| 摘要 |
Disclosed are 4-ureido-N-methyl-piperidine derivatives of formula (I) or a pharmaceutically acceptable salt thereof, wherein: R is aryl optionally substituted with one or more independent R103 substituents; R1 is selected from the group consisting of hydroxyalkyl, alkyl, optionally substituted with one or more independent R103 substituents; R4 is selected from the group consisting of alkyl, aryl, arylalkyl, optionally substituted with one or more independent R103 substituents; or R4 is OR103; R6, R7, R8, R9 are selected from the group consisting of hydrogen and alkyl; R103 is selected from the group consisting of hydrogen, cyano, nitro, -OR104, hydroxy, amino, alkyl, alkenyl, cycloalkyl, halogen, haloalkyl, alkoxy, alkoxyalkyl, aryl, arylalkyl, heterocycloalkyl, heteroaryl, heteroarylalkyl, -C(O)R104, -C(O)OR104, -C(O)NR104R105, -NR104R105, -NR104S(O)2R105, -NR104C(O)R105, -S(O)2R104, -SR104 and -S(O)2NR104R105, and R104 and R105 are each independently selected from the group consisting of hydrogen, cyano, nitro, hydroxy, hydroxyalkyl, amino, alkyl, alkenyl, cycloalkyl, halogen, alkoxy, alkoxyalkyl, aryl, arylalkyl, heterocycloalkyl, heteroaryl and heteroarylalkyl. Also disclosed are representative compounds such as 1-methyl-3-((R)-1-(naphthalen-1-yl)ethyl)-1-(1,3,3-trimethylpiperidin-4-yl)urea, 3-(1-(4-methoxynaphthalen-1-yl)ethyl)-1-methyl-1-(1,3,3-trimethylpiperidin-4-yl)urea, 3-(1-(2,3-dichlorophenyl)ethyl)-1-(3-methoxybenzyl)-1-(1,3,3-trimethylpiperidin-4-yl)urea, 3-(1-(2,3-dichloro-4-methoxyphenyl)ethyl)-1-methyl-1-(1,3,3-trimethylpiperidin-4-yl)urea, 3-(1-(2-methoxynaphthalen-1-yl)ethyl)-1-methyl-1-(1-methylpiperidin-4-yl)urea, 3-(2-cyclopropyl-1-(2,3-dichlorophenyl)ethyl)-1-(3-methoxybenzyl)-1-(1,3,3-trimethylpiperidin-4-yl)urea, 3-(2-hydroxy-1-(naphthalen-1-yl)ethyl)-1-methyl-1-(1-methylpiperidin-4-yl)urea, 1-ethyl-1-(1-methylpiperidin-4-yl)-3-(1-(naphthalen-1-yl)-3-(3-(pyridin-3-yloxy)phenyl)propyl)urea, 1-methyl-1-(1-methylpiperidin-4-yl)-3-(3-morpholino-1-(naphthalen-1-yl)propyl)urea and 3-(1-(3-chloro-2-(pyridin-4-yl)phenyl)ethyl)-1-methyl-1-(1-methylpiperidin-4-yl)urea. Also disclosed is a pharmaceutical composition comprising a therapeutically effective amount of a compound as defined above, and one or more pharmaceutically acceptable excipients, for preventing and/or treating a subject having a disease which is pathophysiologically mediated by the ghrelin receptor, including conditions such as obesity, overweight, eating disorder, diabetes, metabolic syndrome, cachexia resulting from cancer, congestive heart failure, wasting due to ageing or AIDS, chronic liver failure, chronic obstructive pulmonary disease, gastrointestinal disease, gastric disorder or substance abuse. |
