848589-59-3Relevant academic research and scientific papers
METHODS OF IDENTIFYING MODULATORS OF BROMODOMAINS
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Page/Page column 64, (2008/06/13)
The present invention features compounds of the following general formula (I) wherein R1 is selected from the group consisting of hydrogen, lower alkyl, aryl, aralkyl; substituted aralkyl, heteroaryl; substituted heteroaryl, phenyl, SO2, NH2, NO2, SO2, CH2, CH2CH3, OCH3, OCOCH3, CH2COCH3, and OH, CN and halogen; R2 is selected from the group consisting of hydrogen; lower alkyl, aryl, phenyl, aralkyl; substituted aralkyl, heteroaryl; substituted heteroaryl, SO2 NH2NH3+NO2, SO2, CH3, CH2CH3, OCH3, OCOCH3, CH2COCH3, and OH, halogen, carboxy, and alkoxy; X is selected from the group consisting of lower alkyl, SO2, NH, NO2, , CH3, CH2CH3, OCH3, OCOCH3, CH2COCH3, and OH, carboxy, and alkoxy; and n is an integer from O to 10 and their pharmaceutically acceptable salts of acids or bases as well as pharmaceutical compositions comprising these compounds. The invention further provides methods for preventing or inhibiting the binding of bromodomains to acetyl-lysine residues of proteins and methods for treating HIV infection and HW related disease. The present invention also features compounds of the following general formula (II) wherein: R1R2 and R3 are independently selected from the group consisting of hydrogen; lower alkyl, aryl, phenyl, aralkyl; substituted aralkyl, heteroaryl; substituted heteroaryl, SO2, NH2, NH3+ NO2, SO2, CH3, CH2CH3, OCH3, OCOCH3, CH2COCH3, OH, SH, halogen, carboxy; and R4 is selected from the group consisting of lower alkyl, aryl, SO2, NH, NO2, CH3, CH2CH3, OCH3, OCOCH3, CH2COCH3, OH, carboxy, and alkoxy as well as pharmaceutical compositions comprising these compounds. The invention further provides methods for preventing or inhibiting the binding of bromodomains to acetyl-lysine residues of proteins and methods f treating HW infection and HIY related disease. The present invention also features compounds of formula (III) wherein R1, R2, R3, R4 R5, and R6 are independently selected from the group consisting of hydrogen; lower alkyl, aryl, phenyl, aralkyl; substituted aralkyl, heteroaryl, substituted heteroaryl, SO2 NH2, NH3+, NO2, SO2, CH3, CH2CH3, OCH3, OCOCH3, CH2COCH3, OCH2CH3, OCH(CH3)2, OCH2COOH, OCHCH3COOH, OCH2COCH3, OCH2CONH2, OCOCH(CH3)2, OCH2CH2OH, OCH2CH2CH3, O(CH2)3CH3, OCHCH3COOCH3, OCH2CON(CH3)2,NH(CH2)3N(CH3)2, NH(CH2)2N(CH3)2, NH(CH2)2OH, NH(CH2)3CH3, NHCH3, SH, halogen, carboxy, and alkoxy as well as pharmaceutical compositions comprising these compounds. The invention further provides methods for preventing or inhibiting the binding of bromodomains to acetyl-lysine residues of proteins and methods for treating HIV infection and HIV related disease.
Selective small molecules blocking HIV-1 tat and coactivator PCAF association
Zeng, Lei,Li, Jiaming,Muller, Michaela,Yan, Sherry,Mujtaba, Shiraz,Pan, Chongfeng,Wang, Zhiyong,Zhou, Ming-Ming
, p. 2376 - 2377 (2007/10/03)
Development of drug resistance from mutations in the targeted viral proteins leads to continuation of viral production by chronically infected cells, contributing to HIV-mediated immune dysfunction. Targeting a host cell protein essential for viral reproduction, rather than a viral protein, may minimize the viral drug resistance problem as observed with HIV protease inhibitors. We report here the development of a novel class of N1-aryl-propane-1,3-diamine compounds using a structure-based approach that selectively inhibit the activity of the bromodomain of the human transcriptional co-activator PCAF, of which association with the HIV trans-activator Tat is essential for transcription and replication of the integrated HIV provirus. Copyright
