapies of Type 2 Diabetes Mellitus

Somsák¹,

Bokor²,

Czifrák³

et al. 2011

Topics in the Prevention, Treatment and Complications of Type 2 Diabetes

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Novel C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents: 1,3,4-Thiadiazolylmethylphenyl glucoside congeners

Cited by 70 publications

References 19 publications

A specific pharmacophore model of sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors

A specific pharmacophore model of sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors

Untitled

Carbohydrate Derivatives and Glycomimetic Compounds in Established and Investigational Therapies of Type 2 Diabetes Mellitus

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