224 results about "Glucocorticoid receptor" patented technology

Compounds, compositions and methods are provided for modulating the expression of glucocorticoid receptor. The compositions comprise antisense compounds, particularly antisense oligonucleotides which have particular in vivo properties, targeted to nucleic acids encoding glucocorticoid receptor. Methods of using these compounds for modulation of glucocorticoid receptor expression and for treatment of diseases are provided.

Compounds of Formula (IA) and Formula (IB) wherein R1, R2, R3, R4, R5, and R6 are as defined herein for Formula (IA) or Formula (IB), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

A compound of Formula (I) wherein R1, R2, R3, R4, R5, and R6 are as defined herein, or a tautomer, prodrug, solvate, or salt thereof, pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

This invention relates to a low cost rapid response diagnostic system to determine cortisol levels in patients selected as potential candidates for GCR (glucocorticoid receptor) antagonist therapy utilizing a GCR antagonist, such as ORG 34517. The rapid, sensitive, and inexpensive test can be used to determine patients who have non-normal cortisol production or disordered circadian rhythms as a method for selecting subjects for GCR antagonist therapy for whom it is likely to have beneficial and / or therapeutic effects, and can also be used to monitor changes in cortisol levels in response to treatment.

A method for treating a subject having an inflammatory or auto-immune disease with a substituted isoxazolo pyridinone. Also, a method for administering a substituted isoxazolo pyridinone to a cell to retain or increase glucocorticoid receptor transrepression activity with only minimal glucocorticoid receptor transactivation activity.

Compounds of Formula (IA) and Formula (IB) where in R1 stands for the following group (the dashed line indicates the point of attachment) and R2, R3, R4, R5, R6, Y, Z, X1 and X2 are as defined herein for Formula (IA) and Formula (IB), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

Compounds of Formula (I) wherein R1, R2, R3, R4, R5, R6, X, Y, and n are as defined herein, or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

Compounds of Formula (I) wherein R1, R2, R3, R4, R5, R6 and X are as defined herein for Formula (IA) and Formula (IB), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

A compound of Formula (IA) or Formula (IB) wherein R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein, or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

Compounds of Formula (IA) and Formula (IB) wherein R1, R2, R3, R4, R5, and R6 are as defined herein for Formula (IA) or Formula (IB), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

A compound of Formula (I) wherein R1, R2, R3, R4, R5, and R6 are as defined herein, or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

Combination therapy comprising the administration of an 11β-hydroxysteroid dehydrogenase type 1 inhibitor and a glucocorticoid receptor agonist for treating some forms of cancer, diseases and disorders having inflammation as a component, and to minimize the side effects associated with glucorticoid receptor agonist therapy.

The invention involves the treatment, prevention, and reduction of immunoinflammatory disorders involving the combination of an agent that increases the signal activity of a glucocorticoid receptor (e.g., glucocorticoid receptor agonist) and an agent that modulates the signaling activity of one or more signaling pathways selected from the NF-κB pathway, NFAT pathway, AP-1 pathway, and Elk-1 pathway such that proinflammatory cytokine secretion or production, or any other inflammatory response, is reduced. Further, screening methods are provided for identifying candidate compounds and strategies useful for treating, preventing, or reducing such conditions.

Compounds of Formula (I) wherein R1, R2, R3, R4, R5, R6, and R7 are as defined herein, or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

Compounds, compositions and methods are provided for modulating the expression of glucocorticoid receptor. The compositions comprise oligonucleotides, targeted to nucleic acid encoding glucocorticoid receptor. Methods of using these compounds for modulation of glucocorticoid receptor expression and for diagnosis and treatment of diseases and conditions associated with expression of glucocorticoid receptor are provided.

The invention relates to glucocorticoid replacement therapy and provides pharmaceutical compositions and kits designed to deliver one or more glucocorticoids to a subject in need thereof in a manner that results in serum levels of the glucocorticoid that essentially mimic that of a healthy subject for a clinically relevant period of time. The pharmaceutical composition comprises one or more glucocorticoids, wherein a first part of one or more glucocorticoids is substantially immediately released and a second part of one or more glucocorticoids is released over an extended period of time of at least about 8 hours, and the amount of the one or more glucocorticoids of the first part, expressed as hydrocortisone equivalents, is in a range of from about 15 to about 50% of the total hydrocortisone equivalents. The invention also relates to a kit comprising a first and a second component, the first component designed to release one or more glucocorticoids substantially immediately and the second component is designed to release one or more glucocorticoids over an extended period of time of at least 8 hours. The invention also relates to a method for treating diseases requiring glucocorticoid treatment such as in subjects having a glucocorticoid deficiency disorder. In another aspect the invention relates to the use of a first and a second amount of one or more glucocorticoids for the preparation of a pharmaceutical composition or kit for the treatment of a glucocorticoid deficiency disorder.

A process for stereoselective synthesis of a compound of Formula (X) or Formula (X′) wherein R1, R2, and R3 are as defined herein, the process comprising: (a) reacting the starting material of formula A with a chiral sulfoxide anion source in a suitable solvent to prepare a compound of formula C or C′; (b) reducing the sulfoxide of formula C or C′ in a suitable solvent to obtain the compound of formula D or D1; and (c) cyclizing the compound of formula D or D′ in a suitable solvent to form the epoxide compound of Formula (X) or Formula (X′), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

This invention relates to a low cost rapid response diagnostic system to determine cortisol levels in patients selected as potential candidates for GCR (glucocorticoid receptor) antagonist therapy utilizing a GCR antagonist, such as ORG 34517. The rapid, sensitive, and inexpensive test can be used to determine patients who have non-normal cortisol production or disordered circadian rhythms as a method for selecting subjects for GCR antagonist therapy for whom it is likely to have beneficial and / or therapeutic effects, and can also be used to monitor changes in cortisol levels in response to treatment.

This invention relates to the discovery that agents capable of inhibiting the biological action of the glucocorticoid receptor can be used in methods for treating gastroesophageal reflux disease in a subject.

Compounds, compositions and methods are provided for modulating the expression of glucocorticoid receptor. The compositions comprise oligonucleotides, targeted to nucleic acid encoding glucocorticoid receptor. Methods of using these compounds for modulation of glucocorticoid receptor expression and for diagnosis and treatment of diseases and conditions associated with expression of glucocorticoid receptor are provided.

Compounds of Formula (IA) and Formula (IB)wherein R1, R2, R3, R4, R5, and R6 are as defined herein for Formula (IA) or Formula (IB), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

A compound of Formula (IA) or Formula (IB)wherein R1, R2, R3, R4, R5, R6, R7, and R8 are as defined herein, or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

A compound of Formula (IA) or Formula (IB)wherein R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein, or a tautomer prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

Compounds of Formula (I)wherein R1, R2, R3, R4, R5, R6, and R7 are as defined herein, or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

The present invention relates to new class of non-steroidal compounds which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and / or NF-κB activity including obesity, diabetes, inflammatory- and immune-associated diseases, and have the structure including all stereoisomers thereof, tautomers thereof, or a prodrug thereof, or a pharmaceutically acceptable salt thereof, wherein X is selected from N, O, and S; Y is N or CR6; Z is a ring; and where R, Ra, Rb, Rc, Rd, R1, R2, R3, R4, and R5 are as defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.

Provided are antisense oligonucleotides and other agents that target and modulate nuclear hormone receptors (NHRs) such as the glucocorticoid receptor (GR), compositions that comprise the same, and methods of use thereof.

A solved three-dimensional crystal structure of a glucocorticord receptor (GR) α ligand binding domain polypeptide is disclosed, in the form of a crystalline glucocorticord receptor α ligand binding domain polypeptide in complex with the ligand fluticasone propionate (FP) and a peptide derived from the co-activator TIF2. The GR / FP / TIF2 structure includes an expanded binding pocket not seen in other GR structures. Methods of designing steroid and non-steroid modulators of the biological activity of GR and other nuclear receptors (NRs) are also disclosed. In another aspect of the present invention homology models of androgen receptor (AR), progesterone receptor (PR) and mineralcorticoid receptor (MR) are disclosed, as well as methods of forming homology models for other NRs. Methods of forming a soluble GR / FP / TIF2 complex are also disclosed.

Novel non-steroidal compounds are provided which are glucocorticoid receptor modulators which are useful in treating diseases requiring glucocorticoid receptor agonist or antagonist therapy such as obesity, diabetes, inflammatory and immune disorders, and have the structure where Z is CONR1R2 or CH2NR1R2 and where R, Ra, Rb, Rc, Rd, Z, A and B are defined herein.

The compounds represented in general formula (1) and a salt thereof are useful for glucocorticoid receptor modulator.The R1 represents a hydrogen atom or a lower alkyl group; R2 represents a hydrogen atom or a lower alkyl group; R3 and R4 may be the same or different and represent a hydrogen atom or a lower alkyl group; R5 represents a hydrogen atom or a lower alkyl group; R6 represents a halogen atom, a lower alkyl group, a hydroxy group, a lower alkoxy group or a nitro group; X represents —C(O)—, —C(O)NR8—, —S(O)2— and the like; R7 and / or R8 may be the same or different and represent a hydrogen atom, a lower alkyl group which may have a substituent, an aryl group which may have a substituent, a heterocyclic group which may have a substituent, a lower alkoxy group which may have a substituent and the like; Y represents a lower alkylene group; Z represents a chalcogen atom; and P represents 0, 1, 2 or 3.