Disclosed are compounds towards bromodomains, pharmaceutical compositions containing the compounds and use of the compounds in therapy.

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Methods of treating cancer by administering a compound of Formula I,

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or a pharmaceutically acceptable salt or solvate thereof, in combination with other cancer treatments are described, wherein R.sup.1 is halo; R.sup.2 is halo; and Q is CH or N.

The present invention is directed to multi-tyrosine kinase inhibitor compounds. The present invention is further directed to compositions comprising those compounds. Finally, the present invention is directed to methods of treating eye conditions including, but not limited to, diabetic background retinopathy, diabetic macular edema, diabetic proliferative retinopathy, diabetic macular edema with proliferative retinopathy, proliferative fibrovascular disease, diabetic macular edema with proliferative fibrovascular disease, retinopathy of prematurity, dry macular degeneration, dry macular degeneration with drusen and wet macular degeneration, using compounds and compositions of the invention.

The present invention is directed to multi-tyrosine kinase inhibitor compounds. The present invention is further directed to compositions comprising those compounds. Finally, the present invention is directed to methods of treating eye conditions including, but not limited to, diabetic background retinopathy, diabetic macular edema, diabetic proliferative retinopathy, diabetic macular edema with proliferative retinopathy, proliferative fibrovascular disease, diabetic macular edema with proliferative fibrovascular disease, retinopathy of prematurity, dry macular degeneration, dry macular degeneration with drusen and wet macular degeneration, using compounds and compositions of the invention.

Compounds capable of, or usable in, inducing death of cancer cells and/or modulating a biological activity of a chemokine e.g., cell migration, and/or treating diseases and disorders associated with a biological activity of a chemokine and/or cell migration, and/or in treating cancer, are provided herein. The compounds are collectively represented by Formulae Ia or Ib: ##STR00001##
wherein A, B, D, E, G and R.sub.1-R.sub.5 are as defined in the specification, with one or more of D, E and G, preferably E, is hydroxy.

Compounds capable of, or usable in, inducing death of cancer cells and/or modulating a biological activity of a chemokine e.g., cell migration, and/or treating diseases and disorders associated with a biological activity of a chemokine and/or cell migration, and/or in treating cancer, are provided herein. The compounds are collectively represented by Formulae Ia or Ib: ##STR00001##
wherein A, B, D, E, G and R.sub.1-R.sub.5 are as defined in the specification, with one or more of D, E and G, preferably E, is hydroxy.

Novel processes, and intermediates, for making alkylated arylpiperazine and alkylated arylpiperidine compounds of the general formulas (I) and (VII), respectively ##STR00001##
wherein, R.sub.1 and R.sub.2 are individually selected from hydrogen, alkyl, substituted or alkyl; n=0, 1, or 2; Y=NR.sub.3R.sub.4, OR.sub.5, or SR.sub.5, where R.sub.3 and R.sub.4 are individually selected from acyl or sulfonyl, and where R.sub.5 is aryl or heteroaryl, or heterocyclic; and Ar is an aryl, heteroaryl, or heterocyclic compound.

Novel processes, and intermediates, for making alkylated arylpiperazine and alkylated arylpiperidine compounds of the general formulas (I) and (VII), respectively ##STR00001##
wherein, R.sub.1 and R.sub.2 are individually selected from hydrogen, alkyl, substituted or alkyl; n=0, 1, or 2; Y=NR.sub.3R.sub.4, OR.sub.5, or SR.sub.5, where R.sub.3 and R.sub.4 are individually selected from acyl or sulfonyl, and where R.sub.5 is aryl or heteroaryl, or heterocyclic; and Ar is an aryl, heteroaryl, or heterocyclic compound.

The present invention relates a new process to synthesize 6-(7-((1-aminocyclo-propyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide (AL3810) by deprotection of substituted benzyl 1-((6-methoxy-4-(5-(methylcarbamoyl)naphthalen-2-yloxy)quinolin-7-yloxy)-methyl)cyc-lopropylcarbamate (Formula I) under a diluted or weak acidic condition. A stable crystalline form of 6-(7-((1-aminocyclo-propyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide has also been prepared. ##STR00001##

The present invention relates a new process to synthesize 6-(7-((1-aminocyclo-propyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide (AL3810) by deprotection of substituted benzyl 1-((6-methoxy-4-(5-(methylcarbamoyl)naphthalen-2-yloxy)quinolin-7-yloxy)-methyl)cyc-lopropylcarbamate (Formula I) under a diluted or weak acidic condition. A stable crystalline form of 6-(7-((1-aminocyclo-propyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide has also been prepared. ##STR00001##