160727-95-7

Upstream product

• 116-54-1 dichloroacetic acid methyl ester 
• 459-57-4 4-fluorobenzaldehyde 

Downstream Products

• 1007873-79-1 methyl 5-(4-fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylate 
• 1038508-94-9 2-bromo-5-(4-fluoro-phenyl)-thiazole-4-carboxylic acid methyl ester 
• 1355079-11-6 5-bromo-N-(3,4-dichlorobenzyl)-N-[2-(dimethylamino)ethyl]-3-(4-fluorophenyl)imidazo[1,2-a]pyridine-2-carboxamide 
• 1355082-42-6 5-bromo-3-(4-fluorophenyl)imidazo[1,2-a]pyridine-2-carboxylic acid 
• 1355082-41-5 methyl 5-bromo-3-(4-fluorophenyl)imidazo[1,2-a]pyridine-2-carboxylate hydrochloride 
• 433283-22-8 5-(4-fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid 
• 6091-44-7 piperidine hydrochloride 
• 1038508-87-0 2-cyclopropyl-5-(4-fluoro-phenyl)-thiazole-4-carboxylic acid methyl ester 
• 886361-30-4 2-amino-5-(4-fluoro-phenyl)-thiazole-4-carboxylic acid methyl ester 

Relevant academic research and scientific papers

SUBSTITUTED 2-AZABICYCLO[3.1.1]HEPTANE AND 2-AZABICYCLO[3.2.1]OCTANE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS

There is provided a compound of formula (I), wherein L1 to L3, R1 to R4, X, A and B have meanings given in the description, and pharmaceutically acceptable salts, solvates and prodrugs thereof, which compounds are useful as antagonists of the orexin-1 and orexin-2 receptors or as selective antagonists of the orexin-1 receptor, and thus, in particular, in the treatment or prevention of inter alia substance dependence, addiction, anxiety disorders, panic disorders, binge eating, compulsive disorders, impulse control disorders, cognitive impairment and Alzheimer's disease.

Synthetic Studies on Centromere-Associated Protein-E (CENP-E) Inhibitors: 2. Application of Electrostatic Potential Map (EPM) and Structure-Based Modeling to Imidazo[1,2-a]pyridine Derivatives as Anti-Tumor Agents

To develop centromere-associated protein-E (CENP-E) inhibitors for use as anticancer therapeutics, we designed novel imidazo[1,2-a]pyridines, utilizing previously discovered 5-bromo derivative 1a. By site-directed mutagenesis analysis, we confirmed the ligand binding site. A docking model revealed the structurally important molecular features for effective interaction with CENP-E and could explain the superiority of the inhibitor (S)-isomer in CENP-E inhibition vs the (R)-isomer based on the ligand conformation in the L5 loop region. Additionally, electrostatic potential map (EPM) analysis was employed as a ligand-based approach to optimize functional groups on the imidazo[1,2-a]pyridine scaffold. These efforts led to the identification of the 5-methoxy imidazo[1,2-a]pyridine derivative (+)-(S)-12, which showed potent CENP-E inhibition (IC50: 3.6 nM), cellular phosphorylated histone H3 (p-HH3) elevation (EC50: 180 nM), and growth inhibition (GI50: 130 nM) in HeLa cells. Furthermore, (+)-(S)-12 demonstrated antitumor activity (T/C: 40%, at 75 mg/kg) in a human colorectal cancer Colo205 xenograft model in mice.

Synthetic studies of centromere-associated protein-E (CENP-E) inhibitors: 1.Exploration of fused bicyclic core scaffolds using electrostatic potential map

Centromere-associated protein-E (CENP-E), a mitotic kinesin that plays an important role in mitotic progression, is an attractive target for cancer therapeutic drugs. For the purpose of developing novel CENP-E inhibitors as cancer therapeutics, we investigated a fused bicyclic compound identified by high throughput screening, 4-oxo-4,5-dihydrothieno[3,4-c]pyridine-6-carboxamide 1a. Based on this scaffold, we designed inhibitors for efficient binding at the L5 site in CENP-E utilizing homology modeling as well as electrostatic potential map (EPM) analysis to enhance CENP-E inhibitory activity. This resulted in a new lead, 5-bromoimidazo[1,2-a]pyridine 7, which showed potent CENP-E enzyme inhibition (IC50: 50 nM) and cellular activity with accumulation of phosphorylated histone H3 in HeLa cells. Our homology model and EPM analysis proved to be useful tools for the rational design of CENP-E inhibitors.

2-AZA-BICYCLO[3.3.0]OCTANE DERIVATIVES

The invention relates to 2-aza-bicyclo[3.3.0]octane derivatives of Formula (I) wherein A, B, and R1 are as described in the description, and to the use of such compounds, or of pharmaceutically acceptable salts of such compounds, as medicaments, especially as orexin receptor antagonists.

PIPERIDINE AND PYROOLIDINE COMPOUNDS

The invention relates to piperidine and pyrrolidine compounds of formula (I) wherein A, B, n and X are as described in the description; to pharmaceutically acceptable salts thereof, and to the use of such compounds use as medicaments, especially as orexin receptor antagonists.

1,2-DIAMIDO-ETHYLENE DERIVATIVES AS OREXIN ANTAGONISTS

The invention relates to 1,2-diamido-ethylene derivatives of the formula (I) wherein R1, R2, R3, and A are as described in the description and their use as medicaments, especially as orexin receptor antagonists.

AZETIDINE COMPOUNDS AS OREXIN RECEPTOR ANTAGONISTS

The invention relates to novel azetidine compounds of formula (I), wherein R1, R2, and X are as described in the description and their use as orexin receptor antagonists.

OXAZOLIDINE COMPOUNDS AS OREXIN RECEPTOR ANTAGONISTS

The invention relates to oxazolidine derivatives of the formula (I) wherein A, B, and R1 are as described in the description, to salts, especially pharmaceutically acceptable salts, of such compounds and to their use as medicaments, especially

THIAZOLIDINE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS

The invention relates to novel thiazolidine derivatives of the formula (I) wherein A and R1 are as described in the description and their use as medicaments, especially as orexin receptor antagonists.

PYRROLIDINES AND PIPERIDINES AS OREXIN RECEPTOR ANTAGONISTS

The invention relates to compounds of formula (I) wherein Y, A, N and R1 are as described in the description, to salts, especially pharmaceutically acceptable salts, of such compounds and to the use of such compounds as medicaments, especially