1218918-80-9Relevant academic research and scientific papers
CRTH2 antagonist MK-7246: A synthetic evolution from discovery through development
Molinaro, Carmela,Bulger, Paul G.,Lee, Ernest E.,Kosjek, Birgit,Lau, Stephen,Gauvreau, Danny,Howard, Melissa E.,Wallace, Debra J.,O'Shea, Paul D.
, p. 2299 - 2309 (2012/05/20)
In this paper, we report the development of different synthetic routes to MK-7246 (1) designed by the Process Chemistry group. The syntheses were initially designed as an enabling tool for Medicinal Chemistry colleagues in order to rapidly explore structure-activity relationships (SAR) and to procure the first milligrams of diverse target molecules for in vitro evaluation. The initial aziridine opening/cyclodehydration strategy was also directly amenable to the first GMP deliveries of MK-7246 (1), streamlining the transition from milligram to kilogram-scale production needed to support early preclinical and clinical evaluation of this compound. Subsequently a more scalable and cost-effective manufacturing route to MK-7246 (1) was engineered. Highlights of the manufacturing route include an Ir-catalyzed intramolecular N-H insertion of sulfoxonium ylide 41 and conversion of ketone 32 to amine 31 in a single step with excellent enantioselectivity through a transaminase process. Reactions such as these illustrate the enabling impact and efficiency gains that innovative developments in chemo- and biocatalysis can have on the synthesis of pharmaceutically relevant target molecules.
INDOLE DERIVATIVES AS CRTH2 RECEPTOR ANTAGONISTS
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Page/Page column 22, (2010/04/25)
The compound (+) {7R-[[(4-fluorophenyl)sulfonyl](methyl)ammo]-6,7,8,9-tetrahydropyrido[1,2-a]mdol-10-yl}acetic acid and pharmaceutically acceptable salts thereof are antagonists of the PGD2 receptor, CRTH2, and as such are useful in the treatment and/or prevention of CRTH2-meidated diseases such as asthma.
