Zymogenetics, Inc.

Novo Nordisk A/s

James R Piggott

Virender M Labroo

Robert A Smith

Patricia A McKernan

Robert R West

Steven D Bain

Charles R Petrie

Niels Korsgaard

Shirley R Gasper

Steven Bain

Colin Lellis

Lennie Chen

Piperazine derivatives useful in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyroidism, periodontal disease or defect, metastatic bone disorder, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgery and post-dental implantation.

Piperazine derivatives for treating bone deficit conditions

The present invention provides novel uses of compounds of general formula I: ##STR1## wherein R.sup.1, R.sup.4 and R.sup.5 are individually hydrogen, hydroxy, halogen, trifluoromethyl, lower alkyl, lower alkoxy or (tertiary amino)(lower alkoxy); and R.sup.2 and R.sup.3 are individually hydrogen or lower alkyl, or as a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable carrier for the manufacture of a pharmaceutical composition for the treatment or prophylaxis of atrophy of skin and/or mucous membranes.

Atrophy of skin/mucous membrane

The invention provides isolated, biologically active native calcitonin mimetics and related methods. These small 16 and 17 amino acid proteins mimic the interaction of calcitonin on its receptor, and also exhibit bone resorptive inhibiting activity.

Native calcitonin mimetics

Glucagon antagonists and methods relating thereto are disclosed. The glucagon antagonists include skyrin and skyrin analogs, and serve to inhibit the stimulation of a glucagon-induced response pathway, such as the adenylate cyclase response pathway or the inositol phosphate response pathway. The glucagon antagonists may be used within therapeutic compositions to treat disease states associate with elevated glucose levels, including diabetes and hyperglycemia. The present invention also discloses a biologically pure culture of ATCC accession number 74200, as well as methods relating to the production of glucagon antagonists by cultivating the same in a nutrient medium and recovering the glucagon antagonist therefrom.

Method for inhibiting the stimulation of a glucagon-induced response

Methods and pharmaceutical compositions for use in inhibiting calmodulin activity in a patient are disclosed. 2,3-diaryl-1-benzopyrans and their pharmaceutically acceptable salts are formulated into medicaments, including oral and topical medicaments, which are administered to a patient in need of treatment of a non-estrogen dependent condition.

Methods for inhibiting calmodulin activity

Methods and pharmaceutical compositions for the treatment of dermatitis are disclosed. 2,3-diaryl-1-benzopyrans and their pharmaceutically acceptable salts are formulated into medicaments, including oral and topical medicaments, which are administered to a patient suffering from dermatitis. The methods and compositions are particularly useful in the treatment of conditions characterized by hyperproliferation of keratinocytes, such as psoriasis.

Methods for inhibiting hyperproliferation of kerntinocytes

Methods for detecting glucagon antagonists through the use of recombinant DNA techniques are provided. Briefly, subsequent to the expression of glucagon analogs within suitable host cells, the analogs are exposed to a glucagon receptor coupled to a response pathway in the presence of native glucagon. A reduction in the stimulation of the response pathway resulting from the binding of the glucagon analog to the glucagon receptor relative to the stimulation of the response pathway by native glucagon alone indicates the presence of a glucagon antagonist. Glucagon antagonists identified and isolated through the methods are also provided.

Glucagon antagonists

Glucagon antagonists and methods relating thereto

A method for inhibiting is disclosed comprising administering, 3,4-diarylchromans and their pharmaceutically acceptable salts.

3,4-diarylchromans for inhibiting calmodulin activity

Methods and pharmaceutical compositions for reducing bone loss are disclosed. 3,4-diarylchromans and their pharmaceutically acceptable salts are formulated into medicaments for the treatment of bone loss due to osteoporosis or other conditions. An exemplary 3,4-diarylchroman is centchroman (3,4-trans-2,2-dimethyl-3-phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl]-7-me thoxychroman). Formulations include tablets and other forms suitable for oral administration and controlled-release subdermal implants.

Method for inhibiting bone loss using centchroman derivatives

Methods for the treatment of dermatitis are disclosed wherein 3,4-diarylchromans and their pharmaceutically acceptable salts are formulated into medicaments, including oral and topical medicaments, and are administered to a patient suffering from dermatitis.

3,4-diarylchromans for treatment of dermatitis

Method for treating dermatitis and related conditions

Methods for detecting glucagon antagonists

Methods and pharmaceutical compositions for reducing bone loss are disclosed. 3,4-diarylchromans and their pharmaceutically acceptable salts are formulated into medicaments for the treatment of bone loss due to osteoporosis or other conditions. An exemplary 3,4-diarylchroman is centchroman (3,4-trans-2,2-dimethyl-3-phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl]-7-me thoxy-chroman). Formulations include tablets and other forms suitable for oral administration and controlled-release subdermal implants.

Growing community of inventors

Bothell, WA, United States of America

James R Piggott