Orion-yhtyma Oy

Orion Corporation

Orion Corporation/orion Pharmaceutica

Reijo J Backstrom

Erkki J Honkanen

Inge-Britt Y Linden

Erkki A Nissinen

Pentti Pohto

Aino K Pippuri

Jarmo J Pystynen

Kalevi E Heinola

Heimo O Haikala

Pentti T Nore

Pekka J Kairisalo

Tapio J Korkolainen

Paivi A Aho

Seppo K Kaakkola

Pekka I Mannisto

Anne M Luiro

Jorma V Haarala

Tom Wikberg

Erkki A Nissenen

Inge-Birtt Linden

Lawrence Sellin

Irma O Ojala

Atso Raasmaja

Tord K Langenskiold

Pekka T Mannisto

Juoko M Levijoki

A compound of formula I ##STR1## wherein R.sub.1 is nitro, halogeno or cyano group and R.sub.2 is a group selected from ##STR2## wherein Y and Z are independently oxygen, sulfur or NR, wherein R is hydrogen, straight or branched C.sub.1-8 alkyl, C.sub.5-7 cycloalkyl, phenylC.sub.1-8 alkyl or phenyl group and X.sub.1 and X.sub.2 are NR, where R is hydrogen, straight or branched C.sub.1-8 alkyl, C.sub.5-7 cycloalkyl, phenylC.sub.1-8 alkyl or phenyl group, or a pharmaceutically acceptable salt or ester thereof. Pharmaceutical compositions are also disclosed.

Pharmacologically active catechol derivatives

##STR1## Compounds of formula (I), wherein R.sub.1 is an electronegative substituent such as nitro, halogeno or cyano group and R.sub.2 is a group selected from (Ia) and (Ib), wherein R is hydrogen, or an alkyl, cycloalkyl, aralkyl or aryl group, wherein X.sub.1, X.sub.2, Y and Z are independently oxygen, sulfur of NR, wherein R may be as defined above and pharmaceutically acceptable esters and salts thereof are useful in the prevention or treatment of tissue damage induced by lipid peroxidation.

Method for the preparation of 3,4-dihydroxy-5-nitrobenzaldehyde

Diastereomeric intermediate salts of formulae (IIIa) or (IIIb) ##STR1## are prepared.

Anti-ischemic medicament

Known and new catechol derivates may be used as medicinal antioxidants in the prevention or treatment of tissue damage induced by lipid peroxidation. The conditions and diseases to be treated are for example heart disease, rheumatoid arthritis, cancer, inflammatory disease, a rejection reaction in organ transplants, ischemia, cancer and aging.

Catechol derivatives, their physiologically acceptable salts, esters and

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.

##STR1## Substituted cyclic hydroxamic acids of general formula (I) in which R.sub.1, R.sub.2 and R.sub.3 are independently hydrogen, halogen, lower alkyl, lower alkoxy, cycloalkoxy, aryloxy which is optionally substituted by 1 to 3 halogen, or aralkyloxy, which is optionally substituted by 1 to 3 halogen, or R.sub.1 and R.sub.2 together form a --O--CH.sub.2 --O-- group; with the proviso that R.sub.3 is not hydrogen when R.sub.1 and R.sub.2 are both hydrogen; R.sub.4 and R.sub.5 are independently hydrogen or lower alkyl, R.sub.6 is hydrogen or lower alkyl and physiologically acceptable salts and esters thereof are selective inhibitors of phosphodiesterase IV activity and leukotriene B.sub.4 and C.sub.4 synthesis without showing any significant effect on phosphodiesterase III activity, and are therefore useful in the treatment of hypersensitivity and inflammatory diseases.

1-hydroxy-4(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone and

Compound of formula ##STR1## wherein n is 0 or 1, R.sub.1 and R.sub.2 are independently methyl, ethyl or cyclopropyl and R is an optionally substituted phenyl or heteroaryl group or salt or ester thereof are useful in the treatment of inflammatory bowel disease.

Substituted .beta.-diketones and their use

##STR1## wherein R.sub.1 and R.sub.2 are each independently hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, hydroxy, aryl or heteroaryl or amino, the alkyl, aryl, heteroaryl or amino group being optionally substituted; R.sub.3 is hydrogen, optionally substituted alkyl of 1 to 6 carbon atoms or optionally substituted aryl or heteroaryl and salts, ethers and esters thereof are useful as cytoprotective agents, especially as antitulcerogenic or gastroprotective agents.

Substituted .beta.-diketones

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.

Growing community of inventors

Helsinki, Finland

Reijo J Backstrom