- BMS-201620: A selective beta 3 agonist
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A series of N-(4-hydroxy-3-methylsulfonanilidoethanol)arylglycinamides were prepared and evaluated for their human β3 adrenergic receptor agonist activity. SAR studies led to the identification of BMS-201620 (39), a potent β3 full agonist (Ki=93nM, 93% activation). Based on its favorable safety profile, BMS-201620 was chosen for clinical evaluation.
- Washburn,Sun,Bisacchi,Wu,Cheng,Sher,Ryono,Gavai,Poss,Girotra,McCann,Mikkilineni,Dejneka,Wang,Merchant,Morella,Arbeeny,Harper,Slusarchyk,Skwish,Russell,Allen,Tesfamariam,Frohlich,Abboa-Offei,Cap,Waldron,George,Young,Dickinson,Seymour
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p. 3525 - 3529
(2007/10/03)
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- Practical and convenient enzymatic synthesis of enantiopure α-amino acids and amides
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Catalyzed by the nitrile hydratase and the amidease in Rhodococcus sp. AJ270 cells under very mild conditions, a number of α-aryl- and α-alkyl-substituted DL-glycine nitriles 1 rapidly underwent a highly enantioselective hydrolysis to afford D-(-)-α-amino acid amides 2 and L-(+)-α-amino acids 3 in high yields with excellent enantiomeric excesses in most cases. The overall enantioselectivity of the biotransformations of nitriles originated from the combined effects of a high L-enantioselective amidase and a low enantioselective nitrile hydratase. The influence of the substrates on both reaction efficiency and enantioselectivity was also discussed in terms of steric and electronic effects. Coupled with chemical hydrolysis of D-(-)-α-phenylglycine amide, biotransformation of DL-phenylglycine nitrile was applied in practical scale to produce both D- and L-phenylglycines in high optical purity.
- Wang, Mei-Xiang,Lin, Shuang-Jun
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p. 6542 - 6545
(2007/10/03)
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- Highly efficient and enantioselective synthesis of L-arylglycines and D-arylglycine amides from biotransformations of nitriles
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Under very mild conditions, the Rhodococcus sp. AJ270-catalysed biotransformation of arylglycine nitriles 1, prepared easily from the reaction of substituted benzaldehydes, ammonium chloride and potassium cyanide, proceeded efficiently to produce optically active D-arylglycine amides 2 and L-arylglycines 3 in excellent yields with enantiomeric excesses higher than 99%.
- Wang, Mei-Xiang,Lin, Shuang-Jun
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p. 6925 - 6927
(2007/10/03)
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- Quantitative Approaches to Optical Resolution. Part 1. Resolution of DL-Phenylglycine Derivatives with (+)-Tartaric Acid
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The results of 23 cases of resolution of DL-phenyldlycine derivatives (I) with (+)-tartaric acid in various solvents are investigated, using correlation analysis, as a function of the introduced racemic compounds and the solvent used.A procedure, combining three quantitative structure-activity relationship methods, i.e.Golender and Rozenblit's logico-structural approach with the Free-Wilson and Hansch analyses, resulted in statistically significant relationships.It is suggested that the solvent may exert two kinds of influence: (1) the higher the solvent polarity, the more likely the L-(I) salt to crystallise; (2) alcoholic mixtures, although being highly polar, favour the precipitation of the D-(I) salt rather than that of the L-(I) salt, probably due to a selective interaction with the diastereomers.As to the racemic compound, the relationships obtained are in accord with literature statements that resolution proceeds by a multiple interaction mechanism.
- Lopata, Antal,Faigl, Ferenc,Fogassy, Elemer,Darvas, Ferenc
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p. 2930 - 2952
(2007/10/02)
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