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US 2007/0185100 A1Published application
Poly-heterocyclic compounds and their use as metabotropic glutamate receptor antagonists
AssigneeAstraZeneca AB
InventorsJalaj Arora, Louise Edwards, Methvin Isaac, Annika Kers, Karin Staaf, Abdelmalik Slassi, Tomislav Stefanac, David Wensbo, Tao Xin, Bjorn Holm
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Abstract
The present invention relates to new compounds of formula (I), wherein P, Q, X1, X2, X3, X4, X5, X6, R1, R2, R3, m, n, and p are as defined as in formula (I), or salts, or hydrates thereof, processes for their preparation and new intermediates used in the preparation thereof, pharmaceutical compositions containing said compounds and to the use of said compounds in therapy.
Claims38
A compound according to formula I
- wherein
- P is selected from aryl and heteroaryl;
- R1 is attached to P via a carbon atom on ring P and is selected from the group consisting of hydroxy, halo, nitro, C1-6alkylhalo, OC1-6alkylhalo, C1-6alkyl, OC1-6alkyl, C2-6alkenyl, OC2-6alkenyl, C2-6alkynyl, OC2-6alkynyl, C0-6alkylC3-6cycloalkyl, OC0-6alkylC3-6cycloalkyl, C0-6alkylaryl, OC0-6alkylaryl, CHO, (CO)R5, O(CO)R5, O(CO)OR5, O(CNR5)OR5, C1-6alkylOR5, OC2-6alkylOR5, C1-6alkyl(CO)R5, OC1-6alkyl(CO)R5, C0-6alkylCO2R5, OC1-6alkylCO2R5, C0-6alkylcyano, OC2-6alkylcyano, C0-6alkylNR5R6, OC2-6alkylNR5R6, C1-6alkyl(CO)NR5R6, OC1-6alkyl(CO)NR5R6, C0-6alkylNR5(CO)R6, OC2-6alkylNR5(CO)R6, C0-6alkylNR5(CO)NR5R6, C0-6alkylSR5, OC2-6alkylSR5, C0-6alkyl(SO)R5, OC2-6alkyl(SO)R5, C0-6alkylSO2R5, OC2-6alkylSO2R5, C0-6alkyl(SO2)NR5R6, OC2-6alkyl(SO2)NR5R6, C0-6alkylNR5(SO2)R6, OC2-6alkylNR5(SO2)R6, C0-6alkylNR5(SO2)NR5R6, OC2-6alkylNR5(SO2)NR1R6, (CO)NR5R6, O(CO)NR5R6, NR5OR6, C0-6alkylNR5(CO)OR6, OC2-6alkylNR5(CO)OR6, SO3R5 and a 5- or 6-membered ring containing atoms independently selected from the group consisting of C, N, O and S;
- X1 is selected from the group consisting of:
- N, NR4 and CR4;
- X2 is selected from the group consisting of:
- C and N;
- X3 is selected from the group consisting of:
- CR4, N and O;
- X4 is selected from the group consisting of:
- CR4, N, NR4 and O;
- X5 is selected from the group consisting of:
- a bond, CR4R4′, NR4, O, S, SO and SO2;
- X6 is selected from the group consisting of:
- CR4 and N;
- X7 is selected from the group consisting of:
- C and N;
- R4 is independently selected from a group consisting of hydrogen, hydroxy, C1-6alkyl, C0-6alkylcyano, oxo, ═NR5, ═NOR5, C1-4alkylhalo, halo, C3-7cycloalkyl, O(CO)C1-4alkyl, C1-4alkyl(SO)C0-4alkyl, C1-4alkyl(SO2)C0-4alkyl, (SO)C0-4alkyl, (SO2)C0-4alkyl, OC1-4alkyl, C1-4alkylOR5 and C0-4alkylNR5R6;
- Q is selected the group consisting of heterocycloalkyl and heteroaryl;
- R2 and R3 are independently selected from the group consisting of:
- hydroxy, C0-6alkylcyano, oxo, ═NR5, ═NOR5, C1-4alkylhalo, halo, C1-6alkyl, C3-6cycloalkyl, C0-6alkylaryl, C0-6alkylheteroaryl, C1-6alkylcycloalkyl, C0-6alkylheterocycloalkyl, OC1-4alkyl, OC0-6alkylaryl, O(CO)C1-4alkyl, (CO)OC1-4alkyl, C0-4alkyl(S)C0-4alkyl, C1-4alkyl(SO)C0-4alkyl, C1-4alkyl(SO2)C0-4alkyl, (SO)C0-4alkyl, (SO2)C0-4alkyl, C1-4alkylOR5, C0-4alkylNR5R6 and a 5- or 6-membered ring containing atoms independently selected from C, N, O and S, which ring may optionally be fused with a 5- or 6-membered ring containing atoms independently selected from the group consisting of C, N and O and wherein said ring and said fused ring may be substituted by one or more A;
- wherein any C1-6alkyl, aryl, or heteroaryl defined under R1, R2 and R3 may be substituted by one or more A;
- A is selected from the group consisting of:
- hydrogen, hydroxy, halo, nitro, oxo, C0-6alkylcyano, C0-4alkylC3-6cycloalkyl, C1-6alkyl, —OC1-6alkyl, C1-6alkylhalo, OC1-6alkylhalo, C2-6alkenyl, C0-3alkylaryl, C0-6alkylOR5, OC2-6alkylOR5, C0-6alkylSR5, OC2-6alkylSR5, (CO)R5, O(CO)R5, OC2-6alkylcyano, OC1-6alkylCO2R5, O(CO)OR5, OC1-6alkyl(CO)R5, C1-6alkyl(CO)R5, NR5OR6, C0-6NR5R6, OC2-6alkylNR5R6, C0-6alkyl(CO)NR5R6, OC1-6alkyl(CO)NR5R6, OC2-6alkylNR5(CO)R6, C0-6alkylNR5(CO)R6, C0-6alkylNR5(CO)NR5R6, O(CO)NR5R6, C0-6alkyl(SO2)NR5R6, OC2-6alkyl(SO2)NR5R6, C0-6alkylNR5(SO2)R6, OC2-6alkylNR5(SO2)R6, SO3R5, C1-6alkylNR5(SO2)NR5R6, OC2-6alkyl(SO2)R5, C0-6alkyl(SO2)R5, C0-6alkyl(SO)R5, OC2-6alkyl(SO)R5 and a 5- or 6-membered ring containing atoms independently selected from the group consisting of C, N, O and S;
- R5 and R6 are independently selected from, H, C1-6alkyl, C3-7cycloalkyl and aryl;
- m is selected from 0, 1, 2, 3 or 4;
- n is selected from 0, 1, 2, 3 or 4;
- p is selected from 0, 1, 2, 3 or 4;
- and
- a salt or hydrate thereof,
- with the proviso that the compound is not:
- 4,4′-(1,2-piperazinediyl)di-antipyrine;
- 4,4′-(1,2-piperazinediyl)di-antipyrine dihydrochloride;
- or
- 4,4′-(1,2-piperazinediyl)di-antipyrine dipicrate;
32 more elements
(canceled)
Dependencies are inferred from the claim text.