Trisubstituted ureas as potent and selective mPGES-1 inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 5, 2011, Pages 1488-1492

  Chiasson, Jean Franois ^a   Boulet, Louise ^a   Brideau, Christine ^a   Chau, Anh ^a   Claveau, David ^a   Côté, Bernard ^a   Ethier, Diane ^a   Giroux, André ^a   Guay, Jocelyne ^a   Guiral, Sébastien ^a   Mancini, Joseph ^a   Massé, Frédéric ^a   Méthot, Nathalie ^a   Riendeau, Denis ^a   Roy, Patrick ^a   Rubin, Joel ^a   Xu, Daigen ^a   Yu, Hongping ^a   Ducharme, Yves ^a   Friesen, Richard W ^a  

^a MERCK FROSST CENTRE FOR THERAPEUTIC RESEARCH   (Canada)

Author keywords

Inflammation; mPGES 1; PGE synthase; Prostaglandins; Trisubstituted urea

Indexed keywords

PROSTAGLANDIN E SYNTHASE 1; PROSTAGLANDIN SYNTHASE; PROSTAGLANDIN SYNTHASE INHIBITOR; THROMBOXANE SYNTHASE; UREA DERIVATIVE;

AMINATION; ARTICLE; CELL ASSAY; CONTROLLED STUDY; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; HUMAN; IC 50; ONE POT SYNTHESIS; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

CELL LINE, TUMOR; HUMANS; INTRAMOLECULAR OXIDOREDUCTASES; MICROSOMES; STRUCTURE-ACTIVITY RELATIONSHIP; UREA;

EID: 79951726462     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.01.006     Document Type: Article

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17. Typical procedure: To a stirred solution of the amine (1.0 equiv) and the aldehyde (1.0 equiv) in dichloroethane (0.2 M) was added acetic acid (5.0 equiv). The solution was stirred for 18 h, then sodium triacetoxyborohydride (1.2 equiv) was added and the mixture was stirred for 1 h. The appropriate isocyanate (1.5 equiv) was added and the mixture was stirred for an additional 4 h before being quenched with a saturated aqueous solution of sodium bicarbonate. The layers were separated and the aqueous layer was extracted three times with dichloromethane. The organic layers were combined and dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude was purified on silica gel.