Design and synthesis of novel 3-hydroxy-cyclobut-3-ene-1,2-dione derivatives as thyroid hormone receptor β (TR-β) selective ligands

Raval, Saurin; Raval, Preeti; Bandyopadhyay, Debdutta; Soni, Krunal; Yevale, Digambar B.; Jogiya, Digvijay; Modi, Hiren R.; Joharapurkar, Amit; Gandhi, Neha S.; Jain, Mukul; Patel, Pankaj

doi:10.1016/j.bmcl.2008.06.038

Cited by 9 publications

(7 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The substrate 3-[3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)-phenylamino]-4-hydroxycyclobut-3-ene-1,2-dione has demonstrated selectivity towards thyroid hormone receptor (Figure 62) [200].…”

Section: Vitronectin Receptor Antagonistsmentioning

confidence: 99%

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

Kitson¹

2017

J Diagn Imaging Ther

View full text Add to dashboard Cite

Molecular Metaphors is the application of squaryl building blocks towards creative functional group chemistry to produce lead compounds and imaging agents. This strategy is applied to rational drug design and to various imaging agents that would normally contain conventional functional group chemistry. These, include carboxylic acids, α-amino acids, peptide bonds and phosphonates. Moreover, the squaryl metaphor is a precursor to complex organic molecules involving functional group interchange (FGI) and rearrangements. This article discusses the application of these metaphors in the area of neurochemistry, especially NMDA receptors. An important area of drug design is the inhibition of angiotensin II enzyme by the use of losartan. This commercial drug contains a tetrazole moiety that can be modified using the squaryl group to give a semisquarate derivative. These concepts can extend to the semisquarate of ibuprofen. Moreover, a discussion on peptidomimetics regarding the substitution of the peptide bond for squaramide allows for a change in the biological properties due to modification at the peptide bond. Furthermore, the topic on how squaryl metaphors can be exploited primarily by the central 1,3-hydroxyamide sequence to the generation of a novel class of HIV protease inhibitors. Also, squaryl metaphors can be used to develop potential inhibitors of glutathione and novel anti-migraine drugs. The discussion continues on the design of anticancer drugs: in particular, a novel class of metalloproteases, including phosphonates for semisquaramides, leading to squaryl nucleosides. This review concludes with the application of squaryl metaphors in the design of positron emission tomography (PET) and magnetic resonance imaging (MRI) agents towards theranostics. describe the ability of individual functional chemical groups to mimic other moieties [2,3]. KeywordsErlenmeyer rationalised these concepts and categorised isosteres into atoms, ions and molecules based on the valence level of electrons [4]. A further understanding by Friedman led to the term bioisosterism to include all atoms and molecules that fit the broadest definition of isosteres [5]. This approach was independent of whether the drug was an agonist or an antagonist towards biological activity.Moreover, Thornber applied the term bioisosterism to include subunits, groups or molecules that possess physicochemical properties of similar biological effects [6]. Finally, in 1991 Burger widened the definition of bioisosteres to include compounds or groups that possess similar molecular shapes and volumes independent of agonists or antagonists [7]. REVIEW ARTICLE Squaryl KitsonThese bioisosteres would require approximately the same distribution of electrons and give a high probability of generating comparable physical properties such as hydrophobicity [8]. Currently, bioisosterism is one of the most useful tools to the medicinal chemist in rational drug design and in particular regarding the carboxylic acid bioisosteres [9]. The carboxylic acid functional ...

show abstract

Section: Vitronectin Receptor Antagonistsmentioning

confidence: 99%

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

Kitson¹

2017

J Diagn Imaging Ther

View full text Add to dashboard Cite

show abstract

“…Recently, the design and synthesis of a number of novel R 1 cyclobutenedione derivatives were reported [282]. In a thyroid luciferase receptor assay, 20 (Fig.…”

Section: Variation Of the R 1 -Positionmentioning

confidence: 99%

Thyroid Hormones and Thyromimetics

Malm

Grover

2010

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

show abstract

“…Thyroid hormone receptors are essential for proper infant central nervous system (CNS) development, and their production is regulated by the hypothalamic‐pituitary‐thyroid feedback system. Among non‐isoform selective TR‐binding compounds, T 3 is the native hormone in the human body, and is produced by follicular cells of the thyroid gland [1,4]. These cells accumulate iodide from plasma through their membranes and use it for the production of secreted human thyroid hormones.…”

Section: Introductionmentioning

confidence: 99%

“…Developing an ideal STRM is challenging. Several TRβ selective agonists, such as Axitirome and KB‐141, have been discontinued during clinical development due to unexpected side effects [1,2,15,16]. The desire for isoform‐selective compounds, coupled with the difficulties associated with their development, provides a strong impetus for the creation of new screening methods for isotype‐selective TR modulators.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bacterial biosensors for screening isoform‐selective ligands for human thyroid receptors α‐1 and β‐1

Gierach

et al. 2012

FEBS Open Bio

View full text Add to dashboard Cite

Subtype-selective thyromimetics have potential as new pharmaceuticals for the prevention or treatment of heart disease, high LDL cholesterol and obesity, but there are only a few methods that can detect agonistic behavior of TR-active compounds. Among these are the rat pituitary GH3 cell assay and transcriptional activation assays in engineered yeast and mammalian cells. We report the construction and validation of a newly designed TRα-1 bacterial biosensor, which indicates the presence of thyroid active compounds through their impacts on the growth of an engineered Escherichia coli strain in a simple defined medium. This biosensor couples the configuration of a hormone receptor ligand-binding domain to the activity of a thymidylate synthase reporter enzyme through an engineered allosteric fusion protein. The result is a hormone-dependent growth phenotype in the expressing E. coli cells. This sensor can be combined with our previously published TRβ-1 biosensor to detect potentially therapeutic subtype-selective compounds such as GC-1 and KB-141. To demonstrate this capability, we determined the half-maximal effective concentration (EC50) for the compounds T3, Triac, GC-1 and KB-141 using our biosensors, and determined their relative potency in each biosensor strain. Our results are similar to those reported by mammalian cell reporter gene assays, confirming the utility of our assay in identifying TR subtype-selective therapeutics. This biosensor thus provides a high-throughput, receptor-specific, and economical method (less than US$ 0.10 per well at laboratory scale) for identifying important therapeutics against these targets.

show abstract

Design and synthesis of novel 3-hydroxy-cyclobut-3-ene-1,2-dione derivatives as thyroid hormone receptor β (TR-β) selective ligands

Cited by 9 publications

References 31 publications

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

Thyroid Hormones and Thyromimetics

Bacterial biosensors for screening isoform‐selective ligands for human thyroid receptors α‐1 and β‐1

Contact Info

Product

Resources

About