Orion-yhtyma Oy

Orion Corporation

Orion Corporation/orion Pharmaceutica

Kalevi E Heinola

Erkki J Honkanen

Jarmo J Pystynen

Reijo J Backstrom

Aino K Pippuri

Inge-Britt Y Linden

Erkki A Nissinen

Pentti Pohto

Pekka J Kairisalo

Seppo K Kaakkola

Pekka I Mannisto

Heimo O Haikala

Pentti T Nore

Irma O Ojala

Pekka T Mannisto

Lawrence Sellin

Tord K Langenskiold

A compound according to formula 1 ##STR1## wherein R.sub.1 and R.sub.2 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 R.sub.3 represents ##STR2## wherein R.sub.4 represents cyano or alkylcarbonyl of 2 to 5 carbon atoms and R.sub.5 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.

Pharmacologically active catechol derivatives

Catechol compounds of formula I ##STR1## where R.sub.1, R.sub.2, R.sub.3 and X are as described herein are effective Catechol-O-methyltransferase inhibitors.

Pharmacologically active compounds, methods for the preparation thereof

Substituted benzylideneiminophyenylpyridazinones or dihydropyridazinones of formula I ##STR1## in which R.sub.1 and R.sub.8 independently mean hydrogen or lower alkyl, R2 is hydrogen, lower alkyl, trifluoromethyl, hydroxy alkyl, halogen alkyl, alkoxy alkyl, pyridyl, furyl, thienyl or cycloalkyl or one of optionally substituted groups; aryl, aralkyl, aralkenyl or nitrogen containing heterocyclic ring joining through an alkyl or alkenyl group and R.sub.3, R.sub.4 and R.sub.5 independently mean hydrogen, lower alkyl, hydroxy alkyl, halogen, hydroxy, alkoxy, acyloxy, aroyloxy, formyl, acyl, cyano, amino, carboxy or trifluoromethyl, R.sub.6 and R.sub.7 independently mean hydrogen, amino, lower alkyl, hydroxy, nitro or cyano or R.sub.2 and R.sub.7 together form a --CH.sub.2 --NH-- or --CH.dbd.N-- group and A means phenyl, naphtyl or a nitrogen containing heterocyclic ring. The compounds may be used in the treatment of congestive heart failure.

Substituted pyridazinones

The invention concerns a method for the treatment of Parkinson's Disease. The method comprises administering a catechol-O-methyl-transferase inhibiting amount of a compound having the formula I ##STR1## wherein R.sub.1 and R.sub.2 independently represent hydrogen, alkylcarbamoyl of 2 to 5 carbon atoms or alkylcarbonyl of 2 to 5 carbon atoms, X represents nitro or cyano and R.sub.3 represents ##STR2## wherein R.sub.4 represents cyano or alkylcarbonyl of 2 to 5 carbon atoms and R.sub.5 represents cyano; alkylcarbonyl of 2 to 5 carbon atoms; or carbamoyl which is unsubstituted or substituted with alkyl of 1 to 8 carbon atoms, or hydroxyalkyl of 1 to 8 carbon atoms or pharmaceutically acceptable salts or esters thereof; and a sufficient amount of levodopa to treat Parkinson's Disease. A peripheral decarboxylase inhibitor such as carbidopa or benzerazide is also preferably administered.

Method of treating Parkinson's Disease using pentanedione derivatives

A compound of the formula ##STR1## and pharmaceutically acceptable salts thereof, in which A is --N.dbd.N--NH--, --X--C(R.sub.2).dbd.N--, --N.dbd.C(R.sub.2)--X--, --X--C(R.sub.2)--CH(R.sub.2).dbd.N-- or --N.dbd.C(R.sub.2)--CH(R.sub.2)--X--, wherein X is sulphur, oxygen or nitrogen and R.sub.2 is provided that where two R.sub.2 -groups are present in the A group one of the R.sub.2 groups is hydrogen, amino, substituted amino, C.sub.1-6 alkyl, substituted acylamino or one of the following groups: ##STR2## wherein R.sub.a is hydrogen, amino, substituted amino, C.sub.1-6 alkoxy, heterocyclic five membered ring or --NHCOR', wherein R' is C.sub.1-6 alkyl, aryl or heterocyclic five membered ring, R.sub.b is hydrogen, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio or hydroxy, R.sub.c is hydrogen, C.sub.1-6 alkyl or oxygen and R.sub.d is C.sub.1-6 alkyl or oxygen, R.sub.e is hydrogen, hydroxy or C.sub.1-6 alkoxy, R.sub.f is C.sub.1-6 alkyl, provided that where two R.sub.2 -groups are present in the A group, one of the R.sub.2 groups is hydrogen; B is --(CH.sub.2).sub.m --C(R.sub.3 R.sub.4)--(CH.sub.2).sub.n --, --C(R.sub.3).dbd.CH--, --CH.dbd.C(R.sub.3)--, --O--[C(R.sub.3 R.sub.4)].sub.n --, --[C(R.sub.3 R.sub.4)].sub.n --O--, --S--[C(R.sub.3 R.sub.4)].sub.n -- or --[C(R.sub.3 R.sub.4)].sub.n --S-- wherein R.sub.3 and R.sub.4, which can be independently the same or different, are hydrogen, C1-.sub.6 alkyl, aryl (preferably phenyl) or pyridyl and m and n are independently zero or 1; D is either oxygen or sulphur; the two R-groups are indepenently hydrogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, amino, acylamino or substituted acylamino, nitro, halogen, cyano, aldehyde, carboxy, carbamoyl; R.sub.1 is a hydrogen or C.sub.1-6 alkyl or R and R.sub.1 form together a fused 6-membered heterocyclic ring. The compound is effective in the treatment of congestive heart failure.

Heterocyclic lactam compounds

Pharmacologically active catechol derivatives of formula I ##STR1## wherein R.sub.1 and R.sub.2 independently comprise hydrogen, alkyl, acyl, optionally substituted aroyl, lower alkylsulfonyl or alkylcabamoyl or taken together form a lower alkylidene or cycloalkylidene, X comprises an electronegative substituent such as halogen, nitro, cyano, lower alkylsulfonyl, sulfonamido, aldehyde, caboxyl or trifluoromethyl and R.sub.3 comprises hydrogen, halogen, hydroxy alkyl, amino, nitro, cyano, trifluoromethyl, lower alkylsulfonyl, sulfonamide, aldehyde, alkyl carbonyl, aralkylidene carbonyl or carboxyl or a group selected from ##STR2## wherein R.sub.4 comprises hydrogen, alkyl, cyano, carboxyl or acyl and R.sub.5 comprises hydrogen, cyano, carboxyl, alkoxycarbonyl, carboxyalkenyl, nitro, acyl, optionally substituted aroyl or heteroaroyl, hydroxyalkyl or carboxyalkyl or R.sub.4 and R.sub.5 together form a five to seven membered substituted cycloalkanone ring;

Growing community of inventors

Jarvempaa, Finland

Kalevi E Heinola