Provided herein are novel 1,6-naphthridine compounds as SMARCA2 inhibitors, pharmaceutical compositions, use of such compounds in treating non-small cell lung cancer and processes for preparing such compounds.
Provided herein are novel 1,6-naphthridine compounds as SMARCA2 inhibitors, pharmaceutical compositions, use of such compounds in treating non-small cell lung cancer and processes for preparing such compounds.
Mutations in isocitrate dehydrogenase (IDH) 1 or 2 are identified in various cancers. Accumulated (R)-2-hydroxyglutarate (2-HG) caused by mutant IDHs leads to blockage of cell differentiation, thereby inducing malignant transformation. Herein we describe the medicinal chemistry efforts that discovered novel mutant IDH inhibitor HMPL-306 (ranosidenib) via structure-activity relationship studies and pharmacokinetic optimization from internal hit compound 1. HMPL-306 is a potent and selective dual inhibitor of mutant IDH1 and 2. It demonstrated favorable preclinical pharmacokinetics and safety profiles, reduced 2-HG in vivo robustly and sustainably in the mutant IDH1 and 2 tumor xenograft models, and displayed high brain penetration in mice. In the clinical studies, the drug showed good safety and encouraging efficacy in patients with relapsed/refractory myeloid malignancies carrying IDH1 and/or IDH2 mutations.
Mutations in isocitrate dehydrogenase (IDH) 1 or 2 are identified in various cancers. Accumulated (R)-2-hydroxyglutarate (2-HG) caused by mutant IDHs leads to blockage of cell differentiation, thereby inducing malignant transformation. Herein we describe the medicinal chemistry efforts that discovered novel mutant IDH inhibitor HMPL-306 (ranosidenib) via structure–activity relationship studies and pharmacokinetic optimization from internal hit compound 1. HMPL-306 is a potent and selective dual inhibitor of mutant IDH1 and 2. It demonstrated favorable preclinical pharmacokinetics and safety profiles, reduced 2-HG in vivo robustly and sustainably in the mutant IDH1 and 2 tumor xenograft models, and displayed high brain penetration in mice. In the clinical studies, the drug showed good safety and encouraging efficacy in patients with relapsed/refractory myeloid malignancies carrying IDH1 and/or IDH2 mutations.
Provided herein are novel tryptamine compounds as 5-HT2A agonists, pharmaceutical compositions, use of such compounds in treating mood disorders such as depressive disorders and bipolar disorders and processes for preparing such compounds.
This patent describes a novel class of novel indazole/azaindazole-substituted cyclopentapyrroles, which selectively inhibit the Leucine-Rich Repeat Kinase 2 (LRRK2) with G2019S mutation. These LRRK2 inhibitors are proposed for treating Parkinson’s diseases, Alzheimer’s disease, and other central nervous system (CNS) disorders.
Provided herein are novel tryptamine compounds as 5-HT2A agonists, pharmaceutical compositions, use of such compounds in treating mood disorders such as depressive disorders and bipolar disorders and processes for preparing such compounds.
This patent describes a novel class of novel indazole/azaindazole-substituted cyclopentapyrroles, which selectively inhibit the Leucine-Rich Repeat Kinase 2 (LRRK2) with G2019S mutation. These LRRK2 inhibitors are proposed for treating Parkinson's diseases, Alzheimer's disease, and other central nervous system (CNS) disorders.
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