http://rdf.ncbi.nlm.nih.gov/pubchem/patent/TN-2016000546-A1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_9008466a40998f8be8e54cd3aceb10a2 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-4545 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/H05K999-99 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D453-02 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-4436 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-444 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D409-14 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D409-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P11-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P11-06 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P11-04 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P11-08 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D453-02 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61P11-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-439 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D409-14 |
| filingDate | 2015-06-03-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_081e4310bdaf3229a4abf699c8239d58 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_50755a6e51c098904ecfd7c7aa5c278f http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_e789efb9a9059c75a2507ef48ef52c77 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_5dadf195065bbf19a83c76c419324f97 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_a5d436aa1c3a954ca9e8aab0df5d6390 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_e749e265e27cc607d0a5cea214d72619 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_a7d1b11d42f8871cc20416d6ecb12eeb http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_2eaefdf6e34f2345569e67e2408ccd60 |
| publicationDate | 2018-04-04-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | TN-2016000546-A1 |
| titleOfInvention | Aminoester derivatives |
| abstract | The invention relates to novel compounds which are both phosphodiesterase 4 (PDE4) enzyme inhibitors and muscarinic M3 receptor antagonists, methods of preparing such compounds, compositions containing them and therapeutic use thereof. M3 Binging assay: CHO-KI clone cells expressing the human M3- receptor (Swissprot P20309) were harvested in Ca<sup>++</sup>/Mg<sup>++</sup>free phosphate-buffered saline and collected by centrifugation at 1500 rpm for 3 min. The pellets were resuspended in ice cold buffer A (15 mM Tris-HCI pH 7.4, 2 mM MgCI<sub>2</sub>, 0.3 mM EDTA, 1 mM EGTA) and homogenized by a PBI politron (setting 5 for 15 s). The crude membrane fraction was collected by two consecutive centrifugation steps at 40000 g for 20 min at 4°C, separated by a washing step in buffer A. The pellets obtained were finally resuspended in buffer B (75 mM Tris HCI pH 7.4, 12.5mM MgCI<sub>2</sub>, 0.3 mM EDTA, 1 mM EGTA, 250 mM sucrose), and aliquots were stored at - 80°C. The day of experiment, frozen membranes were resuspended in buffer C (50 mM Tris-HCI pH 7.4, 2.5 mM MgCb, 1 mM EDTA). The non selective muscarinic radio ligand [<sup>3</sup>H]-N-methyl scopolamine<em>(Mol.Pharmacol.</em>45:899-907) was used to label the M3 binding sites. Binding experiments were performed in duplicate (ten point concentrations curves) in 96 well plates at radioligand concentration of 0.1-0.3 nM. The non specific binding was determined in the presence of cold N-methyl scopolamine 10 uM. Samples (final volume 0.75 mL) were incubated at room temperature for 90 min. The reaction was terminated by rapid filtration through GF/B Unifilter plates and two washes (0.75 mL) with cold buffer C using a Packard Filtermate Harvester. Radioactivity on the filters was measured by a microplate scintillation counter TriCarb 2500 (PerkinElmer). Representative compounds of the invention, when tested in one of the above reported protocols, displayed an IC<sub>50</sub>lower than 100 nM. Representative compounds of the invention displayed an IC<sub>50</sub> lower than 100 nM in both PDE4 cell free and M3 binding assays. |
| priorityDate | 2014-06-05-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
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