ME02635B - Novi derivati pirola, postupak njihove priprave i farmaceutski pripravci koji ih sadrže - Google Patents

Novi derivati pirola, postupak njihove priprave i farmaceutski pripravci koji ih sadrže

Info

Publication number
ME02635B
ME02635B MEP-2017-63A MEP201763A ME02635B ME 02635 B ME02635 B ME 02635B ME P201763 A MEP201763 A ME P201763A ME 02635 B ME02635 B ME 02635B
Authority
ME
Montenegro
Prior art keywords
formula
compound
dimethyl
morpholin
hydroxyphenyl
Prior art date
Application number
MEP-2017-63A
Other languages
German (de)
English (en)
French (fr)
Inventor
Tiran Arnaud Le
Diguarher Thierry Le
Jérôme-Benoît Starck
Jean-Michel Henlin
Anne-Françoise Guillouzic
Nanteuil Guillaume De
Olivier Geneste
Imre Fejes
Janos Tatai
Miklos Nyerges
James Edward Paul Davidson
James Brooke Murray
I-Jen Chen
Didier Durand
Original Assignee
Servier Lab
Vernalis R&D Ltd
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=50023639&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ME02635(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Servier Lab, Vernalis R&D Ltd filed Critical Servier Lab
Publication of ME02635B publication Critical patent/ME02635B/me

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
    • A61K31/535—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
    • A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero 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
    • A61K31/435—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
    • A61K31/4709—Non-condensed quinolines 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
    • A61K31/435—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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • 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
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • 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
    • 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
    • C07D498/12—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 three hetero rings
    • C07D498/14—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Immunology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Transplantation (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyrrole Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Claims (35)

1. Spoj formule (I): naznačen time, da: ♦ A1 predstavlja atom vodika ili halogena, ravnu ili razgrananu (C1-C6)polihaloalkilnu skupinu, ravnu ili razgrananu (C1-C6)alkilnu skupinu ili cikloalkilnu skupinu, ♦ A2 predstavlja ravnu ili razgrananu (C1-C6)alkilnu skupinu po izboru supstituiranu sa skupinom odabranom od halogena, hidroksi, ravnog ili razgrananog (C1-C6)alkoksi, NR'R'' i morfolina ili A2 predstavlja ravnu ili razgrananu (C1-C6)polihaloalkilnu skupinu ili ciklopropilnu skupinu, gdje se podrazumijeva da R' i R", svaki neovisno jedan o drugome, predstavljanju atom vodika ili ravnu ili razgrananu (C1-C6)alkilnu skupinu, ♦ T predstavlja atom vodika, ravnu ili razgrananu (C1-C6)alkilnu skupinu po izboru supstituiranu s jednim do tri atoma halogena, skupinu (C1-C4)alkil-NR1R2 ili skupinu (C1-C4)alkil-OR6, ♦ R1 i R2, svaki neovisno jedan o drugome, predstavljaju atom vodika ili ravnu ili razgrananu (C1-C6)alkilnu skupinu ili R1 i R2 tvore s dušikovim atomom koji ih nosi heterocikloalkil, ♦ R3 predstavlja arilnu ili heteroarilnu skupinu, pri čemu se podrazumijeva da jedan ili više ugljikovih atoma iz prethodnih skupina ili njihovi mogući supstituenti mogu biti deuterirani, ♦ R4 predstavlja fenilnu skupinu, 4-hidroksifenilnu skupinu, 3-fluoro-4-hidroksifenilnu skupinu, 2-hidroksipirimidinsku skupinu ili 3-hidroksipiridinsku skupinu, pri čemu se podrazumijeva da jedan ili više ugljikovih atoma iz prethodnih skupina ili njihovi mogući supstituenti mogu biti deuterirani, ♦ R5 predstavlja atom vodika ili atom halogena, ravnu ili razgrananu (C1-C6)alkilnu skupinu ili ravnu ili razgrananu (C1-C6)alkoksi skupinu, ♦ R6 predstavlja atom vodika ili ravnu ili razgrananu (C1-C6)alkilnu skupinu, ♦ Ra i Rd svaki predstavlja atom vodika i (Rb,Rc) zajedno s ugljikovim atomom koji ih nose tvore skupinu 1,3-dioksolana ili skupinu 1,4-dioksana ili Ra, Rc and Rd svaki predstavlja atom vodika i Rb predstavlja atom vodika ili halogena ili metoksi skupinu ili Ra i Rd svaki predstavlja atom vodika, Rb predstavlja atom vodika ili atom halogena i Rc predstavlja hidroski ili metoksi skupinu ili: Ra i Rd svaki predstavlja atom vodika, Rb predstavlja hidroksi ili metoksi skupinu i Rc predstavlja atom halogena, gdje se podrazumijeva kako: - "aril" znači fenilna, naftilna, bifenilna ili indenilna skupina, - "heteroaril" znači bilo koja mono- ili bi-ciklička skupina sastavljena od 5 do 10 članova prstena, koja ima najmanje jednu aromatsku polovicu i sastoji se od 1 do 4 heteroatoma odabrana od kisika, sumpora i dušika (uključujući kvaterne dušike), - "cikloalkil” znači bilo koja mono- ili bi-ciklička, ne-aromatska, karbociklička skupina koja se sastoji od 3 do 10 članova prstena, - "heterocikloalkil" znači bilo koja mono- ili bi-ciklička, ne-aromatska, kondenzirana ili spiro skupina koja se sastoji od 3 do 10 članova prstena i sadrži od 1 do 3 heteroatoma odabrana od kisika, sumpora, SO, SO2 i dušika, pri čemu je moguće za tako definirane arilne, heteroarilne, cikloalkilne i heterocikloalkilne skupine i skupine alkila, alkenil, alkinila i alkoksi da budu supstituirane s 1 do 3 skupine odabrane od ravnog ili razgrananog (C1-C6)alkila, (C3-C6)spiro, ravnog ili razgrananog (C1-C6)alkoksi, (C1-C6)alkil-S-, hidroksi, okso (ili N-oksida gdje je prikladno), nitro, cijano, -COOR', -OCOR', NR'R'', ravnog ili razgrananog (C1-C6)polihaloalkila, trifluorometoksi, (C1-C6)alkilsulfonila, halogena, arila, heteroarila, ariloksi, ariltio, cikloalkila, heterocikloalkila po izboru supstituiranog s jednim ili više atoma halogena ili alkilnim skupinama, njegove enantiomere i dijastereoizomere i njihove adicijske soli s s farmaceutski prihvatljivom kiselinom ili lužinom.
2. Spoj formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da A1 predstavlja atom vodika ili metilnu skupinu.
3. Spoj formule (I) u skladu s patentnim zahtjevom 1 ili 2, naznačen time, da A1 i A2 oba predstavljaju metilnu skupinu.
4. Spoj formule (I) u skladu s jednim od patentnih zahtjeva 1 do 3, naznačen time, da T predstavlja metil, aminometil, (morfolin-4-il)metil, (4-metilpiperazin-1-il)metil, 2-(morfolin-4-il)etil, [2-(morfolin-4-il)etoksi]metil, hidroksimetil,[2-(dimetilamino)etoksi]metil, heksahidropirazino[2,1-c][1,4]oksazin-8(1H)-ilmetil, 1-oksa-6-azaspiro[3.3]hept-6-ilmetil, 3-(morfolin-4-il)propilnu ili trifluorometilnu skupinu.
5. Spoj formule (I): u skladu s patentnim zahtjevom 1, naznačen time, da - A1, A2, Ra, Rb, Rc, Rd, T, R4 i R5 jesu definirani u patentnim zahtjevima 1 do 4, - R3 predstavlja skupinu odabranu od fenila, 1H-pirazola, 1H-indola, 1H-indazola, piridina, pirimidina, 1H-pirolo[ 2,3-b]piridina, 2,3-dihidro-1H-pirolo[2,3-b]piridina, 1H-benzimidazola, 1H-pirola, 1H-pirolo[2,3- c]piridina, 1H-pirolo[3,2-b]piridina, 5H-pirolo[3,2-d]pirimidina, tiofena, pirazina, 1H-pirazolo[3,4-b]piridina, 1,2-oksazola i pirazolo[1,5-a]pirimidina, te skupine po izboru imaju jednog ili više supstituenata odabrana od halogena, ravnog ili razgrananog (C1-C6)alkila, ravnog ili razgrananog (C1-C6)alkoksi, cijano, ciklopropila, oksetana, tetrahidrofurana, -CO-O-CH3, trideuteriometila, 2-(morfolin-4-il)etila i 2-(morfolin-4-il)etoksi, njihovih enantiomera i dijastereoizomera te njihovih adicijskih soli s farmaceutski prihvatljivom kiselinom ili lužinom.
6. Spoj formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da je odabran iz sljedeće skupine: - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirazol-4-il)-1H-pirol-3-karboksamid, - 5-(5-kloro-2-{[(3R)-3-metil-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2- dimetil-N-(piridin-4-il)-1H-pirol-3-karboksamida, - N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirazol-4-il)-5-(6-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}-1,3-benzoadioksol-5-il)-1H-pirol-3-karboksamida, - N-(4-hidroksifenil)-1,2-dimetil-5-(6-{[(3R)-3-metil-3,4-dihidroizokinolin-2(1H)-il]karbonil}-1,3-benzodioksol-5-il)-N-(piridin-4-il)-1H-pirol-3-karboksamida, - 5-(5-fluoro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirazol-4-il)-1H-pirol-3-karboksamida, - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirolo[2,3-b]piridin-5-il)-1H-pirol-3-karboksamida, - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(piridin-4-il)-1H-pirol-3-karboksamida, - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(5-cijano- 1-metil-1H-pirol-3-il)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamida, - N-(5-cijano-1-metil-1H-pirol-3-il)-5-(5-fluoro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin- 2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamida, - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(5-cijano- 1,2-dimetil-1H-pirol-3-il)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamida, - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-2,3-dihidro-1H-pirolo[2,3-b]piridin-5-il)-1H-pirol-3-karboksamida, - N-(5-cijano-1,2-dimetil-1H-pirol-3-il)-5-(5-fluoro-2-{[(3S)-3-(morfolin-4-il-metil)-3,4 dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamida, - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-[5-cijano-2-metil-1-(trideuteriometil)-1H-pirol-3-il]-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamida, njihovih enantiomera i dijastereoizomera te njihovih adicijskih soli s farmaceutski prihvatljivom kiselinom ili lužinom.
7. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirazol-4-il)-1H-pirol-3-karboksamid.
8. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3R)-3-metil-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(piridin-4-il)-1H-pirol-3-karboksamid.
9. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirazol-4-il)-5-(6-[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}-1,3-benzodioksol-5-il)-1H-pirol-3-karboksamid.
10. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je N-(4-hidroksifenil)-1,2-dimetil-5-(6-{[(3R)-3-metil-3,4-dihidroizokinolin-2(1H)-il]karbonil}-1,3-benzodioksol-5-il)-N-(piridin-4-il)-1H-pirol-3 karboksamid.
11. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-fluoro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirazol-4-il)-1H-pirol-3-karboksamid.
12. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirolo[2,3-b]piridin-5-il)-1H-pirol-3-karboksamid.
13. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(piridin-4-il)-1H-pirol-3-karboksamid.
14. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(5-cijano-1-metil-1H-pirol-3-il)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamid.
15. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je N-(5-cijano-1-metil-1H-pirol-3-il)-5-(5-fluoro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamid.
16. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(5-cijano-1,2-dimetil-1H-pirol-3-il)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamid.
17. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-2,3-dihidro-1H-pirolo[2,3-b]piridin-5-il)-1H-pirol-3-karboksamid.
18. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je N-(5-cijano-1,2-dimetil-1H-pirol-3-il)-5-(5-fluoro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamid.
19. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-[5-cijano-2-metil-1-(trideuteriometil)-1H-pirol-3-il]-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamid.
20. Postupak za pripravu spojeva formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da je kao početni materijal korišten spoj formule (II): pri čemu su Ra, Rb, Rc i Rd kako je definirano za formulu (I), koji spoj formule (II) je izložen Heckovoj reakciji u vodenom ili organskom mediju u nazočnosti paladijevog katalizatora, lužine, fosfina i spoja formule (III): gdje su skupine A1 i A2 kako je definirano za formulu (I) i Alk predstavlja ravni ili razgranani (C1-C6)alkil, kako bi se dobio spoj formule (IV): pri čemu su A1, A2, Ra, Rb, Rc i Rd definirani za formulu (I) i Alk je ranije gore definiran, funkcija aldehida kojim je spoj formule (IV) oksidiran u karboksilnu kiselinu kako bi se dobio spoj formule (V): pri čemu su A1, A2, Ra, Rb, Rc i Rd defininirani za formulu (I) i Alk je ranije gore definiran, koji se spoj formule (V) potom izlaže spajanju peptida sa spojem formule (VI): pri čemu su T i R5 definirani za formulu (I), kako bi se dobio spoj formule (VII): pri čemu su A1, A2, Ra, Rb, Rc i Rd, T i R5 definirano za formulu (I) i Alk je ranije gore definiran, esterska funkcija kojom je hidraliziran spoj formule (VII) kako bi se dobila odgovarajuća karboksilna kiselina ili karboksilat, koji se može pretvoriti u derivat kiseline poput primjerice u acil-klorida ili anhidrid prije spajanja s NHR3R4 aminom, gdje R3 i R4 imaju ista značenja kao za formulu (I), kako bi se dobio spoj formule (I), koji se spoj formule (I) može pročišćavati u skladu s uobičajenim tehnikama separacije, koji se može pretvoriti, ako je poželjno, u svoje adicijske soli s farmaceutski prihvatljivom kiselinom ili lužinom i koji je po izboru razdvojen u svoje izomere u skladu s uobičajenim tehnikama separacije, gdje se podrazumijeva, da se bilo koje vrijeme smatra prikladnim u smislu gore opisanog postupka, izvjesne skupine (hidroksi, amino...) reagensa ili intermedijera sinteze mogu biti zaštićene a potom im se skida zaštita u skladu sa zahtjevima sinteze.
21. Postupak u skladu s patentnim zahtjevom 20 za pripravu spoja formule (I) gdje je jedna od skupina R3 ili R4 supstituirana s hidroksi funkcijom, naznačen time, da je amin NHR3R4 prije toga izložen reakciji štiteći hidroksi funkciju prije bilo kakvog spajanja s karboksilnom kiselinom dobivenom od spoja formule (VII) ili s odgovarajućim derivatom kiseline, dobiveni zaštićeni spoj formule (I) naknadno se podvrgava reakciji skidanja zaštite a potom se po izboru pretvara u jednu od njegovih adicijskih soli s farmaceutski prihvatljivom kiselinom ili lužinom.
22. Farmaceutski pripravak koji sadrži spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 19 ili njegove adicijske soli s farmaceutski prihvatljivom kiselinom ili lužinom, naznačen time, da je u kombinaciji s jednim ili više farmaceutski prihvatljivih ekscipijensa.
23. Farmaceutski pripravak u skladu s patentnim zahtjevom 22, naznačen time, da je za uporabu kao pro-apoptotičko sredstvo.
24. Farmaceutski pripravak u skladu s patentnim zahtjevom 22, naznačen time, da je za uporabu u liječenju karcinoma, autoimunih bolesti i bolesti imunog sustava.
25. Farmaceutski pripravak u skladu s patentnim zahtjevom 22, naznačen time, da je za uporabu u liječenju raka mjehura, mozga, dojki i maternice, kronične limfoidne leukemije, raka debelog crijeva, raka jednjaka i jetre, leukemije limfoblasta, ne-Hodgkinovog limfoma, melanoma, maligne hemopatije, mijeloma, raka jajnika, raka pluća ne-malih stanica, raka prostate i raka pluća malih stanica.
26. Uporaba farmaceutskog pripravka u skladu s patentnim zahtjevom 22, naznačena time, da je za proizvodnju lijeka za uporabu kao apoptotičkog sredstva.
27. Uporaba farmaceutskog pripravka u skladu s patentnim zahtjevom 22, naznačena time, da je za proizvodnju lijeka za liječenje karcinoma, bolesti imunog sustava i auto-imunih bolesti.
28. Uporaba farmaceutskog pripravka u skladu s patentnim zahtjevom 22, naznačena time, da je za proizvodnju lijeka namijenjenog za liječenje raka mjehura, mozga, dojki i maternice, kronične limfoidne leukemije, raka debelog crijeva, raka jednjaka i jetre, leukemije limfoblasta, ne-Hodgkinovog limfoma, melanoma, maligne hemopatije, mijeloma, raka jajnika, raka pluća ne-malih stanica, raka prostate i raka pluća malih stanica.
29. Spoj formule (I) u skladu s jednim od patentnih zahtjeva 1 do 19, ili njegova adicijska sol s farmaceutksi prihvatljivom kiselinom ili lužinom, naznačen time, da se koristi u liječenju raka mjehura, mozga, dojki i maternice, kronične limfoidne leukemije, raka debelog crijeva, raka jednjaka i jetre, leukemije limfoblasta, ne-Hodgkinovog limfoma, melanoma, maligne hemopatije, mijeloma, raka jajnika, raka pluća ne-malih stanica, raka prostate i raka pluća malih stanica.
30. Uporaba spoja formule (I) u skladu s jednim od patentnih zahtjeva 1 do 19, ili njegova adicijska sol s farmaceutksi prihvatljivom kiselinom ili lužinom, naznačen time, da je za proizvodnju lijeka namijenjenog za liječenje raka mjehura, mozga, dojki i maternice, kronične limfoidne leukemije, raka debelog crijeva, raka jednjaka i jetre, leukemije limfoblasta, ne-Hodgkinovog limfoma, melanoma, maligne hemopatije, mijeloma, raka jajnika, raka pluća ne-malih stanica, raka prostate i raka pluća malih stanica.
31. Kombinacija spoja formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 19, naznačen time, da se kombinira s protutumorskim sredstvom koje je odabrano od genotoksičnih sredstava, mitotičkih otrova, antimetabolita, inhibitora proteazoma, inhibitora kinaze i protutijela.
32. Farmaceutski pripravak koji sadrži kombinaciju u skladu s patentnim zahtjevom 31, naznačen time, da se kombinira s jednim ili više farmaceutski prihvatljivih ekscipijensa.
33. Kombinacija u skladu s patentnim zahtjevom 31, naznačeno time, da je za uporabu u liječenju karcinoma.
34. Uporaba kombinacije u skladu s patentnim zahtjevom 31, naznačena time, da je za proizvodnju lijeka za uporabu u liječenju karcinoma.
35. Spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 19, naznačen time, da je za uporabu u kombinaciji s radioterapijom za liječenje karcinoma.
MEP-2017-63A 2013-07-23 2014-07-22 Novi derivati pirola, postupak njihove priprave i farmaceutski pripravci koji ih sadrže ME02635B (me)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR1357258A FR3008975A1 (fr) 2013-07-23 2013-07-23 Nouveaux derives de pyrrole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
EP14178016.3A EP2829539B1 (fr) 2013-07-23 2014-07-22 Nouveaux derives de pyrrole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

Publications (1)

Publication Number Publication Date
ME02635B true ME02635B (me) 2017-06-20

Family

ID=50023639

Family Applications (1)

Application Number Title Priority Date Filing Date
MEP-2017-63A ME02635B (me) 2013-07-23 2014-07-22 Novi derivati pirola, postupak njihove priprave i farmaceutski pripravci koji ih sadrže

Country Status (48)

Country Link
US (7) US9108983B2 (me)
EP (1) EP2829539B1 (me)
JP (1) JP5923560B2 (me)
KR (2) KR101712111B1 (me)
CN (3) CN104341395B (me)
AR (1) AR096979A1 (me)
AU (1) AU2014203521B2 (me)
BR (1) BR102014017950B1 (me)
CA (1) CA2856505C (me)
CL (1) CL2014001853A1 (me)
CR (1) CR20140307A (me)
CU (1) CU24315B1 (me)
CY (1) CY1118756T1 (me)
DK (1) DK2829539T3 (me)
DO (1) DOP2014000154A (me)
EA (1) EA026906B1 (me)
ES (1) ES2620515T3 (me)
FR (1) FR3008975A1 (me)
GE (1) GEP201706686B (me)
GT (1) GT201400144A (me)
HK (1) HK1203506A1 (me)
HR (1) HRP20170349T1 (me)
HU (1) HUE033361T2 (me)
IL (1) IL233343A (me)
JO (1) JO3275B1 (me)
LT (1) LT2829539T (me)
MA (1) MA37206B1 (me)
MD (1) MD4575C1 (me)
ME (1) ME02635B (me)
MX (1) MX348370B (me)
MY (1) MY173259A (me)
NI (1) NI201400079A (me)
PE (2) PE20150399A1 (me)
PH (1) PH12014000179B1 (me)
PL (1) PL2829539T3 (me)
PT (1) PT2829539T (me)
RS (1) RS55838B1 (me)
RU (1) RU2607788C2 (me)
SA (1) SA114350670B1 (me)
SG (1) SG10201403750UA (me)
SI (1) SI2829539T1 (me)
SV (1) SV2014004770A (me)
TN (1) TN2014000278A1 (me)
TW (1) TWI549948B (me)
UA (1) UA115773C2 (me)
UY (1) UY35639A (me)
WO (1) WO2015011400A1 (me)
ZA (1) ZA201405323B (me)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR3008975A1 (fr) * 2013-07-23 2015-01-30 Servier Lab Nouveaux derives de pyrrole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
BR112019001024A2 (pt) * 2016-07-22 2019-05-14 Les Laboratoires Servier combinação de um inibidor de bcl-2 e um inibidor de mcl-1, seus usos e composições farmacêuticas
WO2018015526A1 (en) 2016-07-22 2018-01-25 Les Laboratoires Servier Combination of a bcl-2 inhibitor and a mcl-1 inhibitor, uses and pharmaceutical compositions thereof
WO2018158225A1 (en) 2017-02-28 2018-09-07 Les Laboratoires Servier Combination of a bcl-2 inhibitor and a mdm2 inhibitor, uses and pharmaceutical compositions thereof
FR3072679B1 (fr) * 2017-10-25 2020-10-30 Servier Lab Nouveaux derives macrocycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
US12448374B2 (en) 2018-06-07 2025-10-21 Disarm Therapeutics, Inc. Inhibitors of SARM1
CA3117559C (en) * 2018-10-31 2023-09-26 Les Laboratoires Servier Hydrogen sulfate salt of a bcl-2 inhibitor, related crystalline form,method for preparing the same and pharmaceutical compositions containing the same
UY38431A (es) * 2018-10-31 2020-05-29 Servier Lab Formulación basada en ciclodextrina de un inhibidor de bcl-2
PL3891156T3 (pl) * 2018-12-06 2024-05-13 Les Laboratoires Servier Nowe krystaliczne formy inhibitora MCL-1, sposób ich wytwarzania oraz zawierające je kompozycje farmaceutyczne
CN113164508B (zh) 2018-12-19 2025-07-08 达萨玛治疗公司 与神经保护剂组合的sarm1抑制剂
AU2019416623B2 (en) 2018-12-27 2022-12-08 Holosmedic Novel compound and pharmaceutical composition comprising same for enhancing anticancer activity
WO2020139044A1 (ko) * 2018-12-27 2020-07-02 홀로스메딕 주식회사 신규한 화합물 및 이를 포함하는 항암 활성 증진용 약학 조성물
CA3139009C (en) * 2019-05-14 2024-06-11 Les Laboratoires Servier Bcl-2 inhibitors for use in the treatment of a bcl-2 mediated cancer carrying the gly101val mutation
CA3138058A1 (en) 2019-05-20 2020-11-26 Matthew T. Burger Mcl-1 inhibitor antibody-drug conjugates and methods of use
CA3190276A1 (en) 2020-07-31 2022-02-03 Les Laboratoires Servier Combination of a bcl-2 inhibitor and a hypomethylating agent for treating cancers, uses and pharmaceutical compositions thereof
WO2022090443A1 (en) 2020-10-30 2022-05-05 Les Laboratoires Servier Administration and dose regimen for a combination of a bcl-2 inhibitor and a mcl1 inhibitor
WO2022115451A1 (en) 2020-11-24 2022-06-02 Novartis Ag Mcl-1 inhibitor antibody-drug conjugates and methods of use
KR20230170644A (ko) 2021-02-02 2023-12-19 르 라보레또레 쎄르비에르 선택적 bcl-xl protac 화합물 및 사용 방법
CN113129644B (zh) * 2021-03-05 2022-03-08 中国人民解放军国防科技大学 基于球面扫描线的船舶三维特征航线提取方法
EP4313964A1 (en) 2021-03-24 2024-02-07 Les Laboratoires Servier New process for the synthesis of 5-{5-chloro-2-[(3s)-3- [(morpholin-4-yl)methyl]-3,4-dihydroisoquinoline-2(1h )-carbonyl]phenyl}-1,2-dimethyl-1h-pyrrole-3-carboxylic acid derivatives and its application for the production of pharmaceutical compounds
AU2022264993A1 (en) * 2021-04-26 2023-11-09 Sunshine Lake Pharma Co., Ltd. Preparation method for pyrrole amide compound
CA3240077A1 (en) * 2021-12-29 2023-07-06 Volodymyr KYSIL Bcl-2 inhibitors
CN114736156B (zh) * 2022-05-18 2024-03-19 中捷四方生物科技股份有限公司 一种白叶藤碱简化衍生物的制备方法及用途
EP4525926A1 (en) 2022-05-20 2025-03-26 Novartis AG Met bcl-xl inhibitor antibody-drug conjugates and methods of use thereof
PE20251072A1 (es) 2022-05-20 2025-04-10 Novartis Ag Conjugados de anticuerpo-farmaco de compuestos antineoplasicos y metodos de uso de los mismos
JP2025517430A (ja) 2022-05-20 2025-06-05 ノバルティス アーゲー Ｅｐｈａ２ ｂｃｌ－ｘｌ阻害剤抗体－薬物コンジュゲートおよびその使用の方法
CN115960121B (zh) * 2022-10-27 2025-09-12 南通药明康德医药科技有限公司 一种合成1-(3-氧杂丁环烷基)-1h-吡唑-4-硼酸频哪醇酯的方法
CN120752058A (zh) 2023-03-10 2025-10-03 诺华股份有限公司 panRAS抑制剂抗体-药物缀合物及其使用方法
PY24103486A (es) 2023-11-22 2025-06-06 Servier Lab Conjugados de anticuerpo anti-cd74-fármaco y métodos de uso de los mismos
TW202540186A (zh) * 2023-11-22 2025-10-16 瑞士商諾華公司 抗ｃｄ７抗體藥物結合物及其使用方法
TW202539634A (zh) 2024-04-10 2025-10-16 瑞士商諾華公司 Ｐａｎｒａｓ抑制劑及其使用方法

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2212092A1 (en) 1995-12-01 1997-06-12 Makoto Shibata Pyrroloazepine derivatives
US7122544B2 (en) 2000-12-06 2006-10-17 Signal Pharmaceuticals, Llc Anilinopyrimidine derivatives as IKK inhibitors and compositions and methods related thereto
US8557812B2 (en) 2004-08-20 2013-10-15 The Regents Of The University Of Michigan Small molecule inhibitors of anti-apoptotic BCL-2 family members and the uses thereof
US7511056B2 (en) 2004-11-10 2009-03-31 Eli Lilly And Company TGF-β inhibitors
RU2007128987A (ru) * 2005-02-15 2009-03-27 Ново Нордиск А/С (DK) 3,4-дигидро-1н-изохинолин-2-карбоновой кислоты 5-аминопиридин-2-2-иловые эфиры
JP2008531671A (ja) * 2005-03-04 2008-08-14 アストラゼネカ アクチボラグ 化合物
US7706888B2 (en) 2006-07-14 2010-04-27 Med-El Elektromedizinische Geraete Gmbh Bi-planar electrode with shunting gates
SE531110C2 (sv) 2006-07-14 2008-12-23 Vaelinge Innovation Ab Låssystem omfattande ett kombinationslås för paneler
EP2044083A1 (en) 2006-07-14 2009-04-08 Genelabs Technologies, Inc. Antiviral agents
WO2009073545A2 (en) 2007-11-30 2009-06-11 Maxthera, Inc. Tetrahydro-isoquinoline ppat inhibitors as antibacterial agents
NZ593537A (en) 2008-12-19 2013-07-26 Genentech Inc Isoquinoline derivatives and methods of use
US8557612B2 (en) 2009-06-26 2013-10-15 California Institute Of Technology Method for fabricating micro and nanostructures in a material
JP2014521595A (ja) * 2011-05-25 2014-08-28 ブリストル−マイヤーズ スクイブ カンパニー 抗アポトーシスＢｃｌ阻害剤として有用な置換スルホンアミド
CN104136429A (zh) * 2011-12-23 2014-11-05 诺华股份有限公司 用于抑制bcl2与结合配偶体相互作用的化合物
CN104125953A (zh) 2011-12-23 2014-10-29 诺华股份有限公司 用于抑制bcl2与结合配偶体相互作用的化合物
FR2986002B1 (fr) * 2012-01-24 2014-02-21 Servier Lab Nouveaux derives d'indolizine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
FR3008975A1 (fr) * 2013-07-23 2015-01-30 Servier Lab Nouveaux derives de pyrrole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

Also Published As

Publication number Publication date
BR102014017950A2 (pt) 2015-11-17
MD20140072A2 (ro) 2015-01-31
KR20170001695A (ko) 2017-01-04
RU2014130125A (ru) 2016-02-20
US10265323B2 (en) 2019-04-23
UY35639A (es) 2015-02-27
TWI549948B (zh) 2016-09-21
AR096979A1 (es) 2016-02-10
BR102014017950B1 (pt) 2020-05-19
US11058689B2 (en) 2021-07-13
MY173259A (en) 2020-01-09
PL2829539T3 (pl) 2017-08-31
WO2015011400A1 (fr) 2015-01-29
KR20150011786A (ko) 2015-02-02
PH12014000179A1 (en) 2016-01-18
UA115773C2 (uk) 2017-12-26
HUE033361T2 (hu) 2017-11-28
US20240245699A1 (en) 2024-07-25
RU2607788C2 (ru) 2017-01-10
HK1203506A1 (en) 2015-10-30
US20200261464A1 (en) 2020-08-20
PE20190653A1 (es) 2019-05-08
SG10201403750UA (en) 2015-02-27
CA2856505C (fr) 2017-06-27
AU2014203521A1 (en) 2015-02-12
EA201400753A1 (ru) 2015-03-31
MX348370B (es) 2017-06-08
ES2620515T3 (es) 2017-06-28
US10688101B2 (en) 2020-06-23
US20150313907A1 (en) 2015-11-05
CR20140307A (es) 2014-11-17
GEP201706686B (en) 2017-06-26
EP2829539A1 (fr) 2015-01-28
US9598427B2 (en) 2017-03-21
HK1201529A1 (en) 2015-09-04
US20190192528A1 (en) 2019-06-27
RS55838B1 (sr) 2017-08-31
DOP2014000154A (es) 2014-10-15
JO3275B1 (ar) 2018-09-16
CN106674201A (zh) 2017-05-17
EA026906B1 (ru) 2017-05-31
SA114350670B1 (ar) 2016-02-09
CN104341395A (zh) 2015-02-11
GT201400144A (es) 2015-11-24
CY1118756T1 (el) 2017-07-12
MD4575C1 (ro) 2019-01-31
NZ626623A (en) 2016-01-29
KR101712111B1 (ko) 2017-03-03
MX2014008867A (es) 2015-05-28
CN104341395B (zh) 2017-07-04
PT2829539T (pt) 2017-01-27
LT2829539T (lt) 2017-02-27
CL2014001853A1 (es) 2015-06-26
CU24315B1 (es) 2018-02-08
HRP20170349T1 (hr) 2017-04-21
AU2014203521B2 (en) 2018-09-27
CN106674196A (zh) 2017-05-17
SI2829539T1 (sl) 2017-04-26
FR3008975A1 (fr) 2015-01-30
US20150031673A1 (en) 2015-01-29
TW201512186A (zh) 2015-04-01
JP2015028018A (ja) 2015-02-12
JP5923560B2 (ja) 2016-05-24
EP2829539B1 (fr) 2016-12-21
US9108983B2 (en) 2015-08-18
PE20150399A1 (es) 2015-04-11
US20210290631A1 (en) 2021-09-23
NI201400079A (es) 2014-10-24
DK2829539T3 (en) 2017-04-03
ZA201405323B (en) 2015-09-30
IL233343A (en) 2017-06-29
US20170202851A1 (en) 2017-07-20
MA37206B1 (fr) 2018-09-28
SV2014004770A (es) 2015-01-28
TN2014000278A1 (fr) 2015-09-30
CU20140081A7 (es) 2016-02-29
MD4575B1 (ro) 2018-06-30
PH12014000179B1 (en) 2016-01-18
CA2856505A1 (fr) 2015-01-23

Similar Documents

Publication Publication Date Title
HRP20170349T1 (hr) Novi derivati pirola, postupak njihove priprave i farmaceutski pripravci koji ih sadrže
US11485745B2 (en) Amido spirocyclic amide and sulfonamide derivatives
AU2018385664B2 (en) Substituted bicyclic heterocyclic compounds as PRMT5 inhibitors
ES2840454T3 (es) Intermedio sintético útil en la preparación de inhibidores de c-Met triazolopiridínicos
AU2013213474B2 (en) New indolizine derivatives, method for preparing same and pharmaceutical compositions containing same
TW202321242A (zh) 雜環化合物及使用方法
HRP20171752T1 (hr) Novi derivati indolizina, postupak za njihovu pripravu i farmaceutski pripravci koji ih sadrže
ME02641B (me) Novi derivati fosfata, postupak njihove priprave i farmaceutski pripravci kojiih sadrže
CA2932175C (en) 3,5-(un)substituted-1h-pyrrolo[2,3-b]pyridine, 1h-pyrazolo[3,4-b]pyridine and 5h-pyrrolo[2,3-b]pyrazine dual itk and jak3 kinase inhibitors
HRP20200107T1 (hr) Novi derivati hidroksiestera, postupak za njihovu pripravu i farmaceutski pripravci koji ih sadrže
CA3198809A1 (en) Heterocyclic spiro compounds and methods of use
EP2324024B1 (en) Diazacarbazoles and methods of use
JP2015508785A (ja) ピリジニル及びピリミジニルスルホキシド及びスルホン誘導体
AU2011311867A1 (en) Furo(3,2-d)pyrimidine compounds
ME02202B (me) Jedinjenja pirolopirimidina kao inhibitori cdk4/6
WO2013130943A1 (en) Alkyl-and di-substituted amido-benzyl sulfonamide derivatives
KR20160086930A (ko) 피롤로피롤론 유도체 및 bet 억제제로서의 그의 용도
JP2015508784A (ja) アミド−ベンジルスルホン及びスルホキシド誘導体
KR20180070696A (ko) Mnk1 및 mnk2를 억제하는 피롤로-, 피라졸로-, 이미다조-피리미딘 및 피리딘 화합물
KR20140103972A (ko) 세린/트레오닌 키나아제 억제제로서의 2,4-다이아민-피리미딘 유도체
JP2023542789A (ja) ピラゾール化合物並びにその調製方法及び使用
JP7860103B2 (ja) 複素環式スピロ化合物及びその使用方法
EP4347594A1 (en) 2, 8-diazaspiro [4.5] decane compounds
CN120936610A (zh) 可用于治疗神经障碍和精神障碍的作为毒蕈碱型乙酰胆碱受体m4正向别构调节剂的1,6-萘啶衍生物
EA041973B1 (ru) Замещенные бициклические гетероциклические соединения в качестве ингибиторов prmt5