70125-17-6Relevant articles and documents
Chelation-assisted de-aryloxylative amination of 2-aryloxy quinolines: A new synthetic route to a key fragment of a bioactive PRMT5 inhibitor
Gupta, Aniket,Kumar, Jogendra,Bhadra, Sukalyan
, p. 3716 - 3720 (2018/05/31)
A highly regioselective de-aryloxylative amination of O- or N-chelating group-functionalized 2-aryloxy quinolines has been accomplished by means of a copper catalyst. The chelating functional groups of the substrate play a crucial role in directing the C-
Novel vanilloid receptor-1 antagonists: 2. Structure-activity relationships of 4-oxopyrimidines leading to the selection of a clinical candidate
Doherty, Elizabeth M.,Fotsch, Christopher,Bannon, Anthony W.,Bo, Yunxin,Chen, Ning,Dominguez, Celia,Falsey, James,Gavva, Narender R.,Katon, Jodie,Nixey, Thomas,Ognyanov, Vassil I.,Pettus, Liping,Rzasa, Robert M.,Stec, Markian,Surapaneni, Sekhar,Tamir, Rami,Zhu, Jiawang,Treanor, James J. S.,Norman, Mark H.
, p. 3515 - 3527 (2008/02/08)
A series of novel 4-oxopyrimidine TRPV1 antagonists was evaluated in assays measuring the blockade of capsaicin or acid-induced influx of calcium into CHO cells expressing TRPV1. The investigation of the structure-activity relationships in the heterocyclic A-region revealed the optimum pharmacophoric elements required for activity in this series and resulted in the identification of subnanomolar TRPV1 antagonists. The most potent of these antagonists were thoroughly profiled in pharmacokinetic assays. Optimization of the heterocyclic A-region led to the design and synthesis of 23, a compound that potently blocked multiple modes of TRPV1 activation. Compound 23 was shown to be effective in a rodent "on-target" biochemical challenge model (capsaicin-induced flinch, ED50 = 0.33 mg/kg p.o.) and was antihyperalgesic in a model of inflammatory pain (CFA-induced thermal hyperalgesia, MED = 0.83 mg/kg, p.o.). Based on its in vivo efficacy and pharmacokinetic profile, compound 23 (N-{4-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl} -acetamide; AMG 517) was selected for further evaluation in human clinical trials.
Certain aryl-aliphatic and heteroaryl-aliphatic piperazinyl pyrazines and their use in the treatment of serotonin-related diseases
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, (2008/06/13)
Compounds of the general formula (I): wherein the variables are as defined in the specification are useful for the prophylaxis or treatment of serotonin-related, especially 5-HT2receptor-related, diseases in human beings or animals, particularly diseases related to the 5-HT2creceptor, especially diseases such as eating disorders, memory disorders, schizophrenia, mood disorders, anxiety disorders, pain, sexual dysfunctionions, and urinary disorders.