Pharmacologically active catechol derivatives

• US 5,446,194 A
• Filed: 09/16/1993
• Issued: 08/29/1995
• Est. Priority Date: 11/28/1986
• Status: Expired due to Term

• Current Assignee: Orion Corporation (Smiths Group International Holdings Ltd.)
• Original Assignee: Orion-Yhtyma OY
• Inventors: Honkanen, Erkki J., Kaakkola, Seppo K., Heinola, Kalevi E., Mannisto, Pekka I., Pystynen, Jarmo J., Kairisalo, Pekka J., Linden, Inge-Britt Y., Pohto, Pentti, Backstrom, Reijo J., Pippuri, Aino K., Nissinen, Erkki A. O.
• Primary Examiner(s): Haley, Jacqueline
• Application Number:
  US08/121,617
• Time in Patent Office: 712 Days
• Field of Search: 558/401, 558/404, 558/414, 564/166, 564/167, 564/169, 560/136
• US Class Current: 558/401
• CPC Class Codes: C07C 205/19 having nitro groups bound to carbon atoms of six-membered aromatic rings and hydroxy groups bound to acyclic carbon atoms
• CPC Class Codes: C07C 205/22 having one nitro groups bound to the ring
• CPC Class Codes: C07C 205/23 having two nitro groups bound to the ring
• CPC Class Codes: C07C 205/26 and being further substituted by halogen atoms
• CPC Class Codes: C07C 205/34 having nitro groups bound to carbon atoms of six-membered aromatic rings and etherified hydroxy groups bound to acyclic carbon atoms of the carbon skeleton
• CPC Class Codes: C07C 205/37 the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
• CPC Class Codes: C07C 205/43 to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
• CPC Class Codes: C07C 205/44 the carbon skeleton being further substituted by —CHO groups
• CPC Class Codes: C07C 205/45 the carbon skeleton being further substituted by at least one doubly—bound oxygen atom, not being part of a —CHO group
• CPC Class Codes: C07C 205/56 having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
• CPC Class Codes: C07C 205/57 having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
• CPC Class Codes: C07C 255/00 Carboxylic acid nitriles cyanogen or compounds thereof C01C3/00
• CPC Class Codes: C07C 317/00 Sulfones; Sulfoxides
• CPC Class Codes: C07C 323/00 Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
• CPC Class Codes: C07C 43/23 containing hydroxy or O-metal groups
• CPC Class Codes: C07C 45/565 by reaction with hexamethylene-tetramine
• CPC Class Codes: C07C 45/673 by change of size of the carbon skeleton
• CPC Class Codes: C07C 45/74 combined with dehydration
• CPC Class Codes: C07C 47/565 all hydroxy groups bound to the ring
• CPC Class Codes: C07C 47/575 containing ether groups, groups, groups, or groups
• CPC Class Codes: C07C 49/835 : having unsaturation outside an aromatic ring
• CPC Class Codes: C07C 49/84 : containing ether groups, groups, groups, or groups
• CPC Class Codes: C07C 59/56 : containing halogen
• CPC Class Codes: C07C 59/64 : containing six-membered aromatic rings
• CPC Class Codes: C07C 59/68 : the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
• CPC Class Codes: C07D 207/333 : Radicals substituted by oxygen or sulfur atoms
• CPC Class Codes: C07D 211/32 : by oxygen atoms
• CPC Class Codes: C07D 211/58 : attached in position 4
• CPC Class Codes: C07D 213/30 : Oxygen atoms
• CPC Class Codes: C07D 215/14 : Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 295/13 : to an acyclic saturated chain
• CPC Class Codes: C07D 295/185 : from aliphatic carboxylic acids
• CPC Class Codes: C07D 317/62 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
• CPC Class Codes: C07D 319/24 : [b,e]-condensed with two six-membered rings
• CPC Class Codes: C07D 405/04 : directly linked by a ring-member-to-ring-member bond

Abstract

A compound according to formula 1 ##STR1## wherein R₁ and R₂ independently represent hydrogen, carbamoyl which is substituted by an alkyl of 1 to 4 carbon atoms, alkylcarbonyl of 2 to 5 carbon atoms or phenyl carbonyl, X represents halogen nitro or cyano and R₃ represents ##STR2## wherein R₄ represents cyano or alkylcarbonyl of 2 to 5 carbon atoms and R₅ represents carbamoyl which is unsubstituted or substituted with alkyl of 1 to 8 carbon atoms or which is substituted with hydroxyalkyl of 1 to 8 carbon atoms or pharmaceutically acceptable esters and salts thereof, and a pharmaceutically acceptable carrier therefor, as well as pharmaceutical compositions containing said compounds as COMT inhibitors.

Claims

1. A compound according to formula I ##STR53## wherein R₁ and R₂ independently represent hydrogen, carbamoyl which is substituted by an alkyl of 1 to 4 carbon atoms, alkylcarbonyl of 2 to 5 carbon atoms or phenyl carbonyl, X represents nitro or cyano and R₃ represents ##STR54## wherein R₄ represents cyano or alkylcarbonyl of 2 to 5 carbon atoms and R₅ represents carbamoyl which is unsubstituted or substituted with alkyl of 1 to 8 carbon atoms or which is substituted with hydroxyalkyl of 1 to 8 carbon atoms or pharmaceutically acceptable esters and salts thereof.

2. The compound according to claim 1, wherein R₄ is cyano and R₅ is carbamoyl which is unsubstituted or substituted with alkyl of 1 to 3 carbon atoms.

3. N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide.

4. A compound selected from the group consisting of 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide, N,N-dimethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide and N-isopropyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-acrylamide.