Provided herein are ergoline-derived heterocyclic compounds which can be useful for methods of treating a disease or for increasing neural plasticity. The compounds can also be useful for increasing dendritic spine density.

Provided herein are ergoline-derived heterocyclic compounds which can be useful for methods of treating a disease or for increasing neural plasticity. The compounds can also be useful for increasing dendritic spine density.

The present application relates to an organic compound, and there are electron transport and injection groups and a conjugated fused heteroaromatic ring in a structure of the organic compound. The organic compound can be used in a functional layer of an organic light-emitting device (OLED). When used in an OLED, the organic compound of the present application can improve the light-emitting efficiency and service life of the OLED.

Novel cannabinoid ligands represented by the general formulas I, II, and III and methods for preparation and use within which one or more of a fluorescent ligand, nitroxide spin label, metal chelate, biotin moiety, or group with enhanced polarity may be incorporated. The compounds can bind to and modulate the cannabinoid CB1 and CB2 receptors and thereby considered specific ligands for these receptors. Some of the disclosed compounds that bind to cannabinoid CB1 and CB2 receptors can exhibit tight or irreversible binding characteristics for these receptors. Due to the presence of the imaging/diagnostic and/or therapeutic functional groups including fluorescent groups, nitroxide spin labels, metal chelates, biotin moieties, and groups with enhanced polarity, the disclosed compounds may be useful as imaging/diagnostic tools and/or therapeutic agents.

Novel cannabinoid ligands represented by the general formulas I, II, and III and methods for preparation and use within which one or more of a fluorescent ligand, nitroxide spin label, metal chelate, biotin moiety, or group with enhanced polarity may be incorporated. The compounds can bind to and modulate the cannabinoid CB1 and CB2 receptors and thereby considered specific ligands for these receptors. Some of the disclosed compounds that bind to cannabinoid CB1 and CB2 receptors can exhibit tight or irreversible binding characteristics for these receptors. Due to the presence of the imaging/diagnostic and/or therapeutic functional groups including fluorescent groups, nitroxide spin labels, metal chelates, biotin moieties, and groups with enhanced polarity, the disclosed compounds may be useful as imaging/diagnostic tools and/or therapeutic agents.

An organic light emitting element produced by using a light emitting composition that contains both a first compound having a PBHT value more than 0.730 and a second compound having ES1 lower than that of the first compound and AEsT less than 0.20 eV is excellent in durability. ES1 is the lowest excited singlet energy level, AEsT is the difference between the lowest excited singlet energy level and the lowest excited triplet energy level.

The present invention relates to a compound of formula (I), wherein X.sup.1, X.sup.2 and X.sup.3 are, independently of each other, N or CH; with the proviso that at least two of X.sup.1X.sup.2 and X.sup.3 are N; Y is N or CH; W is H or F; with the proviso that when W is F, then X.sup.1, X.sup.2 and X.sup.3 are N; R.sup.1 and R.sup.2 are independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R.sup.3 and R.sup.4 are independently of each other H, C.sub.1-C.sub.3alkyl optionally substituted with one or two OH, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.3alkyl, CN, or C(0)0-C.sub.1-C.sub.2alkyl; or R.sup.3 and R.sup.4 form together a bivalent residue —R.sup.5R.sup.6— selected from C.sub.1-C.sub.3alkylene optionally substituted with 1 to 4 F, —CH.sub.2-0-CH.sub.2—, —CH.sub.2—NH—CH.sub.2—, or any of the structures wherein the arrows denote the bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R.sup.7; wherein R.sup.7 is independently at each occurrence C.sub.1-C.sub.3alkyl optionally substituted with one or two OH, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.3alkyl, C.sub.3-C.sub.6cycloalkyl; or two R.sup.7 substituents form together a bivalent residue —R.sup.8R.sup.9— selected from C.sub.1-C.sub.3alkylene optionally substituted with 1 to 4 F, —CH.sub.2-0-CH.sub.2— or -0-CH.sub.2CH.sub.2-0- with the proviso that at least one of R.sup.1 and R.sup.2 is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in a method of treating a skin disorder in a subject, wherein said skin disorder is a genodermatosis, a vascular anomaly or a skin disorder selected from scleroderma, sclerodermatous chronic graft-versus-host disease, lichen sclerosus, lichen planus, lichen ruber planus and scars.

##STR00001##

The present invention relates to a compound of formula (I), wherein X.sup.1, X.sup.2 and X.sup.3 are, independently of each other, N or CH; with the proviso that at least two of X.sup.1X.sup.2 and X.sup.3 are N; Y is N or CH; W is H or F; with the proviso that when W is F, then X.sup.1, X.sup.2 and X.sup.3 are N; R.sup.1 and R.sup.2 are independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R.sup.3 and R.sup.4 are independently of each other H, C.sub.1-C.sub.3alkyl optionally substituted with one or two OH, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.3alkyl, CN, or C(0)0-C.sub.1-C.sub.2alkyl; or R.sup.3 and R.sup.4 form together a bivalent residue —R.sup.5R.sup.6— selected from C.sub.1-C.sub.3alkylene optionally substituted with 1 to 4 F, —CH.sub.2-0-CH.sub.2—, —CH.sub.2—NH—CH.sub.2—, or any of the structures wherein the arrows denote the bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R.sup.7; wherein R.sup.7 is independently at each occurrence C.sub.1-C.sub.3alkyl optionally substituted with one or two OH, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.3alkyl, C.sub.3-C.sub.6cycloalkyl; or two R.sup.7 substituents form together a bivalent residue —R.sup.8R.sup.9— selected from C.sub.1-C.sub.3alkylene optionally substituted with 1 to 4 F, —CH.sub.2-0-CH.sub.2— or -0-CH.sub.2CH.sub.2-0- with the proviso that at least one of R.sup.1 and R.sup.2 is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in a method of treating a skin disorder in a subject, wherein said skin disorder is a genodermatosis, a vascular anomaly or a skin disorder selected from scleroderma, sclerodermatous chronic graft-versus-host disease, lichen sclerosus, lichen planus, lichen ruber planus and scars.

##STR00001##

A compound represented by the formula (12X). In the formula (12X), Py.sub.1 and Py.sub.2 each independently represent a substituted or unsubstituted 1-pyrenyl group, L.sub.1 and L.sub.2 each independently represent a substituted or unsubstituted phenylene group or a substituted or unsubstituted naphthylene group. When L.sub.1 and L.sub.2 each independently represent a substituted or unsubstituted phenylene group, -L.sub.1-L.sub.2- in the formula (12X) represents a group represented by one of the formulae (13-1) to (13-6), (10-1), (20-1), and (30-1). When L.sub.1 and L.sub.2 each independently represent a substituted or unsubstituted naphthylene group, a bonding position of the naphthylene group in L.sub.1 is different from a bonding position of the naphthylene group in L.sub.2.

##STR00001## ##STR00002## ##STR00003##

The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula I, or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof. ##STR00001## For Formula I compounds X, Y, R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b and R.sup.5 are as defined in the specification. The inventive Formula I compounds are inhibitors of eIF4A and find utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.