Methods of utilizing arylpiperazine derivatives
View Patent ↗The present invention provides arylpiperazine derivatives having Formula I which can be advantageously used for treating schizophrenia and related psychoses such as acute manic, bipolar disorder, autistic disorder and depression.
1. A method of treating psychoses, schizophrenia, acute mania, bipolar disorder, autistic disorder or depression, the method comprising administering to a patient in need thereof a compound of Formula 1:
or a pharmaceutically acceptable salt, isomer, racemate, or diastereomeric mixture thereof, 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 —, —(CH 2 ) n —S—CH 2 —CH 2 , —NH—C(O)—(CH 2 ) n —, —CH 2 —C(O)—NH—(CH 2 ) n —, —(CH 2 ) n —C(O)—NH—CH 2 —CH 2 —, or —CH 2 —NH—C(O)—(CH 2 ) n —, wherein n is an integer from 1 to 7;
B is O; and
R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , and R 8 are independently hydrogen, alkyl, aryl, arylalkyl, cycloalkyl, cycloheteroalkyl, heteroaryl, heteroarylalkyl, acylalkyloxycarbonyl, acyloxyalkyloxycarbonyl, acylalkyloxycarbonylamino, acyloxyalkyloxycarbonylamino, alkoxy, alkoxycarbonyl, alkoxycarbonylalkoxy, alkoxycarbonyllalkylamino, 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, and 35 S.
2. The method according to claim 1 , wherein the compound of claim 1 has Formula 1a:
3. The method according to 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 method according to 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 method according to claim 1 , wherein R 4 is H.
6. The method according to claim 1 , wherein R 1 and R 2 are independently H, halogen, or alkoxy.
7. The method according to claim 6 , wherein R 1 is H, and R 2 is methoxy.
8. The method according to claim 1 , wherein R 1 and R 2 are chloro.
9. The method according to claim 1 , wherein A is —O—(CH 2 ) n —; and R 3 , R 4 , R 6 , R 7 , and R 8 are independently hydrogen or alkyl.
10. The method according to claim 1 , wherein R 3 , R 4 , R 6 , R 7 , and R 8 are hydrogen.
11. The method according to claim 1 , wherein the hydrogens of R 1 , R 2 , R 3 , R 4 , R 6 , R 7 and R 8 and A are optionally substituted with 2 H (deuterium).
12. The method according to claim 1 , wherein the compound is in the form of a hydrochloride salt.
13. The method according to claim 1 , wherein the compound is administered in a pharmaceutical composition comprising a pharmaceutically acceptable carrier, excipient, or diluent.
14. The method according to claim 1 , wherein the compound is enantiomerically and/or diastereomerically pure.
15. The method according to claim 1 , wherein said method treats psychosis.
16. The method according to claim 1 , wherein said method treats schizophrenia.
17. The method according to claim 1 , wherein said method treats autistic disorder.
18. The method according to claim 1 , wherein said method treats bipolar disorder.
19. The method according to claim 1 , wherein said method treats depression.
20. The method of claim 1 , wherein n is 4.