- Synergistic Experimental and Computational Investigation of the Bioorthogonal Reactivity of Substituted Aryltetrazines
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Tetrazines (Tz) have been applied as bioorthogonal agents for various biomedical applications, including pretargeted imaging approaches. In radioimmunoimaging, pretargeting increases the target-to-background ratio while simultaneously reducing the radiation burden. We have recently reported a strategy to directly 18F-label highly reactive tetrazines based on a 3-(3-fluorophenyl)-Tz core structure. Herein, we report a kinetic study on this versatile scaffold. A library of 40 different tetrazines was prepared, fully characterized, and investigated with an emphasis on second-order rate constants for the reaction with trans-cyclooctene (TCO). Our results reveal the effects of various substitution patterns and moreover demonstrate the importance of measuring reactivities in the solvent of interest, as click rates in different solvents do not necessarily correlate well. In particular, we report that tetrazines modified in the 2-position of the phenyl substituent show high intrinsic reactivity toward TCO, which is diminished in aqueous systems by unfavorable solvent effects. The obtained results enable the prediction of the bioorthogonal reactivity and thereby facilitate the development of the next generation of substituted aryltetrazines for in vivo applications.
- Battisti, Umberto M.,García-Vázquez, Rocío,Herrmann, Barbara,Herth, Matthias Manfred,L?ffler, Andreas,Mikula, Hannes,Svatunek, Dennis
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- ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 (ENPP1) MODULATORS AND USES THEREOF
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Provided herein are small molecule modulators of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.
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- HETEROCYCLIC COMPOUNDS WITH AN ROR(GAMMA)T MODULATING ACTIVITY
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The present invention relates to a compound that may have an ROR(gamma)t modulating activity and can thus be useful in the treatment of cancer.
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- Cycloalkylated benzothiadiazines, a process for their preparation and pharmaceutical compostions containing them
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Compounds of formula (I): wherein: RCy represents an unsubstituted or substituted cycloalkyl group or cycloalkylalkyl group,R1, R2, R3 and R4, which may be the same or different, each represent a hydrogen or halogen atom or a nitro group; a cyano group; a hydroxy group; an alkoxy group; an alkyl group; an unsubstituted or substituted amino group; a carboxy group; an alkoxycarbonyl group; an aryloxycarbonyl group; an unsubstituted or substituted aminocarbonyl group. Medicinal products containing the same which are useful in treating or preventing conditions treatable by an AMPA receptor modulator.
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Page/Page column 7
(2010/02/17)
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- HETEROCYCLIC GPCR AGONISTS
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Compounds of formula (I) or pharmaceutically acceptable salts thereof, are agonists of GPR119 and are useful as regulators of satiety, e.g. for the treatment of obesity, and for the treatment of diabetes.
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- GPCR AGONISTS
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Compounds of formula (I): or pharmaceutically acceptable salts thereof, are GPCR agonists and are useful as for the treatment of obesity and diabetes.
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Page/Page column 28
(2010/11/25)
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