Synthesis and Characterization of N-alkyl-3-(2,4-dichlorophenyl)-N-fluoroalkyl-2,5- dimethylpyrazolo[1,5-a]pyrimidin-7-amines as Potential CRF1 Receptor PET Radiotracers 公开

Birnbaum, Matthew Samuel (2013)

Permanent URL: https://etd.library.emory.edu/concern/etds/12579s43r?locale=zh
Published

Abstract

N-alkyl-3-(2,4-dichlorophenyl)-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7- amines were synthesized from commercial starting materials. As hypothesized, binding assays indicate that this class of molecules is a strong inhibitor of the CRF1 receptor (Ki= 0.72-33 nM). As lipophilicity of the 7-amine alkyl chains increases, binding strength increases. One molecule has been successfully radiolabeled indicating that these molecules are potential CRF1 receptor PET radiotracers.

Table of Contents

Table of Contents

1. INTRODUCTION...............................................................................................................................1

1.1 POSITRON EMISSION TOMOGRAPHY ..................................................................................................1

1.2 CROSSING THE BLOOD BRAIN BARRIER..............................................................................................3

1.3 CORTICOTROPIN-RELEASING FACTOR ................................................................................................3

1.4 NON-PEPTIDIC CRF1 RECEPTOR ANTAGONISTS.....................................................................................4

1.5 CRF1 PET TRACER DEVELOPMENTS.....................................................................................................5

1.6 PET TRACER DESIGN........................................................................................................................7

2. SYNTHESIS .....................................................................................................................................9

3. EXPERIMENTAL ................................................................................................................................12

3.1 GENERAL EXPERIMENTAL PROCEDURES...............................................................................................12

3.2 CHEMISTRY ...................................................................................................................................12

3.3 BINDING STUDIES ..........................................................................................................................28

4. RESUL TS AND DISCUSSION ..............................................................................................................29

5. CONCLUSIONS.................................................................................................................................33

6. REFERENCES ...................................................................................................................................34

APPENDIX I. NMR SPECTRA ...................................................................................................................A

APPENDIX II. HPLC DATA FOR RADIOLABELING ..........................................................................................S

About this Honors Thesis

Rights statement
  • Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.
School
Department
Degree
Submission
Language
  • English
Research field
关键词
Committee Chair / Thesis Advisor
Committee Members
最新修改

Primary PDF

Supplemental Files