Synthesis, in vitro pharmacology and radiosynthesis of N-(cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl)piperidine-1 -thiocarbonamide (VUF 5000), a potential pet ligand for the histamine H3 receptor

Albert D. Windhorst; Henk Timmerman; Wiro M P B Menge; Rob Leurs; Jacobus D M Herscheid

doi:10.1002/(SICI)1099-1344(199903)42:3

Synthesis, in vitro pharmacology and radiosynthesis of N-(cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl)piperidine-1 -thiocarbonamide (VUF 5000), a potential pet ligand for the histamine H3 receptor

Albert D. Windhorst^*
, Henk Timmerman
, Wiro M P B Menge
, Rob Leurs
, Jacobus D M Herscheid

^*Corresponding author for this work

Vrije Universiteit Amsterdam

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

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 & RADIOPHARMACEUTICALS
Volume	42
Issue number	3
DOIs	https://doi.org/10.1002/(SICI)1099-1344(199903)42:3
Publication status	Published - 1 Jan 1999

Keywords

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

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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 (VUF 5000), a potential pet ligand for the histamine H3 receptor. JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 42(3), 293-307. https://doi.org/10.1002/(SICI)1099-1344(199903)42:3

@article{5f911486869d4c14808552b1edb90802,

title = "Synthesis, in vitro pharmacology and radiosynthesis of N-(cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl)piperidine-1 -thiocarbonamide (VUF 5000), 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 = "Windhorst, \{Albert D.\} and Henk Timmerman and Menge, \{Wiro M P B\} and Rob Leurs and Herscheid, \{Jacobus D M\}",

year = "1999",

month = jan,

day = "1",

doi = "10.1002/(SICI)1099-1344(199903)42:3",

language = "English",

volume = "42",

pages = "293--307",

journal = "JOURNAL OF LABELLED COMPOUNDS \& RADIOPHARMACEUTICALS",

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 (VUF 5000), a potential pet ligand for the histamine H3 receptor', JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, vol. 42, no. 3, pp. 293-307. https://doi.org/10.1002/(SICI)1099-1344(199903)42:3

Synthesis, in vitro pharmacology and radiosynthesis of N-(cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl)piperidine-1 -thiocarbonamide (VUF 5000), a potential pet ligand for the histamine H3 receptor. / Windhorst, Albert D.; Timmerman, Henk; Menge, Wiro M P B et al.
In: JOURNAL OF LABELLED COMPOUNDS & 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 (VUF 5000), a potential pet ligand for the histamine H3 receptor

AU - Windhorst, Albert D.

AU - Timmerman, Henk

AU - Menge, Wiro M P B

AU - Leurs, Rob

AU - Herscheid, Jacobus 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

UR - https://www.scopus.com/pages/publications/0032981986

U2 - 10.1002/(SICI)1099-1344(199903)42:3

DO - 10.1002/(SICI)1099-1344(199903)42:3

M3 - Article

VL - 42

SP - 293

EP - 307

JO - JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS

JF - JOURNAL OF LABELLED COMPOUNDS & 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 (VUF 5000), a potential pet ligand for the histamine H3 receptor. JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS. 1999 Jan 1;42(3):293-307. doi: 10.1002/(SICI)1099-1344(199903)42:3

Synthesis, in vitro pharmacology and radiosynthesis of N-(cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl)piperidine-1 -thiocarbonamide (VUF 5000), a potential pet ligand for the histamine H3 receptor

Abstract

Keywords

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