The present disclosure provides, inter alia, compounds with MASP-2 inhibitory activity, compositions of such compounds and methods of making and using such compounds.

The present technology provides aryl or heteroaryl triazolone derivatives or pharmaceutically acceptable salts thereof, preparation processes thereof, pharmaceutical compositions comprising the same, and the use thereof. The aryl or heteroaryl triazolone derivatives or their pharmaceutically acceptable salts exhibit selective inhibitory activity on VAP-1 and therefore can be usefully applied, e.g., for the treatment and prophylaxis of nonalcoholic hepatosteatosis (NASH).

The present technology provides aryl or heteroaryl triazolone derivatives or pharmaceutically acceptable salts thereof, preparation processes thereof, pharmaceutical compositions comprising the same, and the use thereof. The aryl or heteroaryl triazolone derivatives or their pharmaceutically acceptable salts exhibit selective inhibitory activity on VAP-1 and therefore can be usefully applied, e.g., for the treatment and prophylaxis of nonalcoholic hepatosteatosis (NASH).

Disclosed in the present invention are a 2-(1,2,4-triazolyl)benzoyl arylamine active compound for inhibiting a wheat take-all pathogen, and a preparation method therefor. The active compound has a structure as shown in formula I. R1, R3, and R4 are —H, —F, —Cl, —Br, —I, —CN, —NO2, —CF3, —CHO, —C1-C4 alkyl groups, or —C1-C4 haloalkyl groups, or —O—R5; R2 is —H, —F, —Cl, —Br, —I, —CN, —CF3, —CHO, —C1-C4 alkyl groups, or —C1-C4 haloalkyl groups, or —O—R5; X is —F, —Cl, —Br, —I, —CN, —NO2, —CF3, or —COOR6; Y is —H, —F, —Cl, —Br, —I, —CN, —NO2, —CF3, or —COOR6; R5 is —C1-C4 alkyl groups, or —C1-C4 haloalkyl groups; R6 is —C1-C4 alkyl groups, or —C1-C4 haloalkyl groups. The compound I has an excellent inhibition effect on the wheat take-all pathogen and can be applied to prevention and treatment of wheat take-all.

Disclosed in the present invention are a 2-(1,2,4-triazolyl)benzoyl arylamine active compound for inhibiting a wheat take-all pathogen, and a preparation method therefor. The active compound has a structure as shown in formula I. R1, R3, and R4 are —H, —F, —Cl, —Br, —I, —CN, —NO2, —CF3, —CHO, —C1-C4 alkyl groups, or —C1-C4 haloalkyl groups, or —O—R5; R2 is —H, —F, —Cl, —Br, —I, —CN, —CF3, —CHO, —C1-C4 alkyl groups, or —C1-C4 haloalkyl groups, or —O—R5; X is —F, —Cl, —Br, —I, —CN, —NO2, —CF3, or —COOR6; Y is —H, —F, —Cl, —Br, —I, —CN, —NO2, —CF3, or —COOR6; R5 is —C1-C4 alkyl groups, or —C1-C4 haloalkyl groups; R6 is —C1-C4 alkyl groups, or —C1-C4 haloalkyl groups. The compound I has an excellent inhibition effect on the wheat take-all pathogen and can be applied to prevention and treatment of wheat take-all.

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, wherein: the group X—Y is —NHSO.sub.2— or —SO.sub.2NH—; Z is a monocyclic aryl or heteroaryl group, each of which is optionally substituted by one or more substituents selected from alkyl, cycloalkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.1 is H or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, C land alkyl; R.sub.4 is selected from H and halo; R.sub.5 is selected from H, alkyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, halo, SO.sub.2-alkyl, SO.sub.2NR.sub.12R.sub.13, heteroaryl, CONR.sub.10R.sub.11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.8 is selected from H, alkyl, haloalkyl and halo; and R.sub.9 is H, alkyl or halo; R.sub.10 and R.sub.11 are each independently H or alkyl; and R.sub.12 and R.sub.13 are each independently H or alkyl. Further aspects of the invention relate to such compounds for use in the field of immuno-oncology and related applications. Another aspect of the invention relates to compounds of formulae (la) and (lb).

##STR00001##

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, wherein: the group X—Y is —NHSO.sub.2— or —SO.sub.2NH—; Z is a monocyclic aryl or heteroaryl group, each of which is optionally substituted by one or more substituents selected from alkyl, cycloalkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.1 is H or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, C land alkyl; R.sub.4 is selected from H and halo; R.sub.5 is selected from H, alkyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, halo, SO.sub.2-alkyl, SO.sub.2NR.sub.12R.sub.13, heteroaryl, CONR.sub.10R.sub.11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.8 is selected from H, alkyl, haloalkyl and halo; and R.sub.9 is H, alkyl or halo; R.sub.10 and R.sub.11 are each independently H or alkyl; and R.sub.12 and R.sub.13 are each independently H or alkyl. Further aspects of the invention relate to such compounds for use in the field of immuno-oncology and related applications. Another aspect of the invention relates to compounds of formulae (la) and (lb).

##STR00001##

Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with a defect in glyoxylate metabolism, for example a disease or disorder associated with the enzyme glycolate oxidase (GO) or alterations in oxalate metabolism. Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.

The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of Cbl-b, and the treatment of Cbl-b-mediated disorders.

The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of Cbl-b, and the treatment of Cbl-b-mediated disorders.