46439-10-5Relevant academic research and scientific papers
Potent and Selective Tetrahydroisoquinoline Kappa Opioid Receptor Antagonists of Lead Compound (3 R)-7-Hydroxy- N-[(1 S)-2-methyl-1-(piperidin-1-ylmethyl)propyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (PDTic)
Ondachi, Pauline W.,Kormos, Chad M.,Runyon, Scott P.,Thomas, James B.,Mascarella, S. Wayne,Decker, Ann M.,Navarro, Hernán A.,Fennell, Timothy R.,Snyder, Rodney W.,Carroll, F. Ivy
, p. 7525 - 7545 (2018/09/12)
Past studies have shown that it has been difficult to discover and develop potent and selective κ opioid receptor antagonists, particularly compounds having potential for clinical development. In this study, we present a structure-activity relationship (SAR) study of a recently discovered new class of tetrahydroisoquinoline κ opioid receptor antagonists which led to (3R)-7-hydroxy-N-{(1S)-2-methyl-1-[(-4-methylpiperidine-1-yl)methyl]propyl}-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (12) (4-Me-PDTic). Compound 12 had a Ke = 0.37 nM in a [35S]GTPγS binding assay and was 645- and >8100-fold selective for the κ relative to the μ and δ opioid receptors, respectively. Calculated log BB and CNS (central nervous system) multiparameter optimization (MPO) and low molecular weight values all predict that 12 will penetrate the brain, and pharmacokinetic studies in rats show that 12 does indeed penetrate the brain.
Efficient and chemoselective reduction of pyridines to tetrahydropyridines and piperidines via rhodium-catalyzed transfer hydrogenation
Wu, Jianjun,Tang, Weijun,Pettman, Alan,Xiao, Jianliang
, p. 35 - 40 (2013/03/13)
Promoted by iodide anion the rhodium complex dimer, [Cp RhCl 2]2, catalyzes efficiently the transfer hydrogenation of various quaternary pyridinium salts under mild conditions, affording not only piperidines but also 1,2,3,6-tetrahydropyridines in a highly chemoselective fashion, depending on the substitution pattern at the pyridinium ring. The reduction is conducted in azeotropic formic acid/triethylamine (HCOOH-Et 3N) mixture at 40 °C, with catalyst loadings as low as 0.005mol% being feasible. Copyright
Aqueous aza Diels-Alder reactions catalyzed by lanthanide(III) trifluoromethanesulfonates
Yu, Libing,Chen, Depu,Wang, Peng George
, p. 2169 - 2172 (2007/10/03)
Lanthanide(III) trifluoromethanesulfonates have been demonstrated to catalyze aqueous aza Diels-Alder reactions of an aldehyde and an amine hydrochloride with a diene.
Nitrogen Assistance in Intramolecular Nickel-Promoted Tandem Cyclization-Quenching Processes
Sole, Daniel,Cancho, Yolanda,Llebaria, Amadeu,Moreto, Josep M.,Delgado, Antonio
, p. 5895 - 5904 (2007/10/03)
A diastereoselective and mild cyclization-quenching process based on the treatment of nitrogen-tethered halodienes with stoichiometric Ni(COD)2 is described. The success of this methodology relies on the presence of a distal amino group capable of coordin
TETRAHYDROPYRIDINES IN THE PRINS REACTIONS: A NOVEL 3-OXA-7-AZABICYCLONONANE DERIVATIVE
Casy, Alan,Ogungbamila, Francis
, p. 1913 - 1917 (2007/10/02)
Reaction of tetrahydropyridines obtained by the dehydration of a diastereoisomeric mixture of 1-benzyl-3,4-dimethyl-4-piperidinols with excess of aqueous formaldehyde and sulphuric acid (Prins reaction) gave 7-benzyl-1,9-dimethyl-9-hydroxy-3-oxa-7-azabicyclononane.The stereochemistry of the bicyclic product (cis N/9-OH, piperidinone boat-chair) and of the precursor 4-piperidinols is established from nmr(13C and 1H) and ir spectroscopic evidence.
