The present disclosure provides a preparation method for m-diamide compounds. The method includes the following steps: 2-fluoro-3-nitrobenzoyl chloride and 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline are subjected to a condensation reaction, followed by a reduction reaction and an alkylation reaction to give 2-fluoro-3-(alkylamino)-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide, which reacts with an acyl chloride compound to give 2-fluoro-3-(alkylbenzamido)-N-(4-(perfluoropropane-2-yl)-2-(trifluoromethyl)phenyl)benzamide, which is finally brominated to obtain the m-diamide compound. The reactions are almost quantitative with few by-products. Cryogenic and high-temperature reactions are not used. The introduction of bromine atoms at specific sites can be achieved in the final step. The preparation method has high yield and is more suitable for industrial production.

N-benzylbenzamides that act as dual soluble epoxide hydrolase (sEH)/peroxisome proliferator-activated receptor γ (PPARγ) modulators and are useful as medications in the treatment of Metabolic Syndrome (MetS) cluster diseases, including diabetes. Methods of making and using the same are further provided.

N-benzylbenzamides that act as dual soluble epoxide hydrolase (sEH)/peroxisome proliferator-activated receptor γ (PPARγ) modulators and are useful as medications in the treatment of Metabolic Syndrome (MetS) cluster diseases, including diabetes. Methods of making and using the same are further provided.

The present disclosure provides a benzene fused heterocyclic derivative of Formula (I): is a single or double bond; n is an integer of 0 or 1; A is —CH.sub.2—, —CH(OH)—, or —C(O)—; G is C or N; X is —CH.sub.2—, O, or —C(O)—; Y is alkyl, aryl, or heterocyclic alkyl optionally substituted with at least one substituent independently selected from a group consisting of: H, halogen, alkyl, alkyl substituted with at least one halogen, aryl, aryl substituted with at least one halogen, —NR.sub.y1R.sub.y2, —OR.sub.y1, —R.sub.y1C(O)R.sub.y3, —C(O)R.sub.y1, —C(O)OR.sub.y2, —C(O)OR.sub.y2Ry3, —NR.sub.y1C(O)R.sub.y2, —NR.sub.y1C(O)NR.sub.y2R.sub.y3, —NR.sub.y1C(O)OR.sub.y2R.sub.y3, —NR.sub.y1C(O)R.sub.y2OR.sub.y3, C(O)NR.sub.y1(R.sub.y2R.sub.y3), —C(O)NR.sub.y1(R.sub.y2OR.sub.y1), —OR.sub.y2R.sub.y3, and —OR.sub.y2OR.sub.y3, wherein each of R.sub.y1 and R.sub.y2 is independently selected from a group consisting of H, oxygen, alkyl, and aryl, and R.sub.y3 is aryl optionally substituted with at least one halogen; Z is —NR.sub.z1R.sub.z2, —NR.sub.z1R.sub.z3, —OR.sub.z1, —OR.sub.z1R.sub.z3, —C(O)R.sub.z1R.sub.z3, —C(O)OR.sub.z1R.sub.z3, —NR.sub.z1C(O)R.sub.z2R.sub.z3, —NR.sub.z1C(O)OR.sub.z2R.sub.z3, —C(O)NR.sub.z1R.sub.z3, or OR.sub.z2OR.sub.z3, wherein each of R.sub.z1 and R.sub.z2 is independently selected from a group consisting of H, oxygen, alkyl and aryl, and R.sub.z3 is aryl optionally substituted with at least one substituent independently selected from a group consisting of halogen, OH, —R.sub.zaCOOR.sub.zb, —OR.sub.zaCOOR.sub.zb, —R.sub.zaSO.sub.2R.sub.zb, —R.sub.zaSO.sub.2NR.sub.zbR.sub.zcR.sub.zd, —R.sub.zaC(O)R.sub.zbR.sub.zc, —R.sub.zaC(O)NR.sub.zbR.sub.zcR.sub.zd, —RZ.sub.aC(O)NR.sub.zbSO.sub.2R.sub.zc, wherein Rza is nil or alkyl, R.sub.zb is H or alkyl, each of R.sub.zb and R.sub.zc is independently selected from a group consisting of H, OH, alkyl, aryl, alkoxyl, or NR.sub.zbR.sub.zc is a nitrogen-containing heterocyclic alkyl ring, R.sub.zd is nil or a sulfonyl alkyl group. ##STR00001##

The present disclosure provides a benzene fused heterocyclic derivative of Formula (I): is a single or double bond; n is an integer of 0 or 1; A is —CH.sub.2—, —CH(OH)—, or —C(O)—; G is C or N; X is —CH.sub.2—, O, or —C(O)—; Y is alkyl, aryl, or heterocyclic alkyl optionally substituted with at least one substituent independently selected from a group consisting of: H, halogen, alkyl, alkyl substituted with at least one halogen, aryl, aryl substituted with at least one halogen, —NR.sub.y1R.sub.y2, —OR.sub.y1, —R.sub.y1C(O)R.sub.y3, —C(O)R.sub.y1, —C(O)OR.sub.y2, —C(O)OR.sub.y2Ry3, —NR.sub.y1C(O)R.sub.y2, —NR.sub.y1C(O)NR.sub.y2R.sub.y3, —NR.sub.y1C(O)OR.sub.y2R.sub.y3, —NR.sub.y1C(O)R.sub.y2OR.sub.y3, C(O)NR.sub.y1(R.sub.y2R.sub.y3), —C(O)NR.sub.y1(R.sub.y2OR.sub.y1), —OR.sub.y2R.sub.y3, and —OR.sub.y2OR.sub.y3, wherein each of R.sub.y1 and R.sub.y2 is independently selected from a group consisting of H, oxygen, alkyl, and aryl, and R.sub.y3 is aryl optionally substituted with at least one halogen; Z is —NR.sub.z1R.sub.z2, —NR.sub.z1R.sub.z3, —OR.sub.z1, —OR.sub.z1R.sub.z3, —C(O)R.sub.z1R.sub.z3, —C(O)OR.sub.z1R.sub.z3, —NR.sub.z1C(O)R.sub.z2R.sub.z3, —NR.sub.z1C(O)OR.sub.z2R.sub.z3, —C(O)NR.sub.z1R.sub.z3, or OR.sub.z2OR.sub.z3, wherein each of R.sub.z1 and R.sub.z2 is independently selected from a group consisting of H, oxygen, alkyl and aryl, and R.sub.z3 is aryl optionally substituted with at least one substituent independently selected from a group consisting of halogen, OH, —R.sub.zaCOOR.sub.zb, —OR.sub.zaCOOR.sub.zb, —R.sub.zaSO.sub.2R.sub.zb, —R.sub.zaSO.sub.2NR.sub.zbR.sub.zcR.sub.zd, —R.sub.zaC(O)R.sub.zbR.sub.zc, —R.sub.zaC(O)NR.sub.zbR.sub.zcR.sub.zd, —RZ.sub.aC(O)NR.sub.zbSO.sub.2R.sub.zc, wherein Rza is nil or alkyl, R.sub.zb is H or alkyl, each of R.sub.zb and R.sub.zc is independently selected from a group consisting of H, OH, alkyl, aryl, alkoxyl, or NR.sub.zbR.sub.zc is a nitrogen-containing heterocyclic alkyl ring, R.sub.zd is nil or a sulfonyl alkyl group. ##STR00001##

The present invention provides novel compounds with increased plasma stability that modulate PAR1 signaling, and methods of using them. The present invention provides methods of using the novel PAR1 modulators for the treatment of a number of disorders, including, inflammation, thrombosis, kidney disease, sepsis, stroke, as well as proliferation-related diseases. Furthermore, the PAR1 modulators of the present invention provide cytoprotection for certain cells and tissues, for example, in coronary blood vessels and tissues after a heart attack.

The present invention provides novel compounds with increased plasma stability that modulate PAR1 signaling, and methods of using them. The present invention provides methods of using the novel PAR1 modulators for the treatment of a number of disorders, including, inflammation, thrombosis, kidney disease, sepsis, stroke, as well as proliferation-related diseases. Furthermore, the PAR1 modulators of the present invention provide cytoprotection for certain cells and tissues, for example, in coronary blood vessels and tissues after a heart attack.

Described herein are compounds and compositions for the amelioration of arthritis or joint injuries by inducing mesenchymal stem cells into chondrocytes.

Described herein are compounds and compositions for the amelioration of arthritis or joint injuries by inducing mesenchymal stem cells into chondrocytes.

The present invention refers to a process for transition-metal-assisted .sup.18F-deoxyfluorination of phenols. The transformation benefits from readily available phenols as starting materials, tolerance of moisture and ambient atmosphere, large substrate scope, and translatability to generate doses appropriate for positron emission tomography (PET) imaging.