Synthesis, in vitro pharmacology and radiosynthesis of N-(Cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl) piperidine-1-thiocarbonamide (VUF5000), a potential pet ligand for the histamine H3 receptor.

A.D. Windhorst; H. Timmerman; W.M.P.B. Menge; R. Leurs; J.D.M. Herscheid

doi:https://doi.org/10.1002/(SICI)1099-1344(199903)42:3<293::AID-JLCR191>3.0.CO;2-B

Synthesis, in vitro pharmacology and radiosynthesis of N-(Cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl) piperidine-1-thiocarbonamide (VUF5000), a potential pet ligand for the histamine H3 receptor.

A.D. Windhorst, H. Timmerman, W.M.P.B. Menge, R. Leurs, J.D.M. Herscheid

Research output: Contribution to journal › Article › Academic › peer-review

9 Citations (Scopus)

Abstract

The synthesis of N-(cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl)piperidine-1 -thiocarbonamide (VUF 5000) 3, a fluorinated analogue of the potent (pA₂ value of 8.9 ± 0.1, K(i) = 4.3 ± 0.9 nM) histamine H₃ receptor antagonist thioperamide 2 is described. After the establishment of the H₃ antagonistic activity of VUF 5000, pA₂ value = 9.0 ± 0.2, K(i) = 2.3 ± 0.5 nM, a four step synthesis for the radiolabelling of VUF 5000 with ¹⁸F (half life 110 min) was developed. Within 4 hours of the end of the bombartment, [¹⁸F]VUF 5000 was obtained with an average radiochemical yield of 23% (decay corrected) and a specific activity > 96.2 TBq/μmol (2.6 Ci/μmol).

Original language	English
Pages (from-to)	293-307
Number of pages	15
Journal	Journal of Labelled Compounds and Radiopharmaceuticals
Volume	42
Issue number	3
DOIs	https://doi.org/10.1002/(SICI)1099-1344(199903)42:3<293::AID-JLCR191>3.0.CO;2-B
Publication status	Published - 1 Jan 1999

Keywords

F fluorination
Histamine H receptor
In vitro pharmacology
Radiosynthesis
Thioperamide
VUF 5000

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https://doi.org/10.1002/(SICI)1099-1344(199903)42:3<293::AID-JLCR191>3.0.CO;2-B

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Windhorst, A. D., Timmerman, H., Menge, W. M. P. B., Leurs, R., & Herscheid, J. D. M. (1999). Synthesis, in vitro pharmacology and radiosynthesis of N-(Cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl) piperidine-1-thiocarbonamide (VUF5000), a potential pet ligand for the histamine H3 receptor. Journal of Labelled Compounds and Radiopharmaceuticals, 42(3), 293-307. https://doi.org/10.1002/(SICI)1099-1344(199903)42:3<293::AID-JLCR191>3.0.CO;2-B

@article{22894f7aa1e84e4ca5be0e41b4a02e50,

title = "Synthesis, in vitro pharmacology and radiosynthesis of N-(Cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl) piperidine-1-thiocarbonamide (VUF5000), a potential pet ligand for the histamine H3 receptor.",

abstract = "The synthesis of N-(cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl)piperidine-1 -thiocarbonamide (VUF 5000) 3, a fluorinated analogue of the potent (pA2 value of 8.9 ± 0.1, K(i) = 4.3 ± 0.9 nM) histamine H3 receptor antagonist thioperamide 2 is described. After the establishment of the H3 antagonistic activity of VUF 5000, pA2 value = 9.0 ± 0.2, K(i) = 2.3 ± 0.5 nM, a four step synthesis for the radiolabelling of VUF 5000 with 18F (half life 110 min) was developed. Within 4 hours of the end of the bombartment, [18F]VUF 5000 was obtained with an average radiochemical yield of 23% (decay corrected) and a specific activity > 96.2 TBq/μmol (2.6 Ci/μmol).",

keywords = "F fluorination, Histamine H receptor, In vitro pharmacology, Radiosynthesis, Thioperamide, VUF 5000",

author = "A.D. Windhorst and H. Timmerman and W.M.P.B. Menge and R. Leurs and J.D.M. Herscheid",

year = "1999",

month = jan,

day = "1",

doi = "https://doi.org/10.1002/(SICI)1099-1344(199903)42:3<293::AID-JLCR191>3.0.CO;2-B",

language = "English",

volume = "42",

pages = "293--307",

journal = "Journal of Labelled Compounds and Radiopharmaceuticals",

issn = "0362-4803",

publisher = "John Wiley and Sons Ltd",

number = "3",

}

Windhorst, AD, Timmerman, H, Menge, WMPB, Leurs, R & Herscheid, JDM 1999, 'Synthesis, in vitro pharmacology and radiosynthesis of N-(Cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl) piperidine-1-thiocarbonamide (VUF5000), a potential pet ligand for the histamine H3 receptor.', Journal of Labelled Compounds and Radiopharmaceuticals, vol. 42, no. 3, pp. 293-307. https://doi.org/10.1002/(SICI)1099-1344(199903)42:3<293::AID-JLCR191>3.0.CO;2-B

Synthesis, in vitro pharmacology and radiosynthesis of N-(Cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl) piperidine-1-thiocarbonamide (VUF5000), a potential pet ligand for the histamine H3 receptor. / Windhorst, A.D.; Timmerman, H.; Menge, W.M.P.B. et al.
In: Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 42, No. 3, 01.01.1999, p. 293-307.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Synthesis, in vitro pharmacology and radiosynthesis of N-(Cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl) piperidine-1-thiocarbonamide (VUF5000), a potential pet ligand for the histamine H3 receptor.

AU - Windhorst, A.D.

AU - Timmerman, H.

AU - Menge, W.M.P.B.

AU - Leurs, R.

AU - Herscheid, J.D.M.

PY - 1999/1/1

Y1 - 1999/1/1

N2 - The synthesis of N-(cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl)piperidine-1 -thiocarbonamide (VUF 5000) 3, a fluorinated analogue of the potent (pA2 value of 8.9 ± 0.1, K(i) = 4.3 ± 0.9 nM) histamine H3 receptor antagonist thioperamide 2 is described. After the establishment of the H3 antagonistic activity of VUF 5000, pA2 value = 9.0 ± 0.2, K(i) = 2.3 ± 0.5 nM, a four step synthesis for the radiolabelling of VUF 5000 with 18F (half life 110 min) was developed. Within 4 hours of the end of the bombartment, [18F]VUF 5000 was obtained with an average radiochemical yield of 23% (decay corrected) and a specific activity > 96.2 TBq/μmol (2.6 Ci/μmol).

AB - The synthesis of N-(cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl)piperidine-1 -thiocarbonamide (VUF 5000) 3, a fluorinated analogue of the potent (pA2 value of 8.9 ± 0.1, K(i) = 4.3 ± 0.9 nM) histamine H3 receptor antagonist thioperamide 2 is described. After the establishment of the H3 antagonistic activity of VUF 5000, pA2 value = 9.0 ± 0.2, K(i) = 2.3 ± 0.5 nM, a four step synthesis for the radiolabelling of VUF 5000 with 18F (half life 110 min) was developed. Within 4 hours of the end of the bombartment, [18F]VUF 5000 was obtained with an average radiochemical yield of 23% (decay corrected) and a specific activity > 96.2 TBq/μmol (2.6 Ci/μmol).

KW - F fluorination

KW - Histamine H receptor

KW - In vitro pharmacology

KW - Radiosynthesis

KW - Thioperamide

KW - VUF 5000

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U2 - https://doi.org/10.1002/(SICI)1099-1344(199903)42:3<293::AID-JLCR191>3.0.CO;2-B

DO - https://doi.org/10.1002/(SICI)1099-1344(199903)42:3<293::AID-JLCR191>3.0.CO;2-B

M3 - Article

SN - 0362-4803

VL - 42

SP - 293

EP - 307

JO - Journal of Labelled Compounds and Radiopharmaceuticals

JF - Journal of Labelled Compounds and Radiopharmaceuticals

IS - 3

ER -

Windhorst AD, Timmerman H, Menge WMPB, Leurs R, Herscheid JDM. Synthesis, in vitro pharmacology and radiosynthesis of N-(Cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl) piperidine-1-thiocarbonamide (VUF5000), a potential pet ligand for the histamine H3 receptor. Journal of Labelled Compounds and Radiopharmaceuticals. 1999 Jan 1;42(3):293-307. doi: https://doi.org/10.1002/(SICI)1099-1344(199903)42:3<293::AID-JLCR191>3.0.CO;2-B

Synthesis, in vitro pharmacology and radiosynthesis of N-(Cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl) piperidine-1-thiocarbonamide (VUF5000), a potential pet ligand for the histamine H3 receptor.

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