Disulfide-Isomerase A4 (PDIA4) inhibitors and use thereof for inhibiting pancreatic β-cell pathogenesis and treating diabetes are disclosed. Drug candidates that inhibit PDIA4 with IC50 values ranging from 4 μM to 300 nM are identified. The compounds are highly active in augmenting insulin secretion from pancreatic β-cells. The representative compound No. 8 (4,5-dimethoxy-2-propiolamidobenzoic acid), alone or in combination with metformin, is effective in preserving pancreatic β-cell function, treating and/or reversing, returning blood glucose concentration to a normal level in a diabetic.

This invention is directed to compounds of Formula (I) ##STR00001## pharmaceutically acceptable salts, esters, and prodrugs thereof, to their preparation, to pharmaceutical compositions comprising compounds of Formula I, and to their uses as antimicrobial agents.

This invention is directed to compounds of Formula (I) ##STR00001## pharmaceutically acceptable salts, esters, and prodrugs thereof, to their preparation, to pharmaceutical compositions comprising compounds of Formula I, and to their uses as antimicrobial agents.

This disclosure relates generally to cannabinoid derivatives having the structural formula (I), pharmaceutical compositions comprising them, and methods of using the cannabinoid derivatives. In some embodiments, R.sup.1 is —CH.sub.2CH═C(CH.sub.3).sub.2, R.sup.2 is methyl, R.sup.3 is CsHn, R.sup.4 is —C(O)N(R.sup.4a)(R.sup.4b), R.sup.5 is H, R.sup.6 is OH, and R.sup.7 is H. Compounds of the present disclosure were tested in agonist and antagonist mode for both the CB1 and CB2 receptors. The tested compounds were generally found to exhibit activity in antagonist mode at the CB1 and CB2 receptor.

This disclosure relates generally to cannabinoid derivatives having the structural formula (I), pharmaceutical compositions comprising them, and methods of using the cannabinoid derivatives. In some embodiments, R.sup.1 is —CH.sub.2CH═C(CH.sub.3).sub.2, R.sup.2 is methyl, R.sup.3 is CsHn, R.sup.4 is —C(O)N(R.sup.4a)(R.sup.4b), R.sup.5 is H, R.sup.6 is OH, and R.sup.7 is H. Compounds of the present disclosure were tested in agonist and antagonist mode for both the CB1 and CB2 receptors. The tested compounds were generally found to exhibit activity in antagonist mode at the CB1 and CB2 receptor.

Disclosed are compounds of formula (I) below and pharmaceutically acceptable salts thereof: (I), in which each of variables R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, A.sub.1, A.sub.2, A.sub.3, A.sub.4, X and Y is defined herein. Also disclosed are methods for reducing the glycemic level and treating glucagon-associated disorders with a compound of formula (I) or a salt thereof and a pharmaceutical composition containing same. ##STR00001##

Disclosed are compounds of formula (I) below and pharmaceutically acceptable salts thereof: (I), in which each of variables R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, A.sub.1, A.sub.2, A.sub.3, A.sub.4, X and Y is defined herein. Also disclosed are methods for reducing the glycemic level and treating glucagon-associated disorders with a compound of formula (I) or a salt thereof and a pharmaceutical composition containing same. ##STR00001##

The present invention discloses an N-alkyl-N-cyanoalkylbenzamide compound of General Formula I, an intermediate of General Formula II used to prepare the compound, wherein R.sub.1 is selected from halo or C.sub.1-C.sub.3 alkyl; R.sub.2 is selected from halo or CN; R.sub.3 is selected from halo, or C.sub.1-C.sub.3haloalkyl; R.sub.4 is selected from halo; R.sub.5 is selected from H or halo; R.sub.6 is selected from C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3 haloalkyl or C.sub.1-C.sub.5 alkoxyalkyl; R.sub.7 is selected from C.sub.1-C.sub.5 alkyl; and R.sub.8 is selected from hydrogen or C.sub.1-C.sub.5alkyl. Compared with the compounds in the prior art, the compound of General Formula I has a higher activity at a low concentration. Particularly, the compound of the present invention still has 60% or higher of the insecticidal activity at a concentration below 1 ppm. This greatly reduces the amount of the compound used and the residue of the compound in farmland, and is thus environmentally friendly.

The present invention discloses an N-alkyl-N-cyanoalkylbenzamide compound of General Formula I, an intermediate of General Formula II used to prepare the compound, wherein R.sub.1 is selected from halo or C.sub.1-C.sub.3 alkyl; R.sub.2 is selected from halo or CN; R.sub.3 is selected from halo, or C.sub.1-C.sub.3haloalkyl; R.sub.4 is selected from halo; R.sub.5 is selected from H or halo; R.sub.6 is selected from C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3 haloalkyl or C.sub.1-C.sub.5 alkoxyalkyl; R.sub.7 is selected from C.sub.1-C.sub.5 alkyl; and R.sub.8 is selected from hydrogen or C.sub.1-C.sub.5alkyl. Compared with the compounds in the prior art, the compound of General Formula I has a higher activity at a low concentration. Particularly, the compound of the present invention still has 60% or higher of the insecticidal activity at a concentration below 1 ppm. This greatly reduces the amount of the compound used and the residue of the compound in farmland, and is thus environmentally friendly.

This invention is directed to compounds of Formula (I)

##STR00001## pharmaceutically acceptable salts, esters, and prodrugs thereof, to their preparation, to pharmaceutical compositions comprising compounds of Formula I, and to their uses as antimicrobial agents.