SI3092234T1 - Zlite heterociklične spojine kot ionski kanalni modulatorji - Google Patents

Zlite heterociklične spojine kot ionski kanalni modulatorji Download PDF

Info

Publication number
SI3092234T1
SI3092234T1 SI201430714T SI201430714T SI3092234T1 SI 3092234 T1 SI3092234 T1 SI 3092234T1 SI 201430714 T SI201430714 T SI 201430714T SI 201430714 T SI201430714 T SI 201430714T SI 3092234 T1 SI3092234 T1 SI 3092234T1
Authority
SI
Slovenia
Prior art keywords
compound
alkyl
heterocyclyl
heteroaryl
cycloalkyl
Prior art date
Application number
SI201430714T
Other languages
English (en)
Inventor
Michael Graupe
Yafan Lu
Jeff A. Zablocki
Original Assignee
Gilead Sciences, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gilead Sciences, Inc. filed Critical Gilead Sciences, Inc.
Publication of SI3092234T1 publication Critical patent/SI3092234T1/sl

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic 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
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic 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
    • A61K31/42—Oxazoles
    • A61K31/423—Oxazoles condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic 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
    • A61K31/4245—Oxadiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic 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
    • A61K31/4353—Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic 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
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/20—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Obesity (AREA)
  • Pain & Pain Management (AREA)
  • Hematology (AREA)
  • Hospice & Palliative Care (AREA)
  • Endocrinology (AREA)
  • Urology & Nephrology (AREA)
  • Emergency Medicine (AREA)
  • Vascular Medicine (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Claims (21)

  1. ZLITE HETEROCIKLIČNE SPOJINE KOT IONSKI KANALNI MODULATORJI PATENTNI ZAHTEVKI
    1. Spojina s formulo I:
    kjer Y je -L-R1 ali heterociklilni ali heteroarilni obroč vezan skozi obroč atoma dušika, kjer je vsak heterociklil ali heteroaril po izbiri substituiran z 1 do 3 skupinami, neodvisno izbranimi iz skupine, ki jo sestavljajo C1-C6 alkil, C3-C6 cikloalkil, halo, aril, heterociklil, heteroaril, okso, C1-C6 alkoksi, - OH, -NH2, -COR7, -CO2R7, -NHSO2R7, -NHCO2R7, in -CN; in kjer je vsak Ci-C6 alkil, C3-C6 cikloalkil, aril, heterociklil, heteroaril, in C1-C6 alkoksi po izbiri substituiran z 1 do 3 C1-C6 alkoksi, halo, -CF3, -CN, -OH, -NH2 ali - OCF3; X je CR8 ali N; Z je CR9 ali N; L je -O-, -NR5-, -NR5(CHR6)n-, -0(CHR6)n, -0(CHR6)nC(0)-, - 0(CHR6)nC(0)0-, -0(CHR6)nNH-, -0(CHR6)nC(0)NH-, 0(CHR6)nNHC(0)0-or -0(CHR6)mNHS(0)2-; R1 je vodik, C1-C6 alkil, C3-C8 cikloalkil, aril, heterociklil ali heteroaril; kjer je vsak cikloalkil, aril, heterociklil ali heteroaril po izbiri substituiran z 1 do 3 skupinami neodvisno izbranimi iz skupine, ki jo sestavljajo C1-C6 alkil, C3-C6 cikloalkil, halo, aril, heterociklil, heteroaril, okso, -OH, -NH2, -COR7, -CO2R7, -NHSO2R7, -NHCO2R7, in -CN; in kjer je vsak C1-C6 alkil, C3-C6 cikloalkil, aril, heterociklil, in heteroaril po izbiri substituiran z 1 do 3 C1-C6 alkoksiji, haloji, -CF3, -CN, -OH, -NH2 ali -OCF3; vsak R2 je neodvisno halo, C1-C6 alkil, C1-C6 alkoksi ali -OCF3; R3 je vodik, halo, C1-C3 haloalkil, C1-C3 haloalkoksi, C3-C6 cikloalkil ali fenil, kjer je cikloalkil ali fenil po izbiri substituiran z enim ali dvema atomoma haloa, pod pogojem, da ko je R3 vodik, p je 1 ali 2; vsak R4 je neodvisno C1-C6 alkil, halo, C1-C6 alkoksi ali -OCF3; ali R3 in R4 vzeta skupaj z atomom ogljika k kateremu sta pripeta oblikujeta C4-C8 obroč, po izbiri vsebujoč od ene do terh dvojnih vezi in po izbiri vsebujoč od enega do treh heteroatomov, neodvisno izbranih iz skupine, ki jo sestavljajo O, N, in S, katere obroč je lahko po izbiri substituiran z enim do tremi haloji, C1-C6 alkilom, C1-C3 haloalkilom ali C1-C3 haloalkoksijem; R5 je vodik, C1-C6 alkil, C1-C3 haloalkil ali -COCH3; vsak R6 je neodvisno vodik, C1-C6 alkil, C1-C3 haloalkil, -CN, -OH ali -NH2; R7 je vodik, C1-C6 alkil, aril ali aralkil; R8 je neodvisno vodik, C1-C6 alkil, halo, C1-C6 alkoksi ali -OCF3; ali R3 in R8 vzeta skupaj z atomom ogljika k kateremu sta pripeta oblikujeta C4-C8 obroč po izbiri vsebujoč od ene do tri dvojne vezi in po izbiri vsebuje od enega do treh heteroatomov, neodvisno izbranih iz skupine, ki jo sestavljajo O, N, in S, katerega obroč je lahko po izbiri substituiran z enim do tremi haloji, C1-C6 alkili, C1-C3 haloalkili ali C1-C3 haloalkoksiji; R9 je vodik, halo, C1-C6 alkil, C1-C6 alkoksi ali -OCF3; vsak n je neodvisno 2, 3, 4 ali 5; vsak n je neodvisno 1, 2, 3, 4 ali 5; in p in q sta vsak neodvisno 0, 1 ali 2; ali njena farmacevtsko sprejemljiva sol, stereoizomera ali mešanica stereoi2 omer.
  2. 2. Spojina po zahtevku 1, Y je heterociklilni ali heteroarilni obroč ring vezan skozi obroč atoma dušika, kjer je vsak heterociklil ali heteroaril po izbiri substituiran z 1 do 3 skupinami neodvisno izbranimi iz skupine, ki jo sestavljajo C1-C6 alkil, C3-C6 cikloalkil, halo, aril, heterociklil, heteroaril, okso, C1-C6 alkoksi, - OH, -NH2, -COR7, -CO2R7, -NHSO2R7, -NHCO2R7, in -CN; in kjer je vsak Ci-Ce alkil, C3-C6 cikloalkil, aril, heterociklil, heteroaril, in C1-C6 alkoksi po izbiri substituiran z 1 do 3 C1-C6 alkoksiji, haloji, -CF3, -CN, -OH, -NH2 ali -OCF3, po izbiri kjer je Y heterociklilni ali heteroarilni obroč vezan skozi obroč atoma dušika, kjer je vsak heterociklil ali heteroaril po izbiri substituiran z 1 do 3 skupinami neodvisno izbranimi iz skupine, ki jo sestavljajo C1-C6 alkil, aril, in okso, kjer je C1-C6 alkil po izbiri substituiran z 1 do 3 haloji ali -OH.
  3. 3. Spojina po zahtevku 1, kjer Y je -L-R1, po izbiri kjer L je -0(CHR6)n-, po izbiri kjer vsak R6 je neodvisno vodik ali C1-C6 alkil.
  4. 4. Spojina po zahtevku 1, kjer R1 je C1-C6 alkil, C3-C8 cikloalkil, aril, heterociklil ali heteroaril; kjer je vsak cikloalkil, aril, heterociklil ali heteroaril po izbiri substituiran z 1 do 3 skupinami, neodvisno izbranimi iz skupine, ki jo sestavljajo C1-C6 alkil, C3-C6 cikloalkil, halo, aril, heterociklil, heteroaril, okso, - OH, -IMH2, -COR7, -CO2R7, -NHSO2R7, -NHCO2R7, in -CN; in kjer je vsak C1-C6 alkil, C3-C6 cikloalkil, aril, heterociklil, in heteroaril po izbiri substituiran z 1 do 3 C1-C6 alkoksiji, haloji, -CF3, -CN, -OH, -NH2 ali -OCF3.
  5. 5. Spojina po zahtevku 1, kjer R1 je
  6. 6. Spojina po zahtevku 1, kjer R1 je C1-C6 alkil, po izbiri, kjer R4 je fluor, klor, metil, metoksi ali -OCF3.
  7. 7. Spojina po zahtevku 1, kjer R2 je fluor, metil ali metoksi.
  8. 8. Spojina po zahtevku 1, kjer R3 je vodik, fluor, -CF3, -OCF3, -O-CH2-CF3 ali ciklopropil.
  9. 9. Spojina po zahtevku 1, kjer X je N.
  10. 10. Spojina po zahtevku 1, kjer X je CR8.
  11. 11. Spojina po zahtevku 1, kjer R8 je vodik.
  12. 12. Spojina po zahtevku 1, kjer Z je N.
  13. 13. Spojina po zahtevku 1, kjer Z je CR9.
  14. 14. Spojina po zahtevku 1, kjer R9 je vodik.
  15. 15. Spojina po zahtevku 1, kjer q je 0 ali 1.
  16. 16. Spojina po zahtevku 1, kjer p je 0 ali 1.
  17. 17. Spojina po zahtevku 1, kjer je spojina s formulo I spojina s formulo IA:
    IA. ali spojina s formulo IB: IB.
    ali spojina s formulo IC:
  18. 18. Spojina po zahtevku 1, kjer je omenjena spojina izbrana iz skupine, ki jo sestavljajo:
    /
    • · ·
    • · · · · ·
    in
    ali njena farmacevtsko sprejemljiva sol, stereoizomera ali mešanica stereoizomer.
  19. 19. Farmacevtski sestavek, ki vsebuje farmacevtsko sprejemljivo pomožno snov in terapevtsko učinkovito količino spojine po kateremkoli od zahtevkov 1 do 18 ali njene farmacevtsko sprejemljive soli.
  20. 20. Spojina po kateremkoli od zahtevkov 1 do 18 za uporabo ali pri uporabi spojine po kateremkoli od zahtevkov 1 do 18 pri izdelavi zdravila za zdravljenje stanja bolezni pri človeku, ki je lažje z obdelavo z sredstvo, ki je sposobno za zmanjšanje poznega toka natrija, ki obsega dajanje človeku, ki jo potrebuje, terapevtsko učinkovite doze spojine, po izbiri kjer je stanje bolezni kardiovaskularna bolezen, izbrana izmed ene ali več atrijskih aritmij, ventrikularnih aritmij, srčnega popuščanja (vključno kongestivno srčno popuščanje, diastolično srčno popuščanje, sistolično srčno popuščanje, akutno srčno popuščanje), Prinzmetal (variantne) angine, stabilne angine, nestabilne angine, indukcijske angine, kongestivne srčne bolezni, ishemije, ponavljajoče se ishemije, reperfuzijske poškodbe, miokardnega infarkta, akutnega koronarnega sindroma, periferne arterijske bolezni, pljučne hipertenzije, dolgega QT sindroma, hipertrofične kardiomiopatije in občasne klavdikacije; ali po izbiri, kjer je stanje bolezni sladkorna bolezen ali diabetična periferna nevropatija; ali po izbiri, kjer stanje bolezni povzroči eno ali več nevropatskih bolečin, epilepsijo, migreno, napade ali paralizo.
  21. 21. Spojina po kateremkoli od zahtevkov 1 do 18 za uporabo pri terapiji.
SI201430714T 2013-12-20 2014-12-03 Zlite heterociklične spojine kot ionski kanalni modulatorji SI3092234T1 (sl)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361919605P 2013-12-20 2013-12-20
PCT/US2014/068359 WO2015094670A1 (en) 2013-12-20 2014-12-03 Fused heterocyclic compounds as ion channel modulators
EP14819206.5A EP3092234B1 (en) 2013-12-20 2014-12-03 Fused heterocyclic compounds as ion channel modulators

Publications (1)

Publication Number Publication Date
SI3092234T1 true SI3092234T1 (sl) 2018-06-29

Family

ID=52146745

Family Applications (1)

Application Number Title Priority Date Filing Date
SI201430714T SI3092234T1 (sl) 2013-12-20 2014-12-03 Zlite heterociklične spojine kot ionski kanalni modulatorji

Country Status (19)

Country Link
US (3) US9416115B2 (sl)
EP (1) EP3092234B1 (sl)
JP (2) JP6409067B2 (sl)
KR (1) KR101871613B1 (sl)
CN (1) CN105829303B (sl)
AU (1) AU2014366940B2 (sl)
CA (1) CA2934456C (sl)
EA (1) EA201690988A1 (sl)
ES (1) ES2672476T3 (sl)
HK (2) HK1223358A1 (sl)
IL (1) IL245881A (sl)
MX (1) MX2016008257A (sl)
NO (1) NO3111624T3 (sl)
NZ (1) NZ720807A (sl)
PL (1) PL3092234T3 (sl)
PT (1) PT3092234T (sl)
SG (1) SG11201604466RA (sl)
SI (1) SI3092234T1 (sl)
WO (1) WO2015094670A1 (sl)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20200121823A (ko) * 2018-02-16 2020-10-26 유씨비 바이오파마 에스알엘 약학적 6,5 헤테로비시클릭 고리 유도체

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4859691A (en) * 1987-07-08 1989-08-22 Ciba-Geigy Corporation Certain 1,2-benzisoxazole derivatives
WO1994010158A1 (en) * 1992-10-28 1994-05-11 Toyama Chemical Co., Ltd. Novel 1,2-benzisoxazole derivative or salt thereof, and brain protective agent comprising the same
CA2497351C (fr) * 2002-09-05 2012-08-21 Aventis Pharma S.A. Nouveaux derives d'aminoindazoles a titre de medicaments et compositions pharmaceutiques les renfermant
US20070197610A1 (en) 2004-03-16 2007-08-23 Janssen Pharmaceutica N.V. Benzisoxazoles
DE102005038947A1 (de) * 2005-05-18 2006-11-30 Grünenthal GmbH Substituierte Benzo[d]isoxazol-3-yl-amin-Verbindungen und deren Verwendung in Arzneimitteln
CN101228139A (zh) * 2005-05-18 2008-07-23 格吕伦塔尔有限公司 作为镇痛剂的取代的苯并(d)异唑－3－基－胺化合物
WO2010141360A1 (en) * 2009-06-05 2010-12-09 Merck Sharp & Dohme Corp. Biaryl benzotriazole derivatives
LT2464645T (lt) * 2009-07-27 2017-10-25 Gilead Sciences, Inc. Kondensuoti heterocikliniai junginiai, kaip jonų kanalų moduliatoriai
AU2011340258C1 (en) 2010-12-06 2016-10-20 Autifony Therapeutics Limited Hydantoin derivatives useful as Kv3 inhibitors
WO2013049263A1 (en) * 2011-09-27 2013-04-04 Bristol-Myers Squibb Company Substituted bicyclic heteroaryl compounds
WO2013064984A1 (en) * 2011-10-31 2013-05-10 Xenon Pharmaceuticals Inc. Biaryl ether sulfonamides and their use as therapeutic agents

Also Published As

Publication number Publication date
PL3092234T3 (pl) 2018-07-31
US9920018B2 (en) 2018-03-20
HK1225728B (zh) 2017-09-15
IL245881A0 (en) 2016-08-02
CA2934456A1 (en) 2015-06-25
HK1223358A1 (zh) 2017-07-28
AU2014366940A1 (en) 2016-06-16
NZ720807A (en) 2017-02-24
EA201690988A1 (ru) 2016-11-30
AU2014366940B2 (en) 2017-06-29
JP6409067B2 (ja) 2018-10-17
ES2672476T3 (es) 2018-06-14
CN105829303A (zh) 2016-08-03
CA2934456C (en) 2019-01-29
WO2015094670A1 (en) 2015-06-25
US9416115B2 (en) 2016-08-16
KR101871613B1 (ko) 2018-06-26
US20170088527A1 (en) 2017-03-30
EP3092234B1 (en) 2018-02-14
US20160317504A1 (en) 2016-11-03
NO3111624T3 (sl) 2018-02-17
MX2016008257A (es) 2016-10-14
CN105829303B (zh) 2018-11-06
JP2016540808A (ja) 2016-12-28
IL245881A (en) 2017-08-31
EP3092234A1 (en) 2016-11-16
PT3092234T (pt) 2018-06-12
JP2017206566A (ja) 2017-11-24
US20150175560A1 (en) 2015-06-25
KR20160096715A (ko) 2016-08-16
SG11201604466RA (en) 2016-07-28

Similar Documents

Publication Publication Date Title
AU2016202535B2 (en) Fused heterocyclic compounds as sodium channel modulators
RU2020123547A (ru) Соединения и композиции для модуляции киназной активности мутантов egfr
AR079690A1 (es) Derivados heterociclicos de pirrol[2,3-b]piridina, composiciones farmaceuticas que los contienen, procedimiento para prepararlos y uso de los mismos como agentes anticancer.
BR112014000563A2 (pt) composto, composição farmacêutica, e, uso do composto
RU2017127135A (ru) Терапевтическое средство против рака желчных протоков
EA201490807A1 (ru) Новые замещенные имидазопиримидины как модуляторы рецептора gpbar1
EA201491671A1 (ru) Гетероциклильные соединения
PE20140836A1 (es) Derivados de carboxamida y urea que contienen pirazol heteroaromatico sustituido como ligandos del receptor de vanilloide
PE20110835A1 (es) Piridiloxi-indoles inhibidores del vegf-r2 y uso de los mismos para el tratamiento de enfermedades
RU2017117566A (ru) Активатор kcnq2-5 каналов
AR067886A1 (es) Derivados de acido azabifenilaminobenzoico
SI2978752T1 (sl) Derivati 6-(5-hidroksi-1H-pirazol-1-il)nikotinamida in njihova uporaba kot inhibitorji PHD
CO6650337A2 (es) Derivados de 3- hidroxi-5 -arilisotiazol novedoso
CY1112921T1 (el) Ενεργοποιητες γλυκοκινασης πυρρολιδινονης
PE20151595A1 (es) Compuestos de pirazol-amida y sus usos farmaceuticos
NZ630099A (en) Phenicol antibacterials
JP2018048143A5 (sl)
PH12016500885A1 (en) Novel heterocyclic compounds
CO2020012353A2 (es) Compuestos de pirazol sustituidos con heteroarilo y uso farmacéutico de los mismos
CO2020006789A2 (es) Procedimiento para la preparación de (3s)-3-(4-cloro-3-{[(2s,3r)-2-(4-clorofenil)-4,4,4-trifluor-3-metilbutanoil]amino}fenil)-3-ácido ciclopropilpropanoico y su forma cristalina para uso como principio activo farmacéutico
PH12014501181A1 (en) N- (4 -quinolinylmethyl) sulfonamide derivatives and their use as anthelmintics
TR201900735T4 (tr) Yeni kaynaşık imidazobenzotiyazol bileşikleri.
BR112017021631A2 (pt) composto, composição farmacêutica, combinação farmacêutica, método de tratamento, uso de um composto e processo para preparação de dito composto
SI3092234T1 (sl) Zlite heterociklične spojine kot ionski kanalni modulatorji
JP2016503777A5 (sl)