Provided herein are kallikrein modulating compounds, pharmaceutical compositions comprising the same, and uses thereof.

Stimuli-switchable moieties, monomers incorporating stimuli-switchable moieties, and polymers incorporating such stimuli-switchable moieties are provided. The stimuli-switchable moiety can be a pyrano aryl chromenone-derivative. The stimuli-switchable monomer can be a lactone monomer. The stimuli-switchable monomer can be an amino acid, which can be incorporated into a specific peptide sequence by peptide synthesis.

Stimuli-switchable moieties, monomers incorporating stimuli-switchable moieties, and polymers incorporating such stimuli-switchable moieties are provided. The stimuli-switchable moiety can be a pyrano aryl chromenone-derivative. The stimuli-switchable monomer can be a lactone monomer. The stimuli-switchable monomer can be an amino acid, which can be incorporated into a specific peptide sequence by peptide synthesis.

The invention disclosed a compound of general formula (I), a single stereoisomer thereof, a mixture of stereoisomers thereof, and a prodrug, pharmaceutically acceptable salt and metabolite thereof, X.sub.1, X.sub.2, X.sub.3, X.sub.4, R.sub.1, R.sub.2, x, y and z being as defined in the present invention.

##STR00001##

The invention provides novel compounds having the general formula: ##STR00001##
wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined in the description and in the claims, as well as or pharmaceutically acceptable salts, or tautomerism isomers, or enantiomers, or diastereomers thereof. The invention also contains compositions including the compounds and methods of using the compounds.

The invention provides novel compounds having the general formula: ##STR00001##
wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined in the description and in the claims, as well as or pharmaceutically acceptable salts, or tautomerism isomers, or enantiomers, or diastereomers thereof. The invention also contains compositions including the compounds and methods of using the compounds.

The present invention pertains to the field of pharmaceutical chemicals, and relates to a rapamycin derivative of Formula I, and a preparation method, pharmaceutical composition and use thereof. The compounds of the present invention overcome the defects of rapamycin in terms of water solubility and metabolic properties, and some of the compounds have an in vitro anti-tumor activity superior to rapamycin, have less toxicity to normal cells than rapamycin, and have very good druggability.

##STR00001##

The present invention pertains to the field of pharmaceutical chemicals, and relates to a rapamycin derivative of Formula I, and a preparation method, pharmaceutical composition and use thereof. The compounds of the present invention overcome the defects of rapamycin in terms of water solubility and metabolic properties, and some of the compounds have an in vitro anti-tumor activity superior to rapamycin, have less toxicity to normal cells than rapamycin, and have very good druggability.

##STR00001##

A compound represented by the following general formula (I),

##STR00001## wherein R.sup.1 represents hydrogen, C.sub.1-10 alkyl, cycloalkylalkyl where the cycloalkyl moiety has 3 to 6 carbon atoms and the alkylene moiety has 1 to 5 carbon atoms, or the like, R.sup.2 represents a 4- to 7-membered saturated heterocycle containing one or two heteroatoms which may be the same or different and are selected from N, O, and S, and two or more carbon atoms as ring-constituting atoms, the heterocycle may be substituted with a substituent such as an oxo group, R.sup.2 binds to Y via a carbon atom as a ring-constituting atom of R.sup.2, R.sup.3, R.sup.4, and R.sup.5, which are the same or different, represent hydrogen; hydroxy; or the like, R.sup.6a and R.sup.6b, which are the same or different, represent hydrogen or the like, R.sup.7 and R.sup.8, which are the same or different, represent hydrogen or the like, R.sup.9 and R.sup.10, which are the same or different, represent hydrogen or the like, X represents O or CH.sub.2, and Y represents C(═O) or the like), a tautomer of the compound, a stereoisomer of the compound, a pharmaceutically acceptable salt thereof, or a solvate thereof is used as an anxiolytic, an antidepressant, or the like.

Compounds of general formula

##STR00001##

wherein
the wavy bond ˜ is either a double bond or the epoxide,

##STR00002##

or pharmaceutically acceptable salts, solvates, tautomers, or stereoisomers thereof, for use in the treatment of diseases associated with oxidative stress.