Discovery, SAR study and ADME properties of methyl 4-amino-3-cyano-1-(2-benzyloxyphenyl)-1H-pyrazole-5-carboxylate as an HIV-1 replication inhibitor
Inspired by the antiviral activity of known pyrazole-based HIV inhibitors, we screened our in-house library of pyrazole-based compounds to evaluate theirin celluloactivity against HIV-1 replication. Two hits with very similar structures appeared from single and multiple-round infection assays to be non-toxic and active in a dose-dependent manner. Chemical expansion of their series allowed an in-depth and consistent structure-activity-relationship study (SAR) to be built. Further ADME evaluation led to the selection of 4-amino-3-cyano-1-(2-benzyloxyphenyl)-1H-pyrazole-5-carboxylate with an advantageous pharmacokinetic profile. Finally, examination of its mode of action revealed that this compound does not belong to the three main classes of anti-HIV drugs, a feature of prime interest in the context of viral resistance.
Synthesis of Multifunctionalized 2-Iminothiazolidin-4-ones and Their 2-Arylimino Derivatives
-
Le Corre, Laurent,Dasso Lang, Maria Chiara,Garbay, Christiane,Gravier-Pelletier, Christine,Busca, Patricia,Ethève-Quelquejeu, Mélanie,Braud, Emmanuelle
p. 4569 - 4579
(2016/12/14)
Microwave-assisted preparation of 4-amino-3-cyano-5-methoxycarbonyl-N-arylpyrazoles as building blocks for the diversity-oriented synthesis of pyrazole-based polycyclic scaffolds
The synthesis of 4-amino-3-cyano-N-arylpyrazoles A based on a Thorpe-Ziegler cyclization as the key step has been achieved using microwave activation. Via a new diversity-oriented synthetic pathway, these highly functionalized building blocks allowed the access to various heteroaromatic scaffolds such as pyrazolo-pyridines B, pyrazolo-pyrimidines C and pyrazolo-oxadiazoles D. Interestingly, these platforms contain three to four reactive sites that could be used for post-functionalization in order to further increase the molecular diversity.
Improved protocol for Thorpe reaction: Synthesis of 4-amino-1-arylpyrazole using solid-liquid phase-transfer conditions
Solid-liquid phase-transfer conditions were employed for the first time in the Thorpe reaction to synthesize 4-amino-1-aryl-3,5-substituted-1H-pyrazoles 3. Aryl amines were diazotized and coupled with various active methylene compounds such as cyano aceta
Desai, Nirmal D.,Shah, Rina D.
p. 316 - 327
(2008/09/16)
Synthesis of novel derivatives of 4-amino-3,5-dicyanopyrazole
Diazotisation of substituted arylamines followed by reaction with malononitrile gave substituted arylazomalononitriles. Cyclisation of these intermediates with chloroacetonitrile and triethylamine, as base, gave the corresponding new aminoclicyanopyrazoles, in 22-80% yields.
Goncalves, M. Sameiro T.,Oliveira-Campos, Ana M.F.,Rodrigues, Ligia M.,Proenca, M. Fernanda R.P.,Griffiths, John,Maia, Hernani L.S.,Kaja, Martin,Hrdina, Radim
p. 115 - 117
(2007/10/03)
More Articles about upstream products of 191353-20-5