177948-63-9Relevant academic research and scientific papers
A new chiral synthesis of Wieland-Miescher ketone catalyzed by a combination of (S)-N- benzyl-N(2-pyrrolidinylmethyl)amine derivative and bronsted acid
Akahane, Yuichi,Inomata, Kohei,Endo, Yasuyuki
experimental part, p. 1065 - 1078 (2010/10/03)
New or known N-benzyl-N (2-pyrrolidinylmethyl)amine derivatives bearing a variety of substituents on the aromatic ring were easily prepared from N-Boc-proline or NBoc-prolinol. The enantioselectivity of the intramolecular asymmetric aldol reaction mediated by a combination of the amine derivative and Bronsted acid to prepare Wieland-Miescher ketone was examined in detail. During the examination, remarkable substitutional effects on the aromatic ring were observed. Development of a catalytic version of the reaction was successfully achieved by the use of N(9-anthracenyl)methyl-N(2-pyrrolidinyl-methyl)amine in the presence of dichloroacetic acid.
Synthesis and serotonergic activity of 3-[2-(pyrrolidin-1- yl)ethyl]indoles: Potent agonists for the h5-HT(1D) receptor with high selectivity over the h5-HT(1B) receptor
Sternfeld, Francine,Guiblin, Alexander R.,Jelley, Richard A.,Matassa, Victor G.,Reeve, Austin J.,Hunt, Peter A.,Beer, Margaret S.,Heald, Anne,Stanton, Josephine A.,Sohal, Bindi,Watt, Alan P.,Street, Leslie J.
, p. 677 - 690 (2007/10/03)
The design, synthesis, and biological evaluation of a novel series of 3- [2-(pyrrolidin-1-yl)ethyl]-indoles with excellent selectivity for h5-HT(1D) (formerly 5-HT(1Dα)) receptors over h5-HT(1B) (formerly 5-HT(1Dβ)) receptors are described. Clinically effective antimigraine drugs such as Sumatriptan show little selectivity between h5-HT(1D) and h5-HT(1B) receptors. The differential expression of h5-HT(1D) and h5-HT(1B) receptors in neural and vascular tissue prompted an investigation of whether a compound selective for the h5-HT(1D) subtype would have the same clinical efficacy but with reduced side effects. The pyrrolidine 3b was initially identified as having 9-fold selectivity for h5-HT(1D) over h5-HT(1B) receptors. Substitution of the pyrrolidine ring of 3b with methylbenzylamine groups gave compounds with nanomolar affinity for the h5-HT(1D) receptor and 100-fold selectivity with respect to h5-HT(1B) receptors. Modification of the indole 5-substituent led to the oxazolidinones 24a,b with up to 163-fold selectivity for the h5-HT(1D) subtype and improved selectivity over other serotonin receptors. The compounds were shown to be full agonists by measurement of agonist-induced [35S]GTPγS binding in CHO cells expressed with h5-HT receptors. This study suggests that the h5-HT(1D) and h5-HT(1B) receptors can be differentiated by appropriate substitution of the ligand in the region which binds to the aspartate residue and reveals a large binding pocket in the h5-HT(1D) receptor domain which is absent for the h5-HT(1B) receptor. The compounds described herein will be important tools to delineate the role of h5-HT(1D) receptors in migraine.
