111157-50-7Relevant articles and documents
Discovery and Lead-Optimization of 4,5-Dihydropyrazoles as Mono-Kinase Selective, Orally Bioavailable and Efficacious Inhibitors of Receptor Interacting Protein 1 (RIP1) Kinase
Harris, Philip A.,Faucher, Nicolas,George, Nicolas,Eidam, Patrick M.,King, Bryan W.,White, Gemma V.,Anderson, Niall A.,Bandyopadhyay, Deepak,Beal, Allison M.,Beneton, Veronique,Berger, Scott B.,Campobasso, Nino,Campos, Sebastien,Capriotti, Carol A.,Cox, Julie A.,Daugan, Alain,Donche, Frederic,Fouchet, Marie-Hélène,Finger, Joshua N.,Geddes, Brad,Gough, Peter J.,Grondin, Pascal,Hoffman, Bonnie L.,Hoffman, Sandra J.,Hutchinson, Susan E.,Jeong, Jae U.,Jigorel, Emilie,Lamoureux, Pauline,Leister, Lara K.,Lich, John D.,Mahajan, Mukesh K.,Meslamani, Jamel,Mosley, Julie E.,Nagilla, Rakesh,Nassau, Pamela M.,Ng, Sze-Ling,Ouellette, Michael T.,Pasikanti, Kishore K.,Potvain, Florent,Reilly, Michael A.,Rivera, Elizabeth J.,Sautet, Stéphane,Schaeffer, Michelle C.,Sehon, Clark A.,Sun, Helen,Thorpe, James H.,Totoritis, Rachel D.,Ward, Paris,Wellaway, Natalie,Wisnoski, David D.,Woolven, James M.,Bertin, John,Marquis, Robert W.
, p. 5096 - 5110 (2019)
RIP1 kinase regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including inflammatory and neurological diseases. Currently, RIP1 kinase inhibitors have advanced into early clinical trials for evaluation in inflammatory diseases such as psoriasis, rheumatoid arthritis, and ulcerative colitis and neurological diseases such as amyotrophic lateral sclerosis and Alzheimer's disease. In this paper, we report on the design of potent and highly selective dihydropyrazole (DHP) RIP1 kinase inhibitors starting from a high-throughput screen and the lead-optimization of this series from a lead with minimal rat oral exposure to the identification of dihydropyrazole 77 with good pharmacokinetic profiles in multiple species. Additionally, we identified a potent murine RIP1 kinase inhibitor 76 as a valuable in vivo tool molecule suitable for evaluating the role of RIP1 kinase in chronic models of disease. DHP 76 showed efficacy in mouse models of both multiple sclerosis and human retinitis pigmentosa.
Meta-substituted aryl(thio)ethers as potent partial agonists (or antagonists) for the histamine H3 receptor lacking a nitrogen atom in the side chain
Pelloux-Léon, Nadia,Fkyerat, Abdellatif,Piripitsi, Antonia,Tertiuk, Wasyl,Schunack, Walter,Stark, Holger,Garbarg, Monique,Ligneau, Xavier,Arrang, Jean-Michel,Schwartz, Jean-Charles,Ganellin, C. Robin
, p. 3264 - 3274 (2007/10/03)
4-(3-Aryloxypropyl)-1H-imidazoles, which possess a meta-positioned substituent in the aryl ring, have been synthesized and tested for activity at histamine H3 receptors. The compounds having a CN, Me, or Br substituent were found to be antagoni
SELECTIVE N-ALKYLATION OF (E)-UROCANIC ACID
Lauth- Viguerie, Nancy de,Sergueeva, Natalia,Damiot, Monique,Mawlawi, Hiba,Riviere, Monique,Lattes, Armand
, p. 1561 - 1578 (2007/10/02)
Various methods of selective alkylation of the N(τ)- and N(?)-nitrogen atoms of the (E)-urocanic acid derivatives are reported.Solid-liquid phase transfer catalysis gave the best results for N(τ)-alkylation of urocanic acid alkyl esters.Liquid-liquid phase transfer catalysis allowed direct N(τ)-akylation of urocanic acid itself.The N(?)-nitrogen atom was alkylated after protection of the N(τ)-nitrogen with a phenacyl group.
