Bristol-myers Squibb Compnay

Bial - R&d Investments, S.a.

Kala Pharmaceuticals, Inc.

Pmv Pharmaceuticals, Inc.

Lysosomal Therapeutics Inc.

Genzyme Corporation

Bial-biotech Investments, Inc.

Noliva Therapeutics LLC

Bristol Meyers Squibb Company

Birstol-myers Squibb Company

Kata Pharmaceuticals, Inc.

Bristol-myers Squibb Holdings Ireland

Andrew Charles Good

Nicholas A Meanwell

Makonen Belema

Lawrence B Snyder

Omar D Lopez

Jeffrey Lee Romine

Denis R St Laurent

Lawrence G Hamann

Van N Nguyen

Jason T Goodrich

Fukang Yang

Edward H Ruediger

David R Langley

Alain Martel

Carol Bachand

Daniel H Deon

Clint A James

Renato T Skerlj

Peter T Lansbury

Elyse Marie Josee Bourque

Jeffrey Allen Campbell

Paul Michael Scola

Gan Wang

Ny Sin

Ben C Askew

Winston Zapanta Ong

Pawel Wojciech Nowak

William J Greenlee

Li-Qiang Sun

Binh Vu

Stanley V D'Andrea

Romyr Dominique

Richard B Silverman

Seng H Cheng

Piyasena Hewawasam

Sing-Yuen Sit

Yan Chen

John Marshall

Kenneth M Boy

Bradford Hirth

Yibin Xiang

John F Kadow

John E Macor

Richard Eric Olson

Rico Lavoie

Lawrence R Marcin

Hongju Li

Xiangdong Alan Wang

Fiona McPhee

Bruce Fahr

Cassandra Celatka

Ronald K Scheule

Yong Tu

Brian Lee Venables

Markus Metz

Lorin A Thompson, Iii

Dimitri Krainc

Zhizhen Barbara Zheng

Jianbin Zheng

Zhong Zhao

Thomas A Natoli

Elyse Bourque

Elina Makino

Oxana Beskrovnaya

Jayne Kapur

Amy Ripka

Mario A Cabrera-Salazar

Katherine Jancsics

Herve Husson

John A Bender

Yong-Jin Wu

Michael H Serrano-Wu

Renato Skerlj

Jie Chen

Yuping Qiu

Samuel Gerritz

Jianliang Shi

David J Carini

John P Leonard

Wenying Li

Guo Li

Shirong Zhu

Barry L Johnson

Weixu Zhai

Dmitry S Zuev

Nenghui Wang

Shuhao Shi

Jianqing Li

Renato Tony Skerlj

Ramesh Kakarla

Li-Quang Sun

John Leonard

Katherine Jancisics

Ronald Scheule

Mario Cabrera-Salazar

Elyse Marie Josée Bourque

Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present invention can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

Methods and compounds for restoring mutant p53 function

The invention provides substituted pyrazolo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[1,5-a]pyrimidinyl carboxamide compounds described herein include 2-heterocyclyl-4-alkyl-pyrazolo[1,5-a]pyrimidine-3-carboxamide compounds and variants thereof. The invention provides, in part, a compound of Formula (IV): or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

Substituted pyrazolo[1,5-a]pyrimidines as glucocerebrosidase activators

The invention relates to inhibitors of glucosylceramide synthase (GCS) of the Formula I: represented by the following structural formula or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein, useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, cystic disease and for the treatment of cancer.

Glucosylceramide synthase inhibitors

The invention provides substituted pyrazolo[1,5-a]pyrimidine and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[1,5-a]pyrimidine compounds described herein include 5,7-dimethyl-N-phenylpyrazolo[1,5-a]pyrimidine-3-carboxamide compounds and variants thereof.

Substituted pyrazolo[1,5-a]pyrimidines and their use in the treatment of medical disorders

Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

The invention provides substituted imidazo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted imidazo[1,5-a]pyrimidinyl carboxamide compounds described herein include substituted 2-heterocyclyl-4-alkyl-imidazo[1,5-a]pyrimidine-8-carboxamide compounds and variants thereof.

Imidazo[1,5-a]pyrimidinyl carboxamide compounds and their use in the treatment of medical disorders

The invention provides substituted imidazo[1,5-a]pyrimidines and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted imidazo[1,5-a]pyrimidine compounds described herein include substituted 2,4-dimethyl-N-phenylimidazo[1,5-a]pyrimidine-8-carboxamide compounds and variants thereof.

Substituted imidazo[1,5-a]pyrimidines and their use in the treatment of medical disorders

The invention provides substituted pyrrolo[1,2-a]pyrimidines and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrrolo[1,2-a]pyrimidines compounds described herein include substituted 2,4-dimethyl-N-phenylpyrrolo[1,2-a]pyrimidine-8-carboxamide compounds and variants thereof.

Substituted pyrrolo[1,2-a]pyrimidines and their use in the treatment of medical disorders

The invention provides substituted imidazo[1,2-a]pyridine compounds, substituted imidazo[1,2-a]pyrazine compounds, related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary imidazo[1,2-a] pyridine compounds described herein include substituted 5-methyl imidazo[1,2-a]pyridine-8-carboxamide compounds and variants thereof.

Substituted imidazo[1,2-a]pyridines, substituted imidazo[1,2-a]pyrazines, related compounds, and their use in the treatment of medical disorders

The invention provides substituted pyrazolo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[1,5-a]pyrimidinyl carboxamide compounds described herein include 2-heterocyclyl-4-alkyl-pyrazolo[1,5-a]pyrimidine-3-carboxamide compounds and variants thereof. The invention provides, in part, a compound of Formula (I): or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

Substituted pyrazolo[1,5-a]pyrimidines for the treatment of medical disorders

The invention provides substituted pyrrolo[1,2-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrrolo[1,2-a]pyrimidinyl carboxamide compounds described herein include substituted 2-heterocyclyl-4-alkyl-pyrrolo[1,2-a]pyrimidine-8-carboxarnide compounds and variants thereof.

Pyrrolo[1,2-A]pyrimidinyl carboxamide compounds and their use in the treatment of medical disorders

The invention relates to inhibitors of glucosylceramide synthase (GCS), such as Compound of Formula I, shown below, as defined herein, useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, cystic disease and for the treatment of cancer. 

The present invention provides novel compounds of any one of Formulae (I)-(IV), and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of any one of Formulae (I)-(IV) and pharmaceutical compositions thereof that are mucus penetrating. The invention also provides methods and kits for using the inventive compounds, and pharmaceutical compositions thereof, for treating and/or preventing diseases associated with abnormal or pathological angiogenesis and/or aberrant signaling of a growth factor signaling pathway (e.g., vascular endothelial growth factor (VEGF)), such as proliferative diseases (e.g., cancers, benign neoplasms, inflammatory diseases, autoimmune diseases) and ocular diseases (e.g., macular degeneration, glaucoma, diabetic retinopathy, retinoblastoma, edema, uveitis, dry eye, blepharitis, and post-surgical inflammation) in a subject in need thereof. 

Compounds and uses thereof

Growing community of inventors

Wallingford, CT, United States of America

Andrew Charles Good