| 摘要 |
The present invention relates to compounds of the formula (I);;wherein Ar1, R1, R2, R3, R4a, R4b and (R5)n are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as orexin receptor antagonists. |
| 主权项 |
1. A compound of formula (I) wherein Ar1 represents
phenyl or 5- or 6-membered heteroaryl, wherein said phenyl or 5- or 6-membered heteroaryl independently is mono-, di-, or tri-substituted; wherein
one of said substituents is attached in ortho-position to the point of attachment of Ar1 to the rest of the molecule; wherein said substituent is phenyl or 5- or 6-membered heteroaryl; wherein said phenyl or 5- or 6-membered heteroaryl substituent is independently unsubstituted, mono-, di-, or tri-substituted, wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, cyano, (C1-3)fluoroalkyl, and (C1-3)fluoroalkoxy;or said ortho substituent is benzo[1,3]dioxolyl, or 2-(3-methoxy-phenyl)-ethynyl; and the other of said substituents, if present, is/are independently selected from (C1-4)alkyl; (C1-4)alkoxy; (C3-6)cycloalkyl; halogen; cyano; (C1-3)fluoroalkyl; (C1-3)fluoroalkoxy; —NR10R11, wherein R10 and R11 independently represent hydrogen or (C1-4)alkyl, or R10 and R11 together with the nitrogen to which they are attached to form a pyrrolidine ring; unsubstituted pyridinyl; and phenyl which is unsubstituted, or mono- or di-substituted, wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, cyano, and halogen; one of R2 and R3 represents hydrogen, and the other represents hydrogen or (C1-4)alkyl; and one of R4a and R4b represents hydrogen, and the other represents hydrogen, (C1-4)alkoxy, or halogen; or R4a and R4b together represent a group H2C═; or both R4a and R4b represent fluorine; wherein, in case R3 is different from hydrogen, both R4a and R4b represent hydrogen; R1 represents hydrogen, (C1-4)alkyl, (C3-6)cycloalkyl-(CH2)—, (C2-3)fluoroalkyl, or (C1-4)alkoxy-(C2-4)alkyl; and (R5)n represents one to three optional substituents independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, (C1-4)alkyl-thio-, (C1-3)fluoroalkyl, (C1-3)fluoroalkoxy, (C1-3)fluoroalkyl-thio-, hydroxy-(C1-4)alkyl-, (C1-4)alkoxy-carbonyl-, nitro, hydroxy, and cyano; or (R5)n represents a group —O—CH2—CH2—O—; or (R5)n represents a fused phenyl group which, together with the benzimidazole moiety to which it is fused to, forms a 1H-naphtho[2,3-d]imidazol-2-yl group; with the exception of
[2-(1H-benzimidazol-2-yl)-1-pyrrolidinyl][2-(1H-pyrazol-1-yl)phenyl]-methanone;[2-(1H-benzimidazol-2-yl)-1-pyrrolidinyl][5-(2,5-dimethyl-1H-pyrrol-1-yl)-1-methyl-1H-pyrazol-4-yl]-methanone;[2-(1H-benzimidazol-2-yl)-1-pyrrolidinyl][1,1′-biphenyl]-2-yl-methanone;[2-(6-methyl-1H-benzimidazol-2-yl)-pyrrolidin-1-yl][3-phenyl-isoxazol-4-yl]-methanone;[2-(1H-imidazol-2-yl)phenyl][2-(6-methyl-1H-benzimidazol-2-yl)-pyrrolidin-1-yl]-methanone;[2-(6-methyl-1H-benzimidazol-2-yl)-pyrrolidin-1-yl][3-(thien-2-yl)-1H-pyrazol-4-yl]-methanone;[2-(6-methyl-1H-benzimidazol-2-yl)-pyrrolidin-1-yl][3-phenyl-1H-pyrazol-4-yl]-methanone;[2-(1H-benzimidazol-2-yl)-pyrrolidin-1-yl][3-cyclopropyl-1-phenyl-1H-pyrazol-5-yl]-methanone; and[2-(1H-benzimidazol-2-yl)-pyrrolidin-1-yl][1-(2-fluorophenyl)-5-(1H-pyrrol-1-yl)-1H-pyrazol-4-yl]-methanone; or a pharmaceutically acceptable salt thereof. |
