BENZISOXAZOLES

• US 20200131166A1
• Filed: 12/26/2019
• Published: 04/30/2020
• Est. Priority Date: 10/01/2003
• Status: Abandoned Application

• Current Assignee: Vanda Pharmaceuticals Incorporated
• Original Assignee: Vanda Pharmaceuticals Incorporated
• Inventors: Nozulak, Joachim, Kalkman, Hans
• Application Number:
  US16/727,101
• Publication Number:
  US 20200131166A1
• Time in Patent Office: Days
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond

Abstract

The present invention relates to novel fatty acid esters of the reversible Iloperidone metabolite P-88-8991, their preparation, their use as pharmaceuticals and pharmaceutical compositions containing them.

Claims

1. A compound of Formula I

3. The compound of claim 1, which is decanoic acid 1-(4-{3-[4-(6-fluoro-benzo[d]isoxazole-3-yl)-piperidine-1-yl]propoxy}-3-methoxy-phenyl)-ethyl ester.

4. The compound of claim 1, which is (S)-(-)-decanoic acid 1-(4-{3-[4-(6-fluoro-benzo[d]isoxazole-3-yl)-piperidine-1-yl]propoxy}-3-methoxy-phenyl)-ethyl ester.

5. The compound of claim 1, wherein R is selected from —

(CH₂)₈—

CH₃, —

(CH₂)₆—

CH₃, —

(CH₂)₁₀—

CH₃, —

(CH₂)₁₂—

CH₃, —

(CH₂)₁₄—

CH₃, —

CH₂—

(CH₂—

CH═

CH)₆—

CH₂—

CH₃, or —

(CH₂)₂—

(CH₂—

CH═

CH)₅—

CH₂—

CH₃.

2. A method for the production of the compounds of formula I

6. A pharmaceutical composition for the treatment of a psychotic disorder comprising a compound of Formula I,

wherein R is (C_1-40)alkyl or (C_1-40)alkenyl, in free base or acid addition salt form;

and

a pharmaceutical carrier or diluent.

7. The pharmaceutical composition of claim 6, wherein the compound of Formula I is decanoic acid 1-(4-{3-[4-(6-fluoro-benzo[d]isoxazole-3-yl)-piperidine-1-yl]propoxy}-3-methoxy-phenyl)-ethyl ester.

8. The pharmaceutical composition of claim 6, wherein the compound of Formula I is (S)-(-)-decanoic acid 1-(4-{3-[4-(6-fluoro-benzo[d]isoxazole-3-yl)-piperidine-1-yl]propoxy}-3-methoxy-phenyl)-ethyl ester.

9. The pharmaceutical composition of claim 6, wherein R is selected from —

(CH₂)₈—

CH₃, —

(CH₂)₆—

CH₃, —

(CH₂)₁₀—

CH₃, —

(CH₂)₁₂—

CH₃, —

(CH₂)₁₄—

CH₃, —

CH₂—

(CH₂—

CH═

CH)₆—

CH₂—

CH₃, or —

(CH₂)₂—

(CH₂—

CH═

CH)₅—

CH₂—

CH₃.

10. The pharmaceutical composition of claim 6, wherein the compound of Formula I is present in a unit dosage form from about 0.25 to about 150 mg.

11. The pharmaceutical composition of claim 6, wherein the compound of Formula I is present in a unit dosage form from about 0.25 to about 25 mg.

12. The pharmaceutical composition of claim 6, wherein the psychotic disorder is schizophrenia or a bipolar disorder.