Azabicyclic alcohols. VI. Azabicyclo [2.2.1]heptan-3-ol epimers

Spry, Douglas O.; Aaron, Herbert S.

doi:10.1021/jo01263a118

Cited by 9 publications

(3 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Catalytic hydrogenation gives the cis -hydroxy-ester which is reduced to the diol ( 48a ). Thermolysis in the gas phase in a flow reactor over basic alumina gave the alcohol ( 49 ) which was oxidised to 1-aza-norbornan-3-one ( 41a ) with Jones’ reagent (62% yield) [ 83 ].…”

Section: Muscarinic Agonistsmentioning

confidence: 99%

Muscarinic Receptor Agonists and Antagonists

2001

View full text Add to dashboard Cite

A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes). Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

show abstract

Section: Muscarinic Agonistsmentioning

confidence: 99%

Muscarinic Receptor Agonists and Antagonists

2001

View full text Add to dashboard Cite

show abstract

“…18c, 25-28 (Scheme 3), in reasonable yield. The assignment of the endo stereochemistry for 26, 27, and 28 was based on the known stereochemistry of the starting azabicyclic alcohol precursor 22, 24 23, 25 and 24. 26 Very small amounts of the exo isomers were also obtained in these reactions, probably due to the presence of small amounts of exo alcohols being produced in the hydrogenation of the ketone precursors to the alcohols.…”

Section: Chemistrymentioning

confidence: 99%

“…H NMR (CDCl3) δ 1.07 (3H, t), 1.72-2.08 (5H, m), 2.3 (1H, m), 3.06 (1H, m), 3.16-3.6 (7H, m), 4.23 (1H, m), 5.5 (1H, m).Compounds 25-27 were prepared in the same manner as 28From potassium tertbutoxide (0.85 g, 0.0072 mol), (()-1-azabicyclo[3.2.1]octan-3ol47 (0.91 g, 0.0072 mol), and 19b (1.53 g, 0.0079 mol) was obtained 25 (0.82 g, 35%) after purification by radial chromatography, eluting with 5% EtOH-0.5% NH4OH-CHCl3:1 H NMR (CDCl3) δ 1.06 (3H, t), 1.82 (2H, m), 2.04-2.72 (6H, m), 3.15-3.52 (6H, m), 3.73-4.01 (2H, m). From potassium tert-butoxide (0.26 g, 0.002 mol), (()-endo-1azabicyclo[2.2.1]heptan-3-ol24 (0.23 g, 0.002 mol), and 19b (0.43 g, 0.002 mol) were obtained white crystals of 26 (0.24 g, 29%): NMR (DMSO-d6) δ 0.97 (3H, t), 1.7 (2H, m), 1.86-2.1 (2H, m), 3.05-3.42 (8H, m), 3.75 (1H, t), 5.34 (1H, m). (()-3-(1-Propylthio)-4-(endo-1-azabicyclo[3.2.1]oct-3yloxy)-1,2,5-thiadiazole Hydrochloride, 27.…”

mentioning

confidence: 99%

1,2,5-Thiadiazole Analogues of Aceclidine as Potent m₁ Muscarinic Agonists

et al. 1998

View full text Add to dashboard Cite

The acetyl group of the muscarinic agonist aceclidine 4 was replaced by various 1,2,5-thiadiazoles to provide a new series of potent m1 muscarinic agonists 17 and 18. Optimal m1 muscarinic agonist potency was achieved when the 1,2,5-thiadiazole substituent was either a butyloxy, 17d, or butylthio, 18d, group. Although 1,2,5-oxadiazole 37 and pyrazine 39 are iso-pi-electronic with 1,2,5-thiadiazole 17d, both analogues were substantially less active than 17d. Compounds with high muscarinic affinity and/or m1 muscarinic agonist efficacy were also obtained when the 3-oxyquinuclidine moiety of 17d or 18c was replaced by ethanolamines, hydroxypyrrolidines, hydroxyazetidine, hydroxyisotropanes, or hydroxyazanorbornanes. The structure-activity data support the participation of the oxygen or sulfur atom in the substituent on the 1,2,5-thiadiazole in the activation of the m1 receptor. Several of these new 1,2,5-thiadiazoles have m1 agonist efficacy, potency, and selectivity comparable to those of xanomeline 2 in the muscarinic tests investigated.

show abstract