120737-59-9Relevant articles and documents
Structure-Activity Relationships in Prazosin-Related Compounds. 2. Role of the Piperazine Ring on α-Blocking Activity
Giardina, Dario,Gulini, Ugo,Massi, Maurizio,Piloni, Maria G.,Pompei, Pierluigi,et al.
, p. 690 - 698 (1993)
Several prazosin-related compounds have been synthesized and evaluated for their blocking activity toward α-adrenoreceptors.The structural modification performed on the prazosin structure included the replacement of the piperazine ring with 2,3-dialkylpiperazine or 1,2-cyclohexanediamine moieties to characterize a lipophilic binding pocket in the α1 adrenoreceptor surface.Cyclohexanediamine derivatives 3-6 were almost devoid of potency and selectivity, whereas dialkylpiperazine compounds 7-14 showed high affinity and selectivity toward α1-adrenoreceptors.The cis derivative 13 (cyclazosin) was the most potent and selective with an α1/α2 selectivity ratio value of 7800.The particular trend of antagonist activity within cis/trans stereoisomeric compounds not only supports the presence of a lipophilic binding area on α1-adrenoreceptor surface but also suggests that the lipophilic pocket is endowed with a well-defined size and spatial orientation.The most active compound of the series, 13, was tested also in vivo for antihypertensive activity on spontaneously hypertensive rats.It showed an interesting long-lasting hypotensive effect, very similar to that of doxazosin, which was statistically significant 12 h after oral administration.
New 4-Acyl-1-phenylaminocarbonyl-2-phenylpiperazine Derivatives as Potential Inhibitors of Adenovirus Infection. Synthesis, Biological Evaluation, and Structure-activity Relationships
Sánchez-Céspedes, Javier,Martínez-Aguado, Pablo,Vega-Holm, Margarita,Serna-Gallego, Ana,Candela, José Ignacio,Marrugal-Lorenzo, José Antonio,Pachón, Jerónimo,Iglesias-Guerra, Fernando,Vega-Pérez, José Manuel
, p. 5432 - 5448 (2016)
The search for human adenovirus (HAdV)-specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients continues to be a challenging goal for medicinal chemistry. Here, we report the synthesis, biological evaluation, and struct
Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents
Blackmore, Timothy R.,Jacobson, Jonathan,Jarman, Kate E.,Lewin, Sharon R.,Nguyen, William,Purcell, Damian F.,Sabroux, Helene Jousset,Sleebs, Brad E.
, (2020/04/08)
A persistent latent reservoir of virus in CD4+ T cells is a major barrier to cure HIV. Activating viral transcription in latently infected cells using small molecules is one strategy being explored to eliminate latency. We previously described the use of a FlpIn.FM HEK293 cellular assay to identify and then optimize the 2-acylaminothiazole class to exhibit modest activation of HIV gene expression. Here, we implement two strategies to further improve the activation of viral gene expression and physicochemical properties of this class. Firstly, we explored rigidification of the central oxy-carbon linker with a variety of saturated heterocycles, and secondly, investigated bioisosteric replacement of the 2-acylaminothiazole moiety. The optimization process afforded lead compounds (74 and 91) from the 2-piperazinyl thiazolyl urea and the imidazopyridine class. The lead compounds from each class demonstrate potent activation of HIV gene expression in the FlpIn.FM HEK293 cellular assay (both with LTR EC50s of 80 nM) and in the Jurkat Latency 10.6 cell model (LTR EC50 220 and 320 nM respectively), but consequently activate gene expression non-specifically in the FlpIn.FM HEK293 cellular assay (CMV EC50 70 and 270 nM respectively) manifesting in cellular cytotoxicity. The lead compounds have potential for further development as novel latency reversing agents.
INHIBITORS OF WDR5 PROTEIN-PROTEIN BINDING
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Paragraph 00481, (2017/09/15)
The present application is directed to compounds of Formula I: compounds comprising these compounds and their uses, for example as medicaments for the treatment of diseases, disorders or conditions mediated or treatable by inhibition of binding between WDR5 protein and its binding partners.
