1189816-87-2

Upstream product

• 30766-22-4 methyl 5-hydroxy-3-pyridinecarboxylate 
• 27828-71-3 5-hydroxynicotinic acid 

Downstream Products

• 227752-45-6 2,3-dihydrofuro[3,2-b]pyridine-6-carbaldehyde 
• 227752-44-5 (2,3-dihydrofuro[3,2-b]pyridin-6-yl)methanol 
• 1649471-55-5 methyl furo[3,2-b]pyridine-6-carboxylate 

Relevant academic research and scientific papers

Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor

Embryonic stem cell pathways such as hedgehog and Wnt pathways are central to the tumorigenic properties of cancer stem cells (CSC). Since CSCs are characterized by their ability to self-renew, form differentiated progeny, and develop resistance to anticancer therapies, targeting the Wnt and hedgehog signaling pathways has been an important strategy for cancer treatment. Although molecules targeting either Wnt or hedgehog are common, to the best of our knowledge, those targeting both pathways have not been documented. Here we report a small molecule (compound 1) that inhibits both Wnt (IC50 = 0.5 nM) and hedgehog (IC50 = 71 nM) pathways based on reporter gene assays. We further identified that the molecular target of 1 for Wnt pathway inhibition was porcupine (a member of the membrane-bound O-acyltransferase family of proteins), a post-translational modification node in Wnt signaling; while the target of 1 mitigating hedgehog pathway was Smoothened, a key G protein coupled receptor (GPCR) mediating hedgehog signal transduction. Preliminary analysis of structure-activity-relationship identified key functional elements for hedgehog/Wnt inhibition. In in vivo studies, compound 1 demonstrated good oral exposure and bioavailability while eliciting no overt toxicity in mice. An important consideration in cancer treatment is the potential therapeutic escape through compensatory activation of an interconnected pathway when only one signaling pathway is inhibited. Toward this end, compound 1 may not only lead to the development of new therapeutics for Wnt and hedgehog related cancers, but may also help to develop potential cancer treatment which needs to target Wnt and hedgehog signaling simultaneously.

TETRAHYDRO-BENZOAZEPINE GLYCOSIDASE INHIBITORS

Compounds of formula (I') wherein A, R1, R2, T1, T2, T3, T4, L, W, Z, R''', m and n have the meaning according to the claims can be employed, inter alia, for the treatment of tauopathies and Alzheimer's disease.

FUSED GLYCOSIDASE INHIBITORS

Compounds of formula (I), wherein A, Z, E, R1, R2, m and n have the meaning according to the claims can be employed, inter alia, for the treatment of tauopathies and Alzheimer's disease.

HETEROAROMATIC COMPOUNDS AS VANIN INHIBITORS

The present invention encompasses compounds of the formula (I) wherein the groups A and B are defined herein, which are suitable for the treatment of diseases related to Vanin, and processes for making these compounds, pharmaceutical preparations containi

BICYCLIC HYDROXAMIC ACIDS USEFUL AS INHIBITORS OF MAMMALIAN HISTONE DEACETYLASE ACTIVITY

A compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. The compound is an inhibitor of a histone deacetylase, and as such is useful in terepy, e.g. in the treatment of autoimmune disorders, mental disorders, neurodegenerative disorders, and hyperproliferative disorders.

TBK/IKK INHIBITOR COMPOUNDS AND USES THEREOF

The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TBK/IKKε inhibitors.

BENZOPYRAN AND BENZOXEPIN PI3K INHIBITOR COMPOUNDS AND METHODS OF USE

Benzopyran and benzoxepin compounds of Formulas I and II, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formulas I and II for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.