Universitéde Montreal

Bristol-myers Squibb Compnay

Stéphane Gingras

Guy Sauvageau

Yves Gareau

Anne Marinier

Réjean Ruel

Michel Bouvier

Gaoqiang Yang

Yves Andre Chantigny

Iman Fares

Patricia René

Yves Chantigny

Philippe Dagneau

Irène Baccelli

Rejean Ruel

Nachimuthu Soundararajan

Serge Benoit

Heterocyclic compounds of Formula I: and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed. Such cancers include acute myeloid leukemia (AML), preferably AML characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (NK), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDH1, mutated IDH2, mutated RUNX1, mutated WT1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and/or abnormal chromosome (5/7), and/or a high leukemic stem cell (LSC) frequency.

Heterocyclic mitochondrial activity inhibitors and uses thereof

Heterocyclic compounds of Formula (I) and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed. Such cancers include acute myeloid leukemia (AML), preferably AML characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (A/K), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDH1, mutated IDH2, mutated RUNX1, mutated WT1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and/or abnormal chromosome (5/7), and/or a high leukemic stem cell (LSC) frequency.

Compounds of general formula or salts or prodrugs thereof, are provided and described herein. The compounds are useful to expand hematopoietic stem cell and/or hematopoietic progenitor cell populations. Particularly, the hematopoietic cells are human cells. The compounds are also useful in the medical treatment of hematopoietic disorder/malignancy, an autoimmune disease and/or an inherited immune-deficient disease in a subject. 

Compounds and use thereof in the expansion of hematopoietic stem cells and/or hematopoietic progenitor cells

Pyrimido[4,5-b]indole derivatives are provided. These compounds are useful to expand hematopoietic stem cell populations, particularly, human hematopoietic stem cell populations. The compounds are also useful in the medical treatment of diseases that involve hematopoietic stem cells.

Pyrimido[4,5-B]indole derivatives and use thereof in the expansion of hematopoietic stem cells

Disclosed herein is a compound of Formula I: 

Pyrazolopyridine and pyrazolopyrimidine derivatives as melanocortin-4 receptor modulators

Disclosed herein is a compound of Formula I: wherein X, R, R, and Rare as defend herein, or a pharmaceutically acceptable salt thereof to allow the drug to penetrate the cell membrane; or a prodrug, or the compound is labeled with a detectable label or an affinity tag thereof. Also disclosed is a pharmaceutical composition, a method of treating a disorder mediated by melanocortin-4 receptors, and a method of treating obesity using the compounds described. 

Provided are processes and synthetic intermediates useful for the preparation of azaindole piperazine diamide derivatives of the formula These azaindole piperazine diamide derivatives, among other things, are useful as therapeutic agents for the treatment of HIV and AIDS.

Growing community of inventors

Montreal, Canada

Stéphane Gingras