Alpha-heterocycle substituted tolunitriles

• US 5,352,795 A
• Filed: 05/11/1992
• Issued: 10/04/1994
• Est. Priority Date: 03/07/1986
• Status: Expired due to Term

• Current Assignee: Novartis Pharmaceuticals Corporation (Novartis Ag)
• Original Assignee: Ciba-Geigy Corporation (Novartis Ag)
• Inventors: Bowman, Robert M., Browne, Leslie J.
• Primary Examiner(s): Fan, Jane T.
• Application Number:
  US07/882,188
• Time in Patent Office: 876 Days
• Field of Search: 548/262.2, 548/335, 546/330
• US Class Current: 548/262.2
• CPC Class Codes: C07D 213/57 Nitriles
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 233/56 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 249/08 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles

Abstract

The invention is concerned with aromatase inhibiting compounds of formula I ##STR1## wherein R and Ro represent hydrogen or lower alkyl; or R and Ro located on adjacent carbon atoms and together when combined with the benzene ring to which they are attached form a naphthalene or tetrahydronaphthalene ring; R₁ and R₂ independently represent hydrogen, lower alkyl, (lower alkyl, aryl or aryl-lower alkyl)-thio, lower alkenyl, aryl, aryl-lower alkyl, C₃ -C₆ -cycloalkyl, or C₃ -C₆ -cycloalkyl-lower alkyl; or R₁ and R₂ combined represent lower alkylidene, mono-or di-aryl-lower alkylidene; R₁ and R₂ combined also represent C₄ -C₆ -straight chain alkylene, lower alkyl-substituted straight chain alkylene or ortho-phenylene bridged-C₂ -C₄ -straight chain alkylene, each forming with the carbon atom attached thereto a corresponding optionally substituted or benzo-fused 5, 6 or 7-membered ring; W represents 1-imidazolyl, 1-(1,2,4- or 1,3,4)-triazolyl or 3-pyridyl; or W represents 1-imidazolyl, 1-( 1,2,4 or 1,3,4)-triazolyl or 3-pyridyl substituted by lower alkyl; and pharmaceutically acceptable salts thereof.

Claims

1. A method for preparing a compound of the formula ##STR16## wherein R and R_o represent hydrogen or lower alkyl;

or R and R_o located on adjacent carbon atoms and together when combined with the benzene ring to which they are attached form a naphthalene or tetrahydronaphthalene ting;

R₁ represents hydrogen;

R₂ represents 4-cyanophenyl; and

W represents 1-(1,2,4)-triazolyl;

which comprises condensing under basic conditions using an alkali metal aikoxide a compound of the formula XI ##STR17## wherein R, R_o and W have meaning as defined above, with p-fluorobenzonitrile.

2. A method according to claim 1 wherein the alkali metal alkoxide is potassium t-butoxide.

3. A method according to claim 1 for preparing 4-[alpha-(4-cyanophenyl)-1-(1,2,4-triazolyl)-methyl]benzonitrile which comprises condensing 4-[1-(1,2,4)-triazolylmethyl]benzonitrile with 4-fluorobenzonitrile using potassium tert-butoxide in dimethylformamide.

4. A process according to claim 1 for preparing 4-[alpha-(4-cyanophenyl)-1-(1,2,4-triazolyl)-methyl]benzonitrile.