C07C53/18

Biaryl monobactam compounds and methods of use thereof for the treatment of bacterial infections

The present invention relates to biaryl monobactam compounds of Formula I: ##STR00001##
and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A.sup.1, Q, A.sup.2, M, W, R.sup.X and R.sup.z are as defined herein. The present invention also relates to compositions which comprise a biaryl monobactam compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The invention further relates to methods for treating a bacterial infection comprising administering to the patient a therapeutically effective amount of a compound of the invention, either alone or in combination with a therapeutically effective amount of a second beta-lactam antibiotic.

COMPOSITIONS, METHODS, AND SYSTEMS FOR THE SYNTHESIS AND USE OF IMAGING AGENTS

The present invention generally relates to novel synthetic methods, systems, kits, salts, and precursors useful in medical imaging. In some embodiments, the present invention provides compositions comprising an imaging agent precursor, which may be formed using the synthetic methods described herein. An imaging agent may be converted to an imaging agent using the methods described herein. In some cases, the imaging agent is enriched in .sup.18F. In some cases, an imaging agent including salt forms (e.g., ascorbate salt) may be used to image an area of interest in a subject, including, but not limited to, the heart, cardiovascular system, cardiac vessels, brain, and other organs.

COMPOSITIONS, METHODS, AND SYSTEMS FOR THE SYNTHESIS AND USE OF IMAGING AGENTS

The present invention generally relates to novel synthetic methods, systems, kits, salts, and precursors useful in medical imaging. In some embodiments, the present invention provides compositions comprising an imaging agent precursor, which may be formed using the synthetic methods described herein. An imaging agent may be converted to an imaging agent using the methods described herein. In some cases, the imaging agent is enriched in .sup.18F. In some cases, an imaging agent including salt forms (e.g., ascorbate salt) may be used to image an area of interest in a subject, including, but not limited to, the heart, cardiovascular system, cardiac vessels, brain, and other organs.

METHOD FOR PRODUCING SALT

According to the present invention, there is provided a method of producing a salt, including reacting M.sup.+X.sup.− with YH to generate XH and M.sup.+Y.sup.− and subsequently removing the generated XH to obtain the M.sup.+Y.sup.−.

In the method of producing a salt, M.sup.+X.sup.− is a salt of a cation represented by M.sup.+ and an anion represented by X.sup.−, M.sup.+Y.sup.− is a salt of the cation represented by M.sup.+ and an anion represented by Y.sup.−, XH is a conjugate acid of X.sup.−, YH is a conjugate acid of Y.sup.−, M.sup.+Y.sup.− is a compound that generates an acid upon irradiation with an active ray or a radioactive ray, a pKa of XH is larger than a pKa of YH, and a ClogP value of XH is larger than 2.

Compositions, methods, and systems for the synthesis and use of imaging agents

The present invention generally relates to novel synthetic methods, systems, kits, salts, and precursors useful in medical imaging. In some embodiments, the present invention provides compositions comprising an imaging agent precursor, which may be formed using the synthetic methods described herein. An imaging agent may be converted to an imaging agent using the methods described herein. In some cases, the imaging agent is enriched in .sup.18F. In some cases, an imaging agent including salt forms (e.g., ascorbate salt) may be used to image an area of interest in a subject, including, but not limited to, the heart, cardiovascular system, cardiac vessels, brain, and other organs.

Compositions, methods, and systems for the synthesis and use of imaging agents

The present invention generally relates to novel synthetic methods, systems, kits, salts, and precursors useful in medical imaging. In some embodiments, the present invention provides compositions comprising an imaging agent precursor, which may be formed using the synthetic methods described herein. An imaging agent may be converted to an imaging agent using the methods described herein. In some cases, the imaging agent is enriched in .sup.18F. In some cases, an imaging agent including salt forms (e.g., ascorbate salt) may be used to image an area of interest in a subject, including, but not limited to, the heart, cardiovascular system, cardiac vessels, brain, and other organs.

PROCESS FOR GENERATING ACID ANHYDRIDES

Provided is a method of producing an anhydride of an organic mono-acid comprising contacting an organic mono-acid and a thermally regenerable anhydride to produce the anhydride of the organic mono-acid, and either a diacid of the regenerable anhydride, a partially hydrolyzed regenerable anhydride, or both. In a particular example, acetic acid and glutaric anhydride can be reacted to form acetic anhydride.

PROCESS FOR GENERATING ACID ANHYDRIDES

Provided is a method of producing an anhydride of an organic mono-acid comprising contacting an organic mono-acid and a thermally regenerable anhydride to produce the anhydride of the organic mono-acid, and either a diacid of the regenerable anhydride, a partially hydrolyzed regenerable anhydride, or both. In a particular example, acetic acid and glutaric anhydride can be reacted to form acetic anhydride.

SOLID FORMS, PHARMACEUTICAL COMPOSITIONS AND PREPARATION OF HETEROAROMATIC MACROCYCLIC ETHER COMPOUNDS

Provided herein are solid forms comprising a compound of formula (I), or a stereoisomer, or a mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof. Also provided herein are methods of synthesizing a compound of formula (I), pharmaceutical compositions comprising the same, and methods of treating, preventing, and managing various disorders using the compositions provided herein.

EXTRACORPOREAL CLEARING TRAPS BASED ON INVERSE ELECTRON DEMAND DIELS-ALDER CYCLOADDITION FOR (PRE)-TARGETED THERAPY AND DIAGNOSTICS

The present invention provides extracorporeal removal of targeting vectors applied in pretargeted therapy and diagnostics in animals and humans. The method and the means for extracorporeal removal of the targeting vectors is based on binding agents with inverse electron demand Diels-Alder (IEDDA) cycloaddition reactivity. The targeting vector comprises a therapeutic agent, a diagnostic agent or a theranostic agent and a chemical entity with IEDDA reactivity whereas the extracorporeal means comprises a column with a biocompatible solid support to which a chemical entity with complementary IEDDA reactivity is attached.