Structure-guided design and synthesis of isoflavone analogs of GW4064 with potent lipid accumulation inhibitory activities

Qiu, Rongmao; Luo, Guoshun; Cai, Xuerong; Liu, Linyi; Chen, Mingqi; Chen, Deying; Qin, You; Xiang, Hua

doi:10.1016/j.bmcl.2018.10.021

Cited by 13 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on isoflavones showing antidyslipidemic effect, Xiang et al. described a series of isoflavones and GW4064 hybrids as FXR agonists and evaluated their lipid-lowering activities . Compound 2 (Figure ) showed similar FXR agonistic activity to GW4064 at 10 μM and exhibited a stronger inhibitory effect on lipid accumulation than GW4064.…”

Section: Medicinal Chemistry Of Fxr Ligandsmentioning

confidence: 99%

Recent Advances in the Medicinal Chemistry of Farnesoid X Receptor

et al. 2021

View full text Add to dashboard Cite

Farnesoid X receptor (FXR) is an important regulator of bile acid, lipid, amino acid, and glucose homeostasis, hepatic inflammation, regeneration, and fibrosis. FXR has been recognized as a promising drug target for various metabolic diseases such as lipid disorders, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and chronic kidney disease. A large number of FXR ligands have been developed by pharmaceutical companies and academic institutions, and several candidates have progressed into clinical trials in the past decade. However, it is continually a challenge to discover drugs targeting FXR due to side effects associated with long-term administration. In this perspective, we summarize the research progress on medicinal chemistry of FXR modulators from 2018 to the present by discussing the diverse structures of synthetic FXR modulators including steroidal and non-steroidal ligands, their structure–activity relationships (SARs), and their therapeutic applications.

show abstract

Section: Medicinal Chemistry Of Fxr Ligandsmentioning

confidence: 99%

Recent Advances in the Medicinal Chemistry of Farnesoid X Receptor

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Although the effect of 8d in modulating FXR gene expression was less pronounced than that of GW4064synthetic FXR agonist, 8d showed less toxicity in HepG2 cells. Overall, results obtained by the authors indicated that 8d could act as a promising lead compound for the design of novel FXR modulators against dyslipidemia [19]. Moreover, amidation turned out to be a necessary condition for the high level of biological activity as the acid itself and its ester demonstrated much more modest performance.…”

Section: Biological Activity Of 3-(carboxyphenyl)chromones Their Esters and Amidesmentioning

confidence: 98%

“…The authors did not reported a hydrolysis of the ester group neither during the Houben-Hoesch reaction nor during the isolation and subsequent cyclization to isoflavone (Scheme 10). Isoflavone amides with an isoxazole moietycompounds 8were synthesized in a similar manner; slight differences were related to the temperature regime of the Houben-Hoesch reaction, the conditions of hydrolysis of the ester, and the formation of the amide bond (Scheme 11) [19][20]. Another promising modern method for producing isoflavones is the catalytic arylation of 3-halogenochromones.…”

Section: Synthesis Of 3-(carboxyphenyl)chromones Their Esters and Amidesmentioning

confidence: 99%

Features of the synthesis and biological evaluation of 3-(carboxyphenyl)chromones

2020

View full text Add to dashboard Cite

Flavonoids and their derivatives have historically been a source of therapeutic agents. Every year, more and more data is published on new flavonoid compounds, both synthetic and isolated from natural sources, and their innumerable physiological and pharmacological activities. This review presents synthetic routes towards 3-(carboxyphenyl)chromones and evaluation of their biological activity as published in both journal and patent literature. We have focused specifically on the 3-(carboxyphenyl)chromones, because while methods of synthesis and biological activity of 2(3)-substituted and 2,3-disubstituted chromones are well studied, literature data on isoflavones containing a carboxyl, ester, or amide group in ring B is scarce and fragmentary. The presented generalization of synthetic strategies and biological activity of 3-(carboxyphenyl)chromone derivatives demonstrates that this class of compounds can be targeted for discovery of new drugs and can be readily prepared owing to recent advances in synthetic organic and medicinal chemistry.

show abstract

“…In the case of 2-arylsubstituted intermediates 5 (Scheme 44), they can be obtained through Friedel-Crafts reaction of phenols with phenylacetic acids catalyzed by zinc chloride at 120 °C315 and by BF 3 ÁOEt 2 at 70-110 °C, under an inert (argon or nitrogen) atmosphere, 49,50,[316][317][318][319][320][321] and through acylation of phenols with substituted benzoacetonitriles, using HCl gas/anhydrous ZnCl 2 catalytic system in 1,4-dioxane 322 or dry diethyl ether. 323,324 Lee developed a versatile three-step protocol for the synthesis of 2-aryl-2 0 -hydroxyacetophenones starting from 2-methoxybenzoic acids.…”

Section: Starting From 2-substituted 2 0 -Hydroxyacetophenonesmentioning

confidence: 99%