The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof: ##STR00001##
which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable slat thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

The present invention relates to a compound of formula (I), wherein X is C═O, C═S or B—OH; Y is an electrophile and Z is a leaving group, or Y═Z is an electrophile; R.sup.1 comprises or consists of (a) (i) a first group binding to a proteolytic site of a proteasome, the first group being bound to X; and (ii) optionally a second group enhancing delivery; or (b) a group binding between subunits β1 and β2 of a proteasome; R.sup.2 and R.sup.3 are independently selected from H, methyl, methoxy, ethyl, ethenyl, ethynyl and cyano, wherein methyl and ethyl may be substituted with OH or halogen. ##STR00001##

The present invention is to provide a method for producing a peptide containing an N-alkylamino acid, which comprises the following Steps (1) to (3). Step (1): a step of mixing an N-terminal protected amino acid or an N-terminal protected peptide with a carboxylic acid halide or a halogenated alkyl formate; Step (2): a step of mixing an amino acid or a peptide in which the N-terminal and the C-terminal are not protected with a trialkylsilylating agent; and Step (3): a step of mixing the product obtained in Step (1) with the product obtained in Step (2).

In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Methods of treating aging related skin changes and of increasing skin thickness with topical administration of N-acyldipeptide derivatives are described. Compositions comprising N-acyldipeptide derivatives, are therapeutically effective for increasing skin thickness, and for treating extrinsic and intrinsic aging and aging related skin changes, such as fine lines, wrinkles, photoaging, hyperpigmentation, laxity, age spots, lentigines, mottled skin, and cellulite.

In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Disclosed are compounds comprising ketamine (2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone) chemically conjugated to one or more oxoacids, amino acids, polyethylene glycols (PEG or PEO), peptides, phosphates, and/or vitamin compounds, and salts of such compounds. Also disclosed are compositions comprising at least one ketamine compound, or a salt thereof, methods of making such compounds, and methods of using such ketamine compounds and compositions.

The present disclosure relates to certain molecules, pharmaceutical compositions containing them, and methods of using them to treat viral infections.

The present application is directed to a sensor for detection and/or concentration determination of metal ions in a fluid comprising a complexing agent suitable for binding the metal ions to be detected, detection means and a linker moiety, wherein the detection means comprises a polymer membrane with nanopores. The sensor according to the present application can be used for fast, highly selective and ultrasensitive detection of metal ions in a fluid, in particular of Cu.sup.2+ ions. With such a sensor a qualitative and/or quantitative detection of metal ions can be achieved, which can be useful in the diagnosis and/or monitoring of diseases linked to abnormal metal ion concentrations such as for example Alzheimer's disease.

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof:

##STR00001##

which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable slat thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.