Development of novel liver X receptor modulators based on a 1,2,4-triazole scaffold

Goher, Shaimaa S.; Griffett, Kristine; Hegazy, Lamees; Elagawany, Mohamed; Arief, M. M. H.; Avdagic, Amer; Banerjee, Subhashis; Burris, Thomas P.; Elgendy, Bahaa

doi:10.1016/j.bmcl.2018.12.025

Cited by 19 publications

(13 citation statements)

References 23 publications

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“…Successful economic production of biorenewable chemicals in a terpene biorefinery requires access to a range of reaction pathways that can be used to transform multiple biorenewable terpene feedstocks into different value-added product streams. Petroleum derived p -MA, p -toluic acid, and PTA are widely used as chemical intermediates for the industrial synthesis of a wide range of commercially available products (e.g., perfumes, drugs, inks, polymers, solar cells, antioxidants, and MOFs). − Therefore, use of scalable catalytic aerobic transformations to convert terpene derived bio- p -cymene into bio- p -MA, bio- p -toluic acid, and bio-PTA is particularly useful for increasing the range of aromatic bioproducts that can be produced in a terpene biorefinery (Figure ).…”

Section: Results and Discussionmentioning

confidence: 99%

Efficient Syntheses of Biobased Terephthalic Acid, p-Toluic Acid, and p-Methylacetophenone via One-Pot Catalytic Aerobic Oxidation of Monoterpene Derived Bio-p-cymene

Tibbetts

Russo

Lapkin

et al. 2021

ACS Sustainable Chem. Eng.

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An efficient elevated-pressure catalytic oxidative process (2.5 mol % Co(NO 3 ) 2 , 2.5 mol % MnBr 2 , air (30 bar), 125 °C, acetic acid, 6 h) has been developed to oxidize p -cymene into crystalline white terephthalic acid (TA) in ∼70% yield. Use of this mixed Co 2+ /Mn 2+ catalytic system is key to obtaining high 70% yields of TA at relatively low reaction temperatures (125 °C) in short reaction times (6 h), which is likely to be due to the synergistic action of bromine and nitrate radicals in the oxidative process. Recycling studies have demonstrated that the mixed metal catalysts present in recovered mother liquors could be recycled three times in successive p -cymene oxidation reactions with no loss in catalytic activity or TA yield. Partial oxidation of p -cymene to give p -methylacetophenone ( p -MA) in 55–60% yield can be achieved using a mixed CoBr 2 /Mn(OAc) 2 catalytic system under 1 atm air for 24 h, while use of Co(NO 3 ) 2 /MnBr 2 under 1 atm O 2 for 24 h gave p -toluic acid in 55–60% yield. Therefore, access to these simple catalytic aerobic conditions enables multiple biorenewable bulk terpene feedstocks (e.g., crude sulfate turpentine, turpentine, cineole, and limonene) to be converted into synthetically useful bio- p -MA, bio- p -toluic acid, and bio-TA (and hence bio-polyethylene terephthalate) as part of a terpene based biorefinery.

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Section: Results and Discussionmentioning

confidence: 99%

Efficient Syntheses of Biobased Terephthalic Acid, p-Toluic Acid, and p-Methylacetophenone via One-Pot Catalytic Aerobic Oxidation of Monoterpene Derived Bio-p-cymene

Tibbetts

Russo

Lapkin

et al. 2021

ACS Sustainable Chem. Eng.

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“…The reaction yields and times were successfully optimized by using microwave heating (Scheme 2). Specifically, in the case of compounds 2 and 3 the reaction times were reduced to 2 hours and the yields were considerable improved [29] …”

Section: Resultsmentioning

confidence: 99%

The Triazole Ring as a Privileged Scaffold for Putative Antifungals: Synthesis and Evaluation of a Series of New Analogues

et al. 2020

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The significant antifungal activity of a series of novel 1,2,4‐triazole derivatives against different strains of Candida albicans, Candida krusei and Aspergillus fumigatus, compared to the commercial fungicides ketoconazole and itraconazole, is reported. Systemic mycosis and invasive fungal infections, whether from immunodeficiency or hospital‐acquired infection, have been on an upward trend for several years. The 1,2,4‐triazole ring substituted with other aromatic and heteroaromatic systems plays an important role in the field of antifungal drug discovery and development. Thus, an extensive series of 29 triazoles, substituted in different positions with a variety of aromatic rings, has been designed, synthesized, and evaluated for their fungicidal activity. Almost all the agents tested in vitro showed high activity against all examined fungal strains. It is noteworthy that, in the case of A. fumigatus, all the examined compounds achieved equal or higher antifungal activity than ketoconazole, but less activity than itraconazole. Among all the derivatives studied, the dichlorourea analogue and bromo‐substituted triazole stand out as the most promising compounds. Quantitative structure‐activity relationship (QSAR) models were built for a systematic structure‐activity relationship (SAR) profile to explain and potentially explore the potency characteristics of 1,2,4‐triazole analogues.

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“…The synthesized triazoles and their acetylated compounds showed LXRα/β partial agonist activity with an EC 50 in a range of 100 and 50 nM for LXRα and β, respectively. Interestingly, these compounds act as inverse agonists in terms of inducing FASN but without effect on SREBP-1c expression (Goher et al, 2019). Overall, these compounds open a new range for potential SLiMs, and it is expected that their unique properties will be tested in in vivo models.…”

Section: Other Potential Lxr Agonistsmentioning

confidence: 99%

Screening for liver X receptor modulators: Where are we and for what use?

Buñay

Fouache

Trousson

et al. 2020

British J Pharmacology

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Liver X receptors (LXRs) are members of the nuclear receptor superfamily that are canonically activated by oxidized derivatives of cholesterol. Since the mid-90s, numerous groups have identified LXRs as endocrine receptors that are involved in the regulation of various physiological functions. As a result, when their expression is genetically modified in mice, phenotypic analyses reveal endocrine disorders ranging from infertility to diabetes and obesity, nervous system pathologies such Alzheimer's or Parkinson's disease, immunological disturbances, inflammatory response, and enhancement of tumour development. Based on such findings, it appears that LXRs could constitute good pharmacological targets to prevent and/or to treat these diseases. This review discusses the various aspects of LXR drug discovery, from the tools available for the screening of potential LXR modulators to the current situational analysis of the drugs in development.

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Development of novel liver X receptor modulators based on a 1,2,4-triazole scaffold

Cited by 19 publications

References 23 publications

Efficient Syntheses of Biobased Terephthalic Acid, p-Toluic Acid, and p-Methylacetophenone via One-Pot Catalytic Aerobic Oxidation of Monoterpene Derived Bio-p-cymene

Efficient Syntheses of Biobased Terephthalic Acid, p-Toluic Acid, and p-Methylacetophenone via One-Pot Catalytic Aerobic Oxidation of Monoterpene Derived Bio-p-cymene

The Triazole Ring as a Privileged Scaffold for Putative Antifungals: Synthesis and Evaluation of a Series of New Analogues

Screening for liver X receptor modulators: Where are we and for what use?

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Development of novel liver X receptor modulators based on a 1,2,4-triazole scaffold

Cited by 19 publications

References 23 publications

Efficient Syntheses of Biobased Terephthalic Acid, p-Toluic Acid, and p-Methylacetophenone via One-Pot Catalytic Aerobic Oxidation of Monoterpene Derived Bio-p-cymene

Efficient Syntheses of Biobased Terephthalic Acid, p-Toluic Acid, and p-Methylacetophenone via One-Pot Catalytic Aerobic Oxidation of Monoterpene Derived Bio-p-cymene

The Triazole Ring as a Privileged Scaffold for Putative Antifungals: Synthesis and Evaluation of a Series of New Analogues

Screening for liver X receptor modulators: Where are we and for what use?

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Development of novel liver X receptor modulators based on a 1,2,4-triazole scaffold