Provided are an azabicyclic substituted oxaspiro derivative, a preparation method therefor and a medical use thereof. Specifically, provided are compounds represented by formula (I) and formula (II) or pharmaceutically acceptable salts, stereoisomers or solvates thereof, and a preparation method therefor and an application thereof.

##STR00001##

Compounds of formula (I) are provided which are useful in the treatment of diseases or conditions modulated at least in part by CCR6:

##STR00001##

Compounds of formula (I) are provided which are useful in the treatment of diseases or conditions modulated at least in part by CCR6:

##STR00001##

Disclosed are compounds of the general formula (I), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its polymorph, or solvate thereof, wherein, ring A, ring B, R.sup.1 to R.sup.4, and n are as defined herein, for use as SOS1 inhibitors in the treatment of proliferative, infectious and RASopathy diseases or disorders. Also disclosed are methods of synthesizing the compound of formula I, pharmaceutical compositions containing the compound of formula I, method of treatment of proliferative, infectious and RASopathy diseases or disorder, for example, a cancer, by administering the said compound and combinations of the compound of formula I with other active ingredients.

##STR00001##

Disclosed are compounds of the general formula (I), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its polymorph, or solvate thereof, wherein, ring A, ring B, R.sup.1 to R.sup.4, and n are as defined herein, for use as SOS1 inhibitors in the treatment of proliferative, infectious and RASopathy diseases or disorders. Also disclosed are methods of synthesizing the compound of formula I, pharmaceutical compositions containing the compound of formula I, method of treatment of proliferative, infectious and RASopathy diseases or disorder, for example, a cancer, by administering the said compound and combinations of the compound of formula I with other active ingredients.

##STR00001##

Provided is a compound having the structure: (SIG)-(SI-MOD).sub.m
where SIG is a signaling molecule, SI is a self-immolative structure bound to SIG such that SIG has a reduced signal relative to the signal of SIG without SI, MOD is a moiety bound to SI that is subject to modification by an activator, and m is an integer from 1 to about 10. When MOD is modified by an activator, SI is destabilized and self-cleaved from SIG such that SIG generates an increased signal. Also provided are methods of determining whether a sample, such as a cell, comprises an activator, such as a nitroreducase, using the compound. Further provided are methods of determining whether a mammalian cell is hypoxic using the compound where nitroreductase is the activator. A method of detecting a microorganism that comprises a nitroreductase using the compound where nitroreductase is the activator is also provided.

Provided is a compound having the structure: (SIG)-(SI-MOD).sub.m
where SIG is a signaling molecule, SI is a self-immolative structure bound to SIG such that SIG has a reduced signal relative to the signal of SIG without SI, MOD is a moiety bound to SI that is subject to modification by an activator, and m is an integer from 1 to about 10. When MOD is modified by an activator, SI is destabilized and self-cleaved from SIG such that SIG generates an increased signal. Also provided are methods of determining whether a sample, such as a cell, comprises an activator, such as a nitroreducase, using the compound. Further provided are methods of determining whether a mammalian cell is hypoxic using the compound where nitroreductase is the activator. A method of detecting a microorganism that comprises a nitroreductase using the compound where nitroreductase is the activator is also provided.

Pyrano[4,3-b]indole derivatives as alpha-1-antitrypsin modulators for treating alpha-1-antitrypsin deficiency (AATD)

Pyrano[4,3-b]indole derivatives as alpha-1-antitrypsin modulators for treating alpha-1-antitrypsin deficiency (AATD)

Disclosed are prodrug compounds that can be converted to mesembrine under biologically relevant conditions, such as hydrolysis in vivo; and related methods of preparing and using these compounds. Stable preparations of isolated mesembrine stereoisomers are also provided.