N-methyl piperazine compounds having dopamine receptor affinity

• US 5,700,445 A
• Filed: 12/12/1994
• Issued: 12/23/1997
• Est. Priority Date: 12/12/1994
• Status: Expired due to Term

• Current Assignee: Exxon Research and Engineering Company (Exxon Mobil Corporation), NPS Pharmaceuticals Incorporated (Shire plc)
• Original Assignee: Allelix Biopharmaceuticals, Inc. (NPS Allelix Corp.)
• Inventors: Fu, Jian-Min, Rakhit, Sumanas
• Primary Examiner(s): Kight, John
• Assistant Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US08/354,905
• Time in Patent Office: 1,107 Days
• Field of Search: 424/1.81, 424/1.11, 424/1.65, 424/1.69, 514/211, 514/220, 514/217, 540/555, 540/557
• US Class Current: 424/1.81
• CPC Class Codes: C07D 243/38 [b, e]- or [b, f]-condensed with six-membered rings
• CPC Class Codes: C07D 267/18 [b, e]-condensed
• CPC Class Codes: C07D 337/14 [b,f]-condensed

Abstract

Described herein are D4 receptor-selective compounds of the general formula: ##STR1## wherein X₁ is selected from CH₂, NH, O and S;

X₂ - - is selected from CH═, CH₂ 13 , and N═;

R₁ to R₈ are each independently selected from H, C_1-4 alkyl, halo, cyano, nitro and halo-substituted C_1-4 alkyl

and acid addition salts, solvates and hydrates thereof. Their use as ligands for dopamine receptor identification and in a drug screening program, and as pharmaceuticals to treat indications in which the D4 receptor is implicated, such as schizophrenia, is also described.

Claims

1. A compound of Formula I ##STR8## wherein X₁ is NH;

X₂ - - is N═

;

R₁ to R₄ to R₈ are H and R₅ is Cl, and

wherein said compound is 4-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo b,e! 1,4!diazepine.

2. A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to claim 1, and a pharmaceutically acceptable carrier.

3. A compound according to claim 1, in a radiolabelled form.

4. A pharmaceutical composition for treating a condition mediated by the D4 receptor, comprising a compound according to claim 1 in an amount effective to inhibit the D4 receptor, and a pharmaceutically acceptable carrier thereof.

6. A pharmaceutical composition for treating schizophrenia, comprising a compound according to claim 1 in an amount sufficient to produce an antischizophrenia effect, and a pharmaceutically acceptable carrier therefor.

7. A method for the treatment of schizophrenia, comprising the step of administering to a mammal in need of such treatment, a composition according to claim 6.

8. A pharmaceutical composition for treating anxiety, comprising a compound according to claim 1 in an amount sufficient to produce an antianxiety effect, and a pharmaceutically acceptable carrier therefor.

9. A method for the treatment of anxiety, comprising the step of administering to a mammal in need of such treatment, a composition according to claim 8.

5. A method for the treatment of a condition mediated by the D4 receptor, comprising the step of administering to a mammal in need of such treatment a composition according to claim 5.