N-substituted piperidine derivatives as serotonin receptor agents

A method of inhibiting an activation of a 5HT2A receptor comprising contacting the 5HT2A receptor with an amount of a compound of one or more of the compounds of Formula I that is effective in inhibiting the activation of the 5HT2A receptor, wherein the compound of Formula I has the structure:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• R1 is an optionally substituted heterocyclyl;
• R2 and R3 are independently selected from the group consisting of hydrogen, C1-6-alkyl and halogen or such that R2 together with R3 forms a 3-, 4-, 5-, 6-, 7-membered ring system with the atoms of the piperdinyl ring;
• m is 1;
• n is selected from the group consisting of 1, 2, and 3;
• Ar1 is an optionally substituted aryl or heteroaryl;
• W is selected from the group consisting of oxygen and sulfur;
• X is selected from the group consisting of optionally substituted methylene, optionally substituted ethylene, optionally substituted propylene, optionally substituted vinylene, and CH2N(RN), wherein RN is selected from hydrogen and C1-6-alkyl;
• and
• Ar2 is an optionally substituted aryl or heteroaryl.

A method of treating a disease condition selected from the group consisting of schizophrenia, schizoaffective disorders, psychosis, and drug induced psychosis comprising administering to a subject in need of such treatment a therapeutically effective amount of one or more of the compounds of Formula I, wherein the compound of Formula I has the structure:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• R1 is an optionally substituted heterocyclyl;
• R2 and R3 are independently selected from the group consisting of hydrogen, C1-6-alkyl and halogen or such that R2 together with R3 forms a 3-, 4-, 5-, 6-, 7-membered ring system with the atoms of the piperdinyl ring;
• m is 1;
• n is selected from the group consisting of 1, 2, and 3;
• Ar1 is an optionally substituted aryl or heteroaryl;
• W is selected from the group consisting of oxygen and sulfur;
• X is selected from the group consisting of optionally substituted methylene, optionally substituted ethylene, optionally substituted propylene, optionally substituted vinylene, and CH2N(RN), wherein RN is selected from hydrogen and C1-6-alkyl;
• and
• Ar2 is an optionally substituted aryl or heteroaryl.

A method of treating a psychotic symptom induced by a dopamine agonist during the treatment of Parkinson's disease comprising administering a therapeutically effective amount of one or more of the compounds of Formula I to a subject suffering from said psychotic symptom, wherein the compound of Formula I has the structure:

• or a pharmaceutically acceptable salt thereof,
• wherein
• R1 is an optionally substituted heterocyclyl;
• R2 and R3 are independently selected from the group consisting of hydrogen, C1-6-alkyl and halogen or such that R2 together with R3 forms a 3-, 4-, 5-, 6-, 7-membered ring system with the atoms of the piperdinyl ring;
• m is 1;
• n is selected from the group consisting of 1, 2, and 3;
• Ar1 is an optionally substituted aryl or heteroaryl;
• W is selected from the group consisting of oxygen and sulfur;
• X is selected from the group consisting of optionally substituted methylene, optionally substituted ethylene, optionally substituted propylene, optionally substituted vinylene, and CH2N(RN), wherein RN is selected from hydrogen and C1-6-alkyl;
• and
• Ar2 is an optionally substituted aryl or heteroaryl.