130717-61-2

Upstream product

• 16982-21-1 ethyl 2-amino-2-thioxoacetate 
• 71193-36-7 (α-chloro-4-methoxybenzyl)-(4-methoxyphenyl)-ketone 
• 119-52-8 4,4'-dimethoxybenzoin 
• 27895-95-0 2-bromo-1,2-bis(4-methoxyphenyl)ethanone 

Downstream Products

• 156500-91-3 [4,5-Bis-(4-methoxy-phenyl)-thiazol-2-yl]-piperazin-1-yl-methanone 
• 130717-64-5 2-(hydroxymethyl)-4,5-bis(4-methoxyphenyl)thiazole 
• 130735-49-8 2-formyl-4,5-bis(4-methoxyphenyl)thiazole 
• 145150-34-1 3-<4,5-bis(4-methoxyphenyl)thiazol-2-yl>-(E)-propenoic acid 
• 145150-31-8 ethyl 3-<4,5-bis(4-methoxyphenyl)thiazol-2-yl>-(E)-propenoate 

Relevant academic research and scientific papers

Novel bisaryl substituted thiazoles and oxazoles as highly potent and selective peroxisome proliferator-activated receptor δ agonists

The discovery, synthesis, and optimization of compound 1 from a high-throughput screening hit to highly potent and selective peroxisome proliferator-activated receptor δ (PPARδ) agonists are reported. The synthesis and structure-activity relationship in this series are described in detail. On the basis of a general schematic PPAR pharmacophore model, scaffold 1 was divided into headgroup, linker, and tailgroup and successively optimized for PPAR activation using in vitro PPAR transactivation assays. A (2-methylphenoxy)acetic acid headgroup, a flexible linker, and a five-membered heteroaromatic center ring with two hydrophobic aryl substituents were required for efficient and selective PPARδ activation. The fine-tuning of these aryl substituents led to an array of highly potent and selective compounds such as compound 38c, displaying an excellent pharmacokinetic profile in mouse. In an in vivo acute dosing model, selected members of this array were shown to induce the expression of pyruvate dehydrogenase kinase-4 (PDK4) and uncoupling protein-3 (UCP3), genes that are known to be involved in energy homeostasis and regulated by PPARδ in skeletal muscle.

COMPOUNDS AND COMPOSITIONS AS PPAR MODULATORS

The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of the Peroxisome Proliferator-Activated Receptor (PPAR) families, particularly the activity of PPAR.

4, 5-DIARYLTHIAZOLE DERIVATIVES AS CB-1 LIGANDS

The present invention relates to compounds of formula (I): in which R1 and R2 independently represent phenyl, thienyl or pyridyl and R3represents a group -X-Y-NR4R5 in which X is CO or SO2; Y is absent or represents NH and the other substituente are as defined in the description and their use in the treatment of obesity, psychiatric and neurological disorders and to pharmaceutical compositions containing them.

AQUEOUS DISPERSION COMPRISING STABLE NANOPARTICLES OF A WATER-INSOLUBLE THIAZOLE DERIVATIVE AND EXCIPIENTS LIKE MIDDLE CHAIN TRIGLYCERIDES

A process for the preparation of a stable dispersion of solid particles, in an aqueous medium comprising combining (a) a first solution comprising a substantially water-insoluble substance which is a thiazole compound of Formula I, a water-miscible organic solvent and an inhibitor with (b) an aqueous phase comprising water and optionally a stabiliser, thereby precipitating solid particles comprising the inhibitor and the substantially water-insoluble substance; and optionally removing the water-miscible organic solvent; wherein the inhibitor is a non-polymeric hydrophobic organic compound as defined in the description. Also claimed are stable dispersions obtainable by the process, solid particles obtainable by the process and use of such particles. The process provides a dispersion of solid particles in an aqueous medium, which particles exhibit reduced or substantially no particle growth mediated by Ostwald ripening. The process is particlularly suitable for the preparation of small (sub-micron) aqueous dispersions of a substantially water-insoluble pharmacologically active substance.

Antiplatelet Agents Based on Cyclooxygenase Inhibition without Ulcerogenesis. Evaluation and Synthesis of 4,5-Bis(4-methoxyphenyl)-2-substituted-thiazoles

The syntheses, biological evaluations, and structure-activity relationships of a series of 4,5-bis(4-methoxyphenyl)-2-substituted-thiazoles as potent antiplatelet agents with vasodilatory activity are described. 2-Guanidino-4,5-bis(4-methoxyphenyl)thiazole (3), designed from two parent compounds (itazigrel and timegadine), showed inhibitory activity of malondialdehyde (MDA, IC50 = 31 μM) production which is formed from the cyclooxygenase (CO)-catalyzed oxygenation of arachidonic acid in the synthesis of prostanoids in platelets, with vasodilatory activity (ED50 = 2.0 μM). Further structure-activity relationship studies on 3 culminated in the preparation of 4,5-bis(4-methoxyphenyl)-2-thiazole (10a, FR122047) which exhibited potent inhibitory activity on MDA synthesis in vitro (IC50 = 0.088 μM) and platelet aggregation in guinea pigs ex vivo (100percent inhibition even 6 h after 1.0 mg/kg administration) with vasodilatory activity in vitro (ED50 = 6.2 μM). Moreover, 10a demonstrated no ulcerogenesis effect in rats even at 100 mg/kg dosage (safety margin in rats is more than 70 while that of aspirin is only 1.2) in spite of its potent CO inhibition (IC50 = 0.43 μM), while the use of aspirin, a CO inhibitor and the most popular thromboembolic drug, is restricted by the side effect. Pharmacokinetic studies on 10a have revealed that 10a is detectable in platelet-rich plasma but not in platelet-poor plasma 1 day after oral administration, which indicates that 10a tends to be localized in platelets. This property could be responsible for its low toxicity and reduction of side effects in clinical studies.