89880-53-5Relevant academic research and scientific papers
MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 4
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Page/Page column 38-39, (2020/07/25)
The present application provides picolinamide compounds that can be used as allosteric positron emission tomography ("PET") imaging probes. Methods of using these compounds for treating a neurodegenerative disease are also provided.
Improved synthesis of the thiophenol precursor N-(4-chloro-3-mercaptophenyl)picolinamide for making the mGluR4 PET ligands
Wang, Junfeng,Shoup, Timothy M.,Brownell, Anna-Liisa,Zhang, Zhaoda
, p. 3917 - 3922 (2019/06/24)
Recently [11C]mG4P012 (previously [11C]KALB012 and presently named as [11C]PXT012253 by Prexton Therapeutics) had been used as a biomarker during the preclinical development of a potential therapeutic drug, PXT0002331 (an mGluR4 PAM), for PD and L-dopa-induced dyskinesia. [11C]mG4P012 was shown to be a promising PET radioligand for mGluR4 in the monkey brain and for further development in human subjects. However, the previously reported multi-step synthesis of the thiophenol precursor suffered from low yields and difficult workup procedures. To support the translational research of [11C]mG4P012 and the other potential applications, we have developed a new route for synthesis of the thiophenol precursor and optimized the reaction conditions. The synthesis of N-(4-chloro-3-mercaptophenyl)picolinamide from 1-chloro-4-nitrobenzene has been greatly improved from 8% to 52% total yield with easy handling and in gram scales.
Synthesis and evaluation of N-(methylthiophenyl)picolinamide derivatives as PET radioligands for metabotropic glutamate receptor subtype 4
Kil, Kun-Eek,Poutiainen, Pekka,Zhang, Zhaoda,Zhu, Aijun,Kuruppu, Darshini,Prabhakar, Shilpa,Choi, Ji-Kyung,Tannous, Bakhos A.,Brownell, Anna-Liisa
supporting information, p. 133 - 139 (2015/12/18)
In recent years, mGlu4 has received great research attention because of the potential benefits of mGlu4 activation in treating numerous brain disorders, such as Parkinson's disease (PD). A specific mGlu4 PET radioligand could be an important tool in understanding the role of mGlu4 in both healthy and disease conditions, and also for the development of new drugs. In this study, we synthesized four new N-(methylthiophenyl)picolinamide derivatives 11-14. Of these ligands, 11 and 14 showed high in vitro binding affinity for mGlu4 with IC50 values of 3.4 nM and 3.1 nM, respectively, and suitable physicochemical parameters. Compound 11 also showed enhanced metabolic stability and good selectivity to other mGluRs. [11C]11 and [11C]14 were radiolabeled using the [11C]methylation of the thiophenol precursors 20a and 20c with [11C]CH3I in 19.0% and 34.8% radiochemical yields (RCY), and their specific activities at the end of synthesis (EOS) were 496 ± 138 GBq/μmol (n = 6) and 463 ± 263 GBq/μmol (n = 4), respectively. The PET studies showed that [11C]11 accumulated fast into the brain and had higher uptake, slower washout and 25% better contrast than [11C]2, indicating improved imaging characteristics as PET radiotracer for mGlu4 compared to [11C]2. Therefore, [11C]11 will be a useful radioligand to investigate mGlu4 in different biological applications.
MOLECULAR ACTUATORS, AND METHODS OF USE THEREOF
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Page 81, (2010/02/04)
The synthesis of thiophene based conducting polymer molecualr actuators, exhibiting electrically triggered molecular conformational transitions is reported. Actuation is believed to be the result of conformational rearrangement of the polymer backbone at
A VERSATILE SYNTHETIC ROUTE TO SUBSTITUTED THIANTHRENES
Still, Ian W. J.,Sayeed, Vilayat A.
, p. 1181 - 1192 (2007/10/02)
2,7-Dinitrothianthrene has been prepared by the base-catalyzed cyclization of 2-chloro-5-nitrobenzenethiol and proves to be a versatile starting point for the preparation of several 2,7-disubstituted thianthrenes, both symmetrically and unsymmetrically su
