Synthesis, in vitro and in vivo evaluation of [O-methyl-11C] 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]-triazine-3, 5-dione: A novel agonist 5-HT1A receptor PET ligand

Jaya Prabhakaran; Ramin V. Parsey; Vattoly J. Majo; Shu Chi Hsiung; Matthew S. Milak; Hadassah Tamir; Norman R. Simpson; Ronald L. Van Heertum; J. John Mann; J. S. Dileep Kumar

doi:10.1016/j.bmcl.2006.01.052

Synthesis, in vitro and in vivo evaluation of [O-methyl-¹¹C] 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]-triazine-3, 5-dione: A novel agonist 5-HT_1A receptor PET ligand

Jaya Prabhakaran
, Ramin V. Parsey
, Vattoly J. Majo
, Shu Chi Hsiung
, Matthew S. Milak
, Hadassah Tamir
, Norman R. Simpson
, Ronald L. Van Heertum
, J. John Mann
, J. S. Dileep Kumar

Psychiatry

Stony Brook University

Columbia University

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

19 Scopus citations

Abstract

Synthesis and in vivo evaluation of 2-{4-[4-(3-methoxyphenyl)piperazin-1- yl]-butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione (5 or MMT), a high affinity and selective serotonin 5-HT_1AR agonist PET tracer, are described. GTPγS assay shows that MMT is an agonist with an EC₅₀ comparable to 5-HT. Radiolabeling of 5 was achieved in 30% yield (EOS) from desmethyl-MMT (4) with >99% chemical and radiochemical purities and a specific activity >1000 Ci/mmol. PET studies in baboon show that [ ¹¹C]5 penetrates the blood-brain barrier but, because of low specific binding and fast clearance of radioactivity it is not a suitable PET tracer for the in vivo quantification of 5-HT_1AR.

Original language	English
Pages (from-to)	2101-2104
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2006.01.052
State	Published - Apr 15 2006

Keywords

Agonism
Positron emission tomography
Radiotracer
[C]MMT

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10.1016/j.bmcl.2006.01.052

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Prabhakaran, J., Parsey, R. V., Majo, V. J., Hsiung, S. C., Milak, M. S., Tamir, H., Simpson, N. R., Van Heertum, R. L., Mann, J. J., & Dileep Kumar, J. S. (2006). Synthesis, in vitro and in vivo evaluation of [O-methyl-¹¹C] 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]-triazine-3, 5-dione: A novel agonist 5-HT_1A receptor PET ligand. Bioorganic and Medicinal Chemistry Letters, 16(8), 2101-2104. https://doi.org/10.1016/j.bmcl.2006.01.052

@article{d29122442afe49989fb58f5cf8b1af6b,

title = "Synthesis, in vitro and in vivo evaluation of [O-methyl-11C] 2-\{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl\}-4-methyl-2H-[1,2,4]-triazine-3, 5-dione: A novel agonist 5-HT1A receptor PET ligand",

abstract = "Synthesis and in vivo evaluation of 2-\{4-[4-(3-methoxyphenyl)piperazin-1- yl]-butyl\}-4-methyl-2H-[1,2,4]triazine-3,5-dione (5 or MMT), a high affinity and selective serotonin 5-HT1AR agonist PET tracer, are described. GTPγS assay shows that MMT is an agonist with an EC50 comparable to 5-HT. Radiolabeling of 5 was achieved in 30\% yield (EOS) from desmethyl-MMT (4) with >99\% chemical and radiochemical purities and a specific activity >1000 Ci/mmol. PET studies in baboon show that [ 11C]5 penetrates the blood-brain barrier but, because of low specific binding and fast clearance of radioactivity it is not a suitable PET tracer for the in vivo quantification of 5-HT1AR.",

keywords = "Agonism, Positron emission tomography, Radiotracer, [C]MMT",

author = "Jaya Prabhakaran and Parsey, \{Ramin V.\} and Majo, \{Vattoly J.\} and Hsiung, \{Shu Chi\} and Milak, \{Matthew S.\} and Hadassah Tamir and Simpson, \{Norman R.\} and \{Van Heertum\}, \{Ronald L.\} and Mann, \{J. John\} and \{Dileep Kumar\}, \{J. S.\}",

year = "2006",

month = apr,

day = "15",

doi = "10.1016/j.bmcl.2006.01.052",

language = "English",

volume = "16",

pages = "2101--2104",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

number = "8",

}

Prabhakaran, J, Parsey, RV, Majo, VJ, Hsiung, SC, Milak, MS, Tamir, H, Simpson, NR, Van Heertum, RL, Mann, JJ & Dileep Kumar, JS 2006, 'Synthesis, in vitro and in vivo evaluation of [O-methyl-¹¹C] 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]-triazine-3, 5-dione: A novel agonist 5-HT_1A receptor PET ligand', Bioorganic and Medicinal Chemistry Letters, vol. 16, no. 8, pp. 2101-2104. https://doi.org/10.1016/j.bmcl.2006.01.052

Synthesis, in vitro and in vivo evaluation of [O-methyl-¹¹C] 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]-triazine-3, 5-dione: A novel agonist 5-HT_1A receptor PET ligand. / Prabhakaran, Jaya; Parsey, Ramin V.; Majo, Vattoly J. et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 8, 15.04.2006, p. 2101-2104.

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

TY - JOUR

T1 - Synthesis, in vitro and in vivo evaluation of [O-methyl-11C] 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]-triazine-3, 5-dione

T2 - A novel agonist 5-HT1A receptor PET ligand

AU - Prabhakaran, Jaya

AU - Parsey, Ramin V.

AU - Majo, Vattoly J.

AU - Hsiung, Shu Chi

AU - Milak, Matthew S.

AU - Tamir, Hadassah

AU - Simpson, Norman R.

AU - Van Heertum, Ronald L.

AU - Mann, J. John

AU - Dileep Kumar, J. S.

PY - 2006/4/15

Y1 - 2006/4/15

N2 - Synthesis and in vivo evaluation of 2-{4-[4-(3-methoxyphenyl)piperazin-1- yl]-butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione (5 or MMT), a high affinity and selective serotonin 5-HT1AR agonist PET tracer, are described. GTPγS assay shows that MMT is an agonist with an EC50 comparable to 5-HT. Radiolabeling of 5 was achieved in 30% yield (EOS) from desmethyl-MMT (4) with >99% chemical and radiochemical purities and a specific activity >1000 Ci/mmol. PET studies in baboon show that [ 11C]5 penetrates the blood-brain barrier but, because of low specific binding and fast clearance of radioactivity it is not a suitable PET tracer for the in vivo quantification of 5-HT1AR.

AB - Synthesis and in vivo evaluation of 2-{4-[4-(3-methoxyphenyl)piperazin-1- yl]-butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione (5 or MMT), a high affinity and selective serotonin 5-HT1AR agonist PET tracer, are described. GTPγS assay shows that MMT is an agonist with an EC50 comparable to 5-HT. Radiolabeling of 5 was achieved in 30% yield (EOS) from desmethyl-MMT (4) with >99% chemical and radiochemical purities and a specific activity >1000 Ci/mmol. PET studies in baboon show that [ 11C]5 penetrates the blood-brain barrier but, because of low specific binding and fast clearance of radioactivity it is not a suitable PET tracer for the in vivo quantification of 5-HT1AR.

KW - Agonism

KW - Positron emission tomography

KW - Radiotracer

KW - [C]MMT

UR - https://www.scopus.com/pages/publications/33644796770

U2 - 10.1016/j.bmcl.2006.01.052

DO - 10.1016/j.bmcl.2006.01.052

M3 - Article

C2 - 16458504

SN - 0960-894X

VL - 16

SP - 2101

EP - 2104

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 8

ER -

Synthesis, in vitro and in vivo evaluation of [O-methyl-¹¹C] 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]-triazine-3, 5-dione: A novel agonist 5-HT_1A receptor PET ligand

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