3-hydroxy-3-cyclobutene-1,2-dione: Application of novel carboxylic acid bioisostere to an in-vivo active non-tetrazole angiotensin-II antagonist

Söll, Richard; Kinney, William A.; Primeau, John L.; Garrick, Lloyd; McCaully, Ronald J.; Colatsky, Thomas; Oshiro, G.; Park, C.H.; Hartupee, D. A.; White, V.; McCallum, Jeremy; Russo, Alessio; Dinish, J. L.; Wojdan, A.

doi:10.1016/s0960-894x(01)81269-5

Cited by 23 publications

(17 citation statements)

References 5 publications

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“…23). 41 They compared carboxylic acid 68 (275 nM), trifluoromethane sulfonamide 69 (100 nM), tetrazole 70 (3 nM) and squaric acid 71 (25 nM), illustrating the squaric acid to be an isosteric replacement for a carboxylic acid. Further building on this idea, the group at Wyeth developed methods to convert squarates into amino acid isosteres of glycine, alanine and g-aminobutyric acid.…”

Section: Squaramides As Isosteric Replacements For Carboxylic Acids A...mentioning

confidence: 99%

Squaramides: physical properties, synthesis and applications

2011

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Squaramides are remarkable four-membered ring systems derived from squaric acid that are able to form up to four hydrogen bonds. A high affinity for hydrogen bonding is driven through a concomitant increase in aromaticity of the ring. This hydrogen bonding and aromatic switching, in combination with structural rigidity, have been exploited in many of the applications of squaramides. Substituted squaramides can be accessed via modular synthesis under relatively mild or aqueous conditions, making them ideal units for bioconjugation and supramolecular chemistry. In this tutorial review the fundamental electronic and structural properties of squaramides are explored to rationalise the geometry, conformation, reactivity and biological activity.

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Section: Squaramides As Isosteric Replacements For Carboxylic Acids A...mentioning

confidence: 99%

Squaramides: physical properties, synthesis and applications

2011

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“…Metcalf et al [51] and Holt et al [52] have suggested that vinyl carboxylates can serve as equivalents for enolates and two other pharmaceutical groups have reported that semisquarates can be cognated to carboxylates [53,54]. Combining the above methodology that carboxylates are equivalent to enolates, and semisquarates are equivalent to carboxylates then semisquarates can act as stable mimics for enolates.…”

Section: Squaryl Syllogismmentioning

confidence: 99%

“…The treatment of 3,4-di-ethoxysquarate with nBu3SnSiMe3/catalytic cyanide, afforded Liebeskind's reagent in 65% yield ( Figure 38). This compound crosscoupled with organic iodides -attached to sp 2 -and sphybridized carbon atoms -to provide 3-ethoxy-4-substituted-cyclobutenediones in a reasonable chemical yield [136]. Hence, highly substituted and functionalized cyclobutenediones are prepared under mild reaction conditions, to generate carbon-carbon bonds.…”

Section: Losartan Semisquaratementioning

confidence: 99%

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

Kitson¹

2017

J Diagn Imaging Ther

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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 ...

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“…3 A very important reaction is the successive amidation of squaric acid esters, as it is a feasible pathway to unsymmetrical bisamides with applications ranging from antibiotics to chelating ligands. 4,23 In addition, squaric acid derivatives can be regarded as isoesters for several functional groups, such as carboxylic acids, 24 amino acids, 25 phosphates 26 or ureas 27 for use in catalytical and medicinal chemistry (vide infra). A review by Shinada et al summarizes the chemistry of amino acid analogues based on squaric acid, and some biorelated applications (note: the review is written in Japanese).…”

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confidence: 99%

Be squared: expanding the horizon of squaric acid-mediated conjugations

2013

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Squaric acid diesters can be applied as reagents to couple two amino-functional compounds. Consecutive coupling of two amines allows the synthesis of asymmetric squaric acid bisamides with either low molecular weight compounds but also biomolecules or polymers. The key feature of the squaric acid diester mediated coupling is the reduced reactivity of the resulting ester-amide after the first amidation step of the diester. This allows the sequential amidation and generation of asymmetric squaramides with high selectivity and in high yields. This article gives an overview of the well-established squaric acid diester mediated coupling reactions for glycoconjugates and presents recent advances that aim to expand this very versatile reaction protocol to the modification of peptides and proteins.

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3-hydroxy-3-cyclobutene-1,2-dione: Application of novel carboxylic acid bioisostere to an in-vivo active non-tetrazole angiotensin-II antagonist

Cited by 23 publications

References 5 publications

Squaramides: physical properties, synthesis and applications

Squaramides: physical properties, synthesis and applications

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

Be squared: expanding the horizon of squaric acid-mediated conjugations

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