Synthesis of carbon-11-labeled 4-(phenylamino)-pyrrolo[2,1-f][1,2,4] triazine derivatives as new potential PET tracers for imaging of p38α mitogen-activated protein kinase

Min Wang, Mingzhang Gao, Qi-Huang Zheng

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The reference standards methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino) -5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4] triazine-6-carboxylate (10b) and corresponding precursors 4-(2-methyl-5- (methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6- carboxylic acid (11a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5- methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11b) were synthesized from methyl crotonate and 3-amino-4-methylbenzoic acid in multiple steps with moderate to excellent yields. The target tracer [11C]methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4] triazine-6-carboxylate ([11C]10a) and [11C]methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4] triazine-6-carboxylate ([11C]10b) were prepared from their corresponding precursors with [11C]CH3OTf under basic condition through O-[11C]methylation and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields at end of bombardment (EOB) with 185-555 GBq/μmol specific activity at end of synthesis (EOS).

Original languageEnglish
Pages (from-to)3700-3705
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number16
DOIs
StatePublished - Aug 15 2014

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p38 Mitogen-Activated Protein Kinases
Carbon
Derivatives
Imaging techniques
Carboxylic Acids
Crotonates
Methylation
Solid Phase Extraction
pyrrolo(2,1-f)(1,2,4)triazine
1,2,4-triazine

Keywords

  • Cancer
  • Carbon-11-labeled 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazine derivatives
  • Diabetes
  • Inflammation
  • p38α mitogen-activated protein kinase (MAPK)
  • Positron emission tomography (PET)

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Medicine(all)

Cite this

@article{c42f4a94c7934c1fa60b1dc6df60ea6f,
title = "Synthesis of carbon-11-labeled 4-(phenylamino)-pyrrolo[2,1-f][1,2,4] triazine derivatives as new potential PET tracers for imaging of p38α mitogen-activated protein kinase",
abstract = "The reference standards methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino) -5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4] triazine-6-carboxylate (10b) and corresponding precursors 4-(2-methyl-5- (methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6- carboxylic acid (11a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5- methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11b) were synthesized from methyl crotonate and 3-amino-4-methylbenzoic acid in multiple steps with moderate to excellent yields. The target tracer [11C]methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4] triazine-6-carboxylate ([11C]10a) and [11C]methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4] triazine-6-carboxylate ([11C]10b) were prepared from their corresponding precursors with [11C]CH3OTf under basic condition through O-[11C]methylation and isolated by a simplified solid-phase extraction (SPE) method in 50-60{\%} radiochemical yields at end of bombardment (EOB) with 185-555 GBq/μmol specific activity at end of synthesis (EOS).",
keywords = "Cancer, Carbon-11-labeled 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazine derivatives, Diabetes, Inflammation, p38α mitogen-activated protein kinase (MAPK), Positron emission tomography (PET)",
author = "Min Wang and Mingzhang Gao and Qi-Huang Zheng",
year = "2014",
month = "8",
day = "15",
doi = "10.1016/j.bmcl.2014.07.017",
language = "English",
volume = "24",
pages = "3700--3705",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "16",

}

TY - JOUR

T1 - Synthesis of carbon-11-labeled 4-(phenylamino)-pyrrolo[2,1-f][1,2,4] triazine derivatives as new potential PET tracers for imaging of p38α mitogen-activated protein kinase

AU - Wang, Min

AU - Gao, Mingzhang

AU - Zheng, Qi-Huang

PY - 2014/8/15

Y1 - 2014/8/15

N2 - The reference standards methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino) -5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4] triazine-6-carboxylate (10b) and corresponding precursors 4-(2-methyl-5- (methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6- carboxylic acid (11a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5- methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11b) were synthesized from methyl crotonate and 3-amino-4-methylbenzoic acid in multiple steps with moderate to excellent yields. The target tracer [11C]methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4] triazine-6-carboxylate ([11C]10a) and [11C]methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4] triazine-6-carboxylate ([11C]10b) were prepared from their corresponding precursors with [11C]CH3OTf under basic condition through O-[11C]methylation and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields at end of bombardment (EOB) with 185-555 GBq/μmol specific activity at end of synthesis (EOS).

AB - The reference standards methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino) -5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4] triazine-6-carboxylate (10b) and corresponding precursors 4-(2-methyl-5- (methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6- carboxylic acid (11a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5- methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11b) were synthesized from methyl crotonate and 3-amino-4-methylbenzoic acid in multiple steps with moderate to excellent yields. The target tracer [11C]methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4] triazine-6-carboxylate ([11C]10a) and [11C]methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4] triazine-6-carboxylate ([11C]10b) were prepared from their corresponding precursors with [11C]CH3OTf under basic condition through O-[11C]methylation and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields at end of bombardment (EOB) with 185-555 GBq/μmol specific activity at end of synthesis (EOS).

KW - Cancer

KW - Carbon-11-labeled 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazine derivatives

KW - Diabetes

KW - Inflammation

KW - p38α mitogen-activated protein kinase (MAPK)

KW - Positron emission tomography (PET)

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U2 - 10.1016/j.bmcl.2014.07.017

DO - 10.1016/j.bmcl.2014.07.017

M3 - Article

VL - 24

SP - 3700

EP - 3705

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 16

ER -