Abstract:The synthesis and structure-activity relationship (SAR) of thiophene-C-glucosides have been explored, and the human sodium-dependent glucose cotransporter 2 (hSGLT2) inhibitory activities and rat urinary glucose excretion (UGE) effects of 3a-f were evaluated. As a result, they showed good hSGLT2 inhibitory activities and rat UGE effects. In particular, the chlorothiophene derivative 3f showed remarkable inhibitory activity against hSGLT2.
“…Alternatively, the thiophene nucleus has been familiar as an essential part in the synthesis of heterocyclic compounds which shows potential pharmacological characteristics. A widespread multiplicity of therapeutic applications of thiophene derivatives has been surveyed in the literature [18, 19, 20, 21]. Thiophene moiety and their derivatives are known as best pharmacophore in the diabetes mellitus [22], antimicrobial [23], hepatitis B virus inhibitors [24], cholesterol inhibitors [25], antiviral [26], antitumor [27] and antitubercular agents [28].…”
2-Amino-5-(3-fluoro-4-methoxyphenyl)thiophene-3-carbonitrile have been synthesized from 1-(3-fluoro-4-methoxyphenyl)ethanone, malononitrile, a mild base and sulfur powder using Gewald synthesis technique and the intermediate was treated with 1,3-disubstituted pyrazole-4-carboxaldehyde to obtain the novel Schiff bases. 1,3-disubstituted pyrazole-4-carboxaldehyde derivatives have been synthesized by Vilsmeier-Haack reaction in the course of a multi-step reaction. The structure of novel compounds were established on the basis of their elemental analyses IR,
1
H NMR,
13
C NMR, and mass spectral data and then screened for their
in vitro
antimicrobial activity. Among them 5a, 5c, 5f and 5h showed excellent activity when compared to other derivatives. Remaining derivatives showed moderate activity.
“…Alternatively, the thiophene nucleus has been familiar as an essential part in the synthesis of heterocyclic compounds which shows potential pharmacological characteristics. A widespread multiplicity of therapeutic applications of thiophene derivatives has been surveyed in the literature [18, 19, 20, 21]. Thiophene moiety and their derivatives are known as best pharmacophore in the diabetes mellitus [22], antimicrobial [23], hepatitis B virus inhibitors [24], cholesterol inhibitors [25], antiviral [26], antitumor [27] and antitubercular agents [28].…”
2-Amino-5-(3-fluoro-4-methoxyphenyl)thiophene-3-carbonitrile have been synthesized from 1-(3-fluoro-4-methoxyphenyl)ethanone, malononitrile, a mild base and sulfur powder using Gewald synthesis technique and the intermediate was treated with 1,3-disubstituted pyrazole-4-carboxaldehyde to obtain the novel Schiff bases. 1,3-disubstituted pyrazole-4-carboxaldehyde derivatives have been synthesized by Vilsmeier-Haack reaction in the course of a multi-step reaction. The structure of novel compounds were established on the basis of their elemental analyses IR,
1
H NMR,
13
C NMR, and mass spectral data and then screened for their
in vitro
antimicrobial activity. Among them 5a, 5c, 5f and 5h showed excellent activity when compared to other derivatives. Remaining derivatives showed moderate activity.
“…In 2013, Sakamaki and coworkers described the synthesis and structure–activity relationship of thiophene- C -glucosides [ 58 ]. The synthetic route to thiophene- C -glucosides 199 is shown in Scheme 31 , based on the reaction of aryl halide 196 with glucal-boronate ester 195 .…”
Section: -Glycosides As Antidiabetic Agentsmentioning
confidence: 99%
“…As a result, they showed good hSGLT2 inhibitory activities. In particular, the chlorothiophene derivative 199 showed remarkable inhibitory activity against hSGLT2 (IC 50 = 4.0 nM) [ 58 ]. Scheme 31 Synthesis of thiophene- C -glucosides 199 [ 58 ] …”
Section: -Glycosides As Antidiabetic Agentsmentioning
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.
“…7,8 Another example of thiophene C-nucleoside analogues having benzylthiophene as nucleobase surrogate and glucopyranosyl as sugar moiety exhibited remarkable inhibitory activity against hSGLT2 (IC 50 = 4.0 nM) and good rat UGE effect (1381 mg/d). 9 Although the parent thiophene are easily prepared, the thiophene C-nucleoside analogues where the thiophene and sugar are linked through a C-C bond are considerably more challenging. Few thiophene C-nucleosides and their analogues were sporadically obtained only during the synthesis of aryl C-nucleosides or aryl C-glycosides.…”
Concise synthesis of novel benzoylthiophene C-nucleoside analogues has been achieved by the reaction of various terminal sugar alkynes with substituted benzoyl chlorides and 1,4-dithiane-2,5-diol, and subsequent dilute HCl-promoted dehydration in one pot. The sugar alkynes include pyranosides, furanosides, and acyclic sugar. The benzoyl chloride has various substituents. Twenty-eight examples are given. The desired products are obtained in 70–89% yields, and the mechanism has been clarified by isolation of the intermediate.
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