1211592-38-9

Upstream product

• 30766-11-1 5-bromoisonicotinic acid 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 
• 137178-88-2 5-bromopyridine-2-carbonyl chloride 
• 1117-97-1 N,0-dimethylhydroxylamine 

Downstream Products

• 214701-49-2 1-(5-bromopyridin-2-yl)ethanone 
• 1088496-42-7 [6-(1-hydroxy-1-methylethyl)pyridin-3-yl]boronic acid 

Relevant academic research and scientific papers

Investigation of cardiovascular effects of tetrahydro-β-carboline sstr3 antagonists

Antagonism of somatostatin subtype receptor 3 (sstr3) has emerged as a potential treatment of Type 2 diabetes. Unfortunately, the development of our first preclinical candidate, MK-4256, was discontinued due to a dose-dependent QTc (QT interval corrected for heart rate) prolongation observed in a conscious cardiovascular (CV) dog model. As the fate of the entire program rested on resolving this issue, it was imperative to determine whether the observed QTc prolongation was associated with hERG channel (the protein encoded by the human Ether-à-go-go-Related Gene) binding or was mechanism-based as a result of antagonizing sstr3. We investigated a structural series containing carboxylic acids to reduce the putative hERG off-target activity. A key tool compound, 3A, was identified from this SAR effort. As a potent sstr3 antagonist, 3A was shown to reduce glucose excursion in a mouse oGTT assay. Consistent with its minimal hERG activity from in vitro assays, 3A elicited little to no effect in an anesthetized, vagus-intact CV dog model at high plasma drug levels. These results afforded the critical conclusion that sstr3 antagonism is not responsible for the QTc effects and therefore cleared a path for the program to progress.

LDHA ACTIVITY INHIBITORS

The invention provides compounds of formula (I), stereoisomers, tautomers, pharmaceutically acceptable salts and prodrugs thereof: (I) wherein A1 to A6 and R1 to R4 are as defined herein. Such compounds are suit

FACTOR XIa INHIBITORS

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma Kallikrein.

AROMATIC RING COMPOUND

Provided is an aromatic ring compound having a glucagon antagonistic action, which is useful for the prophylaxis or treatment of diabetes and the like. A compound represented by the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a salt thereof has a superior glucagon antagonistic action, and is useful as a glucagon antagonist, a glucose production inhibitor or an agent for the prophylaxis or treatment of diabetes and the like.

USE OF PYRAZOLOPYRIMIDINE DERIVATIVES FOR THE TREATMENT OF PI3K-DELTA RELATED DISORDERS

The present application provides methods of treating PI3Kδ related disorders using compounds of Formula I: or pharmaceutically acceptable salts thereof.

ALKYNE-BRIDGED HETERO-AROMATICS AND USES THEREOF

This invention relates to novel alkyne-bridged hetero-aromatics as described in the specification which are PDE10A inhibitors and useful for the treatment of neurological, psychiatric disorder, metabolic disorders, such as Schizophrenia, Parkinson's disea

Discovery of biphenylketones as dual modulators of inflammation and bone loss

Biphenylketones were identified as novel inhibitors of NFκB activation. Structure-activity studies led to the identification of compound 4c, which had good potency against osteoclasts (IC50 = 0.8 μM), showed oral activity, and was able to compl