Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Jacob M Hoffman

Mark T Bilodeau

Nicholas D P Cosford

Ben E Evans

Johnny Yasuo Nagasawa

Peter J Manley

Anthony M Smith

Peter C Chua

John J Baldwin

George D Hartman

Mark G Bock

Gerald S Ponticello

Clarence S Rooney

Michael A Patane

Jun Liang

John S Wai

Zhicai Wu

Brian Andrew Stearns

Thomas Joseph Tucker

Mark E Layton

B Wesley Trotter

Jeannie M Arruda

Lida R Tehrani

Tony Siu

Mark W Embrey

Brian T Campbell

Linda S Payne

Essa H Hu

Raymond S Chang

James H Jones

John T Sisko

Kenneth E Rittle

Robert M DiPardo

Kevin F Gilbert

Yiwei Li

Kevin J Rodzinak

Debra S Perlow

William C Lumma

M Brad Nolt

Richard C A Isaacs

Leonard Rodman

Ahren Iver Green

The present invention relates to pyridin-3-yl pyridin-3-amine compounds and derivatives thereof having the structure formula (I) useful as potassium channel inhibitors to treat cardiac arrhythmias, and the like. 

Potassium channel inhibitors

The present invention relates to dipyridin-3-ylmethoxy compounds and derivatives thereof having the structure I useful as potassium channel inhibitors to treat cardiac arrhythmias, and the like. 

The present invention is directed to compounds which contain substituted pyridazines and pyrimidines moieties which inhibit the activity of Akt, a serine/threonine protein kinase. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for treating cancer comprising administration of the compounds of the invention.

Inhibitors of Akt activity

The present invention is directed to compounds which contain substituted naphthyridines which inhibit the activity of Akt, a serine/threonine protein kinase. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for treating cancer comprising administration of the compounds of the invention. These substituted naphthyridines have unexpected advantageous properties when compared to other naphthyridines reported in PCT publication WO2003/086394, such unexpected advantageous properties may include increased cellular potency/solubility, greater selectivity, enhanced pharmacokinetic properties, lack of off target activity and so on.

The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.

Tyrosine kinase inhibitors

Arylhydantoin derivatives and their pharmaceutically acceptable salts are disclosed. The synthesis of these compounds and their use as alpha 1a adrenergic receptor antagonists is also described. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are typically selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved.

Arylhydantoin derivatives and uses thereof

Spirotricyclic azacycloalkyl compounds and pharmaceutically acceptable salts thereof are disclosed. The synthesis of these compounds is also described. One application of these compounds, which are alpha 1a adrenergic receptor antagonists, is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved.

Spirotricyclic substituted azacycloalkane derivatives and uses thereof

Spirohydantoin compounds and their pharmaceutically acceptable salts are disclosed. The synthesis of these compounds and their use as alpha 1a adrenergic receptor antagonists is also described. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are typically selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved.

Spirohydantoin compounds and uses thereof

The present invention is directed to conformationally constrained compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.

Inhibitors of prenyl-protein transferase

This invention relates to novel compounds, their synthesis and use as selective .alpha..sub.1a adrenergic receptor antagonists. One application of the compounds is in the treatment of benign prostatic hyperplasia. The compounds are selective in their ability to relax smooth muscle tissue enriched in the .alpha..sub.1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.

.alpha..sub.1a adrenergic receptor antagonists

Alpha 1a adrenergic receptor antagonists

Compounds of general formula: ##STR1## are topically effective carbonic anhydrase inhibitors useful in the treatment of ocular hypertension and related disorders such as glaucoma.

Heterobicyclic sulfonamides

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Lansdale, PA, United States of America

Jacob M Hoffman