Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Walfred S Saari

Joel R Huff

Edward L Engelhardt

William C Lumma, Jr

John S Wai

Allen I Oliff

Stella W King

John J Baldwin

Clarence S Rooney

Paul S Anderson

Jacob M Hoffman, Jr

Thorsten E Fisher

Mark W Riemen

David C Heimbrook

Edward J Cragoe, Jr

William J Greenlee

Theresa M Williams

Brian John Williams

Monique Bodil Van Niel

Philip E Sanderson

Frederick C Novello

Gideon A Rodan

Terrence M Ciccarone

Suresh K Balani

Mark E Goldman

J Christopher Culberson

George H Denny

Anthony G Zacchei

Anthony D Theoharides, Deceased

The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and treatment of cancer.

Inhibitors of farnesyl-protein transferase

Novel indole compounds inhibit HIV reverse transcriptase, and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Inhibitors of HIV reverse transcriptase

Fused tricyclic compounds, pharmaceutical compositions containing them

Novel aminopyridones inhibit HIV reverse transcriptase, and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

The invention relates to acyloxymethyl esters of bisphosphonic acids, halo-bisphosphonic acids and hydroxy-bisphosphonic acids which exhibit oral bioavailability and are useful in the treatment of disturbances involving calcium or phosphate metabolism, in particular, the treatment and prevention of diseases involving bone resorption, especially osteoporosis, Paget's disease, malignant hypercalcemia, and metastatic bone disease.

Acyloxymethyl esters of bisphosphonic acids as bone resorption inhibitors

Described are new agents for treating bone disorders associated with a reduction in bone mass and abnormalities in bone resportion or bone formation including osteoporosis. Paget's disease, bone metastases and malignant hypercalcemia. The agents are hydroxyl containing steroidal hormones, having bone resportion antagonist or bone formation stimulatory activity, covalently linked through the hydroxyl group via a bond hydrolyzable in the human body, e.g. carbamate or carbonate, which is further covalently linked to an amino, or hydroxy substituted alkylidene-1,1-bisphosphonate, through the respective amino or hydroxy group. The alkyl bisphosphonate moiety confers bone affinity. The agent acts by delivering the steroidal hormone directly to the bone target site where it is released for bone resorption antagonist or bone formation stimulatory action by hydrolysis of the hydrolyzable covalent bond.

Bone acting agents

Small cell lung carcinoma cells (SCLC) contain gastrin releasing peptide (GRP) receptors. The response of the cells to GRP is rapid growth. We have found a group of peptide derivatives that act as GRP antagonists by blocking the binding of GRP to its receptor thereby inhibiting the growth of cells that are sensitive to the growth promoting activity of GRP.

Gastrin releasing peptide antagonist

Small cell lung carcinoma (SCLC) cells contain gastrin releasing peptide (GRP) receptors. The response of the cells to GRP is rapid growth. We have found a group of peptide derivatives that act as GRP antagonists by blocking the binding of GRP to its receptor thereby inhibiting the growth of cells that are sensitive to the growth promoting activity of GRP.

Halogenated pyrimidine nucleoside derivatives with improved aqueous solubility and methods of enhancing the concentration of drugs in malignant tumors and promoting uniform distribution of the drug throughout the tumor. These basic and hydrophilic ester prodrugs are designed to undergo conversion to the active drug by an intramolecular chemical reaction at practical rates under physiological conditions.

Halogenated pyrimidine nucleosides and their derivatives

Disclosed are compounds having the formula: ##STR1## wherein: R.sub.1 is hydrogen, analkyl group having 1 to 6 carbon atoms, an alkyl group having 1 to 6 carbon atoms in which one or more of the carbon atoms are substituted with a hydroxy group;

N-substituted-3-nitro-4-(ureidooxymethyl)-benzenesulfonamides as

A compound of the formula: ##STR1## wherein: n is an integer 2,3,4, or 5; R.sub.1 is hydrogen or an alkyl group; and

Dinitrobenzenesulfonamides

Substituted 3-nitropyridines are disclosed to have activity in increasing the sensitivity of hypoxic tumor cells to therapeutic radiation. Also disclosed are methods of preparing such compounds by amination of the corresponding chloro-3-nitropyridine with 2,3-dihydroxypropylamine and pharmaceutical compositions including such compounds.

Derivatives of 3-nitropyridines useful as adjuncts to radiation therapy

A compound of the formula ##STR1## wherein: R.sub.1 and R.sub.2 are defined as follows:

.alpha.-nitroalkylnitrobenzenesulfonamides

2-(Substituted sulfamyl) derivatives of 4-nitrobenzamide are disclosed as agents that increase the sensitivity of hypoxic cancer cells to x-rays and .gamma.-radiation. Methods of preparing such compounds, protocols for administering them to human patients and animals, and pharmaceutical compositions containing them are also disclosed.

Growing community of inventors

Lansdale, PA, United States of America

Walfred S Saari