33081-07-1Relevant academic research and scientific papers
Discovery and SAR of 6-alkyl-2,4-diaminopyrimidines as histamine H 4 receptor antagonists
Savall, Brad M.,Chavez, Frank,Tays, Kevin,Dunford, Paul J.,Cowden, Jeffery M.,Hack, Michael D.,Wolin, Ronald L.,Thurmond, Robin L.,Edwards, James P.
, p. 2429 - 2439 (2014/04/17)
This report discloses the discovery and SAR of a series of 6-alkyl-2-aminopyrimidine derived histamine H4 antagonists that led to the development of JNJ 39758979, which has been studied in phase II clinical trials in asthma and atopic dermatitis. Building on our SAR studies of saturated derivatives from the indole carboxamide series, typified by JNJ 7777120, and incorporating knowledge from the tricyclic pyrimidines led us to the 6-alkyl-2,4-diaminopyrimidine series. A focused medicinal chemistry effort delivered several 6-alkyl-2,4-diaminopyrimidines that behaved as antagonists at both the human and rodent H4 receptor. Further optimization led to a panel of antagonists that were profiled in animal models of inflammatory disease. On the basis of the preclinical profile and efficacy in several animal models, JNJ 39758979 was selected as a clinical candidate; however, further development was halted during phase II because of the observation of drug-induced agranulocytosis (DIAG) in two subjects.
Easy and efficient copper-catalyzed synthesis of bicyclic pyrimidinones under mild conditions
Guo, Qi,Yang, Haijun,Liu, Hongxia,Jiang, Yuyang,Fu, Hua
experimental part, p. 2611 - 2616 (2010/11/24)
A simple and efficient copper-catalyzed method has been developed for synthesis of bicyclic pyrimidinones containing six-, seven-, eight-membered rings under mild conditions. The protocol uses readily available 2-bromocycloalk-1-enecarboxylic acids, amidines, and guanidines as the starting materials, copper-catalyzed cascade couplings provide the corresponding bicyclic pyrimidinones without addition of any ligand or additive, and the method is of economical and practical advantages. Georg Thieme Verlag Stuttgart New York.
Bicyclic pyrimidine compounds and therapeutic use thereof
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, (2008/06/13)
A pyrimidine derivative of the formula (1) or a salt thereof; has an inhibitory activity of production of Th2 type cytokines such as IL-4, IL-5, etc., and is useful as an therapeutic agent for allergic diseases, autoimmune diseases such as systemic lupus erythemathosus, etc., and acquired immunodeficiecy syndrome (AIDS) and so on.
Composition intended for use for retarding hair loss and for inducing and stimulating its growth, containing 2-aminopyrimidine 3-oxide derivatives, and new compounds derived from 2-aminopyrimidine 3-oxide
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, (2008/06/13)
Composition for retarding hair loss and for inducing and stimulating its growth, containing at least one compound of formula: STR1 where R denotes H, alkyl or a ring of formula: STR2 X denotes STR3 --OR3, --SR4 with: the remaining va
Nonclassical 5-substituted tetrahydroquinazolines as potential inhibitors of thymidylate synthase
Gangjee, Aleem,Vasudevan, Anil,Kisliuk, Roy L.
, p. 1669 - 1676 (2007/10/03)
Classical inhibitors of thymidylate synthase such as N10-propargyl- 5,8-dideazafolic acid (1), N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6- ylmethyl)-N-methylamino]-2-thenoyl)-L-glutamic acid (ZD1694, 2) and N-[2- amino-4-oxo-3,4-dihydro(py
