Merck Patent Gesellschaft MIT Beschrankter Haftung

Merck Patent Gesellschaft MIT Beschraenkter Haftung

Zdenek Simane

Erich Schacht

Werner Mehrhof

Herbert Nowak

Detlev Kayser

Joachim Gante

Hans-Adolf Kurmeier

Dieter Orth

Albrecht Wild

Rochus Jonas

Gunter Lauterbach

Reinhard Lissner

Morpholino containing compounds, compositions and use thereof

Alkynols of the formula, ##STR1## wherein X is F, Cl or Br; n is 0 or 1; m is 0 or 1 and R (if m is 0) is hydroxyalkyl of 1-6 carbon atoms or (if m is 1) alkyl, straight-chain hydroxyalkyl or straight-chain tetrahydropyran-2-yloxyalkyl of 2-6 carbon atoms in the alkyl, have anti-inflammatory activity.

Alkynols and process for their preparation

Anti-inflammatory (halo-4-biphenylyl)-alkanolamines

Hydratropic acid derivatives of the formula ##STR1## wherein R.sub.1 is H, alkyl of 1-4 carbon atoms, 2-acetamidoethyl, 1-methyl-4-piperidyl, or 2,3-dihydroxypropyl, and R.sub.2 is Hal, phenyl, 4-Hal-phenyl, 4-Hal-phenoxy, 4-Hal-phenoxymethyl, 1,2,3,4-tetrahydro-1-naphthyl, 1-pyrryl, piperidino, isoindolino, 1,2,3,4-tetrahydroquinolino, 1,2,3,4-tetrahydro-4-quinolyl or 1-methyl-1,2,3,4-tetrahydro-4-quinolyl, Hal being F, Cl, or Br, and the physiologically acceptable salts thereof, which possess cholesterol and triglyceride serum-level-lowering activity, can be prepared by reacting a phenol of the formula ##STR2## with a compound of the formula X--C(CH.sub.3)(C.sub. 6 H.sub.5)--COOR.sub.1 wherein X represents Cl, Br, I, OH, or esterified OH.

Hydratropic acid derivatives and process for the production thereof

Biphenylyl ethers of the formula ##STR1## and their physiologically acceptable acid addition salts exhibit pharmaceutically useful serum cholesterol and triglyceride lowering, fibrinolytic, thrombocyte aggregation inhibition, .beta.-receptor blocking and neuroleptic effects.

Biphenylyl ethers

Indole derivatives of the formula ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are identical or different and each is H or alkyl of 1 - 6 carbon atoms, R.sup.4 is H or methyl and R.sup.5 is methyl, phenyl or chlorophenyl, and their physiologically acceptable salts, are blood cholesterol-lowering agents.

Indole derivatives and process for their preparation

Biphenylyl ethers of the formula R--O--CH.sub.2 --CR.sub.1 (OH)--CH.sub.2 Z wherein R.sub.1 is H or CH.sub.3 ; Z is dialkylamino of 2-8 carbon atoms, morpholino, pyrrolidino, piperidino, homopiperidino, hydroxypyrrolidino, hydroxypiperidino or hydroxyhomopiperidino; R is either biphenylyl substituted by at least one of F, Cl, Br, I, CF.sub.3, NO.sub.2 and piperidino or, when R.sub.1 is CH.sub.3 or when Z is homopiperidino, hydroxypyrrolidino, hydroxypiperidino or hydroxyhomopiperidino, unsubstituted biphenyl, and the physiologically acceptable acid addition salts thereof, possess cholesterol blood-level-lowering activity and can be produced by reacting a compound of the formula R--O--CH.sub.2 --Y wherein Y is ##STR1## or --CR.sub.1 (OH)--CH.sub.2 X, X being Cl, Br, I or a free or functionally modified OH-group, with an amine of the formula H-Z.

Biphenylyl ethers and method of use

Phenoxyacetic acids of the formula ##STR1## wherein R.sub.1 is H or alkyl of 1-4 carbon atoms; R.sub.2 is H, or when R.sub.4 is Q, also alkyl of 1-4 carbon atoms; R.sub.3 is methyl, phenyl or chlorophenyl; and R.sub.4 is piperidino, isoindolino, 1,2,3,4-tetrahydroquinolino, 1-R.sub.5 -1,2,3,4-tetrahydro-4-quinolyl, 4-piperidinophenyl, 4-piperidinophenoxy, 1-pyrryl, or Q, wherein R.sub.5 is H or alkyl of 1-4 carbon atoms; and Q is 4-oxo-1,2,3,4-tetrahydroquinolino, 4-hydroxy-1,2,3,4-tetrahydroquinolino, 4-chromanyl, 4-thiochromanyl or 1-phenyl-1,2,3,4-tetrahydro-4-quinolyl; and the salts thereof, possess cholesterol level-lowering activity.

Cholesterol level-lowering phenoxyacetic acids

Diphenoxyacetic acid derivatives of the general formula ##STR1## wherein R.sub.1 is H or alkyl of 1-4 carbon atoms, R.sub.2 is H or Cl, R.sub.2 is H or Cl, R.sub.3 is piperidino, 4-piperidinophenyl, 1,2,3,4-tetrahydroquinolino, 1-R.sub.4 -1,2,3,4-tetrahydro-4-quinolyl, 4-oxo-1,2,3,4-tetrahydroquinolino, 4-chromanyl, 4-thiochromanyl or 4-chlorophenoxy, and R.sub.4 is H or alkyl of 1-4 carbon atoms, and the physiologically acceptable salts thereof, possess cholesterol level lowering activity and can be prepared by reacting a phenol of the formula ##STR2## with a compound of the formula ##STR3## wherein X is OH, esterified OH, Cl, Br or I, one R is R.sub.2 and the other is R.sub.3 ; or by cyclizing a compound of the formula ##STR4## wherein X.sub.1 is Cl, Br, I, NH.sub.2 OH or an esterified or etherified OH-group and n is 0 or 1; or by treating a compound of the formula ##STR5## wherein Z is a functionally modified carboxyl group different from COOR.sub.1, with a solvolyzing agent, R.sub.1, R.sub.2 and R.sub.3 in each instance having the values given above.

Diphenoxyacetic acid derivatives

Phenoxylakanols of the formula ##STR1## wherein R.sup.1 is H or CH.sub.3 ; R.sup.2 is CH.sub.3 or C.sub.6 H.sub.5 ; R.sup.3 is 4-Hal-phenoxymethyl, 1,2,3,4-tetrahydro-1-naphthyl, 1-pyrryl, piperidino, isoindoline, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydro-1-R.sup.5 -4-quinolyl, 4-chromanyl, 4-thiochromanyl, or, when at least one of R.sup.1 and R.sup.2 is other than CH.sub.3, also Hal, phenyl, 4-Hal-phenyl or 4-Hal-phenoxy, wherein R.sup.4 is H or alkanoyl of 2-4 carbon atoms, R.sup.5 is H or CH.sub.3 and Hal if F, Cl or Br; and physiologically acceptable acid addition salts thereof possess pharmacological activity, particularly cholesterol, triglyceride and uric acid blood-level lowering activity and are also useful as intermediates for the production of the corresponding phenoxyacetic acids.

Phenoxyalkanol derivatives

Phenoxypropionic acid derivatives of the formula ##STR1## wherein Q is H or a halogen atom, R is H or CH.sub.3, Z is --OH, --O--alkyl of 1-4 carbon atoms, 1-methyl-4-piperidyloxy, or --NHCH.sub.2 CH.sub.2 OH, and the physiologically acceptable salts thereof; possess cholesterol and triglyceride blood-level lowering activity and can be prepared, e.g., by reaction of a phenol of the formula ##STR2## with a compound of the formula X--CR(CH.sub.3)--CO--Z wherein X is Cl, Br, I, or a free or esterified OH-group, and Q, R and Z have the values given above.

Phenoxypropionic acid derivatives and pharmaceutical preparations

Phenoxyacetic acids of the formula ##SPC1## Wherein R.sub.1 is H or alkyl of 1-4 carbon atoms; R.sub.2 is H, or when R.sub.4 is Q, also alkyl of 1-4 carbon atoms; R.sub.3 is methyl, phenyl or chlorophenyl; and R.sub.4 is piperidino, isoindolino, 1,2,3,4-tetrahydroquinolino, 1-R.sub.5 -1,2,3,4-tetrahydro-4-quinolyl, 4-piperidinophenyl, 4-piperidinophenoxy, 1-pyrryl, or Q, wherein R.sub.5 is H or alkyl of 1-4 carbon atoms; and Q is 4-oxo-1,2,3,4-tetrahydroquinolino, 4-hydroxy-1,2,3,4-tetrahydroquinolino, 4-chromanyl, 4-thiochromanyl or 1-phenyl-1,2,3,4-tetrahydro-4-quinolyl; and the salts thereof, possess cholesterol level-lowering activity.

4(Quinolyl)phenoxy alkanoic acid derivatives

Phenoxypropionic acid derivatives of the formula ##SPC1## Wherein Q is H or a halogen atom, R is H or CH.sub.3, Z is --OH, --O-alkyl of 1-4 carbon atoms, 1-methyl-4-piperidyloxy, or --NHCH.sub.2 CH.sub.2 OH, and the physiologically acceptable salts thereof; possess cholesterol and triglyceride blood-level lowering activity and can be prepared, e.g., by reaction of a phenol of the formula ##SPC2## With a compound of the formula X--CR(CH.sub.3)--CO--Z wherein X is Cl, Br, I, or a free or esterified OH-group, and Q, R and Z have the values given above.

Phenoxypropionic acid derivatives

Piperidines of the formula ##SPC1## Wherein R is --CH.sub.2 OH, CO--NR,R.sub.2 in which R.sub.1 and R.sub.2 each are H or alkyl of 1-4 carbon atoms, --NHCH.sub.2 CH.sub.2 OH, --N(CH.sub.2 CH.sub.2 OH).sub.2, --NHCH.sub.2 CH.sub.2 SO.sub.3 H, --NHNH.sub.2 or --NHCH.sub.2 COOH, or --COOR.sub.3 in which R.sub.3 is 3-pyridylmethyl, 2-acetamidoethyl, 1-methyl-4-piperidyl or 2,3-dihydroxypropyl and the physiologically acceptable salts thereof, have cholesterol-level-lowering and triglyceride-level-lowering activity and can be prepared from 2-methyl-2-[4-(4-piperidinophenyl)-phenoxy]-propionic acid or a functional derivative thereof by reduction or by reaction with a compound of the formula HZ.

Growing community of inventors

Darmstadt, Germany

Zdenek Simane