The present invention relates to a process for synthesis of a compound according to Formula (A): wherein R.sub.1 is a substituted or unsubstituted aryl having 6 to 20 carbon atoms; preferably substituted or unsubstituted phenyl; R.sub.2 is a straight or branched alkyl having 1 to 12 carbon atoms; and R.sub.3 is a straight or branched alkyl having 1 to 12 carbon atoms; starting from a di-keto compound according to Formula (B) wherein R.sub.3 is as shown above, which compound is converted into a ketoenamine compound according to Formula (C) wherein R.sub.2 and R.sub.3 are as shown above, which ketoenamine compound is then reduced to an amino alcohol according to Formula (D), wherein R.sub.2 and R.sub.3 are as shown above, that is subsequently converted into a compound according to Formula (A): characterized in that the ketoenamine is reduced into an amino alcohol using a nickel aluminium alloy in an aqueous solution of an inorganic base. ##STR00001##

The present invention relates to compounds that are inhibitors of the orexin-1 receptor. The compounds have the structural formula I defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of diseases or disorders associated with orexin-1 receptor activity.

The present invention relates to compounds that are inhibitors of the orexin-1 receptor. The compounds have the structural formula I defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of diseases or disorders associated with orexin-1 receptor activity.

A process for preparing a procatalyst for polymerization of olefins, comprising contacting a magnesium-containing support with a halogen-containing titanium compound, a first internal electron donor represented by Formula A, a second internal electron donor represented by Formula B, and an activator; wherein the molar ratio of the first internal donor to the second internal donor is between 0.01 and 0.7; ##STR00001##
wherein in Formula A each R.sup.80 group is independently a substituted or unsubstituted aromatic group; and R.sup.81, R.sup.82, R.sup.83, R.sup.84, R.sup.85, R.sup.86 and R.sup.87 are each independently selected from a hydrogen or a hydrocarbyl group; wherein in Formula B R.sup.51 and R.sup.52 are each independently selected from a hydrogen or a hydrocarbyl group; and R.sup.53 and R.sup.54 are each independently selected from hydrogen, a halide or a hydrocarbyl group.

A process for preparing a procatalyst for polymerization of olefins, comprising contacting a magnesium-containing support with a halogen-containing titanium compound, a first internal electron donor represented by Formula A, a second internal electron donor represented by Formula B, and an activator; wherein the molar ratio of the first internal donor to the second internal donor is between 0.01 and 0.7; ##STR00001##
wherein in Formula A each R.sup.80 group is independently a substituted or unsubstituted aromatic group; and R.sup.81, R.sup.82, R.sup.83, R.sup.84, R.sup.85, R.sup.86 and R.sup.87 are each independently selected from a hydrogen or a hydrocarbyl group; wherein in Formula B R.sup.51 and R.sup.52 are each independently selected from a hydrogen or a hydrocarbyl group; and R.sup.53 and R.sup.54 are each independently selected from hydrogen, a halide or a hydrocarbyl group.

The present invention relates to a process for synthesis of a compound according to Formula (A): wherein R.sub.1 is a substituted or unsubstituted aryl having 6 to 20 carbon atoms; preferably substituted or unsubstituted phenyl; R.sub.2 is a straight or branched alkyl having 1 to 12 carbon atoms; and R.sub.3 is a straight or branched alkyl having 1 to 12 carbon atoms; starting from a di-keto compound according to Formula (B) wherein R.sub.3 is as shown above, which compound is converted into a ketoenamine compound according to Formula (C) wherein R.sub.2 and R.sub.3 are as shown above, which ketoenamine compound is then reduced to an amino alcohol according to Formula (D), wherein R.sub.2 and R.sub.3 are as shown above, that is subsequently converted into a compound according to Formula (A): characterized in that the ketoenamine is reduced into an amino alcohol using a nickel aluminium alloy in an aqueous solution of an inorganic base.

##STR00001##

The present invention relates to a process for synthesis of a compound according to Formula (A): wherein R.sub.1 is a substituted or unsubstituted aryl having 6 to 20 carbon atoms; preferably substituted or unsubstituted phenyl; R.sub.2 is a straight or branched alkyl having 1 to 12 carbon atoms; and R.sub.3 is a straight or branched alkyl having 1 to 12 carbon atoms; starting from a di-keto compound according to Formula (B) wherein R.sub.3 is as shown above, which compound is converted into a ketoenamine compound according to Formula (C) wherein R.sub.2 and R.sub.3 are as shown above, which ketoenamine compound is then reduced to an amino alcohol according to Formula (D), wherein R.sub.2 and R.sub.3 are as shown above, that is subsequently converted into a compound according to Formula (A): characterized in that the ketoenamine is reduced into an amino alcohol using a nickel aluminium alloy in an aqueous solution of an inorganic base.

##STR00001##

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 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##