Indole derivatives useful for the treatment of CNS disorders
AssigneeH. Lundbeck A/S
InventorsBenny Bang-Andersen, Jakob Felding, Jan Kehler, Kim Andersen
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AssigneeH. Lundbeck A/S
InventorsBenny Bang-Andersen, Jakob Felding, Jan Kehler, Kim Andersen
Estimating the term…
The present invention relates to dopamine D4 ligands having the general formula I 1 wherein (a) one of Y1 and Y2 is N, which is bound to Y4, and the other of Y1 and Y2 is CO, CS, SO, or SO2 and Y4 is CH2; (b) one of Y1 and Y2 is N, which is bound to Y4, and the other of Y1 and Y2 is CH2 and Y4 is CO, CS, SO or SO2; or (c) one of Y1 and Y2 is N, which is bound to Y4, and the other of Y1 and Y2 is CH2 and Y4 is CH2; Y3is Z—CH2, CH2—Z or CH2CH2, and Z is O or S; provided that when Y1 is N, Y3 may not be Z—CH2; W is a bond or an O, S, CO, CS, SO or SO2 group; n is 0-5, m is 0-5 and m+n is 1-10; provided that when W is O or S, then n≧2 and m≧1; when W is CO, CS, SO or SO2, then n≧1 and m≧1; X is C, CH or N; provided that when X is C, the dotted line indicates a bond, and when X is N or CH, the dotted line is absent; R1-R9 are independently selected from hydrogen, halogen, cyano, nitro, amino, hydroxy, C1-6-alkyl-amino, di-C1-6-alkyl-amino, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C1-6 alkoxy, C1-6-alkylthio, C1-6-alkyl substituted with hydroxy or thiol, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, acyl, thioacyl, aryl, trifluoromethyl, trifluoromethylsulfonyl, and C1-6 alkylsulfonyl; R10 is hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C1-6-alkyl substituted with hydroxy or thiol, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, aryl, aryl-C1-6-alkyl, acyl, thioacyl, C1-6-alkylsulfonyl, trifluoromethylsulfonyl or arylsulfonyl, or a pharmaceutically acceptable acid addition salt thereof. The compounds of the invention are potent dopamine D4 receptor ligands.
A substituted indole derivative of formula I
Dependencies are inferred from the claim text.
From the US filing history. Foreign family members aren’t listed.
Backward citations are indexed for grants only.
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
Drugs for disorders of the nervous system
Drugs for disorders of the nervous system: antimigraine agents
For treating abnormal movements, e.g. chorea, dyskinesia: anti-Parkinson drugs
Term end not estimated
The present invention relates to a novel class of indole derivatives having affinity for the dopamine D4 receptor. The compounds have antagonistic effect at the dopamine D4 receptor and are therefore useful in the treatment of certain psychiatric and neurologic disorders, in particular psychoses. Some of the compounds also have affinity for the dopamine D3 receptor, the 5-HT2A receptor and/or the 5-HT2C receptor and some of the compounds are serotonin reuptake inhibitors.
Dopamine D4 ligands related to the compounds of the invention are known from WO 98/28293. The indane and dihydroindole derivatives disclosed therein have the general formula 2
wherein A is an indole and Y is a group completing an indane, or a dihydroindole and the other substituents are as defined in the application.
Preparation of Intermediates
A. Alkylating Reagents
1-(2-Chloroethyl)-3,4-dihydroquinolin-2(1H)-one