2-Amino-1-phenylethanol

Discovery of β-arrestin-biased β2-adrenoceptor agonists from 2-amino-2-phenylethanol derivatives

β-Arrestins are a small family of proteins important for signal transduction at G protein-coupled receptors (GPCRs). β-Arrestins are involved in the desensitization of GPCRs. Recently, biased ligands possessing different efficacies in activating the G protein- versus the β-arrestin-dependent signals downstream of a single GPCR have emerged, which can be used to selectively modulate GPCR signal transduction in such a way that desirable signals are enhanced to produce therapeutic effects while undesirable signals of the same GPCR are suppressed to avoid side effects. In the present study, we evaluated agonist bias for compounds developed along a drug discovery project of β2-adrenoceptor agonists. About 150 compounds, including derivatives of fenoterol, 2-amino-1-phenylethanol and 2-amino-2-phenylethanol, were obtained or synthesized, and initially screened for their β-adrenoceptor-mediated activities in the guinea pig tracheal smooth muscle relaxation assay or the cardiomyocyte contractility assay. Nineteen bioactive compounds were further assessed using both the HTRF cAMP assay and the PathHunter β-arrestin assay. Their concentration-response data in stimulating cAMP synthesis and β-arrestin recruitment were applied to the Black-Leff operational model for ligand bias quantitation. As a result, three compounds (L-2, L-4, and L-12) with the core structure of 5-(1-amino-2-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one were identified as a new series of β-arrestin-biased β2-adrenoceptor agonists, whereas salmeterol was found to be Gs-biased. These findings would facilitate the development of novel drugs for the treatment of both heart failure and asthma.

Separation of octopamine racemate on (R,S)-2-amino-1-phenylethanol imprinted polymer--Experimental and computational studies

Ten molecularly imprinted polymers coded as MIP1-MIP10 were prepared by the radical bulk polymerization using (R,S)-(±)-2-amino-1-phenylethanol as the structural analog of the target analyte (R,S)-octopamine. The functional monomers, 4-vinylbenzoic acid (1), methacrylic acid (2), acrylic acid (3), trifluoromethacrylic acid (4), itaconic acid (5), acrylamide (6), isopropenylbenzene (7), 2-hydroxyethyl methacrylate (8), 2-(diethylamino)ethyl methacrylate (9), allylamine (10) were polymerized consecutively with the ethylene glycol dimethacrylate cross-linker in methanol as the porogen. On the basis of the binding capacity of (R,S)-octopamine MIP1 with affinity factor equal to 6.37 was selected for further analysis. The affinity of polymer matrix MIP1 was tested by the non-competitive binding experiments of eight structurally related analytes. Finally, molecularly imprinted solid phase extraction (MISPE) of (R,S)-octopamine from spiked human serum albumin was carried out in order to verify the applicability of novel sorbent. The molecular modeling was employed to rationalize the stereodifferentiation of the analytes by the stereospecific sites formed in the polymer matrix.

Shape of biomolecules by free jet microwave spectroscopy: 2-amino-1-phenylethanol and 2-methylamino-1-phenylethanol

We report a free jet microwave absorption study of 2-amino-1-phenylethanol and 2-methylamino-1-phenylethanol, which are analogues of noradrenaline and adrenaline, respectively. The spectra, recorded under different expansion conditions and with different carrier gases, show the presence of several conformational species: two conformers for 2-amino-1-phenylethanol and three for 2-methylamino-1-phenylethanol. The assignment is based on the comparison of the experimental rotational constants and the orientation of the molecular dipole moment with the ones predicted by theoretical methods and allows the univocal identification of all observed conformers while intensity measurements give information on their relative stability. All of the observed conformational species are stabilized by an intramolecular hydrogen bond between the hydroxyl hydrogen atom and the amino nitrogen atom, whereas the alkylamino side chain can be in the extended anti or folded gauche conformation. The presence of the bulky methyl group substituent on the alkylamino side chain of 2-methylamino-1-phenylethanol influences the relative stability of the conformers.

Transformation of 2-aminoacetophenone to ( S) -2-amino-1-phenylethanol by Arthrobacter sulfureus

A new isolate of Arthrobacter sulfureus , when incubated at 50 g resting cells (dry cell wt) l(-1) with 50 g glucose l(-1) and 1 g 2-aminoacetophenone l(-1) in 50 mm potassium buffer (pH 7, 4 ml) at 30 degrees C, produced ( S )-2-amino-1-phenylethanol (e.e. >99%) with 75% yield in 6 h.

Case Study of Small Molecules As Antimalarials: 2-Amino-1-phenylethanol (APE) Derivatives

Antiparasitic oral drugs have been associated to lipophilic molecules due to their intrinsic permeability. However, these kind of molecules are associated to numerous adverse effects, which have been extensively studied. Within the Tres Cantos Antimalarial Set (TCAMS) we have identified two small, soluble and simple hits that even presenting antiplasmodial activities in the range of 0.4-0.5 μM are able to show in vivo activity.