ME02215B - Agensi koji induciraju apoptozu za liječenje raka te imunih i autoimunih bolesti - Google Patents

Agensi koji induciraju apoptozu za liječenje raka te imunih i autoimunih bolesti

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Publication number
ME02215B
ME02215B MEP-2015-156A MEP15615A ME02215B ME 02215 B ME02215 B ME 02215B ME P15615 A MEP15615 A ME P15615A ME 02215 B ME02215 B ME 02215B
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Montenegro
Prior art keywords
pyridin
methyl
piperazin
pyrrolo
yloxy
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MEP-2015-156A
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English (en)
Inventor
Milan Bruncko
George Doherty
Laura Hexamer
Aaron R Kunzer
Xiaohong Song
Gerard Sullivan
Zhi-Fu Tao
Le Wang
Xilu Wang
Michael Wendt
Robert A Mantei
Andrew J Souers
Gary T Wang
Todd M Hansen
Hong Ding
Steven Elmore
Lisa Hasvold
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Abbvie Bahamas Ltd
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Application filed by Abbvie Bahamas Ltd filed Critical Abbvie Bahamas Ltd
Publication of ME02215B publication Critical patent/ME02215B/me

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    • 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
    • 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
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    • 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
    • A61K31/495—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
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • 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
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    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/80—[b, c]- or [b, d]-condensed
    • C07D209/82—Carbazoles; Hydrogenated carbazoles
    • C—CHEMISTRY; METALLURGY
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    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
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    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
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  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Oncology (AREA)
  • Transplantation (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Indole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Peptides Or Proteins (AREA)

Claims (4)

1. Spoj ili njegova farmaceutski prihvatljiva sol, naznačen time, da je spoj odabran iz skupine koju čine:metil trans-4-{[( 4-{[ 4-( 4-{[2 -( 4-klorofenil )-4,4-d i metilcikloheks-1-en-1-il] meti l}piperazin-1-il}-2 -(l Hpirolo[2,3-b]piridin-5-iloksi}benzoil]sulfamoil}-2-nitrofenil) amino]metil}cikloheksankarboksilat;trans-4-([(4-{[4-(4-{[2 -( 4-klorofeni1}-4,4-dimetilcikloheks-1-en-1-il] metil}piperazin-1-il)-2-(lH-pirolo[2,3-b] piridin-5-iloksi)benzoil] sulfamoi1-2-nitrofenil)amino] metil} cikloheksankarboksilna kiselina;N-(4-{[4-(4-{[2-(4-klorofenil )-4,4-dimetilcikloheks-1-en-1-il] metil}piperazin-l-il )-2 -(l H-pi rolo[2,3-b) piridin-5-iloksi)benzoil]sulfamoil}-2-nitrofenil)-4-cianopiperidin-1-karboksamid;4-(4-{[2-(4-klorfenil)-4,4-dimetilcikloheks-1-en-1-il) metil}piperazin-1-il)-N-{[4-({[ cis-4-(metoksimetil)cikloheksil]metil}amino)-3-nitrofenil]sulfonil}-2-(1H-pirolo[2,3-b]piridin-5-iloksi)benzamid;4-(4-{[2 -( 4-klorofeni1)-4,4-d imetilcikloheks-1-en-1-il] metil}piperazin-1-il)-N-{[ 4-( {[trans-4-(metoksimetil)cikloheksil]metil}amino)-3-nitrofenil]sulfonil}-2-(1H-pirolo[2,3-b]piridin-5-iloksi)benzamid;4-(4-{[2-(4-klorofeni1)-4,4-dimetilcikloheks-1-en-1-il] metil }piperazin-l-i1)-2-( l H-pirolo [2,3-b) piridin-5-iloksi )N-{[l-(tetrahidro-2H-piran-4-ilmetil)-1H-benzotriazol-5-il] sulfonil} benzamid;N-({5-kloro-6-[ (2-okso-1-oksa-3-azaspiro[4.5] dec-8-il)metoksi] piridin-3-il}sulfonil )-4-( 4-{[2-(4-klorofenil )-4 ,4-dimetilcikloheks-1-en-1-il] metil}piperazin-1-i1)-2-( l H-pirolo[2,3-b] piridin-5-iloksi) benzamid;N-(4-{[4-(4-{[2 -( 4-klorofenil )-4,4-dimetilcikloheks-1-en-1-il]metil)piperazin-l-il)-2 -(l H-pirolo[2,3-b) piridin-5-iloksi)benzoil]sulfamoil}-2-nitrofenil)-4-metoksipiperidin-1-karboksamid;N-({5-kloro-6-[ ( 2-metil-4,5, 6,7-tetrahidro-1,3-benzotiazol-5-il)metoksi] piridin-3-il } sulfonil )-4-( 4-{[2-( 4-klorofeni1)-4,4-dimetilcikloheks-1-en-l-il) metil}piperazi n-l-i1)-2 –( 1H-pi rolo[2,3-b] piridin-5-iloksi)benzamid;4-(4-{[2-(4-klorofenil)-4,4-dimetilcikloheks-1-en-1-il]metil}piperazin-l-il}-2-(1H-pirolo[2,3-b]piridin-5-iloksi)N-{[1-( tetrahidro-2 H-piran-4- ilmetil )-1H-pirolo[ 2,3-b] piridin-5-il]sulfonil}benzamid;4-( 4-{[2-( 4-klorofenil)-4 ,4-dimetilcikloheks-1-en-1-il) metil)piperazin-l-il )-N-{[3-kloro-1-(tetrahidro-2H-piran-4-ilmetil)-1H-pirolo[2,3-b] piridin-5-il]sulfoni1}-2 -(1H-pirolo[2,3-b]piridin-5-iloksi) benzamid;4-(4-{[2-( 4-klorofenil)-4-( metoksimetil )-4-metilcikloheks-1-en-1-il] metil}piperazin-1-il )-N-({3-nitro-4-[(tetrahidro-2H-piran-4-ilmetil)amino]fenil}sulfonil)-2-(1H-pirolo[2,3-b] piridin-5-iloksi)benzamid;N-[(4-{[4,4-bis(hidroksimetil)cikloheksil]metoksi}-3-nitrofenil)sulfonil]-4-(4-{[2-{4-klorofenil)-4,4-dimetilcikloheks-1-en-1-il) metil}piperazin-l-il)-2-( l H-pirolo[2,3-b] piridin-5-iloksi )benzamid;N-(2-kloro-4-{[4-(4-{[2-(4-klorofenil)-4 ,4-dimetilcikloheks-1-en-1-il] m etil}piperazin-l-il)-2 -(l H-pirolo[2,3-b] pi ridin-5-iloksi)benzoil]sulfamoil}fenil )-4-metoksipiperidin-l-karboksamid;N-(2-kloro-4-{[ 4-( 4-{[2-( 4-klorofenil)-4,4-dimetilcikloheks-1-en-1-il] metil)piperazin-1-il)-2-(lH-pirolo[ 2,3-b]piridin-5-iloksi)benzoil]sulfamoil}fenil)-4-cianopiperidin-1-karboksamid;N-{2-kloro-4-{[4-(4-{[2-( 4-klorofenil)-4 ,4-dimetilci kloheks-1-en-l-il] metil)piperazi n-1-il)-2-(H-pirolo[2,3-b ]piridin-5-iloksi )benzoil]sulfamoil}fenil)-4-hid roksi-4-metilpiperidin-1-karboksamid;N-(2-kloro-4-{[4-(4-{[2-(4-klorofenil)-4,4-dimetilcikloheks-l-en-l-il]metil}piperazin-l-il)-2-(1H-pirolo[2,3-b ] piridin-5-iloksi )benzoil] sulfamoil}fenil)-4-(metoksimetil)piperidin-l-karboksamid;N-[ (5-kloro-6-{[ (5r,8r)-2-okso-l-oksa-3-azaspiro[ 4.5] dec-8-il] metoksi}piridin-3-il ) sulfonil]-4-(4-{[2-(4-klorofeni1)-4,4-dimetilci kloheks-1-en-1-il] metil)piperazin-1-i1)-2 –( 1H-pi rolo[2,3-b] piridin-5-iloksi )benzamid;N-[(5-kloro-6-{[(5s,8s)-2-okso-1-oksa-3-azaspiro[4.5]dec-8-il]metoksi}piridin-3-il)sulfonil]-4-(4-{[2-(4-klorofeni1)-4,4-dimeti lcikloheks-1-en-l-il] metil}piperazin-1-i1)-2 -(lH-pi rolo [2,3-b] piridin-5-iloksi )benzamid;N-(2 -kloro-4-{[ 4-(4-{[2-( 4-klorofeni1}-4,4-dimetilcikloheks-1-en-1-il] metil}piperazin-l-il)-2-( lH-pirolo [2,3-b]piridin-5-iloksi)benzoil]sulfamoil}fenil)-4-(morpholin-4-il)piperidin-1-karboksamid;N-[(5-kloro-6-{[trans-4-hidroksi-4-(metoksimetil)cikloheksil]metoksi}piridin-3-il)sulfonil]-4-(4-{[2-(4-klorofeni1)-4,4-dimetilei kloheks-1-en-1-il] metil}piperazin-1-i1)-2-( l H-pirolo [2,3-b] piridin-5-iloksi) benzamid;N-[(5-kloro-6-{[cis-4-hidroksi-4-(hidroksimetil)cikloheksil]metoksi}piridin-3-il)sulfonil]-4-(4-{[2-(4-klorofenil)-4 ,4-dimetilcikloheks-l-en-l-il] metil}piperazin-1-il)-2-{lH-pirolo [2,3-b] piridin-5-iloksi) benzamid;N-[(5-kloro-6-{[trans-4-hidroksi-4-(hidroksimetil)cikloheksil]metoksi}piridin-3-il)sulfonil]-4-(4-{[2-(4-klorofenil)-4,4-dimetilcikloheks-l-en-l-il]metil)piperazin-l-il)-2-{1H-pirolo[2,3-b]piridin-5-iloksi)benzamid;N-[ (5-kloro-6-{[ 4-fluoro-1-( oksetan-3-il )piperidin-4-il] metoksi)piridin-3-il )sulfoni1]-4-(4-{[2 -(4-klorofenil)-5-metoksi-5-metilcikloheks-1-en-1-il] metil}piperazin-l-i1)-2-( l H-pirolo[2,3-b] piridin-5-i loksi) benzamid;4-( 4-{[ 2 -(4-klorofenil)cikloheks-1-en-1-il] metil )piperazin-1-il )-N-({3-nitro-4- [(tetrahidro-2H-piran-4-il-metil)amino]fenil}sulfonil)-2-( 1H-pirolo [2,3-b] piridin-5-iloksi) benzamid;4-(4-klorofenil )-1-meti1-3-[(4-{4-[({3-nitro-4-[ (tetrahidro-2 H-piran-4-ilmetil)amino]fenil} sulfonil)karbamoil]-3-(l H-pirolo[2,3-b]piridin-5-iloksi )fenil}piperazin-l-il )metil]cikloheks-3-en-l-karboksilna kiselinaiN-[(5-kloro-6-{[1-(oksetan-3-il)piperidin-4-il]metoksi}piridin-3-il)sulfonil]-4-(4-{[2-(4-klorofenil)-4,4-dimetilcikloheks-1-en-1-il] metil}piperazin-1-il)-2 -(l H-pirolo[2,3-b] piridin-5-iloksi )benzamid.Patent sadrži još 3 patentna zahtjeva.
2. <!--[endif]-->Farmaceutski pripravak,naznačen time, da sadržava inertni nosač i terapijski učinkovitu količinu spoja ili farmaceutski prihvatljive soli u skladu s patentnim zahtjevom I.
3. Pripravak za uporabu u postupku liječenja raka mokraćnog mjehura, raka mozga, raka dojke, raka koštane srži, raka grlića maternice, kronične limfocitne leukemije, raka debelog crijeva, raka jednjaka, hepatocelularnog raka, leukemije, folikula rnog limfoma, limfne malignosti T-stanica ili B-stanica, melanoma, mijelogene leukemije, mijeloma, oralnog karcinoma, karcinoma jajnika, raka ne-malih stanica pluća, raka prostate, raka malih stanica pluća ili raka slezene kod bolesnika, naznačen time, da sadržava terapijski učinkovitu količinu spoja ili farmaceutski prihvatljive soli u skladu s patentnim zahtjevom l.
4. Pripravak za uporabu u postupku liječenja raka mokraćnog mjehura, raka mozga, raka dojke, raka koštane srži, raka grlića maternice, kronične limfocitne leukemije, raka debelog crijeva, raka jednjaka, hepatocelularnog raka, leukemije, folikularnog limfoma, limfne malignosti T-stanica ili B-stanica, melanoma, mijelogene leukemije, mijeloma, oralnog karcinoma, karcinoma jajnika, raka ne-malih stanica pluća, raka prostate, raka malih stanica pluća ili raka slezene kod bolesnika, naznačen time, da sadržava terapijski učinkovitu količinu spoja ili farmaceutski prihvatljive soli u skladu s patentnim zahtjevom I i terapijski učinkovite količine jednog dodatnog terapijskog sredstva ili više dodatnih terapijskih sredstava.
MEP-2015-156A 2010-05-26 2010-11-22 Agensi koji induciraju apoptozu za liječenje raka te imunih i autoimunih bolesti ME02215B (me)

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Application Number Priority Date Filing Date Title
US12/787,682 US8546399B2 (en) 2009-05-26 2010-05-26 Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases
EP10784398.9A EP2576546B1 (en) 2010-05-26 2010-11-22 Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
PCT/US2010/057587 WO2011149492A1 (en) 2010-05-26 2010-11-22 Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases

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ME02215B true ME02215B (me) 2016-02-20

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