Merrell Dow Pharmaceuticals

Merrell Pharmaceuticals, Inc.

Hoechst Marion Roussel

Aventis Pharma Limited

Jeffrey S Sabol

James R McCarthy

Donald Paul Matthews

Keith A Diekema

Robert J Dinerstein

James R McConnell

Richard E Donaldson

Robert Duquid

James R Mccarthy

Sai P Sunkara

Shawn Christopher Miller

Robert J Cregge

Robert Duguid

Shawn C Miller

Sai Prasad Sunkara

##STR1## The present invention is directed to a class of novel carbocyclic derivatives having formulas (I) and (II) and their use as anti-viral and anti-neoplastic agents, wherein X.sub.1 and X.sub.2 are each independently hydrogen, fluorine, or chlorine, R is hydrogen or hydroxymethyl, J is a radical of formulas (a), (b) and (c). Y.sub.1 is a CH group, a CCl group, a CBr group or a CNH.sub.2 group, Y.sub.2 and Y.sub.3 are each independently nitrogen or a CH group, Y.sub.1 is a CH group, a CCl group, a CBr group or a CNH.sub.2 group, Y.sub.2 and Y.sub.3 are each independently nitrogen or a CH group, Y.sub.4 is hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy or halogen, Y.sub.5 is NH.sub.2 or C.sub.1 -C.sub.4 alkoxy, Q is NH.sub.2, NHOH, NHCH.sub.3, OH, or hydrogen, and V is hydrogen, halogen or NH.sub.2 ; or a pharmaceutically acceptable salt thereof.

Carbo-acyclic nucleoside derivatives as antiviral and antineoplastic

The present invention is directed toward a novel process of preparing 2'-exocyclic vinylfluoride derivatives of cytidine analogues for use as ribonucleotide reductase inhibitors.

Process for the preparation of ribonucleotide reductase inhibitors

The present invention is directed toward a novel process of preparing 2'-exocyclic vinylfluoride derivatives of cytidine analogues for use as ribonucleotide reductase inhibitors. The novel process of the present invention utilizes a cytidine derivative as the required starting material and provides the ribonucleotide reductase inhibitor in a more efficient than the reaction sequence. The process is more efficient than the process disclosed by McCarthy et al. in European Patent Application Publication No. 0 372 268 published Jun. 13, 1990, in that it requires fewer chromatographies and results in an overall yield of greater than 25% for the five steps. The present invention further provides the ribonucleotide reductase inhibitor in a four step reaction sequence and results in an overall yield of greater than 35%.

The present invention provides novel 5-(1-fluorovinyl)-1H-pyrimidine-2,4-dione derivatives which are useful as antineoplastic agents by themselves or in conjunctive therapy with the antineoplastic agent 5-fluorouracil.

5-(1-fluoro-vinyl)-1H-pyrimidine-2,4-dione derivatives useful as

The present invention is directed toward a novel process of preparing 2'-exocyclic vinylfluoride derivatives of cytidine analogues for use as ribonucleotide reductase inhibitors. The novel process of the present invention utilizes a cytidine derivative as the required starting material and provides the ribonucleotide reductase inhibitor in a more efficient five step reaction sequence. The present invention further provides the ribonucleotide reductase inhibitor in a four step reaction sequence and results in an overall yield of greater than 35%.

This invention relates to 1-phenyl-3-phenyl-2-propyne-1-ones, the use of these compounds as calcium uptake inhibitors in leukocytes and thrombocytes, and pharmaceutical compositions containing these compounds as active ingredients, and the process of their preparation.

1-phenyl-3-phenyl-2-propyne-1-ones as calcium uptake inhibitors

This invention relates to 1-phenyl-3-aryl-2-propyne-1-ones, the use of these compounds as calcium uptake inhibitors in leukocytes and thrombocytes, and pharmaceutical compositions containing these compounds as active ingredients, and the process of their preparation.

Calcium uptake inhibitors

1-phenyl-3-aryl-2-propyne-1-one useful as calcium uptake inhibitors

The present invention is directed to 2-hydroxy-4-alkylidenecyclohexanealkanoic acids having a mercaptoalkanoic acid substituent at the 3-position. Esters and amides corresponding to the acids referred to above are also encompassed by the present invention. These compounds are useful in the treatment of bronchial asthma and they are obtained by the reaction of an appropriate 2,3-epoxy-4-alkylidenecyclohexanealkanoate with a mercapto alkanoic acid ester in the presence of a tertiary amine. The indicated process gives the esters of the present invention which can be hydrolyzed to the corresponding free acids by standard procedures. The compounds described can be subjected to other known reactions to give the other compounds of the present invention.

Growing community of inventors

Loveland, OH, United States of America

Jeffrey S Sabol