Corcept Therapeutics Incorporated

Other

Aventis Pharmaceuticals Inc.

Hazel Joan Hunt

Iain Walters

Nicholas Charles Ray

Tony Johnson

Thaddeus S Block

Joseph K Belanoff

Benoit Gourdet

Lorna Duffy

Mark Mills

Andrew William Phillips

Jeffrey Mark Dener

Onno C Meijer

José Van Den Heuvel

Robin D Clark

Joseph Custodio

Thomas Hornsby

Andreas G Moraitis

Christopher Hurley

David Edward Clark

Karen Williams

Thomas Matthew Baker

Ian Strutt

John Francis Unitt

Paul M Blaney

Janusz Jozef Kulagowski

John Gary Montana

Peter Hunt

Paul Robert Eastwood

David Fink

Charles J Gardner

Timothy A Gillespy

Elsa Amandine Dechaux

Lorraine Donaghy

Keith Lorimer

Nathan Jay Dixon

Morgan Jouanneau

Joseph Hill-Cousins

Damien Francis Philippe Crepin

Bin Cao

Sungtaek Lim

Keith John Harris

Jon-Paul Ward

Bas Wilhelmus Theodorus Gruijters

Andrew James Smith

David Stefany

Joacy C Aguiar

Helen Katherine Smith

Arjen Christiaan Breman

Richard Simon Todd

Yukari Perrella

Nicholas David Tyrrell

Bohdan Waszkowycz

Ian McDonald

Ada Lee

Grace Mann

Iulia Cristina Tudor

William Guyer

Angus Morrison

Euan Fordyce

Jonathan Gillespie

Angelo Pugliese

Ray Argenta Discovery Ltd Boffey

David Mark Fink

Applicant discloses methods and compositions for treating a patient suffering from amyotrophic lateral sclerosis (ALS) comprising administration of a heteroaryl ketone fused azadecalin compound. In embodiments, the heteroaryl ketone fused azadecalin compound is dazucorilant: (R)-(1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl) sulfonyl)-4, 4a, 5,6,7,8-hexahydro-1-H-pyrazolo[3,4-g]isoquinolin-4a-yl) (pyridin-2-yl)methanone, having the chemical structure illustrated as Suitable doses include daily administration of 150 milligrams and 300 milligrams of dazucorilant. Suitable doses include daily administration of dazucorilant with food, or with water, or with food and water. Daily administration of dazucorilant is effective to increase dazucorilant exposure up to about 2-fold when continued for seven days or more. Administration of such a heteroaryl ketone fused azadecalin compound may comprise oral administration, enteral administration, or other administration. Pharmaceutical compositions comprising dazucorilant are useful in the treatment of patients suffering from ALS. Suitable pharmaceutical compositions comprising dazucorilant include, e.g., pharmaceutical compositions for oral administration and pharmaceutical compositions for enteral administration.

Treatments for amyotrophic lateral sclerosis using dazucorilant

Methods and compositions for treating a subject hosting a non-ACTH-secreting pancreatic tumor are disclosed. The methods include administering to the subject a chemotherapeutic agent and a glucocorticoid receptor modulator (GRM), preferably a selective glucocorticoid receptor modulator (SGRM), to reduce the tumor load in the subject. The non-ACTH-secreting pancreatic tumor may be an exocrine pancreatic tumor. The GRM may be a nonsteroidal GRM or a nonsteroidal SGRM. The nonsteroidal SGRM may be a nonsteroidal compound comprising: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure. Pharmaceutical compositions comprising a chemotherapeutic agent and a GRM are disclosed. The GRM in such pharmaceutical compositions may be a nonsteroidal GRM, and may be a nonsteroidal SGRM. The nonsteroidal SGRM may comprise: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure.

Glucocorticoid receptor modulators to treat pancreatic cancer

Methods for treating a subject having a cancerous tumor are disclosed. The methods comprise administering to the subject an effective amount of a non-steroidal selective glucocorticoid receptor modulator (SGRM) and an effective amount of a chemotherapeutic agent. The tumor may be cervical cancer. The SGRM may be a fused azadecalin. In embodiments, the SGRM may be a heteroaryl ketone fused azadecalin or an octahydro fused azadecalin.

Glucocorticoid receptor modulators to treat cervical cancer

The present invention provides treatment of fatty liver disease using a class of pyrimidinedione cyclohexyl compounds.

Fatty liver disease treatment using glucocorticoid and mineralocorticoid receptor antagonists

The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators, including their use for treating amyotrophic lateral sclerosis (ALS).

Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators

The present disclosure provides compounds of Formula I or II. Compounds of Formula I or II may be used in pharmaceutical formulations, and may be used for modulating glucocorticoid receptors.

Quaternary indazole glucocorticoid receptor antagonists

This invention provides a method that combines a checkpoint inhibitor and a glucocorticoid receptor modulator to treat cancer, e.g., a checkpoint inhibitor sensitive cancer.

Use of glucocorticoid receptor modulators to potentiate checkpoint inhibitors

The present invention provides octahydro fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

Octahydro fused azadecalin glucocorticoid receptor modulators

The present invention provides crystalline forms of (E)-6-(4-Phenylcyclohexyl)-5-(3-trifluoromethylbenzyl)-1H-pyrimidine-2,4-dione, and methods of making and using the same.

Polymorphs of pyrimidine cyclohexyl glucocorticoid receptor modulators

The present disclosure provides compounds of Formula I, Ia, Ib, Ib-1, Ib-2, Ic, Ic-1, Id-1, and Id-2. Compounds of Formula I, Ia, Ib, Ib-1, Ib-2, Ic, Ic-1, Id-1, and Id-2 may be used in pharmaceutical formulations, and may be used for modulating glucocorticoid receptors.

Bicyclic indazole glucocorticoid receptor antagonists

Provided are piperazine substituted fused azadecalin compounds of Formula J, I, Ia, Ib, Ib-1, Ib-2, Ic and Id for use in pharmaceutical formulations, and for modulating glucocorticoid receptors.

Piperazine indazole glucocorticoid receptor antagonists

The present invention provides a class of pyrimidinedione cyclohexenyl compounds and methods of using these compounds as glucocorticoid receptor modulators.

Pyrimidine cyclohexenyl glucocorticoid receptor modulators

Many drugs useful in treating cancer are metabolized by CYP2C8 enzymes, by CYP3A4 enzymes, or both. The effects of concomitant administration of relacorilant and paclitaxel, a drug used to treat cancer that is a substrate for both CYP2C8 and CYP3A4, are disclosed herein. Relacorilant potently inhibited CYP2C8 and CYP3A4 in in vitro tests, indicating that co-administration of relacorilant and paclitaxel would increase paclitaxel plasma exposure more than 5-fold in vivo, requiring significant reductions in paclitaxel doses when co-administering paclitaxel with relacorilant. Surprisingly, paclitaxel plasma exposure increased only by about 80% instead of the expected more than 5-fold increase expected with concomitant relacorilant and paclitaxel administration. Applicant discloses safe methods of co-administering relacorilant and paclitaxel by reducing the dose of paclitaxel to about half the paclitaxel dose used when paclitaxel is administered alone. Relacorilant and such reduced doses of paclitaxel may be co-administered to treat cancer, e.g., ovarian or pancreatic cancer.

Concomitant administration of glucocorticoid receptor modulator relacorilant and paclitaxel, a dual substrate of CYP2C8 and CYP3A4

Methods of Treating Antipsychotic-Induced Weight Gain with Miricorilant Methods and compositions for treating a subject at risk of, or suffering from antipsychotic-induced weight gain are disclosed. The methods include administration of a cyclohexyl pyrimidine glucocorticoid receptor modulator (GRM) such as miricorilant (CORT118335) to a patient receiving, or who has received, or who is expected to receive, an antipsychotic drug such as olanzapine, risperidone, clozapine, or other weight-inducing antipsychotic medication. The GRM (e.g., miricorilant) may be orally administered. Administration of such a GRM along with antipsychotic medication may reduce the amount of weight, or reduce the rate of weight gain, or prevent weight gain, otherwise due to antipsychotic medication alone. The methods may reverse weight gain in a patient previously administered antipsychotic medication. Administration of such a GRM with antipsychotic medication may reduce, or reduce gain in, or prevent gain in, or reverse gain in, insulin resistance or blood levels of liver enzymes (AST, ALT), triglycerides, or insulin.

Methods of treating antipsychotic-induced weight gain with miricorilant

The present invention provides methods of preparing 2-amino-6-((1r,4r)-4-phenylcyclohexyl)-5-(3-(trifluoromethyl)benzyl)pyrimidin-4(3H)-one, and 2-amino-6-((1r,4r)-4-phenylcyclohexyl)-5-(3-(trifluoromethyl)benzyl)pyrimidin-4(3H)-one monohydrate, as well as new intermediate compounds.

Method of preparing pyrimidine cyclohexyl glucocorticoid receptor modulators

Growing community of inventors

West Sussex, United Kingdom

Hazel Joan Hunt