Design, synthesis and biological activity of a targeted library of potential tryptase inhibitors.
We have designed, synthesized, and tested two small collections of potential tryptase inhibitors. The first library consists of diversely N-substituted 3-aminopiperidin-2-ones 6, and the second (compounds 7) was prepared by dimerising compounds 6 through the 3-amino function using diverse carbon chains. We have established efficient routes for obtaining 6 both in solution and on solid supports. We have also compared the dimerisation on-resin and in solution. Four of the compounds showed a high degree of tryptase inhibition at 1 microM, but none surpassed the tryptase inhibition activity of BABIM.
García
Mónica
M
Laboratori de Química Orgànica, Facultat de Farmàcia, Universitat de Barcelona, Spain.
del Rio
Xavier
X
Silvestre
Sandra
S
Rubiralta
Mario
M
Lozoya
Estrella
E
Segarra
Victor
V
Fernández
Dolors
D
Miralpeix
Montserrat
M
Aparici
Mònica
M
Diez
Anna
A
D019281:Dimerization; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D010881:Piperidones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D053802:Tryptases
C016997:3-aminopiperidine-2-one; D010881:Piperidones; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D053802:Tryptases