Synthesis and muscarinic receptor pharmacology of a series of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridine bioisosteres of arecoline

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Synthesis and muscarinic receptor pharmacology of a series of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridine bioisosteres of arecoline. / Pedersen, H; Bräuner-Osborne, H; Ball, R G; Frydenvang, Karla Andrea; Meier, E; Bøgesø, K P; Krogsgaard-Larsen, P.

In: Bioorganic & Medicinal Chemistry, Vol. 7, No. 5, 1999, p. 795-809.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Pedersen, H, Bräuner-Osborne, H, Ball, RG, Frydenvang, KA, Meier, E, Bøgesø, KP & Krogsgaard-Larsen, P 1999, 'Synthesis and muscarinic receptor pharmacology of a series of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridine bioisosteres of arecoline', Bioorganic & Medicinal Chemistry, vol. 7, no. 5, pp. 795-809.

APA

Pedersen, H., Bräuner-Osborne, H., Ball, R. G., Frydenvang, K. A., Meier, E., Bøgesø, K. P., & Krogsgaard-Larsen, P. (1999). Synthesis and muscarinic receptor pharmacology of a series of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridine bioisosteres of arecoline. Bioorganic & Medicinal Chemistry, 7(5), 795-809.

Vancouver

Pedersen H, Bräuner-Osborne H, Ball RG, Frydenvang KA, Meier E, Bøgesø KP et al. Synthesis and muscarinic receptor pharmacology of a series of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridine bioisosteres of arecoline. Bioorganic & Medicinal Chemistry. 1999;7(5):795-809.

Author

Pedersen, H ; Bräuner-Osborne, H ; Ball, R G ; Frydenvang, Karla Andrea ; Meier, E ; Bøgesø, K P ; Krogsgaard-Larsen, P. / Synthesis and muscarinic receptor pharmacology of a series of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridine bioisosteres of arecoline. In: Bioorganic & Medicinal Chemistry. 1999 ; Vol. 7, No. 5. pp. 795-809.

Bibtex

@article{1a2bc409473a4adb9c49a2a4a47dc438,
title = "Synthesis and muscarinic receptor pharmacology of a series of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridine bioisosteres of arecoline",
abstract = "A series of O- and ring-alkylated derivatives of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridin-3-ol was synthesized via treatment of appropriately substituted 4-benzylamino-1,2,5,6-tetrahydropyridine-3-carboxamides with hydrogen sulfide and subsequent ring closure by oxidation with bromine. The muscarinic receptor affinity as well as estimated relative efficacy and subtype selectivity of this series of bicyclic arecoline bioisosteres were determined using rat brain membranes and a number of tritiated muscarinic receptor ligands. The effects at the five cloned human muscarinic receptor subtypes of a selected series of chiral analogues, with established absolute stereochemistry, were studied using receptor selection and amplification technology (R-SAT). The potency, relative efficacy, and receptor subtype selectivity of these compounds were related to the structure of the O-substituents and the position and stereochemical orientation of the piperidine ring methyl substituents.",
keywords = "Animals, Arecoline, Brain, Carbachol, Crystallography, X-Ray, Dose-Response Relationship, Drug, Humans, Models, Chemical, Models, Molecular, Myocardium, Pyridines, Rats, Receptors, Muscarinic",
author = "H Pedersen and H Br{\"a}uner-Osborne and Ball, {R G} and Frydenvang, {Karla Andrea} and E Meier and B{\o}ges{\o}, {K P} and P Krogsgaard-Larsen",
year = "1999",
language = "English",
volume = "7",
pages = "795--809",
journal = "Bioorganic & Medicinal Chemistry",
issn = "0968-0896",
publisher = "Pergamon Press",
number = "5",

}

RIS

TY - JOUR

T1 - Synthesis and muscarinic receptor pharmacology of a series of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridine bioisosteres of arecoline

AU - Pedersen, H

AU - Bräuner-Osborne, H

AU - Ball, R G

AU - Frydenvang, Karla Andrea

AU - Meier, E

AU - Bøgesø, K P

AU - Krogsgaard-Larsen, P

PY - 1999

Y1 - 1999

N2 - A series of O- and ring-alkylated derivatives of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridin-3-ol was synthesized via treatment of appropriately substituted 4-benzylamino-1,2,5,6-tetrahydropyridine-3-carboxamides with hydrogen sulfide and subsequent ring closure by oxidation with bromine. The muscarinic receptor affinity as well as estimated relative efficacy and subtype selectivity of this series of bicyclic arecoline bioisosteres were determined using rat brain membranes and a number of tritiated muscarinic receptor ligands. The effects at the five cloned human muscarinic receptor subtypes of a selected series of chiral analogues, with established absolute stereochemistry, were studied using receptor selection and amplification technology (R-SAT). The potency, relative efficacy, and receptor subtype selectivity of these compounds were related to the structure of the O-substituents and the position and stereochemical orientation of the piperidine ring methyl substituents.

AB - A series of O- and ring-alkylated derivatives of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridin-3-ol was synthesized via treatment of appropriately substituted 4-benzylamino-1,2,5,6-tetrahydropyridine-3-carboxamides with hydrogen sulfide and subsequent ring closure by oxidation with bromine. The muscarinic receptor affinity as well as estimated relative efficacy and subtype selectivity of this series of bicyclic arecoline bioisosteres were determined using rat brain membranes and a number of tritiated muscarinic receptor ligands. The effects at the five cloned human muscarinic receptor subtypes of a selected series of chiral analogues, with established absolute stereochemistry, were studied using receptor selection and amplification technology (R-SAT). The potency, relative efficacy, and receptor subtype selectivity of these compounds were related to the structure of the O-substituents and the position and stereochemical orientation of the piperidine ring methyl substituents.

KW - Animals

KW - Arecoline

KW - Brain

KW - Carbachol

KW - Crystallography, X-Ray

KW - Dose-Response Relationship, Drug

KW - Humans

KW - Models, Chemical

KW - Models, Molecular

KW - Myocardium

KW - Pyridines

KW - Rats

KW - Receptors, Muscarinic

M3 - Journal article

VL - 7

SP - 795

EP - 809

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

IS - 5

ER -

ID: 40372372