1237526-35-0Relevant articles and documents
BICYCLIC AZAHETEROCYCLIC COMPOUNDS AS NR2B NMDA RECEPTOR ANTAGONISTS
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, (2016/07/05)
Disclosed are chemical entities of Formula (I): wherein R1 and Z are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of Formula (I), and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of Formula (I).
Radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines and its application to new radiotracers for NR2B NMDA receptor visualization
Koudih, Radouane,Gilbert, Gwenaelle,Dhilly, Martine,Barre, Louisa,Debruyne, Daniele,Sobrio, Franck,Abbas, Ahmed
supporting information, p. 8493 - 8500,8 (2012/12/12)
In order to develop a novel and useful building block for the development of radiotracers for positron emission tomography (PET), we studied the radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines. Indeed, 3-fluoropiperidine became a useful building block in medicinal chemistry for the pharmacomodulation of piperidine-containing compounds. The radiofluorination was studied on substituted piperidines with electron-donating and electron-withdrawing N-substituents. In the instance of electron-donating N-substituents such as benzyl or butyl, configuration retention and satisfactory fluoride-18 incorporation yields up to 80% were observed. In the case of electron-withdrawing N-substituents leading to carbamate or amide functions, the incorporation yields depend on the 4-susbtitutent (2 to 63%). The radiolabelling of this building block was applied to the automated radiosynthesis of NR2B NMDA receptor antagonists and effected by a commercially available radiochemistry module. The in vivo evaluation of three radiotracers demonstrated minimal brain uptakes incompatible with the imaging of NR2B NMDA receptors in the living brain. Nevertheless, moderate radiometabolism was observed and, in particular, no radiodefluorination was observed which demonstrates the stability of the 3-position of the fluorine-18 atom. In conclusion, the 1,4-disubstituted 3-[18F]fluoropiperidine moiety could be of value in the development of other radiotracers for PET even if the evaluation of the NR2B NMDA receptor antagonists failed to demonstrate satisfactory properties for PET imaging of this receptor.
2′ Biaryl amides as novel and subtype selective M1 agonists. Part II: Further optimization and profiling
Budzik, Brian,Garzya, Vincenzo,Shi, Dongchuan,Walker, Graham,Lauchart, Yann,Lucas, Adam J.,Rivero, Ralph A.,Langmead, Christopher J.,Watson, Jeannette,Wu, Zining,Forbes, Ian T.,Jin, Jian
supporting information; scheme or table, p. 3545 - 3549 (2010/08/22)
Further optimization of the biaryl amide series via extensively exploring structure-activity relationships resulted in potent and subtype selective M 1 agonists exemplified by compounds 9a and 9j with good rat PK properties including CNS penetration. Synthesis, structure-activity relationships, subtype selectivity for M1 over M2-5, and DMPK properties of these novel compounds are described.
