Abstract: The present invention provides small molecule compounds that can form covalent adducts with specific sequences of RNA, such as the hairpin loop r(CUG)exp sequence which is a cause of myotonic dystrophy type 1 (DM1), or the r(CGG)exp sequence which is a cause of fragile X-associated tremor/ataxia syndrome (FXTAS); to methods of making the small molecule compounds; and to methods of using the small molecular compounds in the treatment of DM1 or of FXTAS in patients afflicted therewith. The invention further provides a method for identifying an RNA target of a small molecule drug in vivo, using a small molecule drug conjugated to an RNA-reactive crosslinker group and a reporter group, contacting a cell or nucleic acid extract with the small molecule drug conjugate, then separating RNA targets crosslinked to the small molecule drug conjugate by interaction of the affinity group with a complementary affinity group.

Abstract: The invention provides a series of bioactive small molecules that target expanded r(CGG) repeats, termed r(CGG)exp, that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium, binds the 5?CGG/3?GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Specifically, dimeric compounds incorporating two 9-hydroxyellipticine analog structures can even more potently bind the 5?CGG/3?GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Structure-activity relationships (SAR) studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition of r(CGG) repeats, such as r(CGG)exp.

Abstract: The present invention provides small molecule compounds that can form covalent adducts with specific sequences of RNA, such as the hairpin loop r(CUG)exp sequence which is a cause of myotonic dystrophy type 1 (DM1), or the r(CGG)exp sequence which is a cause of fragile X-associated tremor/ataxia syndrome (FXTAS); to methods of making the small molecule compounds; and to methods of using the small molecular compounds in the treatment of DM1 or of FXTAS in patients afflicted therewith. The invention further provides a method for identifying an RNA target of a small molecule drug in vivo, using a small molecule drug conjugated to an RNA-reactive crosslinker group and a reporter group, contacting a cell or nucleic acid extract with the small molecule drug conjugate, then separating RNA targets crosslinked to the small molecule drug conjugate by interaction of the affinity group with a complementary affinity group.

Abstract: The present invention provides small molecule compounds that can form covalent adducts with specific sequences of RNA, such as the hairpin loop r(CUG)exp sequence which is a cause of myotonic dystrophy type 1 (DM1), or the r(CGG)exp sequence which is a cause of fragile X-associated tremor/ataxia syndrome (FXTAS); to methods of making the small molecule compounds; and to methods of using the small molecular compounds in the treatment of DM1 or of FXTAS in patients afflicted therewith. The invention further provides a method for identifying an RNA target of a small molecule drug in vivo, using a small molecule drug conjugated to an RNA-reactive crosslinker group and a reporter group, contacting a cell or nucleic acid extract with the small molecule drug conjugate, then separating RNA targets crosslinked to the small molecule drug conjugate by interaction of the affinity group with a complementary affinity group.

Abstract: The invention provides a series of bioactive small molecules that target expanded r(CGG) repeats, termed r(CGG)exp, that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically. 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium, binds the 5?CGG/3?GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Specifically, dimeric compounds incorporating two 9-hydroxyellipticine analog structures can even more potently bind the 5?CGG/3?GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Structure-activity relationships (SAR) studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition of r(CGG) repeats, such as r(CGG)exp.

Abstract: The present invention provides small molecule compounds that can form covalent adducts with specific sequences of RNA, such as the hairpin loop r(CUG)exp sequence which is a cause of myotonic dystrophy type 1 (DM1), or the r(CGG)exp sequence which is a cause of fragile X-associated tremor/ataxia syndrome (FXTAS); to methods of making the small molecule compounds; and to methods of using the small molecular compounds in the treatment of DM1 or of FXTAS in patients afflicted therewith. The invention further provides a method for identifying an RNA target of a small molecule drug in vivo, using a small molecule drug conjugated to an RNA-reactive crosslinker group and a reporter group, contacting a cell or nucleic acid extract with the small molecule drug conjugate, then separating RNA targets crosslinked to the small molecule drug conjugate by interaction of the affinity group with a complementary affinity group.

Abstract: The invention provides a series of bioactive small molecules that target expanded r(CGG) repeats, termed r(CGG)exp, that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium, binds the 5?CGG/3?GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Specifically, dimeric compounds incorporating two 9-hydroxyellipticine analog structures can even more potently bind the 5?CGG/3?GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Structure-activity relationships (SAR) studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition of r(CGG) repeats, such as r(CGG)exp.

Abstract: The present invention provides small molecule compounds that can form covalent adducts with specific sequences of RNA, such as the hairpin loop r(CUG)exp sequence which is a cause of myotonic dystrophy type 1 (DM1), or the r(CGG)exp sequence which is a cause of fragile X-associated tremor/ataxia syndrome (FXTAS); to methods of making the small molecule compounds; and to methods of using the small molecular compounds in the treatment of DM1 or of FXTAS in patients afflicted therewith. The invention further provides a method for identifying an RNA target of a small molecule drug in vivo, using a small molecule drug conjugated to an RNA-reactive crosslinker group and a reporter group, contacting a cell or nucleic acid extract with the small molecule drug conjugate, then separating RNA targets crosslinked to the small molecule drug conjugate by interaction of the affinity group with a complementary affinity group.

Abstract: The invention provides a series of bioactive small molecules that target expanded r(CGG) repeats, termed r(CGG)exp, that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium, binds the 5?CG/3?GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Specifically, dimeric compounds incorporating two 9-hydroxyellipticine analog structures can even more potently bind the 5?CGG/3?GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Structure-activity relationships (SAR) studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition of r(CGG) repeats, such as r(CGG)exp.

Abstract: Photoreactive DNA cleaving conjugate compounds are provided comprising a DNA cleaving moiety which comprises an aryl alkyne group and a polyfunctional pH-regulated DNA-binding moiety which comprises at least one or two amino groups.

Abstract: Compounds and methods for double-stranded DNA cleavage of light-activated lysine conjugates are enhanced at the slightly acidic pH suitable for selective targeting of cancer cells by the presence of two amino groups of different basicities. The first amino group plays an auxiliary role enhancing solubility and affinity to DNA whereas the second amino group which is positioned next to the light-activated DNA-cleaver undergoes protonation at the desired pH threshold. Protonation results in two synergetic effects which account for the increased DNA-cleaving ability at the lower pH: tighter binding to DNA at the lower pH; and the unproductive pathway which quenches the excited state of the photocleaver through intramolecular electron transfer is eliminated once the donor amino group next to the chromophore is protonated. The utility of these molecules for phototherapy of cancer is confirmed by the drastic increase in toxicity of five conjugates against cancer cell lines upon photoactivation.

Abstract: Photoreactive DNA cleaving conjugate compounds are provided comprising a DNA cleaving moiety which comprises an aryl alkyne group and a polyfunctional pH-regulated DNA-binding moiety which comprises at least one or two amino groups.

Abstract: The present invention relates to optically active quinoline carboxylic acid derivatives, their pharmaceutically acceptable salts, their solvates, and a process for the preparation thereof. More specifically, the present invention relates to optically active quinoline carboxylic acid derivatives containing 4-aminomethyl-4methyl-3-(Z)-alkoxyiminopyrrolidine substituents causing optical activity at the 7-position of the quinolone nuclei. As the compounds of the present invention have superior antibacterial activity and pharmacokinetic profiles to their enantiomers, their racemates and conventional antibacterial agents, with nearly no phototoxicity, the compounds of this invention are useful for antibacterial agents.

Abstract: The present invention relates to optically active quinoline carboxylic acid derivatives, their pharmaceutically acceptable salts, their solvates, and a process for the preparation thereof. More specifically, the present invention relates to optically active)quinoline carboxylic acid derivatives containing 4-aminomethyl-4-methyl-3-(Z)-alkoxyiminopyrrolidine substituents causing optical activity at the 7-position of the quinolone nuclei. As the compounds of the present invention have superior antibacterial activity and pharmacokinetic profiles to their enantiomers, their racemates and conventional antibacterial agents, with nearly no phototoxicity, the compounds of this invention are useful for antibacterial agents.

Abstract: The present invention relates to optically active quinoline carboxylic acid derivatives, their pharmaceutically acceptable salts, their solvates, and a process for the preparation thereof. More specifically, the present invention relates to optically active quinoline carboxylic acid derivatives containing 4-aminomethyl-4-methyl-3-(Z)-alkoxyirninopyrrolidine substituents causing optical activity at the 7-position of the quinolone nuclei. As the compounds of the present invention have superior antibacterial activity and pharmacokinetic profiles to their enantiomers, their racemates and conventional antibacterial agents, with nearly no phototoxicity, the compounds of this invention are useful for antibacterial agents.

Abstract: Anti-viral agents of formula (1) have been identified. Their preparation method is described. These 2,5-pyridinedicarboxylic acid derivatives or their pharmaceutically acceptable salts are useful in countering the proliferation of viruses such as hepatitis B virus and human immunodeficiency virus.