Methods for the treatment of primary headache disorders using prostanoid EP4 receptor antagonists, and assays for agents for such treatment
AssigneePharmagene Laboratories Limited
InventorsGordon S. Baxter, Robert A. Coleman, Nicholas Tilford
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Abstract
The present invention provides for the treatment of primary headache disorders, particularly migraine, using antagonists of the EP4 receptor for prostaglandin E2. Particular EP4 receptor antagonists include azole compounds of formula (I): 1 wherein R1 is a group such as lower alkyl substituted with carboxy; R2 is hydrogen or lower alkyl, R3 and R4 are aryl optionally substituted with halogen, 2 in which —A1— is a single bond or lower alkylene, 3 is a cyclo group, —A3— is a single bond or lower alkylene, and X is O, NH or S; or a salt or its solvate thereof.
Claims11
A method of treating a primary headache disorder or drug-induced headache in a human or animal subject which comprises adminstering to said subject a therapeutically effective amount of an EP4 receptor antagonist or a pharmaceutically acceptable salt or solvate thereof.
A method of treating a primary headache disorder or drug-induced headache in a human or animal subject which comprises administering to said subject a therapeutically effective amount of an EP4 receptor antagonist of formula (I):
- 10
- wherein R1 is lower alkyl substituted with hydroxy, protected carboxy or carboxy;
- carboxy;
- protected carboxy;
- carbamyol;
- a heterocyclic group;
- cyano;
- hydroxy;
- halo(lower)alkyl-sulfonyloxy;
- lower alkoxy optionally substituted with hydroxy or carbamoyl;
- aryl substituted with carboxy, protected carboxy, carbamoyl or a heterocyclic group;
- or amino optionally substituted with protected carboxy or lower alkylsulfonyl,
- R2 is hydrogen or lower alkyl,
- R3 is aryl optionally substituted with halogen,
- R4 is aryl optionally substituted with halogen,
- Q is
- 11
- in which —A1— is a single bond or lower alkylene,
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- is cyclo (C5-C9) alkane, bicyclo (C6-C9[alkane or bicycle (C5-C9) alkane and —A3— is a single bond or lower alkylene], and
- X is O, NH or S;
- or a salt or its solvate thereof.
A composition comprising an EP4 receptor antagonist and a second therapeutic agent used in the treatment of a primary headache disorder.
An assay for an agent for the treatment of a primary headache disorder or drug-induced headache, which assay comprises:
- (a) providing an EP4 receptor;
- (b) bringing a potential agent for said treatment into contact with said receptor;
- (c) determining whether said agent is capable of interacting with said EP4 receptor;
- and
- (d) selecting an agent which so interacts as an agent for the treatment of primary headache disorder or drug-induced headache.
An assay for an agent for the treatment of a primary headache disorder, which assay comprises:
- (a) providing an EP4 receptor together with at least one other receptor selected from the group of EP1, EP2 and EP3 receptors;
- (b) bringing a potential agent for said treatment into contact with said receptors;
- (c) determining whether said agent is capable of selectively binding to said EP4 receptor;
- and
- (d) selecting an agent which so binds as an agent for the treatment of primary headache disorders.
Dependencies are inferred from the claim text.