The present invention relates to novel substituted pyrazoloazepin-4-ones with phosphodiesterase inhibitory activity, as well as to their use as therapeutic agents in the treatment of inflammatory diseases and conditions.

The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of use thereof for treating cellular proliferative disorders (e.g., cancer).

The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of use thereof for treating cellular proliferative disorders (e.g., cancer).

The invention provides fluorogenic compounds and probes that can be used as reagents for measuring, detecting and/or screening superoxide. The fluorogenic compounds of the invention can produce fluorescence colors, such as green, yellow, red, or far-red. The invention further provides fluorogenic compounds for selectively staining superoxide in the mitochondria of living cells. The invention also provides methods that can be used to measure, directly or indirectly, the presence and/or amount of superoxide in chemical samples and biological samples such as cells and tissues in living organisms, and a high-throughput screening methods for detecting or screening superoxide or compounds that can increase or decease the level of superoxide in chemical and biological samples.

The invention provides fluorogenic compounds and probes that can be used as reagents for measuring, detecting and/or screening superoxide. The fluorogenic compounds of the invention can produce fluorescence colors, such as green, yellow, red, or far-red. The invention further provides fluorogenic compounds for selectively staining superoxide in the mitochondria of living cells. The invention also provides methods that can be used to measure, directly or indirectly, the presence and/or amount of superoxide in chemical samples and biological samples such as cells and tissues in living organisms, and a high-throughput screening methods for detecting or screening superoxide or compounds that can increase or decease the level of superoxide in chemical and biological samples.

Disclosed are methods for performing dynamic nuclear polarization using the polarizing agents described herein. In general, the methods involve (a) providing a frozen sample in a magnetic field, wherein the frozen sample includes a polarizing agent described herein and an analyte with at least one spin half nucleus; (b) polarizing the at least one spin half nucleus of the analyte by irradiating the frozen sample with radiation having a frequency that excites electron spin transitions in the polarizing agent; (c) optionally melting the sample to produce a molten sample; and (d) detecting nuclear spin transitions in the at least one spin half nucleus of the analyte in the frozen or molten sample. In certain embodiments, the polarizing agents can be peptide-based. In these embodiments, the polarizing agents can be readily prepared by solid-phase peptide synthesis.

Disclosed are methods for performing dynamic nuclear polarization using the polarizing agents described herein. In general, the methods involve (a) providing a frozen sample in a magnetic field, wherein the frozen sample includes a polarizing agent described herein and an analyte with at least one spin half nucleus; (b) polarizing the at least one spin half nucleus of the analyte by irradiating the frozen sample with radiation having a frequency that excites electron spin transitions in the polarizing agent; (c) optionally melting the sample to produce a molten sample; and (d) detecting nuclear spin transitions in the at least one spin half nucleus of the analyte in the frozen or molten sample. In certain embodiments, the polarizing agents can be peptide-based. In these embodiments, the polarizing agents can be readily prepared by solid-phase peptide synthesis.

The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of use thereof for treating cellular proliferative disorders (e.g., cancer).

The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of use thereof for treating cellular proliferative disorders (e.g., cancer).

The present invention provides compounds of the general structure (I), which are suitable as antibiotic compounds for the treatment of N. gonorrhoeae infections and related infections.

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