7 research outputs found
Deoxycyanamidation of alcohols with N-Cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS)
The first one-pot deoxycyanamidation of alcohols has been developed using N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS) as both a sulfonyl transfer reagent and a cyanamide source, accessing a diverse range of tertiary cyanamides in excellent isolated yields. This approach exploits the underdeveloped desulfonylative (NâS bond cleavage) reactivity pathway of NCTS, which is more commonly employed for electrophilic C- and N-cyanation processes
Conception, synthĂšse et Ă©valuation dâagents perturbateurs vasculaires pour le traitement de lâarthrose et des douleurs arthrosiques
Osteoarthritis is a chronic disease leading to the progressive deterioration of joint cartilage. This irreversible degradation causes pain and mobility issues. More than 60% of French people over 65 are affected by this disease, which represents 10% of the global population. Current treatments focus on reducing pain, but none can stop the progression of arthritis. An innovative strategy proposes to target osteochondral angiogenesis. Pathological vascularization process in the joints plays an important role in cartilage deterioration. We designed and synthesized several molecular hybrids by combining the pharmacophores of various known vascular disrupting agents such as combretastatin A-4, phenstatin or E7010. The antivascular activity of these « hybrids » was finally evaluated in vitro. Some have shown promising results.Lâarthrose est une maladie chronique des articulations se manifestant par lâaltĂ©ration progressive du cartilage articulaire. Cette dĂ©gradation irrĂ©versible engendre chez le patient des douleurs aiguĂ«s voire chroniques, ainsi quâune difficultĂ© Ă se dĂ©placer. Plus de 60% des Français de plus de 65 ans sont concernĂ©s par cette maladie, soit 10% de la population. Les traitements actuels consistent essentiellement Ă rĂ©duire la douleur du patient, mais aucun ne permet dâinhiber ou dâenrayer la progression de la maladie. Une stratĂ©gie innovante, actuellement en dĂ©veloppement, propose de cibler lâangiogenĂšse ostĂ©ochondrale. En effet, il a Ă©tĂ© dĂ©montrĂ© que ce processus de vascularisation, indĂ©sirable au niveau des articulations, jouait un rĂŽle important dans la dĂ©gradation du cartilage. Nous avons conçu et synthĂ©tisĂ© diffĂ©rents hybrides molĂ©culaires, dont les structures combinent les pharmacophores de divers agents perturbateurs vasculaires issus de la littĂ©rature telles que la combretastatine A-4, la phenstatine, ou encore E7010. LâactivitĂ© antivasculaire de ces molĂ©cules « hybrides » a finalement Ă©tĂ© Ă©valuĂ©e in vitro. Certaines prĂ©sentent des rĂ©sultats prometteurs
Design, synthesis and evaluation of vascular disrupting agents for the treatment of osteoarthritis and arthritis pain
Lâarthrose est une maladie chronique des articulations se manifestant par lâaltĂ©ration progressive du cartilage articulaire. Cette dĂ©gradation irrĂ©versible engendre chez le patient des douleurs aiguĂ«s voire chroniques, ainsi quâune difficultĂ© Ă se dĂ©placer. Plus de 60% des Français de plus de 65 ans sont concernĂ©s par cette maladie, soit 10% de la population. Les traitements actuels consistent essentiellement Ă rĂ©duire la douleur du patient, mais aucun ne permet dâinhiber ou dâenrayer la progression de la maladie. Une stratĂ©gie innovante, actuellement en dĂ©veloppement, propose de cibler lâangiogenĂšse ostĂ©ochondrale. En effet, il a Ă©tĂ© dĂ©montrĂ© que ce processus de vascularisation, indĂ©sirable au niveau des articulations, jouait un rĂŽle important dans la dĂ©gradation du cartilage. Nous avons conçu et synthĂ©tisĂ© diffĂ©rents hybrides molĂ©culaires, dont les structures combinent les pharmacophores de divers agents perturbateurs vasculaires issus de la littĂ©rature telles que la combretastatine A-4, la phenstatine, ou encore E7010. LâactivitĂ© antivasculaire de ces molĂ©cules « hybrides » a finalement Ă©tĂ© Ă©valuĂ©e in vitro. Certaines prĂ©sentent des rĂ©sultats prometteurs.Osteoarthritis is a chronic disease leading to the progressive deterioration of joint cartilage. This irreversible degradation causes pain and mobility issues. More than 60% of French people over 65 are affected by this disease, which represents 10% of the global population. Current treatments focus on reducing pain, but none can stop the progression of arthritis. An innovative strategy proposes to target osteochondral angiogenesis. Pathological vascularization process in the joints plays an important role in cartilage deterioration. We designed and synthesized several molecular hybrids by combining the pharmacophores of various known vascular disrupting agents such as combretastatin A-4, phenstatin or E7010. The antivascular activity of these « hybrids » was finally evaluated in vitro. Some have shown promising results
Conception, synthĂšse et Ă©valuation dâagents perturbateurs vasculaires pour le traitement de lâarthrose et des douleurs arthrosiques
Osteoarthritis is a chronic disease leading to the progressive deterioration of joint cartilage. This irreversible degradation causes pain and mobility issues. More than 60% of French people over 65 are affected by this disease, which represents 10% of the global population. Current treatments focus on reducing pain, but none can stop the progression of arthritis. An innovative strategy proposes to target osteochondral angiogenesis. Pathological vascularization process in the joints plays an important role in cartilage deterioration. We designed and synthesized several molecular hybrids by combining the pharmacophores of various known vascular disrupting agents such as combretastatin A-4, phenstatin or E7010. The antivascular activity of these « hybrids » was finally evaluated in vitro. Some have shown promising results.Lâarthrose est une maladie chronique des articulations se manifestant par lâaltĂ©ration progressive du cartilage articulaire. Cette dĂ©gradation irrĂ©versible engendre chez le patient des douleurs aiguĂ«s voire chroniques, ainsi quâune difficultĂ© Ă se dĂ©placer. Plus de 60% des Français de plus de 65 ans sont concernĂ©s par cette maladie, soit 10% de la population. Les traitements actuels consistent essentiellement Ă rĂ©duire la douleur du patient, mais aucun ne permet dâinhiber ou dâenrayer la progression de la maladie. Une stratĂ©gie innovante, actuellement en dĂ©veloppement, propose de cibler lâangiogenĂšse ostĂ©ochondrale. En effet, il a Ă©tĂ© dĂ©montrĂ© que ce processus de vascularisation, indĂ©sirable au niveau des articulations, jouait un rĂŽle important dans la dĂ©gradation du cartilage. Nous avons conçu et synthĂ©tisĂ© diffĂ©rents hybrides molĂ©culaires, dont les structures combinent les pharmacophores de divers agents perturbateurs vasculaires issus de la littĂ©rature telles que la combretastatine A-4, la phenstatine, ou encore E7010. LâactivitĂ© antivasculaire de ces molĂ©cules « hybrides » a finalement Ă©tĂ© Ă©valuĂ©e in vitro. Certaines prĂ©sentent des rĂ©sultats prometteurs
Design, synthesis and biological evaluation of conformationnally-restricted analogues of E7010 as inhibitors of tubulin assembly (ITA) and vascular disrupting agents (VDA)
Vascular-disrupting agents (VDA) specifically target established neovasculature which results in vascular shutdown. This therapeutic strategy could improve the outcome of pathologies involving aberrant angiogenesis. Although several classes of VDA exist, inhibitors of tubulin assembly (ITA) represent the main category. A series of 21 conformationnally-restricted analogues of E7010, a known ITA-VDA, were designed and synthesised as novel inhibitors of tubulin assembly (ITA) and vascular-disrupting agents (VDA). Among them, indole 4j exhibited good potency against HUVEC and HIG-82 cell lines, as well as a good ability to inhibit tubulin assembly. Furthermore, indole 4j reduced HUVEC migration in a dose-dependent manner, indicating a vascular disrupting activity comparable to that of the gold standard, Combretastatin A4 (CA4)
Deoxycyanamidation of Alcohols with <i>N</i>âCyanoâ<i>N</i>âphenyl-<i>p</i>-methylbenzenesulfonamide (NCTS)
The first one-pot
deoxycyanamidation of alcohols has been developed
using <i>N</i>-cyano-<i>N</i>-phenyl-<i>p</i>-methylÂbenzeneÂsulfonamide (NCTS) as both a sulfonyl transfer
reagent and a cyanamide source, accessing a diverse range of tertiary
cyanamides in excellent isolated yields. This approach exploits the
underdeveloped desulfonylative (NâS bond cleavage) reactivity
pathway of NCTS, which is more commonly employed for electrophilic <i>C</i>- and <i>N</i>-cyanation processes