196810-78-3

Upstream product

• 96-49-1 [1,3]-dioxolan-2-one 
• 56426-41-6 3-methyl-5-phenylpyrazole 
• 109-84-2 2-hydroxyethylhydrazine 
• 93-91-4 1-phenylbutan-1,3-dione 
• 3347-62-4 5-methyl-3-phenyl-1H-pyrazole 

Downstream Products

• 1415048-34-8 trans-[PdCl₂(2-(5-methyl-3-phenyl-1H-pyrazol-1-yl)ethanol )] 
• 1415048-36-0 trans-[platinum(II)Cl₂(2-(5-methyl-3-phenyl-1H-pyrazol-1-yl)ethanol )] 
• 196810-79-4 (S)-2-(2-Benzoyl-phenylamino)-3-{4-[2-(5-methyl-3-phenyl-pyrazol-1-yl)-ethoxy]-phenyl}-propionic acid methyl ester 

Relevant academic research and scientific papers

Palladium(II) and platinum(II) complexes with N1-hydroxyethyl-3,5-pyrazole derived ligands

Reaction of the ligands 2-(5-methyl-3-phenyl-1H-pyrazol-1-yl)ethanol (L1) and 2-(3-methyl-5-phenyl-1H-pyrazol-1-yl)ethanol (L2) with [MCl 2(CH3CN)2] (M = Pd(II), Pt(II)) gave the complexes trans-[MCl2L2] (M = Pd(II) and Pt(II), L = L1, L2). The new complexes were characterised by elemental analyses, conductivity measurements, mass spectrometry, IR, 1H and 13C{ 1H} NMR spectroscopies. The crystal and molecular structures of the ligand L2 and the complexes trans-[PdCl2L2] (L = L1, L2) were resolved by X-ray diffraction. Both palladium complexes consisted on monomeric trans-[PdCl2L2] (L = L1, L2) species and molecular packing is determined by intermolecular hydrogen bonding interactions. The NMR spectra of the complexes [PdCl2L2] (L = L1, L2) in CDCl3 solution, is consistent with a very slow rotation of the pyrazolic ligands around the Pd-N bond, so that two conformational isomers can be observed in solution (syn and anti). Different behaviour was observed for complexes [PtCl2L2] (L = L1, L2), for which only the anti isomer was detected in CDCl3 solution at room temperature.

Small molecule library synthesis using segmented flow

Flow chemistry has gained considerable recognition as a simple, efficient, and safe technology for the synthesis of many types of organic and inorganic molecules ranging in scope from large complex natural products to silicon nanoparticles. In this paper

Substituted tridentate pyrazolyl ligands for chromium and nickel-catalyzed ethylene oligomerization reactions. Effect of auxiliary ligand on activity and selectivity

Two new chromium(III) complexes [CrCl3(L)] based on tridentate ligands (1a, L = bis[2-(3-phenyl-1-pyrazolyl)ethyl)]amine; 2a, L = bis[2-(3-methyl-5-phenyl-l-pyrazolyl)ethyl]sulfide) have been prepared and characterized by elemental analysis. Upon activation with methylaluminoxane (MAO), these pre-catalysts showed high turnover frequencies for ethylene oligomerization under optimized conditions (TOFs = 22.9-36.4×10 3 mol C2H4 (mol CrIII)-1 h-1, [Cr] = 10.0 μmol, 80 °C, 20 bar ethylene, MAO:Cr = 300, oligomerization time = 20 min), producing α-olefins in the range C 4-C14+ with high selectively (67.71-73.47%). The catalytic performances are substantially affected by the ligand environment, especially the substituents at the 3- and 5-positions of the pyrazolyl rings. In parallel, the use of nickel complexes such as NiCl2{bis[2-(3,5-dimethyl-1- pyrazolyl)methyl]benzylamine} (3) and NiCl2{bis[2-(3,5-dimethyl-1- pyrazolyl)ethyl)]ether} (5) in oligomerization reactions carried out in the presence of triphenylphosphine (PPh3) afforded highly active catalytic systems with turnover frequencies (TOFs) varying from 36.4 to 154.2×103 mol C2H4 (mol Ni II)-1 h-1. The presence of this auxiliary ligand has a strong impact on the selectivity towards the production of α-olefins, decreasing substantially the amount of 1-butene with a concominat increase of the 2-butene fractions. Attempts to crystallize the nickel complex 3 afforded the tetrametallic [{(L)(μ3-Cl)NiCl} 4] (4, L = 1-anilinomethyl-3,5-dimethylpyrazole) which was characterized by X-ray diffraction analysis.

HETEROCYCLIC COMPOUNDS AS MODULATORS OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS, USEFUL FOR THE TREATMENT AND/OR PREVENTION OF DISORDERS MODULATED BY A PPAR

The present invention is directed to a compound of formula (I), or a pharmaceutically acceptable salt, solvate, hydrate or stereoisomer thereof, which is useful in treating or preventing disorders mediated by a peroxisome proliferator activated receptor (PPAR) such as syndrome X, type II diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, arteriosclerosis, and other disorders related to syndrome X and cardiovascular diseases.

N-(2-benzoylphenyl)-L-tyrosine PPARγ agonists. 2. Structure-activity relationship and optimization of the phenyl alkyl ether moiety

We previously reported the identification of (2S)-((2- benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-phenyloxazol-4- yl)ethoxy]phenyl}propanoic acid (2) (PPARγ pK(i) = 8.94, PPARγ pEC50 = 9.47) as a potent and selective PPARγ agonist. We now report the expanded structure-activity relationship around the phenyl alkyl ether moiety by pursuing both a classical medicinal chemistry approach and a solid-phase chemistry approach for analogue synthesis. The solution-phase strategy focused on evaluating the effects of oxazole and phenyl ring replacements of the 2-(5-methyl-2-phenyloxazol-4-yl)ethyl side chain of 2 with several replacements providing potent and selective PPARγ agonists with improved aqueous solubility. Specifically, replacement of the phenyl ring of the phenyloxazole moiety with a 4-pyridyl group to give 2(S)-((2- benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-pyridin-4-yloxazol-4- yl)ethoxy]phenyl}propionic acid (16) (PPARγ pK(i) = 8.85, PPARγ pEC50 = 8.74) or a 4-methylpiperazine to give 2(S)-((2-benzoylphenyl)amino)-3-(4- {2-[5-methyl-2-(4-methylpiperazin-1-yl)thiazol-4-yl]ethoxy}phenyl)propionic acid (24) (PPARγ pK(i) = 8.66, PPARγ pEC50 = 8.89) provided two potent and selective PPARγ agonists with increased solubility in pH 7.4 phosphate buffer and simulated gastric fluid as compared to 2. The second strategy took advantage of the speed and ease of parallel solid-phase analogue synthesis to generate a more diverse set of phenyl alkyl ethers which led to the identification of a number of novel, high-affinity PPARγ ligands (PPARγ pK(i)'s 6.98-8.03). The combined structure-activity data derived from the two strategies provide valuable insight on the requirements for PPARγ binding, functional activity, selectivity, and aqueous solubility.