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.
GlaxoSmithKline Medicine Research Centre, via Fleming 4, Verona 37135, Italy. fabrizio.e.micheli@gsk.com
Fabrizio
F
Micheli
Romano
R
Di Fabio
Roberto
R
Benedetti
Anna Maria
AM
Capelli
Palmina
P
Cavallini
Paolo
P
Cavanni
Silvia
S
Davalli
Daniele
D
Donati
Aldo
A
Feriani
Sylvie
S
Gehanne
Mahmoud
M
Hamdan
Micaela
M
Maffeis
Fabio Maria
FM
Sabbatini
Maria Elvira
ME
Tranquillini
Monica Valeria Angela
MV
Viziano
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