IKK inhibitory activities of imidazo[1,2-a]pyrazine, imidazo[1,2-a]quinoxaline, imidazo[1,5-a]quinoxaline and pyrazolo[1,5-a]quinoxaline derivatives
| Autor: | Bou Karroum, Nour, Patinote, Cindy, Chouchou, Adrien, Moarbess, Georges, Diab-Assaf, Mona, Cuq, Pierre, Deleuze-Masquéfa, Carine, Kassab, Issam, Bonnet, Pierre-Antoine |
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| Přispěvatelé: | Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Lebanese University [Beirut] (LU), Société d’Accélération du Transfert de Technologies (SATT AxLR), CSU, 950 rue Saint Priest, 34090 Montpellier, France., SATTUniversité de MontpellierUniversité libanaise, Bou Karroum, Nour, Tumorigenèse et Pharmacologie Antitumorale, Lebanese University, EDST, BP 90656, Fanar Jdeideh, Lebanon |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
[CHIM.ORGA]Chemical Sciences/Organic chemistry
[CHIM.THER] Chemical Sciences/Medicinal Chemistry [SDV]Life Sciences [q-bio] [CHIM.THER]Chemical Sciences/Medicinal Chemistry [CHIM.ORGA] Chemical Sciences/Organic chemistry [SDV] Life Sciences [q-bio] [CHIM] Chemical Sciences [CHIM.CRIS]Chemical Sciences/Cristallography [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology [CHIM]Chemical Sciences [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [CHIM.CRIS] Chemical Sciences/Cristallography IKK inhibitory activities ComputingMilieux_MISCELLANEOUS |
| Zdroj: | 24ème journée des jeunes chercheurs en chimie thérapeutique 24ème journée des jeunes chercheurs en chimie thérapeutique, Feb 2017, Paris, France |
| Popis: | International audience; The transcription factor NF-κB plays a key role in multiple cellular processes, including immune signaling, inflammation, development, proliferation and survival. Dysregulated NF-κB activation is associated with autoimmunitya, chronic inflammationb and cancerc. Activation of NF-κB requires IκB kinases IKKα and IKK β, therefore, targeting the activation of NF-κB-dependent pathway by IKK inibitors is becoming an increasingly popular avenue for the development of novel therapeutic interventions for inflammation and cancer and many pharmaceutical companies are developing inhibitors that target IKK. BMS-345541 (4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline) was identified as a selective inhibitor of the catalytic subunits of IKK (IKK2: IC50= 0.3 μM, IKK1: IC50 = 4 μM)d. The aim of this study is to obtain new IKK inhibitors, analogues of BMS-345541. For this purpose, we have synthesized a variety of compounds diversely substituted belonging to four chemical series: imidazo[1,2-a]pyrazine, imidazo[1,2-a]quinoxaline, imidazo[1,5-a]quinoxaline and pyrazolo[1,5-a]quinoxaline. Their biological activities as potential IKK1 and IKK2 inhibitors are describede. Four strategies of synthesis are developed to obtain a variety of compounds with short reaction times by using micro-wave assistance. The preparation of these compounds is particularly simple and is carried out in good yields. |
| Databáze: | OpenAIRE |
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