56835-97-3

Upstream product

• 1201675-09-3 methyl 2-chloro-6-morpholinoisonicotinate 
• 42521-09-5 methyl 2,6-dichloroisonicotinate 
• 110-91-8 morpholine 
• 5398-44-7 2,6-dichloropyridine-4-carboxylic acid 

Relevant academic research and scientific papers

Structure-Activity Relationship Studies of Pyrimidine-4-Carboxamides as Inhibitors of N-Acylphosphatidylethanolamine Phospholipase D

N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is regarded as the main enzyme responsible for the biosynthesis of N-acylethanolamines (NAEs), a family of bioactive lipid mediators. Previously, we reported N-(cyclopropylmethyl)-6-((S)-3-hydroxypyrrolidin-1-yl)-2-((S)-3-phenylpiperidin-1-yl)pyrimidine-4-carboxamide (1, LEI-401) as the first potent and selective NAPE-PLD inhibitor that decreased NAEs in the brains of freely moving mice and modulated emotional behavior [ Mock et al. Nat Chem. Biol., 2020, 16, 667-675 ]. Here, we describe the structure-activity relationship (SAR) of a library of pyrimidine-4-carboxamides as inhibitors of NAPE-PLD that led to the identification of LEI-401. A high-throughput screening hit was modified at three different substituents to optimize its potency and lipophilicity. Conformational restriction of an N-methylphenethylamine group by replacement with an (S)-3-phenylpiperidine increased the inhibitory potency 3-fold. Exchange of a morpholine substituent for an (S)-3-hydroxypyrrolidine reduced the lipophilicity and further increased activity by 10-fold, affording LEI-401 as a nanomolar potent inhibitor with drug-like properties. LEI-401 is a suitable pharmacological tool compound to investigate NAPE-PLD function in vitro and in vivo.

MALIC ENZYME INHIBITORS

The present invention relates to novel compounds useful as malic enzyme (ME) inhibitors, processes for their preparation and use of these compounds for the therapeutic treatment of disorders mediated by ME such as cancers (e.g. pancreatic ductal adenocarcinoma (PDAC)) in humans.

INHIBITORS OF N-ACYLPHOSPHATIDYLETHANOLAMINE PHOSPHOLIPASE D (NAPE-PLD)

The invention relates to a compound of the formula (I) as novel inhibitor of N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD), and to use thereof for the prophylaxis or treatment of diseases associated with NAPE-PLD. wherein in a ring A, X1 is N, or CR4; X2 is N or CR5; X3 is N or CH; with the proviso that at least one of X1 and X3 is N.

PI3 KINASE INHIBITORS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

Amino containing isonicotinic acid derivatives

Compounds of formula STR1 wherein X represents chlorine, bromine or iodine, R1 represents a C1 -C12 -alkyl group optionally substituted by hydroxy, C1 -C4 -alkoxy, amino or mono- or di-C1 -C2 -alkylamino; or a C3 -C4 -alkenyl group, C3 -C8 -cycloalkyl group, benzyl group, p-acetylbenzyl group or phenethyl group, and R2 represents hydrogen or a C1 -C4 -alkyl group or a C3 -C4 -alkenyl group, or R1 and R2 together represent a 5- to 7-membered heterocyclic group, which optionally can additionally contain an oxygen atom, As well as their salts with organic and inorganic bases which are useful as bactericides and fungicides.