- INHIBITOR COMPOUNDS
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The disclosure relates to heterocyclic compounds and methods for their preparation. The disclosure provides compounds that may have beneficial therapeutic activity in the treatment of a disease or condition mediated by excessive or otherwise undesirable Des1 and/or fibrotic activity.
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Page/Page column 63; 220
(2021/01/29)
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- 5,6-Dihydroxypyrimidine Scaffold to Target HIV-1 Nucleocapsid Protein
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The HIV-1 nucleocapsid (NC) protein is a small basic DNA and RNA binding protein that is absolutely necessary for viral replication and thus represents a target of great interest to develop new anti-HIV agents. Moreover, the highly conserved sequence offers the opportunity to escape the drug resistance (DR) that emerged following the highly active antiretroviral therapy (HAART) treatment. On the basis of our previous research, nordihydroguaiaretic acid 1 acts as a NC inhibitor showing moderate antiviral activity and suboptimal drug-like properties due to the presence of the catechol moieties. A bioisosteric catechol replacement approach led us to identify the 5-dihydroxypyrimidine-6-carboxamide substructure as a privileged scaffold of a new class of HIV-1 NC inhibitors. Hit validation efforts led to the identification of optimized analogs, as represented by compound 28, showing improved NC inhibition and antiviral activity as well as good ADME and PK properties.
- Malancona, Savina,Mori, Mattia,Fezzardi, Paola,Santoriello, Marisabella,Basta, Andreina,Nibbio, Martina,Kovalenko, Lesia,Speziale, Roberto,Battista, Maria Rosaria,Cellucci, Antonella,Gennari, Nadia,Monteagudo, Edith,Di Marco, Annalise,Giannini, Alessia,Sharma, Rajhans,Pires, Manuel,Real, Eleonore,Zazzi, Maurizio,Dasso Lang, Maria Chiara,De Forni, Davide,Saladini, Francesco,Mely, Yves,Summa, Vincenzo,Harper, Steven,Botta, Maurizio
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supporting information
p. 766 - 772
(2020/07/14)
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- Substituted 3-aryl-5-aryl-[1,2,4]-oxadiazoles and analogs as activators of caspases and inducers of apoptosis and the use thereof
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The present invention is directed to substituted 3-aryl-5-aryl-[1,2,4]-oxadiazoles and analogs thereof, represented by the Formula I: wherein Ar1, Ar3, A, B and D are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
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- N-phenylcarbamate compound, process for preparing the sasme and biocidal composition for control of harmful organisms
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A novel N-phenylcarbamate compound or its salt where possible, which is useful as the active ingredient of a biocidal composition for control of harmful organisms, is represented by the following general formula (I): STR1 wherein R1 is unsubsti
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