3-phenyl-2-propeneamine derivatives, their preparation and compositions containing them

• US 4,686,309 A
• Filed: 02/15/1985
• Issued: 08/11/1987
• Est. Priority Date: 02/16/1984
• Status: Expired due to Fees

• Current Assignee: Rhone-Poulenc Sante Les Miroirs
• Original Assignee: Rhone-Poulenc Sante (Sanofi )
• Inventors: Paris, Jean-Marc, Barriere, Jean-Claude, Cotrel, Claude, Corbet, Jean-Pierre, Farge, Daniel
• Primary Examiner(s): Warren, Charles F.
• Assistant Examiner(s): NOT, DEFINED
• Application Number:
  US06/702,088
• Time in Patent Office: 907 Days
• Field of Search: 564/340, 564/341, 564/355, 564/339, 564/336, 514/653, 560/163, 560/250, 560/19, 560/20, 560/45, 560/47, 560/107, 558/275, 540/553, 540/544, 540/597, 540/609, 540/610, 544/88, 544/96, 544/158, 544/168, 544/170, 544/171, 544/53, 544/54, 544/55, 544/59, 544/60, 544/288, 544/333, 544/335, 544/360, 544/399, 544/400, 544/401, 546/193, 546/234, 546/239, 546/236, 546/240, 546/300, 546/329, 546/335, 548/146, 548/214, 548/215, 548/240, 548/300, 548/356, 548/518, 548/567, 548/570, 548/573
• US Class Current: 564/355
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: C07D 207/08 with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 213/38 having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
• CPC Class Codes: C07D 213/70 Sulfur atoms
• CPC Class Codes: C07D 295/092 with aromatic radicals attached to the chain
• CPC Class Codes: C07D 307/32 Oxygen atoms
• CPC Class Codes: C07F 9/4006 Esters of acyclic acids which can have further substituents on alkyl

Abstract

The invention provides compounds of formula: ##STR1## in which R=H, halogen, alkyl, alkyloxy, alkythio, NH₂, alkylamino, dialkylamino or CF₃, R₃ =H or alkyl, either R₄ and R₅ =H and R₁ and R₂ =H or alkyl, optionally substituted by alkenyl (2 to 4 C) or alternatively R₁ and R₂ form together a saturated heterocyclic ring containing 4 to 7 ring members and optionally containing another heteroatom such as O, S or N optionally substituted by alkyl, or R₄ =H, R₁ =H or alkyl and R₂ and R₅ together form an alkylene (3 to 4 C) radical and (i) either A=alkyl or phenyl which is unsubstituted or substituted by one or two substituents chosen from halogen, alkyl, alkyloxy, alkylthio, NH₂, alkylamino, dialkylamino, NO₂ or CF₃ or alternatively A=pyridyl, benzyl or cycloalkyl (3 to 6C), Y=S, SO or SO₂ or a radical: ##STR2## in which R₆ =H or alkyl and R₇ =H or alkylcarbonyl, alkyloxycarbonyl, alkylaminocarbonyl or benzoyl, optionally substituted by one or two halogen, alkyl, alkyloxy, alkylthio, NH₂, alkylamino, dialkylamino, NO₂ or CF₃ groups, (ii) or Y and A together form a 1-hydroxycycloalkyl radical, the ring of which contains 5 or 6 C, optionally joined to a benzene ring, it being understood that the alkyl radicals and alkyl parts contain 1 to 4 C as a straight or branched chain, and that the invention relates to all the possible geometric and optical isomers as well as their mixtures.

These compounds are useful as antidepressants.

Claims

1. A 3-phenyl-2-propeneamine of the formula:

##STR36## in which R denotes hydrogen, halogen, alkyl, alkyloxy, alkylthio, amino, alkylamino, dialkylamino or trifluoromethyl, R₃ denotes hydrogen or alkyl;

either R₄ and R₅ each denote hydrogen and R₁ and R₂, which are identical or different, each denote hydrogen or alkyl which is unsubstituted or substituted by alkenyl of 2 to 4 carbon atoms, or R₁ and R₂ form together with the nitrogen atom to which they are linked or saturated heterocyclic radical of 4 to 7 ring atoms optionally containing another heteroatom selected from the group consisting of oxygen, sulphur or nitrogen which is unsubstituted or substituted by alkyl;

or R₄ denotes hydrogen, R₁ denotes hydrogen or alkyl and R₂ and R₅ together form an alkylene radical 3 or 4 carbon atoms; and

either (i)A denotes phenyl which is unsubstituted or substituted by one or two substituents chosen from halogen, alkyl, alkyloxy, alkylthio, amino, alkylamino, dialkylamino, nitro and trifluoromethyl, pyridyl, benzyl or cycloalkyl of 3 to 6 carbon atoms, and Y denotes sulphur, sulphinyl, sulphonyl or a radical of the formula;

##STR37## in which R₆ denotes hydrogen or alkyl and R₇ denotes hydrogen, alkylcarbonyl, alkyloxycarbonyl, alkylaminocarbonyl or benzoyl, which is unsubstituted or substituted by one or two substituents chosen from halogen, alkyl, alkyloxy, alkylthio, amino, alkylamino, dialkylamino, nitro and trifluoromethyl, or (ii) Y and A together form a 1-hydroxycycloalkyl radical the ring of which contains 5 or 6 carbon atoms, optionally joined to a benzene ring; and

its pharmaceutically acceptable salts, the aforesaid alkyl radicals and alkyl parts containing 1 to 4 carbon atoms each as a straight or branched chain, in the form of any geometric or optical isomer or any mixture thereof.

2. A 3-phenyl-2-propeneamine according to claim 1 in which R denotes hydrogen, halogen, alkyl, alkyloxy, alkylthio, amino, alkylamino, dialkylamino or trifluoromethyl;

R₃ denotes hydrogen or alkyl; and

either R₄ and R₅ denote hydrogen and R₁ and R₂ which are identical or different, each denote hydrogen or alkyl unsubstituted or substituted by alkenyl of 2 to 4 carbon atoms, or R₁ and R₂ together form with the nitrogen atom to which they are linked a saturated heterocyclic radical containing 4 to 7 ring atoms;

or R₄ denotes hydrogen, R₁ denotes hydrogen or alkyl and R₂ and R₅ together form alkylene of 3 or 4 carbon atoms; and

either

(i) A denotes phenyl which is unsubstituted or substituted by one or two substituents chosen from halogen, alkyl, alkyloxy, and trifluoromethyl, pyridyl, benzyl or cycloalkyl of 3 to 6 carbon atoms, Y denotes sulphur, sulphinyl, or a radical of formula;

##STR38## in which R₆ denotes hydrogen or alkyl and R₇ denotes hydrogen, alkylcarbonyl, alkyloxycarbonyl, benzoyl or alkylaminocarbonyl, or (ii) Y and A together form a 1-hydroxycycloalkyl radical the ring of which contains 5 or 6 carbon atoms, optionally combined with a benzene, ring, in the Z or E form, the said alkyl radicals and alkyl parts containing 1 to 4 carbon atoms each, as a straight or branched chain, and its pharmaceutically acceptable salts.

3. A 3-phenyl-2-propeneamine according to claim 1 in which R denotes hydrogen, halogen, alkyl, alkyloxy, alkylthio, amino, alkylamino, dialkylamino or trifluoromethyl, R₃ denotes hydrogen, R₄ and R₅ denote hydrogen, and R₁ and R₂, which are identical or different, each denote hydrogen or alkyl unsubstituted or substituted by alkenyl of 2 to 4 carbon atoms;

and A denotes phenyl, which is unsubstituted or substituted by one or two substituents chosen from halogen and alkyl, pyridyl or cycloalkyl of 3 to 6 carbon atoms, Y denotes a sulphur atom, or a radical of formula;

##STR39## in which R₆ denotes hydrogen and R₇ denotes hydrogen or alkylcarbonyl, in the Z form, the said alkyl radicals and alkyl parts containing 1 to 4 carbon atoms each as a straight or branched chain, and its pharmaceutically acceptable salts.

4. A compound according to claim 1 which is 4-dimethylamino-1,2-diphenyl-2-buten-1-ol-(Z) and its pharmaceutically acceptable salts.

5. A compound according to claim 1 which is 4-methylamino-1,2-diphenyl-2-buten-1-ol-(Z) and its pharmaceutically acceptable salts.

6. A compound according to claim 1 which is 1-(3-fluorophenyl)-4-dimethylamino-2-phenyl-2-buten-1-ol-(Z) and its pharmaceutically acceptable salts.

7. A compound according to claim 1 which is 1-(3-chlorophenyl)-4-dimethylamino-2-phenyl-2-buten-1-ol-(Z) and its pharmaceutically acceptable salts.

8. A compound according to claim 1 which is 1-(3-bromophenyl)-4-dimethylamino-2-phenyl-2-buten-1-ol-(Z) and its pharmaceutically acceptable salts.

9. A compound according to claim 1 which is 4-dimethylamino-1-(2-methylphenyl)-2-phenyl-2-buten-1-ol-(Z) and its pharmaceutically acceptable salts.

10. A pharmaceutical composition comprising a compound as claimed in claim 1 as a base or a pharmaceutically acceptable salt thereof in combination with one or more compatible, pharmaceutically acceptable diluents or adjuvants.