Ciba-geigy Corporation

Henkel Kommanditgesellschaft Auf Aktien

Pier G Ferrini

Richard Goschke

Alberto Rossi

Alfred Sallmann

Georges Haas

Ernst Habicht

Raymond Bernasconi

Jacques Gosteli

Knut A Jaeggi

Martin Missbach

Alex Sele

Jonathan Green

Peter H Stahl

Leo Widler

Irmgard Wiesenberg

Carlo Voellmy

Ulrich Feige

Andreas Von Sprecher

Oswald Schier

Andreas V Sprecher

Peter Burckhardt

Aminoalkylphenyl derivatives of formula I ##STR1## wherein alk, R.sub.1 -R.sub.6, X and Y are as defined in the description, and salts thereof, exhibit properties inhibiting the biosynthesis of interleukin-1 (IL-1) and analgesic properties and can therefore be used as active ingredients in medicaments. They are prepared in a manner known per se.

Aminoalkylphenyl compounds

Substituted dialkylthio ethers of formula I ##STR1## wherein R.sub.1 -R.sub.6, alk, X and Y are as defined in the description, and salts thereof, exhibit properties inhibiting the biosynthesis of interleukin-1 (IL-1) and analgesic properties and can therefore be used as active ingredients in medicaments. They are prepared in a manner known per se.

Substituted dialkylthio ethers

N-Benzoyl-N'-(2-phenylethyl)-piperazines of formula I ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 have the meanings as defined in the specification, and salts thereof, have analgesic properties and can be used as analgesic active ingredients in medicaments. They are prepared, for example, as follows: a compound of formula II ##STR2## wherein X.sub.1 is carboxy or reactive functionally modified carboxy, or a salt thereof, is reacted with a compound of formula III ##STR3## wherein X.sub.2 is hydrogen.

Substituted N-benzoyl-N'-(2-phenylethyl)-piperazines

Amino-substituted piperazine derivatives of formula I ##STR1## wherein R.sub.1 -R.sub.6, X and Y are as defined in the description, and salts thereof, have properties inhibiting the biosynthesis of interleukin-1 (IL-1) as well as analgesic properties and can therefore be used as active ingredients in medicaments. They are prepared in a manner known per se.

Amino-substituted piperazine derivatives

Compounds of the formula I ##STR1## in which R.sub.1 is lower alk-2-en-1-yl, lower alk-3-en-2-yl, lower alk-2-yn-1-yl or lower alkyl substituted in the 2,3-position by radicals which can be eliminated to give a double bond, R.sub.2 is hydrogen and R.sub.3 is methyl which is unsubstituted or substituted by radicals which can be eliminated together with hydrogen R.sub.2 to give a double bond or R.sub.2 and R.sub.3 are both hydrogen or lower alkyl or are together methylene and R.sub.4 is a group of the formula Ia, Ib or Ic ##STR2## in which R.sub.5 is hydrogen, lower alkyl, lower alk-2-en-1-yl or lower alk-2-yn-1-yl and R.sub.6 is a group of the formula Id or Ie ##STR3## in which R.sub.1, R.sub.2, R.sub.3 and R.sub.5 are as defined, and their pharmaceutically acceptable salts can be used in a novel manner for the treatment of diseases of the rheumatoid type.

Use of 2-iminothiazolidin-4-one derivatives as novel pharmaceutical

Compounds of formula I ##STR1## wherein X and Y are each independently of the other thio or sulfynyl, R.sub.1 is lower alk-2-en-1-yl, lower alk-3-en-2-yl, lower alk-2--yn-1-yl, or lower alkyl that is substituted in the 2,3-position by radicals that can be eliminated to form a double bond, R.sub.2 is hydrogen and R.sub.3 is unsubstituted methyl or methyl substituted by a radical that can be eliminated together with hydrogen Rhd 2 to form a double bond, or R.sub.2 and R.sub.3 are each hydrogen or lower alkyl or together are methylene, R.sub.4 is free or protected hydroxy, or hydrogen, and R.sub.5 is hydrogen, lower alkyl, lower alk-2-en-1-yl, lower alk-2-yn-1-yl, or lower alkyl that is substituted in the 2,3-position by radicals that can be eliminated to form a double bond, and their pharmaceutically acceptable salts may be used in a novel manner for the treatment of disorders of the rheumatoid type.

Use of carbazones as novel active ingredients in medicaments

Benzo[b]thiophene derivatives of formula ##STR1## their tautomers and salts, in which the index n is 0, 1 or 2, alk is lower alkylene, Ar is phenyl, naphthyl or a monocyclic, five- or six-membered heteroaryl radical, wherein the aromatic radical is unsubstituted or is mono- or poly-substituted by lower alkyl, halo-lower alkyl, halogen and/or nitro, and the ring A is unsubstituted or is mono- or poly-substituted by lower alkyl, lower alkoxy, lower alkylthio, lower alkanesulfinyl, lower alkanesulfonyl, halo-lower alkyl, halogen and/or by nitro, can be used, for example, as active ingredients in medicaments.

2-hydroxy-3-(aryl-alkanoyl)-benzo[B]thiophenes and compositions thereof

The invention relates to topically administrable pharmaceutical preparations containing pharmaceutically acceptable methanediphosphonic acid derivatives of formula ##STR1## and their salts, wherein R.sub.1 and R.sub.2 are hydrogen or C.sub.1 -C.sub.3 alkyl.

Topical formulations

The invention relates to topically adminstrable pharmaceutical preparations containing pharmaceutically acceptable methanediphosphonic acid derivatives of formula ##STR1## and their salts, wherein each of R.sub.1 and R.sub.2 is halogen, or wherein R.sub.1 is hydrogen and R.sub.2 is Ar--S-- or Het.sub.1 --NH--, in which Ar is unsubstituted or substituted phenyl and Het.sub.1 is unsubstituted or substituted, monocyclic, 5- or 6-membered monoaza-, diaza- or thiaza-aryl that is bonded via a ring carbon atom, or wherein R.sub.1 is hydrogen or hydroxy and R.sub.2 is --A--R.sub.3, in which A is alkylene and, on the one hand, R.sub.3 is Het.sub.2, which is Het.sub.1 bonded via a ring carbon or ring nitrogen atom, or, on the other hand, R.sub.3 is hydrogen, or amino that is unsubsituted or mono- or di-substituted by identical or different substituents selected from alkyl, cycloalkyl, Ar-alkyl, Ar-O-alkyl, Ar-S-alkyl and Het.sub.1 -alkyl, or that is disubstituted by optionally Ar-containing alkylene, wherein two alkylene carbon atoms mar additionally be linked to one another via alkylene and Ar and Het.sub.1 are each as defined above, with the proviso that when R.sub.2 is --A--R.sub. 3, A is ethylene and R.sub.3 is unsubstituted or C.sub.1 -C.sub.3 alkyl-substituted amino, R.sub.1 is other than hydroxy.

Topically administrable pharmaceutical preparations

Benzo[b]thiophene derivatives of formula ##STR1## their tautomers and salts, in which the index n is 0, 1 or 2, alk is lower alkylene, Ar is phenyl, naphthyl or a monocyclic, five- or six-membered heteroaryl radical, wherein the aromatic radical is unsubstituted or is mono- or poly-substituted by lower alkyl, halo-lower alkyl, halogen and/or by nitro, and the ring A is unsubstituted or is mono- or poly-substituted by lower alkyl, lower alkoxy, lower alkylthio, lower alkanesulfinyl, lower alkanesulfonyl, halo-lower alkyl, halogen and/or by nitro, can be used, for example, as active ingredients in medicaments.

Benzo-[b]thiophene derivatives

Piperazines of the formula ##STR1## and their salts, in which each of Ar.sub.1 and Ar.sub.2, independently of the other, represents phenyl that is unsubstituted or mono- or di-substituted by C.sub.1 -C.sub.7 -alkyl, C.sub.1 -C.sub.7 -alkoxy, cyano, halogen, trifluoromethyl, amino, C.sub.1 -C.sub.7 -alkylamino, di-C.sub.1 -C.sub.7 -alkylamino and/or by C.sub.1 -C.sub.7 -alkanoylamino, can be used as the active ingredients of medicaments and are manufactured in a manner known per se.

Disubstituted piperazines

Novel substituted 2-mercaptoimidazoles of the formula ##STR1## in which at least one of the radicals R.sub.1 and R.sub.2 is a substituted or unsubstituted heteroaryl group and the other is a substituted or unsubstituted aryl group, R.sub.3 is hydrogen or lower alkyl, n is 0, 1 or 2 and R.sub.4 is a substituted or unsubstituted aliphatic hydrocarbon radical and their pharmaceutically usable salts exhibit anti-inflammatory, anti-nociceptive and/or antithrombotic activity.

2-(Sulphinyl and sulfonyl)-4(5)-phenyl-5(4)-(3'-pyridyl)-imidazols

Novel mercaptoimidazole derivatives

Substituted benzophenones of the formula ##STR1## in which Ph represents unsubstituted or substituted phenyl and R represents free, esterified or amidated carboxy, have anti-inflammatory and/or analgesic properties and can be used as active ingredients in medicaments. They are manufactured, for example, as follows: a compound or a mixture of compounds of the formula ##STR2## in which X.sub.1 and X.sub.2 together represent a group of the formula --C(.dbd.O)--O that is bonded via the carbonyl group to the radical Ph and X.sub.3 represents hydrogen, or one of the radicals X.sub.1 and X.sub.3 represents a group of the formula --C(.dbd.O)--Z, the other represents hydrogen and X.sub.2 represents a group R'O-- in which R' represents hydrogen or a hydroxy-protecting group, is subjected to acid treatment and the primary product is decomposed solvolytically.

Benzophenones

Substituted anthranilamides of the formula ##STR1## in which R.sub.1 is hydrogen or an aliphatic, cycloaliphatic or cycloaliphatic-aliphatic hydrocarbon radical, R.sub.2 is hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl, R.sub.3 is hydrogen or an aliphatic or substituted or unsubstituted araliphatic or heteroaryl-aliphatic hydrocarbon radical and alk and alk' are identical or different lower alkylene radicals which separate the nitrogen atoms by 2 or 3 carbon atoms, and salts thereof, possess analgesic, anti-inflammatory and anti-allergic properties and may be used as active ingredients of analgesic, anti-inflammatory and anti-allergic pharmaceuticals. They are prepared, for example, by reacting an acid of the formula ##STR2## or a reactive functional derivative thereof, with an amine of the formula ##STR3## or a reactive derivative or salt thereof.

Growing community of inventors

Binningen, Switzerland

Pier G Ferrini