Heteroaromatic derivatives having serotonin receptor binding activity
Provided are compounds having a serotonin 5-HT2A receptor inverse agonism, pharmaceutically acceptable salts thereof, and a composition comprising them, A composition comprising the compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein: R 1 is substituted or unsubstituted aromatic heterocyclyl or the like; R 2 is each independently a hydrogen atom or the like; R 3 is each independently a hydrogen atom or the like; n is 1 or 2; R 4 is substituted or unsubstituted non-aromatic nitrogen-containing heterocyclyl or the like; L is —NR 8 — or the like; R 8 is a hydrogen atom or the like; R 5 is each independently a hydrogen atom or the like; R 6 is each independently a hydrogen atom or the like; p is 1 or 2; and R 7 is a group represented by Formula: wherein R 9 is substituted or unsubstituted alkyloxy or the like; R 10 is a hydrogen atom or the like; R 11 is halogen or the like; and m is 0 or 1.
1 . A compound represented by Formula (II):
wherein R 1 is substituted or unsubstituted pyridyl, substituted or unsubstituted pyrrolyl, or substituted or unsubstituted pyrazolyl;
R 2 is a hydrogen atom;
R 3 is a hydrogen atom;
n is 1;
R 4 is a group represented by the formula:
wherein R 21 is a hydrogen atom or substituted or unsubstituted alkyl;
R 22 is a hydrogen atom, halogen or substituted or unsubstituted alkyl;
R 23 is a hydrogen atom, halogen or substituted or unsubstituted alkyl; or
R 22 and R 23 are taken together with the carbon atom to which they are bonded to form a substituted or unsubstituted non-aromatic carbocycle;
R 8 is a hydrogen atom;
R 5 is a hydrogen atom;
R 6 is a hydrogen atom;
R 7 is a group represented by the formula:
wherein R 9 is substituted or unsubstituted alkyloxy;
provided that the following compound is excluded:
or a pharmaceutically acceptable salt thereof.
2 . The compound according to claim 1 , wherein R 1 is pyridyl substituted with halogen, pyridyl substituted with haloalkyl, pyridyl substituted with halogen and haloalkyl, unsubstituted pyridyl, pyrazolyl substituted with haloalkyl, pyrazolyl substituted with alkyl, pyrazolyl substituted with haloalkyl and alkyl, unsubstituted pyrazolyl, pyrrolyl substituted with haloalkyl, pyrrolyl substituted with alkyl, pyrrolyl substituted with haloalkyl and alkyl, or unsubstituted pyrrolyl, or a pharmaceutically acceptable salt thereof.
3 . The compound according to claim 1 , wherein R 1 is pyridyl substituted with halogen, pyrazolyl substituted with alkyl, or pyrrolyl substituted with alkyl, or a pharmaceutically acceptable salt thereof.
4 . The compound according to claim 1 , wherein R 4 is a group represented by the formula:
wherein R 21 is a hydrogen atom or unsubstituted alkyl;
R 22 is a hydrogen atom, halogen or unsubstituted alkyl;
R 23 is a hydrogen atom, halogen or unsubstituted alkyl; or
R 22 and R 23 are taken together with the carbon atom to which they are bonded to form an unsubstituted non-aromatic carbocycle,
or a pharmaceutically acceptable salt thereof.
5 . The compound according to claim 1 , wherein R 4 is a group represented by the formula:
wherein R 21 , R 22 and R 23 are as defined in claim 1 , or a pharmaceutically acceptable salt thereof.
6 . The compound according to claim 1 , wherein R 22 is halogen or substituted or unsubstituted alkyl;
R 23 is a hydrogen atom, halogen or substituted or unsubstituted alkyl; or
R 22 and R 23 are taken together with the carbon atom to which they are bonded to form a substituted or unsubstituted non-aromatic carbocycle,
or a pharmaceutically acceptable salt thereof.
7 . The compound according to claim 1 , wherein R 7 is a group represented by the formula:
wherein R 9 is alkyloxy substituted with halogen or unsubstituted alkyloxy,
or a pharmaceutically acceptable salt thereof.
8 . The compound according to claim 1 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
9 . A pharmaceutical composition comprising the compound according to claim 8 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.
10 . A pharmaceutical composition comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.
11 . The pharmaceutical composition according to claim 10 , wherein the composition is a serotonin 5-HT2A receptor inverse agonist.
12 . A method for treating and/or preventing a disease related to serotonin 5-HT2A receptor comprising administering an effective amount of the compound according to claim 3 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.
13 . The compound according to claim 1 , wherein R 1 is pyridyl substituted with halogen, pyrazolyl substituted with alkyl, or pyrrolyl substituted with alkyl;
R 4 is a group represented by the formula:
wherein R 21 is a hydrogen atom or unsubstituted alkyl;
R 22 is a hydrogen atom, halogen or unsubstituted alkyl;
R 23 is a hydrogen atom, halogen or unsubstituted alkyl; or
R 22 and R 23 are taken together with the carbon atom to which they are bonded to form an unsubstituted non-aromatic carbocycle; and
R 7 is a group represented by the formula:
wherein R 9 is alkyloxy substituted with halogen or unsubstituted alkyloxy;
or a pharmaceutically acceptable salt thereof.