80109-91-7Relevant academic research and scientific papers
Modulation of Pharmacologically Relevant Properties of Piperidine Derivatives by Functional Groups in an Equatorial or Axial β-Position to the Amino Group
Schnider, Patrick,Dolente, Cosimo,Stalder, Henri,Martin, Rainer E.,Reinmüller, Viktoria,Marty, Roman,Wyss Gramberg, Caroline,Wagner, Bj?rn,Fischer, Holger,Alker, André M.,Müller, Klaus
, p. 212 - 234 (2020)
Thirteen epimeric pairs of 5-substituted N-piperonyl-3-phenylpiperidine derivatives were synthesized in order to explore the stereospecific modulation of basicity, lipophilicity, aqueous solubility, and membrane permeation by functional groups in equatorial or axial positions beta to the amine unit. While this comprehensive data set provides enhanced insight into multiple factors that affect basicity and lipophilicity, it fills an important knowledge gap, providing a frame of reference for the property-based design of bioactive compounds. Impacts on amine basicity are very pronounced for the β-equatorial functional groups and parallel basicity-lowering effects known for acyclic amine derivatives. For β-axial functional groups, the basicity-lowering effects are generally decreased, with the nitrile group as the only exception. Basicity and lipophilicity modulations observed for β-axial functional groups are quite diverse and rationalized in terms of intramolecular hydrogen bonding, dipolar interactions, and special solvation effects. Aqueous solubility and (artificial) membrane permeability are discussed with reference to lipophilicity.
LACTAMS. XIX. THE ALKALINE FERRICYANIDE OXIDATION OF 1,3-DISUBSTITUTED PYRIDINIUM SALTS: EFFECTS OF BRANCHED ALKYL GROUPS AT THE 3-POSITION
Fujii, Tozo,Hiraga, Takashi,Ohba, Masashi
, p. 2503 - 2508 (2007/10/02)
In the oxidation of 3-substituted 1-methylpyridinium salts (type III) with potassium ferricyanide and KOH at 32 deg C, the isopropyl and the tert-butyl group at the 3-position were found to orient oxidation to both the 2- (type IV) and the 6-position (typ
