Tetrazole derivatives

• US 10,577,332 B2
• Filed: 04/19/2016
• Issued: 03/03/2020
• Est. Priority Date: 04/23/2015
• Status: Active Grant

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Hoener, Marius, Wichmann, Juergen
• Primary Examiner(s): Otton, Alicia L
• Application Number:
  US15/569,349
• Publication Number:
  US 20180297961A1
• Time in Patent Office: 1,414 Days
• Field of Search: None
• 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: C07D 257/04 Five-membered rings
• CPC Class Codes: C07D 257/06 with nitrogen atoms directly attached to the ring carbon atom
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to compounds of formula I

wherein

• R^1′ is CH₃
• R¹ is methyl, ethyl, CF₃, CH₂OH, cyclopropyl or cyano, or
  • R^1′ and R¹ may form together a 1,1-dioxo-tetrahydro-thiophen-3-yl ring;
• R² is hydrogen, methyl, ethyl, isopropyl, tertbutyl, cyclopropyl or CF₃;
• R³ is Cl, F, CF₃, methyl, methoxy, isopropyl or cyclopropyl;
• R⁴ is hydrogen, methyl, F or Cl;
  or to a pharmaceutically acceptable salt or acid addition salt, to a racemic mixture, or to its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof for use in the treatment of schizophrenia, bipolar disorder, obsessive-compulsive disorder or autism spectrum disorder.

Claims

1. A compound according to formula IA-7:

2. A compound of claim 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

(RS)-3-(4-Fluorophenyl)-N-(3-methyl-1,1-dioxothiolan-3-yl)-5-(tetrazol-1-yl)-benzamide;

(RS)-3-(4-Chlorophenyl)-N-(3-methyl-1,1-dioxothiolan-3-yl)-5-(tetrazol-1-yl)-benzamide (RS)—

N-(3-methyl-1,1-dioxothiolan-3-yl)-3-(4-methylphenyl)-5-(5-propan-2-yltetrazol-1-yl)-benzamide;

(RS)—

N-(3-Methyl-1,1-dioxothiolan-3-yl)-3-(4-methylphenyl)-5-(5-methyltetrazol-1-yl)-benzamide;

(RS)-3-(5-Cyclopropyltetrazol-1-yl)-N-(3-methyl-1,1-dioxothiolan-3-yl)-5-(4-methylphenyl)-benzamide;

(RS)-3-(5-Ethyltetrazol-1-yl)-N-(3-methyl-1,1-dioxothiolan-3-yl)-5-(4-methylphenyl)-benzamide;

(RS)-3-(4-Chlorophenyl)-N-(3-methyl-1,1-dioxothiolan-3-yl)-5-(5-propan-2-yltetrazol-1-yl)benzamide;

(RS)—

N-(3-methyl-1,1-dioxothiolan-3-yl)-3-(5-propan-2-yltetrazol-1-yl)-5 44-(trifluoromethyl)phenyl]benzamide;

(RS)-3-(4-Chlorophenyl)-5-(5-cyclopropyltetrazol-1-yl)-N-(3-methyl-1,1-dioxothiolan-3-yl)-benzamide;

(RS)-3-(4-Fluorophenyl)-N-(3-methyl-1,1-dioxothiolan-3-yl)-5-(5-propan-2-yltetrazol-1-yl)-benzamide;

(RS)-3-(4-Chlorophenyl)-N-(3-methyl-1,1-dioxothiolan-3-yl)-5-(5-methyltetrazol-1-yl)-benzamide;

(RS)-3-(5-Cyclopropyltetrazol-1-yl)-5-(4-fluorophenyl)-N-(3-methyl-1,1-dioxothiolan-3-yl)-benzamide;

(RS)-3-(4-Fluorophenyl)-N-(3-methyl-1,1-dioxothiolan-3-yl)-5-(5-methyltetrazol-1-yl)-benzamide;

(RS)-3-(5-tert-Butyltetrazol-1-yl)-5-(4-chlorophenyl)-N-(3-methyl-1,1-dioxothiolan-3-yl)benzamide; and

(RS)-3-(5-tert-Butyltetrazol-1-yl)-5-(4-fluorophenyl)-N-(3-methyl-1,1-dioxothiolan-3-yl)-benzamide

of formula I according to claim 1, wherein R^1′

and R¹ may form together a 1,1-dioxo-tetrahydrothiophen-3-yl ring.

3. A pharmaceutical composition comprising a compound of formula I as claimed in claim 1, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

4. A method for the treatment of schizophrenia, bipolar disorder, obsessive-compulsive disorder or autism spectrum disorder which method comprises administering an effective amount of a compound of formula I as claimed in claim 1, or a pharmaceutically acceptable salt thereof.