ME02486B - Sigma ligandi za primjenu u prevenciji 1/ili lijecenju postoperaтivnog bola - Google Patents

Sigma ligandi za primjenu u prevenciji 1/ili lijecenju postoperaтivnog bola

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Publication number
ME02486B
ME02486B MEP-2016-112A MEP11216A ME02486B ME 02486 B ME02486 B ME 02486B ME P11216 A MEP11216 A ME P11216A ME 02486 B ME02486 B ME 02486B
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Montenegro
Prior art keywords
substituted
unsubstituted
sigma ligand
use according
aromatic
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MEP-2016-112A
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English (en)
French (fr)
Inventor
Hernández José Miguel Vela
Castanedo Daniel Zamanillo-
De Conias Margarita Puig-Riera
Original Assignee
Esteve Labor Dr
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Publication of ME02486B publication Critical patent/ME02486B/me

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4151,2-Diazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4151,2-Diazoles
    • A61K31/4161,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/41781,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41961,2,4-Triazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/472Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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  • Animal Behavior & Ethology (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Claims (10)

1.Sigma ligand za prijmenu u prevenciji i/ili liječenju bola nastalog kao posledica hirurške intervencije, pri čemu sigma ligand ima opštu formulu (I):pri čemuR1 je izabran iz grupe koju čine vodonik, supstituisani ili nesupstituisani alkil, supstituisani ili nesupstituisani cikloalkil, supstituisani ili nesupstituisani alkenil, supstituisani ili nesupstituisani aril, supstituisani ili nesupstituisani arilalkil, supstituisani ili nesupstituisani nearomatični heterociklil, supstituisani ili nesupstituisani aromatični heterociklil, supstituisani ili nesupstituisani heterociklilalkil, -COR8, -C(O)OR8,-C(O)NR8R9, -CH=NR8, -CN, -OR8, -OC(O)R8, -S(O) t-R8, -NR8R9, - NR8C(O)R9, -NO2, -N=CR8R9, i halogen;R2 je izabran iz grupe koju čine vodonik, supstituisani ili nesupstituisani alkil, supstituisani ili nesupstituisani cikloalkil, supstituisani ili nesupstituisani alkenil, supstituisani ili nesupstituisani aril, supstituisani ili nesupstituisani arilalkil, supstituisani ili nesupstituisani, aromatični ili nearomatični heterociklil, supstituisani ili nesupstituisani heterocikilalkil, -COR8, -C(O)OR8, -C(O)NR8R9, -CH=NR8, -CN, -OR8, -OC(O)R8, -S(O)t-R8, -NR8R9, -NR8C(O)R9, -NO2, -N=CR8R9, i halogen;R3 i R4 su nezavisno izabrani iz grupe koju čine vodonik, supstituisani ili nesupstituisani alkil, supstituisani ili nesupstituisani cikloalkil, supstituisani ili nesupstituisani alkenil, supstituisani ili nesupstituisani aril, supstituisani ili nesupstituisani arilalkil, supstituisani ili nesupstituisani, aromatični ili nearomatični heterociklil, supstituisani ili nesupstituisani heterociklilalkil, -COR8, -C(O)OR8, -C(O)NR8R9, -CH=NR8, -CN, -OR8,-OC(O)R8, -S(O)t-R8, -NR8R9, -NR8C(O)R9, -NO2, -N=CR8R9, i halogen, ili oni zajedno obrazuju opciono supstituisani kondenzovani prstenasti sistem;R5 i R6 su nezavisno izabrani iz grupe koju čine vodonik, supstituisani ili nesupstituisani alkil, substituted ili nesupstituisani cikloalkil, supstituisani ili nesupstituisani alkenil, supstituisani ili nesupstituisani aril, supstituisani ili nesupstituisani arilalkil, supstituisani ili nesupstituisani, aromatični ili nearomatični heterociklil, supstituisani ili nesupstituisani heterociklil alkil, -COR8, -C(O)OR8, -C(O)NR8R9, -CH=NR8, -CN, -OR8,-OC(O)R8, -S(O)t-R8, -NR8R9, -NR8C(O)R9, -NO2, -N=CR8R9, i halogen, ili zajedno obrazuju, sa atomom azota za koji su vezani, supstituisanu ili nesupstituisanu, aromatičnu ili nearomatičnu heterocikličnu grupu;n je izabran između 1, 2, 3, 4, 5, 6, 7 i 8;t je 1,2 ili 3;svaki R8 i R9 je nezavisno izabran između sledećeg: vodonik, supstituisani ili nesupstituisani alkil, supstituisani ili nesupstituisani cikloalkil, supstituisani ili nesupstituisani alkenil, supstituisani ili nesupstituisani aril, supstituisani ili nesupstituisani, aromatični ili nearomatični heterociklil, supstituisani ili nesupstituisani alkoksi, supstituisani ili nesupstituisani ariloksi, i halogen;ili njegove farmaceutski prihvatljive soli, stereoizomeri ili solvati.
2.Sigma ligand za primjenu prema zahtjevu 1, pri čemu je bol izabran između akutnog i/ili hroničnog bola nastalog kao posledica hirurške intervencije.
3.Sigma ligand za primjenu prema zahtjevu 2, pri čemu je bol izabran između površinskog i/ili dubokog bola zbog sekundarne povrede tkiva prilikom hirurške intervencije, i/ili neuropatskog bola, neuralgije, alodinije, kauzalgije, hiperalgezije, hiperestezije, hiperpatije, neuritisa i neuropatije nastalih posle hirurške procedure.
4.Sigma ligand za primjenu prema prema bilo kom od prethodnih zahtjeva, koji je izabran između antagonista sigma receptora, a prvenstveno je izabran između neutralnog antagonista, inverznog agonista ili delimičnog antagonista.
5.Sigma ligand za primjenu prema prema bilo kom od prethodnih zahtjeva, pri čemu je R1 izabran između H, -COR8 i supstituisanog ili nesupstituisanog alkila.
6.Sigma ligand za primjenu prema prema bilo kom od prethodnih zahtjeva, pri čemu R2 je H ili alkil.
7.Sigma ligand za primjenu prema prema bilo kom od prethodnih zahtjeva, pri čemu R3 i R4 zajedno obrazuju kondenzovani naftil prstenasti sistem.
8.Sigma ligand za primjenu prema prema bilo kom od prethodnih zahtjeva, pri čemu R5 i R6 zajedno obrazuju morfolin-4-il grupu.
9.Sigma ligand za primjenu prema prema bilo kom od prethodnih zahtjeva, pri čemu je sigma ligand 4-{2-[5-metil-1-(naftalenlen-2-il)-1H-pirazol-3-iloksi]etil} morfolin, ili njegova farmaceutski prihvatljiva so, stereoizomer ili solvat.
10.Sigma ligand za primjenu prema prema bilo kom od prethodnih zahtjeva, pri čemu je sigma ligand 4-{2-[5-metil-1-(naftalenlen-2-il)-1H-pirazol-3-iloksi]etil} morfolin hidrohlorid.
MEP-2016-112A 2010-02-04 2011-02-04 Sigma ligandi za primjenu u prevenciji 1/ili lijecenju postoperaтivnog bola ME02486B (me)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP10382024A EP2353598A1 (en) 2010-02-04 2010-02-04 Sigma ligands for use in the prevention and/or treatment of postoperative pain
EP11702057.8A EP2531191B1 (en) 2010-02-04 2011-02-04 Sigma ligands for use in the prevention and/or treatment of postoperative pain
PCT/EP2011/051643 WO2011095584A1 (en) 2010-02-04 2011-02-04 Sigma ligands for use in the prevention and/or treatment of postoperative pain

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EP2116539A1 (en) 2008-04-25 2009-11-11 Laboratorios Del. Dr. Esteve, S.A. 1-aryl-3-aminoalkoxy-pyrazoles as sigma ligands enhancing analgesic effects of opioids and attenuating the dependency thereof
EP2353598A1 (en) 2010-02-04 2011-08-10 Laboratorios Del. Dr. Esteve, S.A. Sigma ligands for use in the prevention and/or treatment of postoperative pain
EP2353591A1 (en) 2010-02-04 2011-08-10 Laboratorios Del. Dr. Esteve, S.A. Sigma ligands for potentiating the analgesic effect of opioids and opiates in post-operative pain and attenuating the dependency thereof
EP2388005A1 (en) 2010-05-21 2011-11-23 Laboratorios Del. Dr. Esteve, S.A. Sigma ligands for the prevention and/or treatment of emesis induced by chemotherapy or radiotherapy
EP2415471A1 (en) 2010-08-03 2012-02-08 Laboratorios Del. Dr. Esteve, S.A. Use of sigma ligands in opioid-induced hyperalgesia
EP2426111A1 (en) * 2010-08-09 2012-03-07 Laboratorios Del. Dr. Esteve, S.A. 4-[-2-[[5-methyl-1-(2-naphtalenyl)-1h-pyrazol-3-yl]oxy]ethyl]morpholine hydrochloride amorphous solid forms
RU2469712C2 (ru) * 2010-12-16 2012-12-20 Государственное бюджетное учреждение здравоохранения Московской области "Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского" (ГБУЗ МО "МОНИКИ им. М.Ф. Владимирского") Способ профилактики и лечения послеоперационного болевого синдрома при торакоскопических операциях
EP2524694A1 (en) 2011-05-19 2012-11-21 Laboratorios Del. Dr. Esteve, S.A. Use of sigma ligands in diabetes type-2 associated pain
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CN105611925A (zh) * 2013-09-12 2016-05-25 埃斯蒂维实验室股份有限公司 NSAID与σ受体配体的组合物
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ES2848710T3 (es) 2014-02-07 2021-08-11 Tamogatott Kutatocsoportok Irodaja Nuevo uso de compuestos agonistas del receptor sigma-1
MA41177A (fr) * 2014-12-15 2017-10-24 Esteve Labor Dr Utilisation de ligands des récepteurs sigma dans l'arthrose
EP3233830A1 (en) * 2014-12-15 2017-10-25 Laboratorios Del. Dr. Esteve, S.A. 1-methylpyrazole-piperazine compounds having multimodal activity against pain
CN107868033B (zh) 2016-09-27 2021-05-18 深圳微芯生物科技股份有限公司 一种苯丙氨酸类化合物的制备方法
US10195192B2 (en) * 2016-11-01 2019-02-05 Anavex Life Sciences Corp. Analgesic therapeutic and method, 1-(3-4(((1R,3S,5S)-adamantan-1-yl)(phenyl)methyl)propyl)-4-methylpiperazine and salts thereof
CA3044746A1 (en) 2016-11-24 2018-05-31 Sigmadrugs Kutato Korlatolt Felelossegu Tarsasag Compositions for organ preservation
CA3121202A1 (en) 2018-11-30 2020-06-04 Nuvation Bio Inc. Pyrrole and pyrazole compounds and methods of use thereof
WO2025255170A1 (en) * 2024-06-03 2025-12-11 Actio Biosciences, Inc. Heterocyclic compounds useful as kcnt1 inhibitors

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