Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions associated with the enzyme glucosylceramide synthase (GCS).

The present invention relates to specific complexes comprising heavy metal ions having an atomic number of 23 or higher and 83 or lower (in particular Ag.sup.1+, Ba.sup.2+, Pb.sup.2+, Gd.sup.3+ and Bi.sup.3+) and one or more hematein ligand(s). In particular, the invention relates to the use of the complexes as ex vivo contrast agents for a computed tomography scanning of a biological sample. Moreover, the invention relates to specific ex vivo methods for investigating a biological sample by means of computed tomography scanning methods, wherein the method comprises staining the biological sample with a solution comprising one or more of the complex(es); or wherein the method comprises staining the biological sample with a staining solution comprising hematein, and separately contacting the biological sample with one or more staining solution(s) comprising one or more heavy metal ions having an atomic number of 23 or higher and 83 or lower (in particular Ag.sup.1+, Ba.sup.2+, Pb.sup.2+, Gd.sup.3+ and Bi.sup.3+).

The invention describes extracts from plants of the genus Stachytarpheta enriched with ipolamiide derivatives as immunosuppressants for treating immunological disorders. The isolated active compounds and a process of producing these are also disclosed.

The invention describes extracts from plants of the genus Stachytarpheta enriched with ipolamiide derivatives as immunosuppressants for treating immunological disorders. The isolated active compounds and a process of producing these are also disclosed.

The present disclosure provides isolated nepetalactone oxidoreductase polypeptides (NORs), nepetalactol synthases (NEPSs), and related polynucleotides, engineered host cells, and cultures, as well as methods for producing NORs and NEPSs, and for using them to produce nepetalactol, nepetalactone, and dihydronepetalactone. The present disclosure also provides methods for engineering cells (e.g., microbial cells) to produce nepetalactone from a fermentation substrate such as glucose, as well as engineered cells having this capability and related cultures and methods for producing nepetalactone.

The present invention relates to methods of making fused ring compounds, such as indeno-fused naphthols, and fused ring indenopyran compounds, such as indeno-fused naphthopyrans, that each employ an unsaturated compound represented by the following Formula II. ##STR00001##
Referring to the unsaturated compound of Formula II: Ring-A can be selected from optionally substituted aryl (e.g., phenyl); m can be, for example, from 0 to 4; R.sup.1 for each m can be selected from optionally substituted hydrocarbyl (e.g., C.sub.1-C.sub.6 alkyl) optionally interrupted with at least one linking group (e.g., O); and R.sup.3 and R.sup.16 can each be independently selected from, for example, hydrogen or optionally substituted hydrocarbyl, such as C.sub.1-C.sub.8 alkyl. When Ring-A is a phenyl group, the unsaturated compound represented by Formula II can be referred to as an unsaturated indanone acid/ester compound, or an indenone acid/ester compound (depending on whether R.sup.16 is hydrogen, or an optionally substituted hydrocarbyl group).

The present invention relates to methods of making fused ring compounds, such as indeno-fused naphthols, and fused ring indenopyran compounds, such as indeno-fused naphthopyrans, that each employ an unsaturated compound represented by the following Formula II. ##STR00001##
Referring to the unsaturated compound of Formula II: Ring-A can be selected from optionally substituted aryl (e.g., phenyl); m can be, for example, from 0 to 4; R.sup.1 for each m can be selected from optionally substituted hydrocarbyl (e.g., C.sub.1-C.sub.6 alkyl) optionally interrupted with at least one linking group (e.g., O); and R.sup.3 and R.sup.16 can each be independently selected from, for example, hydrogen or optionally substituted hydrocarbyl, such as C.sub.1-C.sub.8 alkyl. When Ring-A is a phenyl group, the unsaturated compound represented by Formula II can be referred to as an unsaturated indanone acid/ester compound, or an indenone acid/ester compound (depending on whether R.sup.16 is hydrogen, or an optionally substituted hydrocarbyl group).

method for decarboxylating a carboxylated phytocannabinoid compound of Formula I to form a phytocannabinoid compound of Formula II: Formula I Formula II wherein: R1 is selected from the group consisting of: substituted or unsubstituted C.sub.1-C.sub.5 alkyl; R2 is selected from the group consisting of: OH or O, and R3 is selected from the group consisting of: a substituted or unsubstituted cyclohexene, a substituted or unsubstituted C.sub.2-C.sub.8 alkene, or a substituted or unsubstituted C.sub.2-C.sub.8 dialkene; or R2 is O, and R2 and R3 together form a ring structure in which R2 is an internal ring atom; wherein the method includes heating a reaction mixture comprising the carboxylated phytocannabinoid compound and a polar aprotic solvent in the presence of a LiCl for a time sufficient to decarboxylate at least a portion of the carboxylated phytocannabinoid compounds and form the phytocannabinoid compound.

##STR00001##

method for decarboxylating a carboxylated phytocannabinoid compound of Formula I to form a phytocannabinoid compound of Formula II: Formula I Formula II wherein: R1 is selected from the group consisting of: substituted or unsubstituted C.sub.1-C.sub.5 alkyl; R2 is selected from the group consisting of: OH or O, and R3 is selected from the group consisting of: a substituted or unsubstituted cyclohexene, a substituted or unsubstituted C.sub.2-C.sub.8 alkene, or a substituted or unsubstituted C.sub.2-C.sub.8 dialkene; or R2 is O, and R2 and R3 together form a ring structure in which R2 is an internal ring atom; wherein the method includes heating a reaction mixture comprising the carboxylated phytocannabinoid compound and a polar aprotic solvent in the presence of a LiCl for a time sufficient to decarboxylate at least a portion of the carboxylated phytocannabinoid compounds and form the phytocannabinoid compound.

##STR00001##

The present disclosure provides a compound of Formula (I):

##STR00001##

or a pharmaceutically acceptable salt thereof as described herein. The present disclosure also provides pharmaceutical compositions comprising a compound of Formula (I), processes for preparing compounds of Formula (I), and therapeutic methods for treating inflammatory disease.