Synthesis of pyridazine and thiazole analogs as SGLT2 inhibitors

Kang, Suk Youn; Song, Kwon‐Ho; Lee, Junwon; Lee, Sung-Han; Lee, Jinhwa

doi:10.1016/j.bmc.2010.06.076

Cited by 48 publications

(28 citation statements)

References 21 publications

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“…Compound 10 was synthesized starting from structure 8 in 92% by Albright-Goldman oxidation, and the 3 J HH constants were determined to be 2.9 and 1.7 Hz. For compound 11 the literature values of 3.2 Hz and 2.4 Hz were used [22]. Finally, a simplified structural model was employed (12) (Scheme 2) and the theoretical 3 J g HH and 3 J a HH were calculated based on estimated group electronegativities of F = 1.71, OBn = 1.20, OAc = 1.57 and CH 2 OMe = 0.13 [23].…”

Section: Resultsmentioning

confidence: 99%

Delineating the physical organic profile of the 6-fluoro glycosyl donor

Santschi

Aiguabella

Lewe

et al. 2015

Journal of Fluorine Chemistry

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Section: Resultsmentioning

confidence: 99%

Delineating the physical organic profile of the 6-fluoro glycosyl donor

Santschi

Aiguabella

Lewe

et al. 2015

Journal of Fluorine Chemistry

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“…In 2010, Kang and coworkers designed and synthesized pyridazinyl and thiazolyl derivative of C -glycosides [ 52 ]. They wanted to check if replacement of the phenyl ring with the corresponding heterocyclic ring could improve the GLT2 inhibitor.…”

Section: -Glycosides As Antidiabetic Agentsmentioning

confidence: 99%

In the Search of Glycoside-Based Molecules as Antidiabetic Agents

et al. 2019

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This review is an effort to summarize recent developments in synthesis of O -glycosides and N -, C -glycosyl molecules with promising antidiabetic potential. Articles published after 2000 are included. First, the O -glycosides used in the treatment of diabetes are presented, followed by the N -glycosides and finally the C -glycosides constituting the largest group of antidiabetic drugs are described. Within each group of glycosides, we presented how the structure of compounds representing potential drugs changes and when discussing chemical compounds of a similar structure, achievements are presented in the chronological order. C -Glycosyl compounds mimicking O -glycosides structure, exhibit the best features in terms of pharmacodynamics and pharmacokinetics. Therefore, the largest part of the article is concerned with the description of the synthesis and biological studies of various C -glycosides. Also N -glycosides such as N -(β- d -glucopyranosyl)-amides, N -(β- d -glucopyranosyl)-ureas, and 1,2,3-triazolyl derivatives belong to the most potent classes of antidiabetic agents. In order to indicate which of the compounds presented in the given sections have the best inhibitory properties, a list of the best inhibitors is presented at the end of each section. In summary, the best inhibitors were selected from each of the summarizing figures and the results of the ranking were placed. In this way, the reader can learn about the structure of the compounds having the best antidiabetic activity. The compounds, whose synthesis was described in the article but did not appear on the figures presenting the structures of the most active inhibitors, did not show proper activity as inhibitors. Thus, the article also presents studies that have not yielded the desired results and show directions of research that should not be followed. In order to show the directions of the latest research, articles from 2018 to 2019 are described in a separate Sect. 5 . In Sect. 6 , biological mechanisms of action of the glycosides and patents of marketed drugs are described.

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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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Synthesis of pyridazine and thiazole analogs as SGLT2 inhibitors

Cited by 48 publications

References 21 publications

Delineating the physical organic profile of the 6-fluoro glycosyl donor

Delineating the physical organic profile of the 6-fluoro glycosyl donor

In the Search of Glycoside-Based Molecules as Antidiabetic Agents

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

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