Methods of utilizing arylpiperazine derivatives

1. A compound of Formula 1:

or a pharmaceutically acceptable salt, isomer, racemate, diastereomeric mixture thereof, wherein:

A is —(CH 2 ) n —, —O—(CH 2 ) n —, —S—(CH 2 ) n —, —S(O)(O)—(CH 2 ) n —, —NH—(CH 2 ) n —, —CH 2 —O—(CH 2 ) n —, —(CH 2 ) n —O—CH 2 —CH 2 —, —CH 2 —S—(CH 2 ) n —, —(CH 2 ) n —S—CH 2 —CH 2 —, —CH 2 —S(O)(O)—(CH 2 ) n —, —(CH 2 ) n —S(O)(O)—CH 2 —CH 2 —, —O—C(O)—(CH 2 ) n —, —S—C(O)—(CH 2 ) n —, —NH—C(O)—(CH 2 ) n —, —CH 2 —C(O)—O—(CH 2 ) n —, —CH 2 —C(O)—NH—(CH 2 ) n —, —CH 2 —C(O)—S—(CH 2 ) n —, —(CH 2 ) n —C(O)—O—CH 2 —CH 2 —, —(CH 2 ) n —C(O)—NH—CH 2 —CH 2 —, —(CH 2 ) n —C(O)—S—CH 2 —CH 2 —, —CH 2 —O—C(O)—(CH 2 ) n —, —CH 2 —NH—C(O)—(CH 2 ) n —, —CH 2 —S—C(O)—(CH 2 ) n —, —(CH 2 ) n —O—C(O)—CH 2 —CH 2 —, (CH 2 ) n —NH—C(O)—CH 2 —CH 2 —, or (CH 2 ) n —S—C(O)—CH 2 —CH 2 —, wherein n is an integer from 1 to 7;

B is NR 5 ; and

R 1 , R 2 , R 3 , R 4 , R 5 ,R 6 , R 7 , and R 8 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, acylalkyloxycarbonyl, acyloxyalkyloxycarbonyl, acylalkyloxycarbonylamino, acyloxyalkyloxycarbonylamino, alkoxy, alkoxycarbonyl, alkoxycarbonylalkoxy, alkoxycarbonylalkylamino, alkylsulfinyl, alkylsulfonyl, alkylthio, amino, alkylamino, arylalkylamino, dialkylamino, arylalkoxy, arylalkoxycarbonylalkoxy, arylalkoxycarbonylalkylamino, aryloxycarbonyl, aryloxycarbonylalkoxy, aryloxycarbonylalkylamino, carboxy, carbamoyl, carbamate, carbonate, cyano, halogen, heteroaryloxycarbonyl, hydroxy, phosphate, phosphonate, sulfate, sulfonate, or sulfonamide; wherein R 1 , R 2 , R 3 , R 4 , R 6 , R 7 and R 8 and A are optionally substituted with isotopes selected from the group consisting of 2 H (deuterium), 3 H (tritium), 13 C, 36 Cl, 18 F, 15 N, 17 O, 18 O, 31 P, 32 P, and 35 S.

2. The compound of claim 1 , wherein the compound has Formula 1a:

3. The compound of claim 1 , wherein A is —O—(CH 2 ) n —, —S—(CH 2 ) n —, —CH 2 —O—(CH 2 ) n —, —(CH 2 ) n —O—CH 2 —CH 2 —, —CH 2 —S—(CH 2 ) n —, or —(CH 2 ) n —S—CH 2 —CH 2 —.

4. The compound of claim 1 , wherein A is —NH—C(O)—(CH 2 ) n —, —CH 2 —NH—C(O)—(CH 2 ) n —, —CH 2 —C(O)—NH—(CH 2 ) n — or —(CH 2 ) n —C(O)—NH—CH 2 —CH 2 —.

5. The compound of claim 1 , wherein A is —(CH 2 ) n —.

6. The compound of claim 1 , wherein R 4 is H.

7. The compound of claim 1 , wherein R 1 and R 2 are independently H, halogen, or alkoxy.

8. The compound of claim 7 , wherein R 1 is H, and R 2 is methoxy.

9. The compound of claim 1 , wherein R 1 and R 2 are chloro.

10. The compound of claim 7 , wherein A is —O—(CH 2 ) n —; and R 3 , R 4 , R 6 , R 7 , and R 8 are independently hydrogen or alkyl.

11. The compound of claim 7 , wherein R 3 , R 4 , R 6 , R 7 , and R 8 are hydrogen.

12. The compound of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 6 , R 7 and R 8 and A are optionally substituted with 2 H (deuterium).

13. The compound of claim 1 , wherein the compound is in the form of a hydrochloride salt.

14. The compound of claim 1 , wherein the compound is enantiomerically pure and/or diastereomerically pure.

15. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable carrier, excipient, or diluent.

16. A method of treating psychosis, schizophrenia, acute mania, bipolar disorder, autistic disorder or depression, the method comprising administering to a patient in need thereof the pharmaceutical formulation claim 15 .

17. The method of claim 16 , wherein said method treats depression.

18. The method of claim 16 , wherein said method treats schizophrenia.

19. The method of claim 16 , wherein said method treats psychosis.

20. The method of claim 16 , wherein said method treats autistic disorder.