HRP20200819T1 - Spojevi indol karboksamida korisni kao inhibitori kinaze - Google Patents

Spojevi indol karboksamida korisni kao inhibitori kinaze Download PDF

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Publication number
HRP20200819T1
HRP20200819T1 HRP20200819TT HRP20200819T HRP20200819T1 HR P20200819 T1 HRP20200819 T1 HR P20200819T1 HR P20200819T T HRP20200819T T HR P20200819TT HR P20200819 T HRP20200819 T HR P20200819T HR P20200819 T1 HRP20200819 T1 HR P20200819T1
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Croatia
Prior art keywords
indole
carboxamide
fluoro
dimethyl
piperidin
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HRP20200819TT
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English (en)
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Saleem Ahmad
Joseph A. Tino
John E. Macor
Andrew J. Tebben
Hua Gong
Qingjie Liu
Douglas G Batt
Khehyong Ngu
Scott Hunter Watterson
Weiwei Guo
Myra Beaudoin Bertrand
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Bristol-Myers Squibb Company
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Publication of HRP20200819T1 publication Critical patent/HRP20200819T1/hr

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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
    • C07D401/10—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
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • 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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
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    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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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
    • C07D401/06—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 only aliphatic carbon atoms
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    • 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
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    • C07D403/10—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 carbon chain containing aromatic rings
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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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    • C07D417/04—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 directly linked by a ring-member-to-ring-member bond
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    • 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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  • Indole Compounds (AREA)

Claims (10)

1. Spoj Formule (I): [image] ili njegova sol ili solvat, gdje: X je CR4; A je: [image] ili [image] Q2 je -C(O)CH=CH2, -C(O)CH=CHCH2N(CH3)2, -C(O)C≡CR7, -C(O)C≡C(fenil), -C(O)C≡C(C1-3 hidroksialkil), -C(O)C≡CSi(CH3)3, ili -S(O)2CH=CH2; R1 je H, -CH3, -CF3, ili fenil supstituiran sa nula ili 1 R12; R2 je H, -CH3, ciklopropil, ili fenil supstituiran sa nula ili 1 R12, pod uvjetom da najmanje jedan od R1 i R2 je -CH3; R3 je F ili Cl; R4 je H ili F; R7, pri svakom pojavljivanju, je nezavisno H, C1-4 alkil, ili ciklopropil; i R12 je F, Cl, -CN, -CF3, ili C1-3 alkoksi.
2. Spoj prema patentnom zahtjevu 1 ili njegova sol ili solvat, gdje: R1 je CH3 i R2je CH3.
3. Spoj prema patentnom zahtjevu 1 ili njegova sol ili solvat, gdje: R3 je F.
4. Spoj prema patentnom zahtjevu 1 ili njegova sol ili solvat, gdje: R7 pri svakom pojavljivanju je H ili C1-2 alkil.
5. Spoj prema patentnom zahtjevu 1 koje ima strukturu: [image]
6. Spoj prema patentnom zahtjevu 1 ili njegova sol ili solvat, gdje navedeno spoj je odabran od: (S)-4-(3-akrilamidopiperidin-1-il)-5-fluoro-2,3-dimetil-1H-indol-7-karboksamid; (S)-4-(3-akrilamidopirolidin-1-il)-5-fluoro-2,3-dimetil-1H-indol-7-karboksamid; (S)-5-fluoro-2,3-dimetil-4-(3-(N-metilbut-2-inamido)piperidin-1-il)-1H-indol-7-karboksamid; (S)-5-fluoro-2,3-dimetil-4-(3-(pent-2-inamido) piperidin-1-il)-1H-indol-7-karboksamid; (S)-5-fluoro-2,3-dimetil-4-(3-(N-metilpent-2-inamido)piperidin-1-il)-1H-indol-7-karboksamid; (S)-5-fluoro-4-(3-(heks-2-inamido)piperidin-1-il)-2,3-dimetil-1H-indol-7-karboksamid; (S)-4-(3-(N-etilbut-2-inamido)piperidin-1-il)-5-fluoro-2,3-dimetil-1H-indol-7-karboksamid; (S)-4-(3-(but-2-inamido)pirolidin-1-il)-5-fluoro-2,3-dimetil-1H-indol-7-karboksamid; (S)-4-(3-(3-ciklopropilpropiolamido)piperidin-1-il)-5-fluoro-2,3-dimetil-1H-indol-7-karboksamid; (S)-5-fluoro-2,3-dimetil-4-(3-(vinilsulfonamido)piperidin-1-il)-1H-indol-7-karboksamid; (S)-4-(3-(N-ciklopropilbut-2-inamido)piperidin-1-il)-5-fluoro-2,3-dimetil-1H-indol-7-karboksamid; 4-(4-(but-2-inoil)piperazin-1-il)-5-fluoro-2,3-dimetil-1H-indol-7-karboksamid; 4-(4-akriloilepiperazin-1-il)-5-fluoro-2,3-dimetil-1H-indol-7-karboksamid; 4-(1-akriloil-1,2,5,6-tetrahidropiridin-3-il)-5-fluoro-2,3-dimetil-1H-indol-7-karboksamid; (RS)-4-(1-akriloilpiperidin-3-il)-5-fluoro-2,3-dimetil-1H-indol-7-karboksamid; 4-(1-akriloilpiperidin-3-il)-5-fluoro-2,3-dimetil-1H-indol-7-karboksamid, pojedinačni enantiomeri; (RS)-4-(1-(but-2-inoil)piperidin-3-il)-5-fluoro-2,3-dimetil-1H-indol-7-karboksamid; i (S)-4-(3-(but-2-inamido)piperidin-1-il)-5-fluoro-2,3-dimetil-1H-indol-7-karboksamid.
7. Farmaceutska kompozicija koja sadrži spoj prema bilo kojem od patentnih zahtjeva 1-6 ili njegovu farmaceutski-prihvatljivu sol ili solvat; i farmaceutski prihvatljiv nosač.
8. Spoj prema bilo kojem od patentnih zahtjeva 1-6 ili njegova farmaceutski-prihvatljiva sol ili solvat, za primjenu u terapiji.
9. Spoj prema bilo kojem od patentnih zahtjeva 1-6 ili njegova farmaceutski-prihvatljiva sol ili solvat, za primjenu u terapiji za liječenje autoimune bolesti ili kronične inflamatorne bolesti.
10. Spoj za primjenu prema patentnom zahtjevu 9 gdje navedena autoimuna bolest ili kronična inflamatorna bolest je odabrana od sistemskog eritemskog lupusa (SLE), reumatoidnog artritisa, multiple skleroze (MS), i Sjögrenovog sindroma.
HRP20200819TT 2014-10-24 2020-05-20 Spojevi indol karboksamida korisni kao inhibitori kinaze HRP20200819T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462068225P 2014-10-24 2014-10-24
EP15790407.9A EP3209656B1 (en) 2014-10-24 2015-10-23 Indole carboxamides compounds useful as kinase inhibitors
PCT/US2015/057055 WO2016065226A1 (en) 2014-10-24 2015-10-23 Indole carboxamides compounds useful as kinase inhobitors

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HRP20200819T1 true HRP20200819T1 (hr) 2020-08-07

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HRP20201146TT HRP20201146T1 (hr) 2014-10-24 2020-07-22 Spojevi indol karboksamida korisni kao inhibitori kinaze

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