Schering Corporation

Icn Pharmaceuticals, Inc.

Other

Joseph T Witkowski

Roland K Robins

Elizabeth M Smith

Brooks R Sunday

Ronald J Doll

Michael F Czarniecki

Leon F Christensen

Richard E Chipkin

Frank A Lehmkuhl

Phosphinylalkanoyl imino acids useful in the treatment of hypertension are disclosed.

Phosphinylalkanoyl imino acids

The compound 4,7-dimethyl-2-(4-pyridinyl)-1,2,4-triazolo[1,5-a]pyrimidin-5(4H)-one and the pharmaceutically acceptable salts thereof are analgesic and anti-inflammatory agents. Methods for preparing and using the compound and salts are described.

Methods of treating pain and inflammation with

Certain 2-(4'-pyridinyl)-thiazoles additionally substituted in either the 4- or 5- position are bronchodilating agents. Methods for their preparation and use are disclosed.

Anti-bronchoconstriction 2-(4'-pyridinyl)-thiazole derivatives,

The pyridinyl-thiazole derivatives of the present invention exhibit good cardiotonic activity.

2-(4'-Pyridinyl)-thiazole compounds and their use in increasing cardiac

Disclosed are 2-(pyridinyl)-1,2,4-triazolo[1,5-a]pyrimidines and derivatives which are effective in increasing cardiac contractility. These compounds are useful in the treatment of congestive heart failure preferably by oral or parenteral administration.

2-(Pyridinyl)-1,2,4-triazolo[1,5-a]pyrimidines and derivatives useful in

Compounds of the formula ##STR1## and the pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2 and R.sup.4 are independently selected from hydrogen and lower alkyl; R.sup.3 is hydrogen, lower alkyl or amino lower alkyl; A and B taken together with the carbons to which they are attached form an alkylene ring having six carbon atoms or A and B are hydrogen; and Z is ##STR2## are disclosed. The compounds are useful as anti-hypertensive agents.

Antihypertensive agents

Compounds of the formula ##STR1## and the pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently selected from hydrogen or lower alkyl; n is 1 or 0; A and B taken together with the carbons to which they are attached form an alkylene ring having six carbon atoms or A and B are hydrogen; and Z is ##STR2## The compounds are useful as hypertensive agents.

The compound 1-B-D-ribofuranosyl-1,2,4-triazole-3-carboxamide is used to treat diseases in humans which are caused by viral infections.

Treatment of human viral diseases with

1-.beta.-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide is prepared by a process wherein a suitably substituted formimidic acid hydrazide is condensed with a blocked derivative of D-ribose and the intermediate is ring closed with a reagent which donates one carbon atom to yield a 3-substituted-1-(blocked .beta.-D-ribofuranosyl)-1,2,4-triazole. Treatment of this intermediate with ammonia and/or removal of the blocking group yields the product.

Process for preparing 1,2,4-triazole nucleosides

Antiviral 1-(G)-1,2,4-triazole carboxamides, thiocarboxamides and carboxamidines wherein G is an acid labile hydrocarbon moiety, e.g., 1-(.alpha.-alkoxyalkyl), are prepared by, e.g., the acid-catalyzed addition reaction of appropriately substituted 1,2,4-triazole and an .alpha.,.beta.-unsaturated ether.

N-substituted 1,2,4-triazoles

Phosphate and carboxylic acid esters of 1-(.beta.-D-ribofuranosyl)-1,2,4-triazoles are prepared by a variety of methods and their antiviral activity reported.

1-(.beta.,-D-ribofuranosyl)-1,2,4-triazole acid esters

The use of 1,2,4-triazole-3-carboxamide and 1,2,4-triazole-3-thiocarboxamide and physiologically compatible salts thereof as antiviral agents is disclosed. A process for synthesizing 1-.beta.-D-ribofuranosyl-1,2,4-triazole-3-carboxamide is also disclosed.

1,2,4-Triazol E-3-carboxamides as antiviral agents

Novel substituted 1,2,3-triazole nucleosides such as 4-R'-2-.beta.-D-ribofuranosyl-1,2,3-triazole wherein R' is a nitro, carboxylic acid ester, cyano, carboxamide or thiocarboxamide group are prepared by a procedure entailing fusion of an appropriately substituted 1,2,3-triazole with a tetra-0-acyl blocked ribofuranose. The resulting compounds exhibit significant antimicrobial activity in in vitro testing or are useful in preparing compounds which exhibit such activity.

1,2,3-Triazole nucleosides

A 5-hydroxy-1,2,3-triazole-4-carboxamide nucleoside, related to the C-nucleoside pyrazomycin, is facilely synthesized by condensation of acyl-blocked ribofuranose with trimethylsilylated 5-hydroxy-1,2,3-triazole-4-carboxamide or, alternatively, by cycloaddition of suitably blocked .beta.-D-ribofuranosyl azide and the anion of ethyl malonamate, and demonstrated to exhibit antiviral properties. The triazole precursor of the former route, as well as certain of its novel salts, are also disclosed as potential antiviral agents.

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Morris Township, NJ, United States of America

Joseph T Witkowski