Derivatives of 2,3-dihydro-1H-inden-1-yl-2,7-diazaspiro 3.6 nonane and its use as antagonists or inverse agonists of the ghrelin receptor

摘要

A compound of formula (I) ** Formula ** in which: R1 is -L1-R1, phenyl or a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently selected from N, O or S, wherein said phenyl or said 5- to 6-membered heteroaryl is optionally fused to a cycloalkyl (C4-C7), cycloalkenyl (C5-C6), phenyl, saturated or partially unsaturated 5- to 6-membered heterocyclyl containing 1 to 4 heteroatoms each independently selected from N, O or S, or a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently selected from N, O, or S, wherein said phenyl optionally condensed and said 5 to 6 membered heteroaryl optionally condensed is optionally substituted with 1 to 3 substituents selected from halo, hydroxy, oxo, cyano, (C1-C3) alkyl, halogen substituted (C1-C3) alkyl, alkoxy ( C1-C3), halogen-substituted (C1-C3) alkoxy, (C1-C3) -S (O) n-, c icloalkyl (C3-C6), cycloalkoxy (C3-C6), alkyl- (C0-C3) NRXRY, alkyl- (C0-C3) NRXC (O) RY, and alkyl- (C0-C3) C (O) NRXRY; R1 'is phenyl or a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently selected from N, O or S, wherein said phenyl or said 5- to 6-membered heteroaryl is optionally fused to a cycloalkyl (C4-C7), cycloalkenyl (C5-C6), phenyl, 5- or 6-membered saturated or partially unsaturated heterocyclyl containing 1 to 4 heteroatoms each independently selected from N, O or S, or a heteroaryl of 5 to 6 members containing 1 to 4 heteroatoms each independently selected from N, O, or S, wherein said optionally condensed phenyl and said optionally condensed 5 to 6 member heteroaryl is optionally substituted with 1 to 3 substituents selected from halo, hydroxy, oxo, cyano, (C1-C3) alkyl, halogen substituted (C1-C3) alkyl, (C1-C3) alkoxy, halogen substituted (C1-C3) alkoxy, (C1-C3) alkyl ) -S (O) n, (C3-C6) cycloalkyl, (C3-C6) cycloalkoxy, alkyl- (C0-C3) NR XRY, alkyl- (C0-C3) NRXC (O) RY, and alkyl- (C0-C3) C (O) NRXRY; L1 is O, S, NH, N (C1-C3 alkyl) or (C1-C3) alkylene; Ra each time it appears it is independently selected from hydrogen, (C1-C3) alkyl and halogen; Z, Z1 and Z2 are each independently N or CH optionally substituted with halo, (C1-C3) alkoxy or (C1-C3) alkyl; L is a direct bond, O, S, NH, N (C1-C3 alkyl) or (C1-C3) alkylene; R2 is hydrogen, halo, cyano, (C1-C6) alkyl, (C3-C6) cycloalkyl, phenyl, 5- or 6-membered saturated or partially unsaturated heterocyclyl containing from 1 to 4 heteroatoms each independently selected from N, O or S, or 5 to 6 membered heteroaryl containing 1 to 4 heteroatoms each independently selected from N, O, or S, wherein said (C1-C6) alkyl, (C3-C6) cycloalkyl, saturated or partially unsaturated 5 to 6 membered phenyl, heterocyclyl or saturated or unsaturated 5 to 6 membered heteroaryl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, (C1-) alkyl C3), (C1-C3) alkyl substituted with halo, (C1-C3) alkoxy, (C1-C3) alkoxy substituted with halo, (C1-C3) -S (O) n, cycloalkyl (C3-C6) alkyl, (C3-C6) cycloalkoxy, (C0-C3) NRxRY alkyl, (C0-C3) NRxC (O) RY alkyl and (C0-C3) C (O) NRxRY alkyl, with the proviso that when L is O, N , S, NH or alkyl (C1-C3), R2 is not halo; n, each time it appears is, independently, 0, 1 or 2; and RX and RY each time they appear are independently selected from hydrogen and (C1-C6) alkyl, wherein said (C1-C6) alkyl is optionally interrupted by one or two groups independently selected from NH, N ( C1-C3 alkyl), O and S, and is optionally substituted with 1 to 4 halo; or Rx and Ry taken together are a (C2-C6) alkylene which is optionally interrupted with one or two groups independently selected from NH, N (C1-C3 alkyl) O and S;