1283095-48-6

Usage

Uses

Used in Pharmaceutical and Medicinal Chemistry:
t-Butyl Spiro[4,5-dihydrothieno[2,3-c]pyran-7,4-piperidine]-1-carboxylate is used as a building block for the synthesis of other compounds in pharmaceutical and medicinal chemistry. Its unique spirocyclic structure may impart interesting properties that could be beneficial for drug development.
Used in Drug Development:
t-Butyl Spiro[4,5-dihydrothieno[2,3-c]pyran-7,4-piperidine]-1-carboxylate is used as a potential candidate for drug development due to its unique structure and potential biological activities. Its t-butyl ester group may provide steric hindrance that could influence its reactivity and interactions with biological targets, making it a valuable component in the design and synthesis of new drugs.

Upstream product

• 6964-21-2 thiophen-3-yl-acetic acid 
• 41979-39-9 4-piperidone hydrochloride 
• 13781-67-4 3-(2-hydroxyethyl)thiophene 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 1307248-40-3 4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-ium trifluoroacetate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 1283095-47-5 4′,5′-dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran] 

Downstream Products

• 1307248-42-5 2'-chloro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran] hydrochloride 
• 1307245-86-8 [2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]-3-pyridyl]methanol 
• 1307248-45-8 tert-butyl 2′-chloro-4′,5′-dihydrospiro-[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 
• 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 
• 1307249-95-1 3-(2'-fluoro-4',5'-dihydro-1H-spiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-yl)2-(2-fluorobenzyl)-N,N-dimethylpropanamide 
• 1307381-31-2 2'-chloro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran] 
• 1283095-55-5 2-[(2-chlorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno-[2,3-c]pyran-7,4'-piperidine]-1'-yl)propanoic acid 
• 1283095-54-4 2-[(2-fluorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno-[2,3-c]pyran-7,4'-piperidine]-1'-yl)propanoic acid 
• 1283095-53-3 tert-butyl 2-[(2-chlorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)propanoate 
• 1283095-73-7 (2R)-2-[(2-fluorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno-[2,3-c]pyran-7,4'-piperidine]-1'-yl)-N-methylpropanamide 

Relevant academic research and scientific papers

Defining Target Engagement Required for Efficacy in Vivo at the Retinoic Acid Receptor-Related Orphan Receptor C2 (RORγt)

The Th17 pathway has been implicated in autoimmune diseases. The retinoic acid receptor-related orphan receptor C2 (RORγt) is a master regulator of Th17 cells and controls the expression of IL-17A. RORγt is expressed primarily in IL-17A-producing lymphoid cells. Here we describe a virtual screen of the ligand-binding pocket and subsequent screen in a binding assay that identified the 1-benzyl-4′,5′-dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran]-2′-carboxamide scaffold as a starting point for optimization of binding affinity and functional activity guided by structure-based design. Compound 12 demonstrated activity in a mouse PK/PD model and efficacy in an inflammatory arthritis mouse model that were used to define the level and duration of target engagement required for efficacy in vivo. Further optimization to improve ADME and physicochemical properties with guidance from simulations and modeling provided compound 22, which is projected to achieve the level and duration of target engagement required for efficacy in the clinic.

Synthesis of an ORL-1 Receptor Antagonist via a Radical Bromination and Deoxyfluorination to Afford a gem-Difluorospirocycle

The development of a synthesis of an ORL-1 receptor antagonist is described. The key process improvements in the synthetic sequence include a multikilogram bromination process and the development of a convergent coupling strategy. The process improvements resulted in the production of the active pharmaceutical ingredient (API) on a multikilogram scale.

SPIROPIPERIDINE COMPOUNDS AS ORL-1 RECEPTOR ANTAGONISTS

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

Synthesis and evaluation of radioligands for imaging brain nociceptin/orphanin FQ peptide (NOP) receptors with positron emission tomography

Positron emission tomography (PET) coupled to an effective radioligand could provide an important tool for understanding possible links between neuropsychiatric disorders and brain NOP (nociceptin/orphanin FQ peptide) receptors. We sought to develop such a PET radioligand. High-affinity NOP ligands were synthesized based on a 3-(2′-fluoro-4′,5′- dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran]-1-yl)-2(2-halobenzyl) -N-alkylpropanamide scaffold and from experimental screens in rats, with ex vivo LC-MS/MS measures, three ligands were identified for labeling with carbon-11 and evaluation with PET in monkey. Each ligand was labeled by 11C-methylation of an N-desmethyl precursor and studied in monkey under baseline and NOP receptor-preblock conditions. The three radioligands, [11C](S)-10a-c, gave similar results. Baseline scans showed high entry of radioactivity into the brain to give a distribution reflecting that expected for NOP receptors. Preblock experiments showed high early peak levels of brain radioactivity, which rapidly declined to a much lower level than seen in baseline scans, thereby indicating a high level of receptor-specific binding in baseline experiments. Overall, [11C](S)-10c showed the most favorable receptor-specific signal and kinetics and is now selected for evaluation 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. 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.