- Synthesis, characterization, and biological evaluation of a novel class of N-(arylethyl)-N-alkyl-2-(1-pyrrolidinyl)ethylamines: Structural requirements and binding affinity at the σ receptor
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By synthesizing and testing a part-structure, N-[2-(3,4- dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3), derived from our previously reported high affinity σ receptor ligands (1S,2R)-(-)-N-[2- (3,4-dichlorophenyl)-ethyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine [(-)- 2] and (+)-2, we have identified a novel class of superpotent (subnanomolar affinity) σ ligands specific for the σ receptor labeled by [3H]-(+)-3-PPP. When 3 was tested for its capacity to displace [3H]-(+)-3-PPP from guinea pig brain membranes, it exhibited a K(i) of 0.34 nM, which is better than either of its parent compounds (-)-2 (K(i) = 1.3 nM) and (+)-2 (K(i) = 6.0 nM). Other compounds related to 3 such as N-[2-(3,4-dichlorophenyl)ethyl]-N- methyl-2-(1-homopiperidinyl)ethylamine (19) exhibited K(i) = 0.17 nM ([3H]- (+)-3-PPP). The determinants for high σ receptor affinity of 3 were examined by manipulation of this structure in a number of different ways. The high efficacy of these compounds for the σ receptor, their relative chemical simplicity and ease of synthesis, and their high degree of selectivity identifies N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1- pyrrolidinyl)ethylamine (3) and related compounds as a highly promising base for determination of the functional role of σ receptors as well as the development of novel therapeutic agents.
- De Costa,Radesca,Di Paolo,Bowen
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- Asymmetric synthesis catalyzed by chiral ferrocenylphosphine transition metal complexes. 10 gold(I)-catalyzed asymmetric aldol reaction of isocyanoacetate
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Optically active ferrocenylbisphosphine ligands containing 2-(dialkylamino)ethylamino group on the ferrocenylmethyl position have been prepared and used for the gold(I)-catalyzed asymmetric aldol reaction of isocyanoacetate with aldehydes. Six-membered ring amines, such as morpholino or piperidino group, at the terminal of the side chain were most stereoselective to give optically active trans-4- methoxycarbonyl-5-alkyl-2-oxazolines (up to 97% ee) with high enantio- and diastereoselectivity in a quantitative yield.
- Hayashi, Tamio,Sawamura, Masaya,Ito, Yoshihiko
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p. 1999 - 2012
(2007/10/02)
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