1161205-04-4

Basic information

• Product Name: N-(4-Chloro-3-methoxyphenyl)-2-pyridinecarboxamide
• Synonyms: N-(4-Chloro-3-methoxyphenyl)-2-pyridinecarboxamide;VU 0361737;2-Pyridinecarboxamide, N-(4-chloro-3-methoxyphenyl)-;CID-44191096;ML128
• CAS NO: 1161205-04-4
• Molecular Formula: C₁₃H₁₁ClN₂O₂
• Molecular Weight: 263
• EINECS: 200-256-5
• Product Categories: Inhibitors
• Mol File: 1161205-04-4.mol
• Article Data: 4

Chemical Properties

• Appearance: white/
• Storage Temp.: Store at RT
• Solubility: DMSO: soluble15mg/mL (clear solution)
• CAS DataBase Reference: N-(4-Chloro-3-methoxyphenyl)-2-pyridinecarboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-(4-Chloro-3-methoxyphenyl)-2-pyridinecarboxamide(1161205-04-4)
• EPA Substance Registry System: N-(4-Chloro-3-methoxyphenyl)-2-pyridinecarboxamide(1161205-04-4)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 1161205-04-4(Hazardous Substances Data)

Usage

Uses

VU0361737 is an mGluR4-specific positive allosteric modulator (PAM).

Biological Activity

vu0361737 is a selective, positive allosteric modulator and brain-permeable for mglur4 (mglu4 receptor), (ec?? = 240 and 110 nm for human and rat receptors respectively), >50 fold selectivity over other mglur subtypes. inactive at mglur-1, mglur-2, mglur-3, mglur-6 and mglur-7 receptors and showed weak activity at mglur-5 and mglur-8 receptors. [1]the mglur (metabotropic glutamate receptor) is a group of g-protein coupled receptors and is active through an indirect metabotropic process. mglur4 are invoinved in parkinson as it decrease gabaerigic transmission at inhibitory striato-pallidal synapse with the basal ganglia.[1][2]following the administration of vu0361737 into rat intraperitoneally (10mg/kg), the amount of compound present in brain and plasma was determined at 0.5, 1 and 8 hours. it showed a short half-life (t1/2 20 minutes) and a pronounced brain exposure (brain: plasma ratio = 4.1) [1]

references

[1] engers dw, niswender cm, weaver cd, jadhav s, menon un, zamorano r, conn pj, lindsley cw, hopkins cr. synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mglur4) positive allosteric modulators (pams). j med chem. 2009 jul 23;52(14):4115-8. [2] engers dw, field jr, le u, zhou y, bolinger jd, zamorano r, blobaum al, jones ck, jadhav s, weaver cd, conn pj, lindsley cw, niswender cm, hopkins cr. discovery, synthesis, and structure-activity relationship development of a series of n-(4-acetamido)phenylpicolinamides as positive allosteric modulators of metabotropic glutamate receptor 4 (mglu(4)) with cns exposure in rats. j med chem. 2011 feb 24;54(4):1106-10.

Upstream product

• 5029-67-4 2-iodopyridine 
• 15226-74-1 dicobalt octacarbonyl 
• 1009-36-5 2-chloro-5-nitroanisole 
• 98-98-6 2-Picolinic acid 
• 13726-14-2 4-chloro-m-anisidine 

Relevant articles and documents

Amide synthesis: Via nickel-catalysed reductive aminocarbonylation of aryl halides with nitroarenes

Aminocarbonylation of aryl halides is one of the most useful methods in amide synthesis, but nitroarenes have not been used as a nitrogen source in this method even though they are more economical and accessible than anilines. Reported here is the development of nickel catalysis for the first three-component reactions of aryl halides, Co2(CO)8, and nitroarenes under reductive conditions to produce aryl amides. A wide range of (hetero)aryl iodides and bromides as well as nitro(hetero)arenes are suitable reaction partners, and high functional group compatibility has been achieved. The method might be used for the streamlined synthesis of aryl amides.

Radiosynthesis of N-(4-chloro-3-[11C]methoxyphenyl)-2- picolinamide ([11C]ML128) as a PET radiotracer for metabotropic glutamate receptor subtype 4 (mGlu4)

N-(Chloro-3-methoxyphenyl)-2-picolinamide (3, ML128, VU0361737) is an mGlu4 positive allosteric modulator (PAM), which is potent and centrally penetrating. 3 is also the first mGlu4 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 ([11C]3) as a PET radiotracer for mGlu4, and characterized its biological properties in Sprague Dawley rats. [11C]3 was synthesized from N-(4-chloro-3-hydroxyphenyl)-2-picolinamide (2) using [11C]CH 3I. Total synthesis time was 38 ± 2.2 min (n = 7) from the end of bombardment to the formulation. The radioligand [11C]3 was obtained in 27.7 ± 5.3% (n = 5) decay corrected radiochemical yield based on the radioactivity of [11C]CO2. The radiochemical purity of [11C]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 mGlu4 modulator (4) to investigate specificity and 3 studies blocking with an mGlu5 modulator (MTEP) to investigate selectivity. These studies showed fast accumulation of [11C]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 mGlu4 modulator 4 showed 22-28% decrease of [11C]3 accumulation while studies of selectivity showed only minor decrease supporting good selectivity over mGlu5. Biodistribution studies and blood analyses support fast metabolism. Altogether this is the first PET imaging ligand for mGlu4, in which the labeled ML128 was used for imaging its in vivo distribution and pharmacokinetics in brain.