1307249-95-1

Upstream product

• 13781-67-4 3-(2-hydroxyethyl)thiophene 
• 1283095-48-6 tert-butyl-4′,5′-dihydro-1H-spiro[piperidine-4,7′-thieno[2,3-c]pyran]-1-carboxylate 
• 1283095-52-2 tert-butyl 2-[(2-fluorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)propanoate 
• 1283095-51-1 t-butyl 3-(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)propanoate 
• 1283095-50-0 2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine] 
• 1283095-49-7 t-butyl 2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine]-1'-carboxylate 
• 1307248-40-3 4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-ium trifluoroacetate 
• 1283095-47-5 4′,5′-dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran] 
• 1307250-00-5 2-[(2-fluorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)propanoic acid trifluoroacetate 
• 506-59-2 N,N-dimethylammonium chloride 

Relevant academic research and scientific papers

Development of LC-MS/MS-based receptor occupancy tracers and positron emission tomography radioligands for the nociceptin/orphanin FQ (NOP) receptor

Currently, a lack of sufficient tools has limited the understanding of the relationship between neuropsychiatric disorders and the nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor. Herein, we describe the discovery and development of an antagonist NOP receptor occupancy (RO) tracer and a novel positron emission tomography (PET) radioligand suitable to probe the NOP receptor in human clinical studies. A thorough structure-activity relationship (SAR) around the high-affinity 3-(2′-fluoro-4′,5′- dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran]-1-yl)-2-(2-halobenzyl) -N-alkylpropanamide scaffold identified a series of subnanomolar, highly selective NOP antagonists. Subsequently, these unlabeled NOP ligands were evaluated in vivo by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in rat to determine brain uptake, kinetics and specific binding. (S)-27 was identified as a suitable unlabeled preclinical RO tracer to accurately quantify NOP receptor engagement in rat brain. Three compounds were selected for evaluation in nonhuman primates as PET tracers: (-)-26, (-)-30, and (-)-33. Carbon-11 labeling of (+)-31 yielded [11C]-(S)-30, which exhibited minimal generation of central nervous system (CNS) penetrant radiometabolites, improved brain uptake, and was an excellent PET radioligand in both rat and monkey. Currently [11C]-(S)-30 is being evaluated as a PET radiotracer for the NOP receptor in human subjects.

SPIROPIPERIDINE COMPOUNDS AS ORL-1 RECEPTOR ANTAGONISTS

An ORL-1 receptor antagonist of the formula: its uses, and methods for its preparation are described.

SPIROPIPERIDINE COMPOUNDS AS ORL-1 RECEPTOR ANTAGONISTS

An ORL-1 receptor antagonist of the formula: its uses, and methods for its preparation are described. ORL-1 antagonists are deemed to be useful in the treatment of depression and/or the treatment of overweight, obesity, and/or weight maintenance post treatment for overweight or obesity. Certain compounds have also demonstrated through animal models that the compounds of the present invention are useful for the treatment of migraines.