335266-05-2Relevant articles and documents
Enantioselective synthesis of 2-aryl-4-piperidones via rhodium/ phosphoramidite-catalyzed conjugate addition of arylboroxines
Jagt, Richard B. C.,De Vries, Johannes G.,Feringa, Ben L.,Minnaard, Adriaan J.
, p. 2433 - 2435 (2005)
(Chemical Equation Presented) The highly enantioselective synthesis of 2-aryl-4-piperidones by rhodium/phosphoramidite-catalyzed conjugate addition of arylboroxines to 2,3-dihydro-4-pyridones is described. Both enantiomers of a variety of products with sterically and electronically different R substituents were obtained in high isolated yield and with excellent enantioselectivity up to 99%.
Synthesis of Aminoethyl-Substituted Piperidine Derivatives as σ1 Receptor Ligands with Antiproliferative Properties
Catapano, Carlo V.,Civenni, Gianluca,Holtschulte, Catharina,Laurini, Erik,Marson, Domenico,Pricl, Sabrina,Schepmann, Dirk,B?rgel, Frederik,Wünsch, Bernhard,Westph?linger, Stefanie
, (2022/02/19)
A series of novel σ1 receptor ligands with a 4-(2-aminoethyl)piperidine scaffold was prepared and biologically evaluated. The underlying concept of our project was the improvement of the lipophilic ligand efficiency of previously synthesized potent σ1 ligands. The key steps of the synthesis comprise the conjugate addition of phenylboronic acid at dihydropyridin-4(1H)-ones 7, homologation of the ketones 8 and introduction of diverse amino moieties and piperidine N-substituents. 1-Methylpiperidines showed particular high σ1 receptor affinity and selectivity over the σ2 subtype, whilst piperidines with a proton, a tosyl moiety or an ethyl moiety exhibited considerably lower σ1 affinity. Molecular dynamics simulations with per-residue binding free energy deconvolution demonstrated that different interactions of the basic piperidine-N-atom and its substituents (or the cyclohexane ring) with the lipophilic binding pocket consisting of Leu105, Thr181, Leu182, Ala185, Leu186, Thr202 and Tyr206 are responsible for the different σ1 receptor affinities. Recorded logD7.4 and calculated clogP values of 4a and 18a indicate low lipophilicity and thus high lipophilic ligand efficiency. Piperidine 4a inhibited the growth of human non-small cell lung cancer cells A427 to a similar extent as the σ1 antagonist haloperidol. 1-Methylpiperidines 20a, 21a and 22a showed stronger antiproliferative effects on androgen negative human prostate cancer cells DU145 than the σ1 ligands NE100 and S1RA.
THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF
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, (2017/08/01)
The invention provides a compound of formula: or a salt thereof, wherein the variables RAA, n, ring A, ring B, R1a, R1b, R2, R3, R4, R5, R6, R7, R8, and R9 have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.
