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.

The present disclosure provides for compounds of Formula (I)

##STR00001##

wherein A.sup.2, A.sup.3, A.sup.4, A.sup.6, A.sup.7, A.sup.8, A.sup.15, R.sup.A, R.sup.5, R.sup.9, R.sup.10A, R.sup.10B, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.16, W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents for the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).

The present disclosure provides for compounds of Formula (I)

##STR00001##

wherein A.sup.2, A.sup.3, A.sup.4, A.sup.6, A.sup.7, A.sup.8, A.sup.15, R.sup.A, R.sup.5, R.sup.9, R.sup.10A, R.sup.10B, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.16, W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents for the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).

The present application provides methods for treating or preventing diseases and conditions associated with tissue fibrosis.

The present application provides methods for treating or preventing diseases and conditions associated with tissue fibrosis.

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 Xi, 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(O)O—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—O—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—O—CH.sub.2— or —O—CH.sub.2CH.sub.2—O—; 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 Xi, 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(O)O—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—O—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—O—CH.sub.2— or —O—CH.sub.2CH.sub.2—O—; 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##

Provided is a heterocyclic compound of Chemical Formula 1:

##STR00001## a is a substituted or unsubstituted tetracyclic or higher aromatic or heteroaromatic ring, and b is a benzene or naphthalene ring; at least two of G1 to G3 are a group of Chemical Formula A, and any remaining group, and G101, is hydrogen, deuterium, halogen, cyano, nitro, or a substituted or unsubstituted: silyl, boron, alkyl, alkoxy, cycloalkyl, aryl, or heteroaryl group;

##STR00002## L1 and L2 are a direct bond, or a substituted or unsubstituted arylene or heteroarylene group; Ar1 and Ar2 are hydrogen, deuterium, halogen, cyano, nitro, or a substituted or unsubstituted: silyl, boron, alkyl, alkoxy, cycloalkyl, aryl, or a heteroaryl group, or a fused ring group of an aromatic hydrocarbon ring and aliphatic hydrocarbon ring, or bond to each other to form a substituted or unsubstituted heteroring; and an organic light emitting device including the same.

Provided is a heterocyclic compound of Chemical Formula 1:

##STR00001## a is a substituted or unsubstituted tetracyclic or higher aromatic or heteroaromatic ring, and b is a benzene or naphthalene ring; at least two of G1 to G3 are a group of Chemical Formula A, and any remaining group, and G101, is hydrogen, deuterium, halogen, cyano, nitro, or a substituted or unsubstituted: silyl, boron, alkyl, alkoxy, cycloalkyl, aryl, or heteroaryl group;

##STR00002## L1 and L2 are a direct bond, or a substituted or unsubstituted arylene or heteroarylene group; Ar1 and Ar2 are hydrogen, deuterium, halogen, cyano, nitro, or a substituted or unsubstituted: silyl, boron, alkyl, alkoxy, cycloalkyl, aryl, or a heteroaryl group, or a fused ring group of an aromatic hydrocarbon ring and aliphatic hydrocarbon ring, or bond to each other to form a substituted or unsubstituted heteroring; and an organic light emitting device including the same.

The present disclosure provides SWIR-active small molecule polymethine dyes with improved properties for use in optical imaging, photothermal therapy, photodynamic therapy, and SWIR-promoted drug delivery.