101768-07-4Relevant academic research and scientific papers
β-Hydroxypiperidinecarboxylates: Additions to the chiral pool from bakers' yeast reductions of β-ketopiperidinecarboxylates
Knight, David W.,Lewis, Neil,Share, Andrew C.,Haigh, David
, p. 3673 - 3683 (2007/10/03)
Reduction of the piperidine keto esters 16-19 using fermenting bakers' yeast provides high yields of the corresponding hydroxy esters 20, 26, 32 and 37 respectively, exclusively as the cis-diastereoisomers and with good levels (≥80%) of enantiomeric enrichment. The relative stereochemistries of the products were deduced from NMR data while the absolute configurations were determined by degradation to known piperidinemethanol derivatives or, in the case of hydroxy ester 37, by homologation to (R)-3-quinuclidinol 41b.
Synthesis, Calcium-Channel-Blocking Activity, and Antihypertensive Activity of 4-(Diarylmethyl)-1-piperidines and Structurally Related
Shanklin, James R.,Johnson, Christopher P.,Proakis, Anthony G.,Barrett, Richard J.
, p. 3011 - 3022 (2007/10/02)
A series of 4-(diarylmethyl)-1-piperidines and structurally related compounds were synthesized as calcium-channel blockers and antihypertensive agents.Compounds were evaluated for calcium-channel-blocking activity by determineng their ability to antagonize calcium-induced contractions of isolated rabbit aortic strips.The most potent compounds were those with fluoro substituents in the 3- and/or 4-positions of both rings of the diphenylmethyl group.Bis(4-fluorophenyl)acetonitrile analogue 79 was similar in potency to bis(4-fluorophenyl)methyl compound 1.The methylene analogue of 1 (78) and derivatives of 1 that contained a hydroxyl (76), carbamoyl (80), amino (81), or acetamido (82) substituent on the methyl group were less potent.In most cases substituents on the phenoxy ring, changes in the distance between the aryloxy group and the piperidine nitrogen, and the substitution of S, N(CH3), or CH2 for the oxygen atom of the aryloxy group had only a small to moderate effect on the potency.The best compounds in this series were more potent than verapamil, diltiazem, flunarizine, and lidoflazine, but were less potent than nifedipine.Compounds were evaluated for antihypertensive activity in spontaneusly hypertensive rats (SHR) at an oral dose of 30 mg/kg.Of the 55 compounds tested, only nine produced a statistically significant (p-1-piperidinyl>propoxy>-3-methoxyphenyl>ethanone (63), which produced a 35percent reduction in blood pressure and was similar in activity to nifedipine.At lower doses, however, 4--1-piperidine (93) was one of the most effective antihypertensive agents, producing reductions in blood pressure of 17 and 11percent at oral doses of 10 and 3 mg/kg, respectively; 63 was inactive at 10 mg/kg.
