Warner-lambert Company

Other

John Shavel, Jr

Richard E Brown

Harold Zinnes

Chester Puchalski

Jerome D Genzer

Arthur C Fabian

Charles Francis Kasulanis

Sylvester R Klutchko

Max Von Strandtmann

Marvin P Cohen

Charles F Schwender

Neil A Lindo

Jagadish C Sircar

Maximilian Von Strandtmann

George Bobowski

Arch Christian Sonntag

Jeffrey M Gottlieb

Substituted benzopyrano[3,4-c]pyridines and processes for their preparation are disclosed. The compounds are active as bronchodilators.

Substituted benzopyrano[3,4-c]pyridines, compositions and use thereof

Substituted tetrahydrobenzazepines and tetrahydronaphthazepines which are useful as pharmacological agents, especially in the treatment of cardiac arrhythmias, are disclosed. These compounds can be prepared by cyclizing an appropriately substituted (.beta.-hydroxy-.beta.-phenylethyl)(.beta.-phenylethyl)amine.

Substituted tetrahydrobenzazepines and tetrahydronaphthazepines and

A novel process for preparing 4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxides is disclosed. The process involves the base catalyzed rearrangement of a saccharinacetamide of structure I to give II, ##STR1## wherein R.sup.1 is hydrogen or lower alkyl and R.sup.2 is lower alkyl, aryl or a heterocyclic ring selected from the group consisting of pyridyl, substituted-pyridyl, and thiazolyl. Compounds of the formula II have useful anti-inflammatory properties. In addition, they can be used as intermediates in the preparation of known anti-inflammatory agents.

2-[(N-2-pyridylcarbamoyl)methyl]saccharin

There is described 3-(1H-tetrazol-5-yl)chromones having the following structural formula: ##STR1## in which R is lower alkoxy having 1 to 3 carbon atoms, aryl such as phenyl, halogen or trihalo lower alkyl. These compounds exhibit anti-allergic properties and are indicated in the treatment of allergic conditions such as hay fever and asthma.

3-(1H-Tetrazol-5-yl)chromones

Disclosed are novel substituted benzopyranopyridines which are active as bronchodilators.

Bronchodilating piperidinoethyl benzopyranopyridinones

This invention relates to a process for the preparation of 1-{[5-(4-hydroxy-2H-1,2-benzothiazin-3-yl)-1,2,4-oxadiazol-3-yl]methyl}eth anone S,S-dioxide (III), a novel intermediate useful in the preparation of the known anti-inflammatory agent, 4-hydroxy-3-(5-methyl-3-isoxazolylcarbamoyl)-2-methyl-2H-1,2-benzothiazine 1,1-dioxide (IV). According to the process of this invention, the saccharin compound, 2,3-dihydro-N-(5-methyl-3-isoxazolyl)-3-oxo-1,2-benzisothiazole-2-acetamid e 1,1-dioxide (I) is reacted with an alkali metal alkoxide of a lower alcohol in an inert solvent at temperatures below 30.degree. C. to form the benzenesulfonylglycineamide, alkyl 2-{[({[(5-methyl-3-isoxazolyl)amino]carbonyl}methyl)amino]sulfonyl}benzoat e (II), which is ring closed and rearranged by reaction with an alkali metal alkoxide of a lower alcohol in an inert solvent at temperatures of from 60.degree. to 70.degree. C. to form the desired oxadiazole compound III.

Composition containing alkyl

A novel process for preparing 4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxides is disclosed. The process involves the base catalyzed rearrangement of a saccharinacetamide of structure I to give II, ##STR1## wherein R.sup.1 is hydrogen or lower alkyl and R.sup.2 is lower alkyl, aryl or a heterocyclic ring selected from the group consisting of pyridyl, substituted-pyridyl, and thiazolyl. Compounds of the formula II have useful anti-inflammatory properties. In addition, they can be used as intermediate in the preparation of known anti-inflammatory agents.

Process for the preparation of

A novel process for preparing 4-hydroxy-3-(5-methyl-3-isoxazolylcarbamoyl)-2-methyl-2H-1,2-benzothiazine 1,1-dioxide (I), starting with 3-amino-5-methylisoxazole (II) is disclosed. Compound I exhibits anti-inflammatory properties and is useful for treating inflammation. In the process of the invention an intermediate obtained, 2,3-dihydro-N-(5-methyl-3-isoxazolyl)-3-oxo-1,2-benzisothiazole-2-acetamid e 1,1-dioxide (IV) undergoes rearrangement to provide 1-{[5-(4-hydroxy-2H-1,2-benzothiazin-3-yl)-1,2,4-oxadiazol-3-yl]methyl}eth anone S,S-dioxide (V), which is methylated, according to conventional procedures. The methylated intermediate VI, upon further treatment, undergoes a second rearrangement to obtain the desired anti-inflammatory compound I.

Intermediate composition

The present invention relates to [2-(4-oxo-4H-1-benzopyran-2-yl)ethenyl]benzonitrile and benzoic acids having the following structural formula: ##STR1## in which R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are hydrogen, lower alkyl, halogen or lower alkoxy, and A is COOH or CN. The compounds of this invention exhibit anti-allergy properties and are indicated in the management of allergic manifestations such as bronchial asthma.

[2-(4-Oxo-4H-1-benzopyran-2-yl)ethenyl]benzonitriles and benzoic acids

A novel process for preparing 4-hydroxy-3-(5-methyl-3-isoxazolylcarbamoyl)-2-methyl-2H-1,2-benzothiazine 1,1-dioxide (I), starting with 3-amino-5-methylisoxazole (II) is disclosed. Compound I exhibits anti-inflammatory properties and is useful for treating inflammation. In the process of the invention an intermediate obtained, 2,3-dihydro-N-(5-methyl-3-isoxazolyl)-3-oxo-1,2-benzisothiazole-2-actamide 1,1-dioxide (IV) undergoes rearrangement to provide 1-{[5-(4-hydroxy-2H-1,2-benzothiazin-3-yl)-1,2,4-oxadiazol-3-yl]methyl}eth anone, S,S-dioxide (V), which is methylated, according to conventional procedures. The methylated intermediate VI, upon further treatment, undergoes a second rearrangement to obtain the desired anti-inflammatory compound I.

2,3-Dihydro-N-(5-methyl-3-isoxazolyl)-3-oxo-1,2-

Compounds of the formula: ##STR1## are disclosed, wherein R.sub.1 and R.sub.2 are hydrogen; or where R.sub.1 is methyl, R.sub.2 is hydrogen, phenyl, or phenyl substituted in the para-position by hydroxy, alkoxy, chloro, phenyl or alkyl having 1-6 carbon atoms. The compounds of this invention are useful in the treatment of bronchial asthma. These compounds exhibit unique biological properties in that they provide the desired bronchial dilation effect without accompanying cardiac stimulation.

5-Hydroxy-.alpha.-(substituted

The present invention relates to substituted [4-oxo-4H-1-benzopyran-2-yl]cyclopropane carboxylic acids and esters having the following structural formula: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are hydrogen, alkyl, lower alkoxy, phenyl or when R.sub.1 and R.sub.2 are hydrogen, R.sub.3 and R.sub.4 taken together form an additional aromatic ring and A is hydrogen or ethyl. The compounds of this invention exhibit anti-allergy properties and are indicated in the management of allergic manifestations such as bronchial asthma.

Substituted (4-oxo-4H-1-benzopyran-2-yl)cyclopropane carboxylic acids

Substituted benzopyrano[3,4-c]pyridine-5-ones

Substituted benzopyrano[3,4-c]pyridines having the following structural formula are disclosed: ##STR1## In the above formula, R.sub.1 R.sub.2 are hydrogen, a hydroxyl group or a lower alkoxyl group of from 1 to 6 carbon atoms; R.sub.3 is hydrogen or a lower alkyl group of from 1 to 6 carbon atoms and X is an oxygen atom, a sulfur atom, a methylene group or a nitrogen atom substituted by hydrogen, a lower alkyl group of from 1 to 6 carbon atoms or a lower alkanoyl group of from 1 to 6 carbon atoms. The compounds of this invention are prepared by reacting an R.sub.1, R.sub.2 -substituted phenol with a 3-carbethoxy-4-piperidone in the presence of an acid catalyst to give an intermediate R.sub.1, R.sub.2 -substituted benzopyrano[3,4-c] pyridine. N-aminoalkylbenzopyrano[3,4-c]pyridines are obtained by treating the benzopyrano[3,4-c]pyridine with an appropriately substituted alkyl halide. The compounds of this invention are useful as bronchodilators for the treatment of bronchial asthma.

Growing community of inventors

Mendham, NJ, United States of America

John Shavel, Jr