Ortho Pharmaceutical Corporation

Ortho-mcneil Pharmaceutical Corp.

Bristol-myers Squibb Compnay

Donald W Combs

Robert Falotico

Philip J Rybczynski

Victor T Bandurco

Stanley Charles Bell

Thomas P Burris

David M Ritchie

Yuping Qiu

Alfonso J Tobia

Fred Christopher Zusi

James P Demers

Charles Malcolm Langevine

Joseph Dudash

Judith Hope Cohen

The present invention provides for triazolopurine-based tricyclic compounds having the formula (I), wherein R, R, R, R, and Rare as described herein. The present invention further provides pharmaceutical compositions comprising such compounds, as well as the use of such compounds for treating inflammatory and immune diseases.

Triazolopurine-based tricyclic compounds and pharmaceutical compositions comprising same

The invention is directed to 4h-benzo[1,4]oxazin-3-ones useful as peroxisome proliferator activated receptor gamma (PPAR&#x3b3;) agonists or antagonists. Pharmaceutical compositions comprising compounds of the present invention and methods of treating conditions such as NIDDM and obesity are also disclosed.

Biologically active 4H-benzo [1,4] oxazin-3-ones

The invention is directed to 4h-benzo&lsqb;1,4&rsqb;oxazin-3-ones useful as peroxisome proliferator activated receptor gamma (PPAR&ggr;) agonists or antagonists. Pharmaceutical compositions comprising compounds of the present invention and methods of treating conditions such as NIDDM and obesity are also disclosed.

Biologically active 4H-benzo &lsqb;1,4&rsqb;oxazin-3-ones

1,2-Disubstituted cyclopropanes

1-Arylsulphonyl, arylcarbonyl and arylthiocarbonyl pyridazino derivatives and processes for making said derivatives are described. The novel derivatives are non-steroidal heterocyclic compounds which act as selective progestins and/or antiprogestins having a high in-vitro affinity for either the uterine, breast or bone progestin receptor. As such, the non-steroidal heterocyclic derivatives are useful in contraception, menopause, osteoporosis or endometriosis.

1-arylsulphonyl, arylcarbonyl and arylthiocarbonyl pyridazino

1-arylsulphonyl, arylcarbonyl and

Novel 2,2,4-trialkyl-1,2-dihydroquinazoline-3-oxides and their synthesis are described. These compounds possess cardiotonic activity, and are useful for the treatment of heart failure.

2,2,4-trialkyl-1,2-dihydroquinazoline-3-oxides

The invention relates to a process for the synthesis of compounds of the formula I ##STR1## wherein R.sub.1 -R.sub.5 are as defined herein. The process is a multistep process which comprises acylating a 2-benzoxazolinone with an alkanoic anhydride to form an acylated carbamate, hydrolyzing the carbamate, reacting the resultant aminophenol with haloalkanoyl halide to form a substituted benzoxazine, reacting the benzoxazine with an aldehyde, alkylating the resultant aminomethyl compound with an alkylating agent to form a quaternary ammonium salt, reacting the salt with an alkali metal cyanide to form a nitrile, hydrolyzing the nitrile and reacting the resultant carboxylic acid with hydrazine. The compounds are useful as cardiotonic and vasodilating agents and as inhibitors of phosphodiesterase fraction III and platelet aggregation. In addition, the compounds are active as smooth muscle relaxants and bronchodilators.

Process for the preparation of

The invention relates to novel compounds, 2,9-dihydro(6 or 7)-3-oxo-2,3,4,5-tetrahydropyridazinyl)pyrazolo[4,3-b]benzoxazines. The claimed compounds are inhibitors of phosphodiesterase fraction III and have potent positive inotropic activity. These compounds are useful as cardiotonics or platelet aggregation inhibitors. This invention also pertains to compositions comprising an effective amount of the compounds, to methods for preparing the claimed compounds and to methods for treating a mammal with the compounds.

2,9-dihydro-(6 or 7)-(3-oxo-2,3,4,5-tetrahydropyridazinyl)-pyrazolo

The synthesis of benzoxazinyl- and benzothiazinylpyridazinone compounds is described. The novel compounds are cardiotonic agents and inhibitors of phosphodiesterase. In addition, the compounds are useful as smooth muscle relaxants and bronchodilators.

6-benzoxazinyl- and 6-benzothiazinyl 2,3,4,5-tetrahydropyridazin-3-ones

Novel 6,7-dimethoxy-1,2-dihydro-2-arylquinazoline-3-oxides and their synthesis are described. These novel compounds are cardiotonic agents and bronchodilating agents, and as such are useful for the treatment of heart failure and asthma.

6-7-dimethoxy-1,2-dihydro-2-arylquinazoline-3-oxides

6,7-dimethoxy-1,2-dihydro-2-arylquinazoline-3-oxides

6-benzoxazinyl- and 6-benzothiazinyl-2,3,4,5-tetrahydropyridazin-3-ones

Novel substituted quinazoline-3-oxides are disclosed as are methods of increasing cardiotonic activity and bronchodilation in which an unit dose of a composition containing an effective amount of a cardiotonic agent or a bronchodilating agent dispersed in a pharmaceutically acceptable carrier are administered to a mammalian host.

Substituted quinazoline-3-oxides providing pharmacological activity

The synthesis of benzoxazinyl-pyridazinone compounds is described. The novel compounds are cardiotonic agents and inhibitors of phosphodiesterase fraction III. In addition, the compounds are useful as smooth muscle relaxants and bronchodilators.

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Piscataway, NJ, United States of America

Donald W Combs