3-Methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester: an exploration of the C-2 position. Part I.
Following the recent disclosure of 3-methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester, a potent and selective mGluR1 non-competitive antagonist, we report here a detailed exploration of the C-2 position of this scaffold with the preparation of differently substituted amides. Great improvement of the pharmacokinetic properties has been achieved through this exercise.
Micheli
Fabrizio
F
GlaxoSmithKline Medicine Research Centre, via Fleming 4, Verona 37135, Italy. fabrizio.e.micheli@gsk.com
Di Fabio
Romano
R
Benedetti
Roberto
R
Capelli
Anna Maria
AM
Cavallini
Palmina
P
Cavanni
Paolo
P
Davalli
Silvia
S
Donati
Daniele
D
Feriani
Aldo
A
Gehanne
Sylvie
S
Hamdan
Mahmoud
M
Maffeis
Micaela
M
Sabbatini
Fabio Maria
FM
Tranquillini
Maria Elvira
ME
Viziano
Monica Valeria Angela
MV
D000577:Amides / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000818:Animals; D001386:Azides / Q000138:chemical synthesis / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004952:Esters / Q000138:chemical synthesis* / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000493:pharmacokinetics; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008968:Molecular Conformation; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
C485660:3-methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester; D000577:Amides; D001386:Azides; D004952:Esters; D006877:Hydroxamic Acids; D007202:Indicators and Reagents; D011758:Pyrroles; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1