| 摘要 |
The present invention relates to compounds of the formula (I);;wherein R1a, R1b, R2, R3, and X 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), to methods for the preparation of such compounds of formula (I), and especially to their use as TPH modulators. |
| 主权项 |
1. A compound of Formula (I) wherein X represents —CH2—, —CH2—CH2—, —CH2—CH2—CH2—, —S—, *—CH2—O—, or *—CH2—NRx— wherein Rx represents hydrogen, —CO—(C1-4)alkyl, —(C1-3)alkyl-(C3-6)cycloalkyl, (C3-6)cycloalkyl, or —CO—(C1-4)alkoxy; wherein the asterisks indicate the bond attached to the imidazole ring; R1a and R1b independently represent hydrogen, methyl, ethyl; or R1a and R1b together with the carbon atom to which they are attached to form a cyclopropyl ring;R2 represents aryl, or heteroaryl, wherein said aryl or heteroaryl independently is unsubstituted, or mono-, di-, or tri-substituted, wherein the substituents are independently selected from:
(C1-4)alkyl; (C1-4)alkoxy; (C3-6)cycloalkyl; (C1-3)fluoroalkyl; (C1-3)fluoroalkoxy; halogen; cyano; —(CH2)n—NR21R22; wherein n represents the integer 0 or 1; and
R21 and R22 independently represent hydrogen or (C1-4)alkyl; orR21 and R22 together with the nitrogen atom to which they are attached to form a 4- to 7-membered saturated ring, wherein said ring optionally includes one ring oxygen atom; —CO—NR23R24, wherein R23 and R24 independently represent hydrogen or (C1-4)alkyl; —CO—NH—CN; —NR25—CO—NR26R27, wherein R25, R26 and R27 independently represent hydrogen or (C1-4)alkyl; —CO—(C1-4)alkoxy; phenyl; hydroxy-(C1-4)alkyl; (C1-3)alkoxy-(C1-4)alkyl; hydroxy-(C2-4)alkoxy; or (C1-3)alkoxy-(C2-4)alkoxy;R3 represents aryl, or heteroaryl, wherein said aryl or heteroaryl independently is unsubstituted, or mono-, di-, or tri-substituted, wherein the substituents are independently selected from:
—NR4—SO2—Y—R5, wherein
R4 represents hydrogen or (C1-3)alkyl; Y represents a direct bond; and R5 represents (C1-4)alkyl, or (C3-6)cycloalkyl; orR4 represents hydrogen or (C1-3)alkyl; Y represents —NRY— wherein RY represents (C1-3)alkyl; and R5 represents (C1-4)alkyl; orR4 and R5 together with the nitrogen and the —SO2—Y-group to which they are attached to form a 5-, 6-, or 7-membered ring, wherein Y represents a direct bond or —NRY— wherein RY represents (C1-3)alkyl; —CO—NR6R7, wherein R6 and R7 independently represent hydrogen, (C1-4)alkyl, or (C3-6)cycloalkyl; —SO2—R8 wherein R8 represents (C1-5)alkyl, or —NR81R82, wherein R81 and R82 independently represent hydrogen or (C1-4)alkyl; —(CH2)m—NR9R10; wherein m represents the integer 0 or 1; and
R9 and R10 independently represent hydrogen, (C1-4)alkyl, (C2-3)fluoroalkyl, hydroxy-(C2-4)alkyl, (C1-4)alkoxy-(C2-4)alkyl; orR9 and R10 together with the nitrogen to which they are attached to form a 4- to 7-membered ring optionally including an oxygen ring atom or a group —NR11— wherein R11 represents (C1-4)alkyl, and wherein said ring is optionally substituted with one or two fluorine substituents; (C1-4)alkyl; (C3-6)cycloalkyl; (C1-4)alkoxy; (C1-3)fluoroalkyl; (C1-3)fluoroalkoxy; halogen; cyano; or 5-membered heteroaryl;or a pharmaceutically acceptable salt thereof. |
