243665-10-3Relevant articles and documents
Design and synthesis of bitopic 2-phenylcyclopropylmethylamine (pcpma) derivatives as selective dopamine d3 receptor ligands
Tan, Liang,Zhou, Qingtong,Yan, Wenzhong,Sun, Jian,Kozikowski, Alan P.,Zhao, Suwen,Huang, Xi-Ping,Cheng, Jianjun
, p. 4579 - 4602 (2020/06/08)
2-Phenylcyclopropylmethylamine (PCPMA) analogues have been reported as selective serotonin 2C agonists. On the basis of the same scaffold, we designed and synthesized a series of bitopic derivatives as dopamine D3R ligands. A number of these new compounds show a high binding affinity for D3R with excellent selectivity. Compound (1R,2R)-22e and its enantiomer (1S,2S)-22e show a comparable binding affinity for the D3R, but the former is a potent D3R agonist, while the latter acts as an antagonist. Molecular docking studies revealed different binding poses of the PCPMA moiety within the orthosteric binding pocket of the D3R, which might explain the different functional profiles of the enantiomers. Compound (1R,2R)-30q shows a high binding affinity for the D3R (Ki = 2.2 nM) along with good selectivity, as well as good bioavailability and brain penetration properties in mice. These results reveal that the PCPMA scaffold may serve as a privileged scaffold for the design of aminergic GPCR ligands.
Copper-Catalyzed Asymmetric Conjugate Addition of Dimethylzinc to Acyl-N-methylimidazole Michael Acceptors: A Powerful Synthetic Platform
Drissi-Amraoui, Sammy,Morin, Marie S. T.,Crévisy, Christophe,Baslé, Olivier,Marciadefigueiredo, Renata,Mauduit, Marc,Campagne, Jean-Marc
supporting information, p. 11830 - 11834 (2015/10/05)
An efficient copper-catalyzed enantioselective conjugate addition of dimethylzinc to α,β- and α,β,γ,δ-unsaturated 2-acyl-N-methylimidazoles has been achieved using a chiral bidentate hydroxyalkyl-NHC ligand. The reactions proceeded with both excellent regio- and enantioselectivity (14 examples, 87-95 % ee) to afford the desired 1,4-adducts, which were easily transformed to the corresponding aldehydes, esters, and ketones. Subsequently, this powerful methodology was therefore successfully applied in the synthesis of natural products. Furthermore, an iterative process was also disclosed leading to highly desirable 1,3-desoxypropionate skeletons (up to 94 % d.e.). The enantioselective conjugate addition of dimethylzinc to (poly)unsaturated 2-acyl-N-methylimidazoles proceeds under Cu catalysis with excellent regio- and enantioselectivities (up to 95 % ee). The resulting 1,4-adducts can be easily transformed to the corresponding aldehydes, esters, ketones, and amines. This methodology was successfully applied in the synthesis of 1,3-desoxypropionate subunits and natural products.
A Weinreb amide approach to the synthesis of trifluoromethylketones
Rudzinski, Diandra M.,Kelly, Christopher B.,Leadbeater, Nicholas E.
supporting information, p. 9610 - 9612 (2012/10/29)
A novel route to access trifluoromethylketones (TFMKs) from Weinreb amides is reported. This represents the first documented case of the Ruppert-Prakash reagent (TMS-CF3) reacting in a constructive manner with an amide and enables synthesis of TMFKs without risk of over-trifluoromethylation.
