Abstract: CRF1 receptor antagonists have the potential to directly inhibit ACTH release in patients with CAH and thereby allow normalization of androgen production while using lower, more physiologic doses of hydrocortisone, and thus reducing treatment-associated side effects.
Abstract: This disclosure relates generally to VMAT2 inhibitor compounds of Formula (Ia): and pharmaceutically acceptable salts thereof, as well as compositions and methods related thereto.
Type:
Grant
Filed:
January 12, 2023
Date of Patent:
August 8, 2023
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Nicole Harriott, Nicholas Pagano, Byron A. Boon
Abstract: GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R1d, R2, R2a, and A are as defined herein, including stereoisomers, esters, solvates and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.
Type:
Grant
Filed:
December 18, 2020
Date of Patent:
August 1, 2023
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Graham Beaton, Mi Chen, Timothy Richard Coon, Todd Ewing, Wanlong Jiang, Willy Moree, Martin Rowbottom, Warren Wade, Liren Zhao, Richard Lowe, Nicole Smith, Neil Ashweek, Yun-Fei Zhu
Abstract: Provided are methods of administering a vesicular monoamine transport 2 (VMAT2) inhibitor chosen from valbenazine and (+)-?-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,1 1b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol, or a pharmaceutically acceptable salt and/or isotopic variant thereof, to a patient in need thereof wherein the patient is also being administered digoxin.
Type:
Grant
Filed:
October 20, 2020
Date of Patent:
May 23, 2023
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Christopher F. O'Brien, Haig P. Bozigian
Abstract: The present invention relates to processes and intermediates for preparing Gonadotropin-Releasing Hormone (GnRH) receptor antagonists of structure (VI); and stereoisomers and pharmaceutically acceptable salts thereof.
Type:
Grant
Filed:
January 10, 2020
Date of Patent:
October 4, 2022
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Donald J. Gallagher, Laszlo R. Treiber, Robert Michael Hughes, Onorato Campopiano, Peng Wang, Yuxin Zhao, Shine K. Chou, Michael Allen Ouellette, Donald Nicholas Hettinger
Abstract: Provided are methods of administering a vesicular monoamine transport 2 (VMAT2) inhibitor chosen from valbenazine and (+)-?-3-isobutyl-9,10-dimethoxy-1, 3,4, 6,7,11 b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol, or a pharmaceutically acceptable salt and/or isotopic variant thereof, to a patient in need thereof wherein the patient is a CYP2D6 poor metabolizer.
Type:
Grant
Filed:
October 26, 2020
Date of Patent:
September 13, 2022
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Christopher F. O'Brien, Haig P. Bozigian
Abstract: CRF1 receptor antagonists have the potential to directly inhibit ACTH release in patients with CAH and thereby allow normalization of androgen production while using lower, more physiologic doses of hydrocortisone, and thus reducing treatment-associated side effects.
Abstract: Solid pharmaceutical compositions with high drug loading are provided. A formulation useful for the solid pharmaceutical composition includes valbenazine, or a pharmaceutically acceptable salt thereof, silicified microcrystalline cellulose, isomalt, hydroxypropyl methylcellulose, partially pregelatinized maize starch, and magnesium stearate.
Type:
Grant
Filed:
October 19, 2020
Date of Patent:
April 26, 2022
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Richard Alexander Moore, Jr., Gregory A. McClelland, Christopher F. O'Brien
Abstract: Compounds having a structure of formula (I), including stereoisomers and pharmaceutically acceptable salts and solvates thereof: wherein R1 is as defined herein. Such compounds are inhibitors of the vesicular monoamine transporter 2 (VMAT2) and have utility for treating, for example, hyperkinetic disorders. Also disclosed are compositions containing these compounds in combination with a pharmaceutically acceptable carrier or diluent, as well as methods relating to the use in a subject in need thereof.
Abstract: Provided is a compound selected from compounds of Formula (I) and pharmaceutically acceptable salts, solvates, and hydrates thereof: (I) wherein R1, R2, R3 and R4 are as defined herein. Such compounds are inhibitors of the vesicular monoamine transporter 2 (VMAT2) and have utility for treating, for example, neurological and psychiatric diseases and disorders. Also disclosed are compositions containing such compounds in combination with a pharmaceutically acceptable carrier, as well as methods relating to their use in subjects in need thereof.
Type:
Grant
Filed:
April 17, 2018
Date of Patent:
June 22, 2021
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Nicole Harriott, Donald Hettinger, Shawn Branum, Jeffrey C. Culhane
Abstract: Provided are methods of administering a vesicular monoamine transport 2 (VMAT2) inhibitor chosen from valbenazine and (+)-?-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol, or a pharmaceutically acceptable salt and/or isotopic variant thereof, to a patient in need thereof wherein the patient is also being administered a strong cytochrome P450 2D6 (CYP2D6) inhibitor.
Type:
Grant
Filed:
May 8, 2020
Date of Patent:
June 22, 2021
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Christopher F. O'Brien, Haig P. Bozigian
Abstract: Provided herein are small molecule compounds of the following formula (I): or a stereoisomer, tautomer, solvate, ester or pharmaceutically acceptable salt thereof, wherein A, B, C, L1, L2, R2, R3, R4, R3, w, x, y and z are as defined herein. Methods for treating diseases/disorders by antagonizing muscarinic receptors, including specifically antagonizing muscarinic receptor 4 (M4), are also disclosed. Such diseases/disorders are e.g. neurological diseases/disorders such as e.g. Alzheimer's Disease, Lewy Body Dementia and the cognitive deficits associated with schizophrenia, Parkinson's Disease, drug induced Parkinsonism, dyskinesias, dystonia, chorea, levodopa induced dyskinesia, cerebral palsy, progressive supranuclear palsy, and Huntington's disease. Preferred compounds are e.g. N-[2-(1-benzylpiperidin-4-yl)ethyl]-4-(pyrazin-2-yl)-piperazine-1-carboxamide derivatives and related compounds wherein the pyrazine has been replaced by e.g. pyridazine, pyrimidine, pyridine or phenyl.
Abstract: Solid pharmaceutical compositions with high drug loading are provided. A formulation useful for the solid pharmaceutical composition includes valbenazine, or a pharmaceutically acceptable salt thereof, silicified microcrystalline cellulose, isomalt, hydroxypropyl methylcellulose, partially pregelatinized maize starch, and magnesium stearate.
Type:
Grant
Filed:
October 19, 2020
Date of Patent:
June 8, 2021
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Richard Alexander Moore, Jr., Gregory A. McClelland, Christopher F. O{grave over ( )}Brien
Abstract: Provided are methods of administering a vesicular monoamine transport 2 (VMAT2) inhibitor chosen from valbenazine, or a pharmaceutically acceptable salt and/or isotopic variant thereof, to a patient in need thereof.
Type:
Grant
Filed:
August 3, 2020
Date of Patent:
June 8, 2021
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Grace S. Liang, Christopher F. O'Brien, Dao Tuyet Thai-Cuarto
Abstract: Substituted 1,2,3-triazole compounds are disclosed which have utility in the treatment of a variety of neurological disorders. The compounds provided herein have the general structure: wherein R1, R2, R3 and n are as defined herein, including stereoisomers, esters, solvates and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound provided herein in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for treating neurological disorders in a subject in need thereof.
Type:
Grant
Filed:
June 4, 2020
Date of Patent:
June 1, 2021
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Neil J. Ashweek, John P. Williams, Deborah Slee, Manisha Moorjani
Abstract: Provided are methods of administering a vesicular monoamine transport 2 (VMAT2) inhibitor chosen from valbenazine and (+)-?-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol, or a pharmaceutically acceptable salt and/or isotopic variant thereof, to a patient in need thereof wherein the patient has mild, moderate, or severe hepatic impairment.
Type:
Grant
Filed:
May 8, 2020
Date of Patent:
May 4, 2021
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Christopher F. O'Brien, Haig P. Bozigian
Abstract: Provided are methods of administering a vesicular monoamine transport 2 (VMAT2) inhibitor chosen from valbenazine and (+)-a-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol, or a pharmaceutically acceptable salt and/or isotopic variant thereof, to a patient in need thereof wherein the patient is also being administered a strong cytochrome P450 3A4 (CYP3A4) inhibitor.
Type:
Grant
Filed:
May 8, 2020
Date of Patent:
March 23, 2021
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Christopher F. O'Brien, Haig P. Bozigian
Abstract: Provided is a method of administering a vesicular monoamine transporter 2 (VMAT2) inhibitor to a subject in need thereof, wherein the subject has severe renal impairment.
Abstract: GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R1d, R2, R2a, and A are as defined herein, including stereoisomers, esters, solvates and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.
Type:
Grant
Filed:
July 2, 2019
Date of Patent:
March 9, 2021
Assignee:
Neurocrine Biosciences, Inc.
Inventors:
Graham Beaton, Mi Chen, Timothy Richard Coon, Todd Ewing, Wanlong Jiang, Willy Moree, Martin Rowbottom, Warren Wade, Liren Zhao, Richard Lowe, Nicole Smith, Neil Ashweek, Yun-Fei Zhu
Abstract: Provided herein are processes for the preparation of (S)-(2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-yl 2-amino-3-methylbutanoate di(4-methylbenzenesulfonate), or a solvate, hydrate, or polymorph thereof.