CAS: 1161205-04-4; N-(4-Chloro-3-Methoxyphenyl)Picolinamide

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2-Picolinic acid 4-chloro-m-anisidine 2-iodopyridine dicobalt °Ctacarbonyl

📜2-吡啶甲酸,3-甲氧基-4-氯苯胺置于1-羟基苯并三唑,盐酸-N-乙基-N'-(3-二甲氨基丙基)碳二亚胺,N,N-二异丙基乙胺体系中,用 1,4-二氧六环 用作溶剂,以53%的收率获得vu 0361737; N-(4-氯-3-甲氧基苯基)-2-吡啶甲酰胺
参考文献:Radiosynthesis Of N-(4-Chloro-3-[11C]Methoxyphenyl)-2-Picolinamide ([11C]Ml128) As A Pet Radiotracer For Metabotropic Glutamate Receptor Subtype 4 (Mglu4)
标题:Radiosynthesis Of N-(4-Chloro-3-[11C]Methoxyphenyl)-2-Picolinamide ([11C]Ml128) As A Pet Radiotracer For Metabotropic Glutamate Receptor Subtype 4 (Mglu4)
摘要:N-(Chloro-3-Methoxyphenyl)-2-Picolinamide (3,Ml128,Vu0361737) Is An Mglu(4) Positive Allosteric Modulator (Pam),Which Is Potent And Centrally Penetrating. 3 Is Also The First Mglu(4) Pam To Show Efficacy In A Preclinical Parkinson Disease Model Upon Systemic Dosing. As A Noninvasive Medical Imaging Technique And A Powerful Tool In Neurological Research,Positron Emission Tomography (Pet) Offers A Possibility To Investigate Mglu(4) Expression In Vivo Under Physiologic And Pathological Conditions. We Synthesized A Carbon-11 Labeled Ml128 ([c-11]3) As A Pet Radiotracer For Mglu(4),And Characterized Its Biological Properties In Sprague Dawley Rats. [c-11]3 Was Synthesized From N-(4-Chloro-3-Hydroxyphenyl)-2-Picolinamide (2) Using [c-11]Ch3I. Total Synthesis Time Was 38 +/-2.2 Min (N = 7) From The End Of Bombardment To The Formulation. The Radioligand [c-11] 3 Was Obtained In 27.7 +/-5.3% (N = 5) Decay Corrected Radiochemical Yield Based On The Radioactivity Of [c-11]Co2. The Radiochemical Purity Of [c-11]3 Was >99%. Specific Activity Was 188.7 +/-88.8 Gbq/mol (N = 4) At The End Of Synthesis (Eos).Pet Images Were Conducted In 20 Normal Male Sprague Dawley Rats Including 11 Control Studies,6 Studies Blocking With An Mglu(4) Modulator (4) To Investigate Specificity And 3 Studies Blocking With An Mglu(5) Modulator (Mtep) To Investigate Selectivity. These Studies Showed Fast Accumulation Of [c-11]3 (Peak Activity Between 1-3 Min) In Several Brain Areas Including Striatum,Thalamus,Hippocampus,Cerebellum,And Olfactory Bulb Following With Fast Washout. Blocking Studies With The Mglu(4) Modulator 4 Showed 22-28% Decrease Of [c-11]3 Accumulation While Studies Of Selectivity Showed Only Minor Decrease Supporting Good Selectivity Over Mglu(5). Biodistribution Studies And Blood Analyses Support Fast Metabolism. Altogether This Is The First Pet Imaging Ligand For Mglu(4),In Which The Labeled Ml128 Was Used For Imaging Its In Vivo Distribution And Pharmacokinetics In Brain. (C) 2013 Elsevier Ltd. All Rights Reserved.
Doi:10.1016/j.Bmc.2013.07.046