[EN] AMIDOPYRAZOLE INHIBITORS OF INTERLEUKIN RECEPTOR-ASSOCIATED KINASES<br/>[FR] INHIBITEURS DE KINASES ASSOCIÉES AUX RÉCEPTEURS D'INTERLEUKINE À BASE D'AMIDOPYRAZOLE
申请人:MERCK SHARP & DOHME
公开号:WO2012129258A1
公开(公告)日:2012-09-27
This invention relates to amidopyrazole compounds that are inhibitors of Interleukin receptor-associated kinases, in particular IRAK-4, and are useful in the treatment of cellular proliferative diseases, for example, cancer, hyperplasia, restenosis, cardiac hypertrophy, immune disorders and inflammation.
A facile synthesis of 3<i>H</i>-indolium perchlorates by one-pot hydrazone formation/fischer indolization
作者:Thomas Zimmermann
DOI:10.1002/jhet.5570370626
日期:2000.11
α-branched ketones 2 and perchloric acid react in boiling ethanol to give via the in situ formed hydrazones 3 1,2,3,3-tetrasubstituted 3H-indoliumperchlorates 4. The scope and limitations of this facilesynthesis of 3H-indolium derivatives which combines the hydrazoneformation and the Fischerindolization to an one-pot procedure are discussed.
A diversity-oriented approach to indolocarbazoles via Fischer indolization and olefin metathesis: total synthesis of tjipanazole D and I
作者:Sambasivarao Kotha、Mohammad Saifuddin、Vikas R. Aswar
DOI:10.1039/c6ob01679k
日期:——
Starting with cyclohexanone, a bench-top starting material, this methodology has been extended to the total synthesis of natural products such as tjipanazoles D and I as well as the core structure of asteropusazole and racemosin B. Here, atom economical reactions like ring-closing metathesis, enyne-metathesis, and the Diels–Alder reaction have been used as key steps. Diverse strategies demonstrated
displayed moderate binding affinity and selectivity at the μ receptor, with compound 7b showing the highest affinity at this receptor with a Ki value of 40 nM, and 6- and 25-fold selectivity against δ and κ receptors, respectively. Function assays showed that indolopropellanes 7b and 7c possessed full agonistic activity at all the opioidreceptors indicating a different interaction model existed.