Allergan, Inc.

Allergan Sales, Inc.

Eli Lilly and Company

The Johns Hopkins University

Other

Sunil Nagpal

Roshantha A Chandraratna

Vidyasagar Pradeep Vuligonda

Elliott S Klein

Richard L Beard

Min Teng

Alan T Johnson

Tien T Duong

Ying Kwong Yee

Samuel J Gillett

Jianliang Lu

Andrew M Standeven

Tianwei Ma

Charles David Jones

Larry Allen Wheeler

Robert Peter Gajewski

Peter Anthony Campochiaro

Alan M Warshawsky

Eugene De Juan, Jr

Quanrong Shen

Emilio Enrique Bunel

Tae K Song

Jared Harris Linebarger

Michael John Rupp

Tainwei Ma

Jyoti Athanikar

Daniel DiSepio

Ryan Edward Stites

Karl Robert Dahnke

Jason Matthew Ochoada

Todd Parker Simard

Elliot S Klein

The present invention relates to novel, non-secosteroidal, phenyl-benzothiophene compounds with vitamin D receptor (VDR) modulating activity that are less hypercalcemic than 1&#x3b1;,25 dihydroxy vitamin D3. These compounds are useful for treating bone disease and psoriasis.

Vitamin D receptor modulators

The present invention relates to novel, non-secosteroidal, diaryl compounds with vitamin D receptor (VDR) modulating activity that are less hypercalcemic than 1&#x3b1;,25 dihydroxy vitamin D3. These compounds are useful for treating bone disease and psoriasis.

The present invention relates to novel, non-secosteroidal, sulfonate and sulfonamide functional diaryl compounds with vitamin D receptor (VDR) modulating activity that are less hypercalcemic than 1&#x3b1;,25 dihydroxy vitamin D3. These compounds are useful for treating bone disease and psoriasis.

The present invention relates to novel, non-secosteroidal, phenyl-thiophene compounds with vitamin D receptor (VDR) modulating activity that are less hypercalcemic than 1&#x3b1;,25 dihydroxy vitamin D3. These compounds are useful for treating bone disease and psoriasis.

Phenyl-thiophene type vitamin D receptor modulators

The present invention relates to novel, non-secosteroidal, hydroxyl substituted, carbon-linked diaryl compounds with vitamin D receptor (VDR) modulating activity that are less hypercalcemic than 1?,25 dihydroxy vitamin D3. These compounds are useful for treating bone disease and psoriasis.

The present invention relates to novel, non-secosteroidal, phenyl-benzofuran compounds with vitamin D receptor (VDR) modulating activity that are less hypercalcemic than 1&#x3b1;,25 dihydroxy vitamin D3. These compounds are useful for treating bone disease and psoriasis.

The present invention relates to novel, non-secosteroidal, phenyl-furan compounds with vitamin D receptor (VDR) modulating activity that are less hypercalcemic than 1&#x3b1;,25dihydroxy vitamin D3. These compounds are useful for treating bone disease and psoriasis.

Phenyl-furan compounds as vitamin D receptor modulators

Methods of characterizing and identifying negative hormones of nuclear receptors. Also disclosed are methods of making modulators of retinoid nuclear receptor transactivation activity, assays for agonists, antagonists, and negative hormones of the RAR receptor, and specific retinoid modulators of retinoid nuclear receptors.

Methods of identifying compounds having nuclear receptor negative hormone and/or antagonist activities

Proliferation of retinal pigment epithelium following surgery or trauma or resulting in ocular diseases associated with choroidal neovascularization, such as age related macular degeneration and histoplasmosis syndrome, is prevented by contacting retinal pigment epithelium cells with a therapeutic amount of a retinoic acid receptor (RAR agonist, preferably one with specific activity for retinoic acid receptors. Preferably the RAR agonist is also a potent antagonist of AP1-dependent gene expression. Alternatively, the proliferation of retinal pigment epithelium is ameliorated with a therapeutic amount of an AP-1 antagonist, alone or in combination with an RAR agonist. The drug can be administered by bolus injection into the vitreous cavity using a dosage from about 50 to 150 &mgr;g. Or by slow release from liposomes or an oil tamponade injected into the vitreous cavity. Formulations for preventing proliferation of retinal pigment epithelium are also provided.

Method of preventing proliferation of retinal pigment epithelium by retinoic acid receptor agonists

Aryl-substituted and aryl and (3-oxo-1-propenly)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, transactivation assays can be used to identify compounds having negative hormone activity. These assays are based on the ability of negative hormones to down-regulate the activity of chimeric retinoid receptors engineered to possess a constitutive transcription activator domain.

Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities

Synthesis and use of retinoid compounds having negative hormone and/or anatgonist activities

Retinoid compounds which repress expression of the gene promoted by AP1 protein but which do not significantly activate expression of the genes having RA-responsive elements in their promoter region through RAR&agr; and RAR&Ggr; receptor subtypes, are used, with reduced side effects, for treating diseases and conditions which are responsive to therapy with retinoids.

Method for inhibiting gene expression promoted by AP1 protein with RAR&bgr; selective retinoids and method for treatment of diseases and conditions with such retinoids

A novel human cDNA, called TIG3 (Tazarotene Induced Gene 3), inducible by RAR-selective retinoids and structurally related to a known tumor suppressor gene. Methods of detecting the TIG3 polynucleotide.

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Carmel, IN, United States of America

Sunil Nagpal