Prodrugs of substituted ergolines

Abstract

A compound of formula (1) wherein X is selected from CO and SO2; Y is selected from a single chemical bond, O, S, and a C1-8 alkylene, C2-8 alkenylene, C2-4 alkynylene, or O-C1-6 alkylene radical, each of which alkylenes, alkenylenes, or alkynylenes may be optionally substituted with C1-3 alkyl or halogen; Z is selected from hydrogen, halogen, cyano, C1-3 trialkylsilyl, C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, C3-7 cycloalkyl, C4-7 cycloalkenyl, C1-12 alkoxy, C1-12 alkylthio, aryl, heterocyclyl, heteroaryl, metallocenyl, COOH, CO-C1-6 alkyl, CO-C3-7 cycloalkyl, O-CO-C1-6-alkyl, O-CO-C3-7-cycloalkyl, CO-C1-6-alkoxy or CO-C3-7-cycloalkoxy, wherein the alkyl, alkoxy, alkylthio, cycloalkyl, cycloalkoxy, aryl, heterocyclyl, heteroaryl or metallocenyl may each be optionally substituted with C1-5-alkyl, C1-4-alkoxy, C3-6-cycloalkyl, C1-3-haloalkyl, halogen, nitro, amino, hydroxy, oxo, COOH and CONH2;R2 is selected from hydrogen, C1-3 alkyl, C3-5 cycloalkyl, oxetane, C1-3 haloalkyl, C1-3 alkylthio, halogen, cyano, COOH, and CONH2; R6 is selected from C1-4 alkyl, C3-5 cycloalkyl, C2-4 alkenyl, C2-4 alkynyl, cyano, and oxetane; Ra and Rb are each independently selected from hydrogen, C1-6 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-7 cycloalkyl, C2-4 haloalkyl, 2-methoxyethyl, and 2-ethoxyethyl; or Ra and Rb together with the adjacent nitrogen atom form a three- to seven-membered heterocyclic ring, which heterocyclic ring may be optionally substituted with C1-3 alkyl or halogen; andis a single or double bond or a cyclopropyl ring;with the proviso that compounds of formula (1) having a linear C1-5 acyl group, a valeroyl group, or a cyclopropylcarbonyl group as -XYZ are excluded; or a pharmaceutically acceptable salt thereof.;