| 摘要 |
Compounds of Formula I which bind with high selectivity and/or affinity to CRF1 receptors (Corticotropin Releasing Factor type 1 Receptors) are described wherein: R1 is selected from H, C1-4alkyl, C2-4alkenyl, C2-4 alkynyl, halogen, trifluoromethyl, trifluoromethoxy, -NH(C1-4alkyl), - N(C1-4alkyl)(C1-4 alkyl), -O(C1-4alkyl), and S (O)n(C1-4alkyl); R2 is selected from -XRA and Y, wherein-X, RA, and Y are defined below; and with the proviso that R2 is not -NH2; R3 is selected from the group consisting of hydrogen, halogen, C1-4alkyl , -O(C1-4alkyl), NH(C1-4alkyl), -N(C1- 4alkyl)(C1-4alkyl), and-S (O)n(C1-4alkyl), haloalkyl, trifluoromethyl, trifluoromethoxy, -XRA and Y; R4 is absent or an oxygen atom; Ar is phenyl, mono-, di-, or tri-substituted with RC, or Ar is selected from naphthyl, pyridyl, pyridonyl, pyrimidinyl, and thiophenyl, each of which is unsubstituted or mono-, di-, or tri-substituted with RC; with the proviso that if Ar is phenyl substituted with halogen, napthyl, or naphthyl substituted with halogen, then the compounds where R3 is hydrogen are excluded; RA and RB which may be the same or different, are selected from hydrogen and straight, branched, or cyclic alkyl groups consisting of 1 to 8 carbon atoms, which may contain one or more double or triple bonds, each of which may be further substituted with one or more substituent(s) selected from oxo, hydroxy, halogen, -O(C1-4alkyl), -NH(C1-4alkyl), -N(C1- 4alkyl)(C1-4alkyl), -NHC(O)(C1-4alkyl), -N(C1-4alkyl)C(=O)(C1-4alkyl), -NHS(O)n(C1-4 alkyl), -S(O)n(C1-4alkyl), - S(O)nNH(C1-4alkyl), -S(O)nN(C1-4alkyl)(C1-4alkyl), and Z; RC is selected from halogen, cyano, haloalkyl, trifluoromethyl, trifluoromethoxy, hydroxy, amino, and C1-6alkyl optionally substituted with 0-2 RD, C2-6alkenyl substituted with 0-2 RD, C1-4alkynyl substituted with 0-2 RD, C3-7cycloalkyl substituted with 0-2RD, (C3-7cycloalkyl)C1-4 alkyl substituted with 0-2 RD, -O(C1-4alkyl) substituted with 0-2 RD, -NH (C1-4alkyl) substituted with 0-2 RD, -N(C1-4alkyl)(C1-4 alkyl) each independently substituted with 0-2 RD, -XRA, and Y; RD is selected from halogen, hydroxy, cyano, C1-4alkyl, -O(C1-4alkyl), -NH(C1-4alkyl), -N(C1-4alkyl)(C1-4alkyl), morpholino, pyrrolidino, piperidino, thiomorpholino, piperazino, 4 hydroxypiperidino, -S(O)n(C1-4alkyl), trifluoromethyl, trifluoromethoxy, CO(C1-4alkyl), CONH(C1-4alkyl), CON(C1-4alkyl)(C1-4alkyl), -XRA, and Y; X is from -CH2-, -CHRB-, -O-, -C(=O)-, -C(=O)O-, -S(O)n-, -NH-, -NRB-, -C(=O)NH-, -C(=O)NRB-, -S(O)nNH-, - S(O)nNRB-, -OC(=S)S-, -NHC(=O)-, -NRBC(=O)-, -NHS(O)n-, OSiH, (C1-4alkyl)2-n-, and -NRBS(O)n-; Y and Z are independently selected at each occurrence from the group consisting of : 3- to 7- membered carbocyclic and heterocyclic groups, which are saturated, unsaturated, or aromatic, which may be substituted with one or more substituents selected from halogen, haloalkyl, oxo, hydroxy, amino, C1-4alkyl, -O(C1-4 alkyl), NH(C1-4alkyl), -N(C1- 4alkyl) (C1-4alkyl), and-S(O)n(C1-4alkyl), and said 3-to 7-membered heterocyclic groups contain one or more heteroatom(s) selected from N, O, and S, with the point of attachment being either carbon or nitrogen; n is selected from 0, 1, and 2. The compounds can be used in the pharmaceutical composition for treating anxiety disorder, stress-related disorders and eating disorders and used in methods for localizing CRF receptors in tissue section samples. |
