Genzyme Corporation

Imago Biosciences, Inc.

Massachusetts Institute of Technology

Harvard College

Daimed

Cassandra Celatka

Yibin Xiang

Cecilia M Bastos

Amy E Tapper

Michael John Clare

Craig S Siegel

David J Harris

Edward R Lee

Richard A Silva

Hugh Young Rienhoff, Jr

Frederic Vinick

Junkai Liao

Lisa M Cuff

John Kane

Angeles Dios

Mikaela Levine

John Michael McCall

Thomas Henry Jozefiak

Bradford Hirth

Renato Tony Skerlj

Seng H Cheng

Andrew Charles Good

John Marshall

Ronald K Scheule

Markus Metz

Zhong Zhao

Jon Clardy

Thomas A Natoli

Elyse Bourque

Dyann F Wirth

Elina Makino

Oxana Beskrovnaya

Roger Wiegand

Mario A Cabrera-Salazar

Katherine Jancsics

Herve Husson

Joseph Cortese

Ralph Mazitschek

Jian Lin

Arthur Glenn Romero

He Zhao

Renato Skerlj

Kerry Leigh Spear

Lei Jin

Amy Ripka

Thomas D Bannister

Manuel A Navia

Tsvetelina Ivanova Lazarova

John P Leonard

Hongfeng Deng

Roger Xie

Elisabeth C A Brot

Michael Rynkiewicz

Zihong Guo

Nizal Chandrakumar

Xuemei Chen

Jian-Xie Chen

Zhihua Li

Xiaoming Liao

Mary Lynn Baniecki

Scott T Moe

Pamela Nagafuji

Sameer Urgaonkar

James E Stickler

John Leonard

Toni Chancellor

Elyse M J Bourque

Michael L Booker

Vishal P Patel

Betina Biolatto

Thomas H Jozafiak

Elyse MJ Bourque

Yabin Xiang

Katherine Jancisics

Jr Hugh Y Reinhoff

John M Mccall

Parag Ved

Patricia Soulliac

Namrata Vora

Mario Cabrera-Salazar

Ronald Scheule

Hugh Young Rienhoff

Jon C Clardy

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 present disclosure relates to compounds and methods which may be useful as inhibitors of KDM1A for the treatment or prevention of diseases. Methods of inhibition of KDM1A, methods of increasing gamma globin gene expression, and methods to induce differentiation in cancer cells in a human or animal subject are also provided for treatment of disease such as acute myelogenous leukemia.

KDM1A inhibitors for the treatment of disease

Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDM1A, methods of increasing gamma globin gene expression, and methods to induce differentiation of cancer cells in a human or animal subject are also provided for the treatment of diseases such as acute myelogenous leukemia.

Provided in this disclosure are methods for the synthesis of substituted 2-arylcyclopropylamines and 2-heteroarylcyclopropylamines and related compounds. Also provided are methods for reduction of thioesters to aldehydes, and methods for reductive animation of cyclopropylamines.

Methods and processes for the preparation of KDM1A inhibitors

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. 

A compound for use in treating polycystic kidney disease is represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. A method of treating polycystic kidney disease in a subject in need thereof comprises administering to the subject a therapeutically effective amount of a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. Methods of treating in polycystic kidney disease in a subject in need thereof respectively comprise administering to the subject a therapeutically effective amount of a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof.

2-acylaminopropoanol-type glucosylceramide synthase inhibitors

A compound is represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. A method of treating a subject in need thereof comprises administering to the subject a therapeutically effective amount of a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. The subject has type 2 diabetes; renal hypertrophy or hyperplasia associated with diabetic nephropathy; Tay-Sachs; Gaucher's; or Fabry's disease. Methods of decreasing plasma TNF-&#x3b1;, lowering blood glucose levels, decreasing glycated hemoglobin levels, inhibiting glucosylceramide synthase, and lowering glycosphingolipid concentrations in a subject in need thereof respectively comprise administering to the subject a therapeutically effective amount of a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof.

The present invention relates to methods of treating a subject with malaria comprising administering a 2-aminoindole compound represented by Formula: (I)&#x2014;The values and preferred values of the variables in Structural Formula I are defined herein. 

2-aminoindole compounds and methods for the treatment of malaria

Inhibitors of dihydroorotate dehydrogenase (DHODH) for theenzyme have been identified and characterized. The inhibitors have high specificity, submicromolar efficacy against cultured parasite strains, exhibit drug-like properties, and are not overtly cytotoxic.

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Hull, MA, United States of America

Cassandra Celatka