NZ532755A - N-adamantylmethyl derivates and intermediates as pharmaceutical compositions and processes for their preparation - Google Patents
N-adamantylmethyl derivates and intermediates as pharmaceutical compositions and processes for their preparationInfo
- Publication number
- NZ532755A NZ532755A NZ532755A NZ53275502A NZ532755A NZ 532755 A NZ532755 A NZ 532755A NZ 532755 A NZ532755 A NZ 532755A NZ 53275502 A NZ53275502 A NZ 53275502A NZ 532755 A NZ532755 A NZ 532755A
- Authority
- NZ
- New Zealand
- Prior art keywords
- formula
- compound
- adamantylmethyl
- amino
- chloro
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 64
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 239000000543 intermediate Substances 0.000 title abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 264
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 82
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 75
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 71
- 125000000217 alkyl group Chemical group 0.000 claims description 65
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 49
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 47
- VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 claims description 45
- 229910052736 halogen Inorganic materials 0.000 claims description 40
- 150000002367 halogens Chemical class 0.000 claims description 38
- 238000006243 chemical reaction Methods 0.000 claims description 36
- -1 nitro, amino, hydroxyl Chemical group 0.000 claims description 33
- 125000001424 substituent group Chemical group 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 28
- 239000012453 solvate Substances 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 125000005843 halogen group Chemical group 0.000 claims description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
- 239000001301 oxygen Substances 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 17
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 16
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 14
- 239000000725 suspension Substances 0.000 claims description 14
- 238000006268 reductive amination reaction Methods 0.000 claims description 13
- 102100037602 P2X purinoceptor 7 Human genes 0.000 claims description 12
- 101710189965 P2X purinoceptor 7 Proteins 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 10
- 239000002585 base Substances 0.000 claims description 10
- 238000005984 hydrogenation reaction Methods 0.000 claims description 10
- 238000007254 oxidation reaction Methods 0.000 claims description 9
- UDHZYEWSTDYKCZ-UHFFFAOYSA-N pyridine-4-carboxamide;hydrochloride Chemical compound Cl.NC(=O)C1=CC=NC=C1 UDHZYEWSTDYKCZ-UHFFFAOYSA-N 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
- 239000005864 Sulphur Chemical group 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000001821 azanediyl group Chemical group [H]N(*)* 0.000 claims description 4
- 238000010511 deprotection reaction Methods 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
- 208000027771 Obstructive airways disease Diseases 0.000 claims description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 3
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 claims description 3
- 229960005542 ethidium bromide Drugs 0.000 claims description 3
- 230000002140 halogenating effect Effects 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 239000000556 agonist Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- LMACPPZMORVSQL-UHFFFAOYSA-N n-(1-adamantylmethyl)-5-chloro-2-[3-(3-hydroxypropylamino)propyl]pyridine-4-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1=NC(CCCNCCCO)=CC(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1Cl LMACPPZMORVSQL-UHFFFAOYSA-N 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- 239000002464 receptor antagonist Substances 0.000 claims description 2
- 229940044551 receptor antagonist Drugs 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 2
- 239000005557 antagonist Substances 0.000 claims 2
- 239000007853 buffer solution Substances 0.000 claims 2
- 229910052700 potassium Inorganic materials 0.000 claims 2
- 239000011591 potassium Substances 0.000 claims 2
- 230000005284 excitation Effects 0.000 claims 1
- BREUFVGNRUSMOR-UHFFFAOYSA-N n-(1-adamantylmethyl)-5-chloro-2-[3-(1,3-dihydroxypropan-2-ylamino)propyl]pyridine-4-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1=NC(CCCNC(CO)CO)=CC(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1Cl BREUFVGNRUSMOR-UHFFFAOYSA-N 0.000 claims 1
- CGGJIIQCOPNPSH-UHFFFAOYSA-N n-(1-adamantylmethyl)-5-chloro-2-[3-(2-hydroxyethylamino)propyl]pyridine-4-carboxamide;hydrochloride Chemical compound Cl.C1=NC(CCCNCCO)=CC(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1Cl CGGJIIQCOPNPSH-UHFFFAOYSA-N 0.000 claims 1
- SDLBWYUTUVJYOH-UHFFFAOYSA-N n-(1-adamantylmethyl)-5-chloro-2-[3-[2-(2-hydroxyethylamino)ethylamino]propyl]pyridine-4-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1=NC(CCCNCCNCCO)=CC(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1Cl SDLBWYUTUVJYOH-UHFFFAOYSA-N 0.000 claims 1
- QZPNZYXPHFHKFX-LRYXAPPNSA-N n-(1-adamantylmethyl)-5-chloro-2-[3-[[(2r)-2-hydroxypropyl]amino]propyl]pyridine-4-carboxamide Chemical compound C1=NC(CCCNC[C@H](O)C)=CC(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1Cl QZPNZYXPHFHKFX-LRYXAPPNSA-N 0.000 claims 1
- HHLKXTRSDRQIDD-UHFFFAOYSA-N n-(1-adamantylmethyl)-5-chloro-2-[[2-(methylamino)ethylamino]methyl]pyridine-4-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1=NC(CNCCNC)=CC(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1Cl HHLKXTRSDRQIDD-UHFFFAOYSA-N 0.000 claims 1
- 239000004033 plastic Substances 0.000 claims 1
- 229920003023 plastic Polymers 0.000 claims 1
- 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 claims 1
- 239000011589 pyridoxal 5'-phosphate Substances 0.000 claims 1
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 claims 1
- 229960001327 pyridoxal phosphate Drugs 0.000 claims 1
- 239000000018 receptor agonist Substances 0.000 claims 1
- 229940044601 receptor agonist Drugs 0.000 claims 1
- 239000012085 test solution Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 207
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 179
- 239000000243 solution Substances 0.000 description 135
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- 239000000203 mixture Substances 0.000 description 63
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 39
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 38
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 38
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
- 238000004587 chromatography analysis Methods 0.000 description 35
- 239000000741 silica gel Substances 0.000 description 34
- 229910002027 silica gel Inorganic materials 0.000 description 34
- 239000007787 solid Substances 0.000 description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 32
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 32
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 30
- 101150041968 CDC13 gene Proteins 0.000 description 27
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 27
- 239000000284 extract Substances 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- 239000000463 material Substances 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000000843 powder Substances 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- 229910052757 nitrogen Inorganic materials 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 14
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 238000004007 reversed phase HPLC Methods 0.000 description 11
- 239000012312 sodium hydride Substances 0.000 description 11
- 229910052801 chlorine Inorganic materials 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 9
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 8
- 229910052731 fluorine Inorganic materials 0.000 description 8
- 239000011737 fluorine Substances 0.000 description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 6
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 239000011630 iodine Substances 0.000 description 6
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 6
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 5
- 239000006286 aqueous extract Substances 0.000 description 5
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 5
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 239000000908 ammonium hydroxide Substances 0.000 description 4
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 4
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 4
- 229910000160 potassium phosphate Inorganic materials 0.000 description 4
- 235000011009 potassium phosphates Nutrition 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
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- OAIXBIYKCGTYOA-UHFFFAOYSA-N n-(1-adamantylmethyl)-5-chloro-2-[3-[(3-hydroxy-2,2-dimethylpropyl)amino]propyl]pyridine-4-carboxamide Chemical compound C1=NC(CCCNCC(C)(CO)C)=CC(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1Cl OAIXBIYKCGTYOA-UHFFFAOYSA-N 0.000 description 1
- SPSNTVLBCXIIQD-UHFFFAOYSA-N n-(1-adamantylmethyl)-5-chloro-2-[3-[(3-hydroxy-2,2-dimethylpropyl)amino]propyl]pyridine-4-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1=NC(CCCNCC(C)(CO)C)=CC(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1Cl SPSNTVLBCXIIQD-UHFFFAOYSA-N 0.000 description 1
- ISXVFSNOJOISRT-SCUMNGBJSA-N n-(1-adamantylmethyl)-5-chloro-2-[3-[[(2s)-1-hydroxypropan-2-yl]amino]propyl]pyridine-4-carboxamide Chemical compound C1=NC(CCCN[C@H](CO)C)=CC(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1Cl ISXVFSNOJOISRT-SCUMNGBJSA-N 0.000 description 1
- QZPNZYXPHFHKFX-SCUMNGBJSA-N n-(1-adamantylmethyl)-5-chloro-2-[3-[[(2s)-2-hydroxypropyl]amino]propyl]pyridine-4-carboxamide Chemical compound C1=NC(CCCNC[C@@H](O)C)=CC(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1Cl QZPNZYXPHFHKFX-SCUMNGBJSA-N 0.000 description 1
- YNTOKMNHRPSGFU-UHFFFAOYSA-N n-Propyl carbamate Chemical compound CCCOC(N)=O YNTOKMNHRPSGFU-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000004634 pharmacological analysis method Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 102220060025 rs141586345 Human genes 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 201000005679 sclerosing keratitis Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- GSJJCZSHYJNRPN-UHFFFAOYSA-N tert-butyl n-(2-sulfanylethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCS GSJJCZSHYJNRPN-UHFFFAOYSA-N 0.000 description 1
- PNQYAMWGTGWJDW-UHFFFAOYSA-N tert-butyl n-(3-aminopropyl)-n-methylcarbamate Chemical compound NCCCN(C)C(=O)OC(C)(C)C PNQYAMWGTGWJDW-UHFFFAOYSA-N 0.000 description 1
- DBOWXZAOBJXBEV-UHFFFAOYSA-N tert-butyl n-[3-[[4-(1-adamantylmethylcarbamoyl)-3-chloropyridin-2-yl]amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC=CC(C(=O)NCC23CC4CC(CC(C4)C2)C3)=C1Cl DBOWXZAOBJXBEV-UHFFFAOYSA-N 0.000 description 1
- QUFBSMRRKUFHOO-UHFFFAOYSA-N tert-butyl n-ethyl-n-prop-2-enylcarbamate Chemical compound C=CCN(CC)C(=O)OC(C)(C)C QUFBSMRRKUFHOO-UHFFFAOYSA-N 0.000 description 1
- SCCPQPQIOJNZIE-UHFFFAOYSA-N tert-butyl n-methyl-n-prop-2-enylcarbamate Chemical compound C=CCN(C)C(=O)OC(C)(C)C SCCPQPQIOJNZIE-UHFFFAOYSA-N 0.000 description 1
- DSPYCWLYGXGJNJ-UHFFFAOYSA-N tert-butyl n-prop-2-ynylcarbamate Chemical compound CC(C)(C)OC(=O)NCC#C DSPYCWLYGXGJNJ-UHFFFAOYSA-N 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
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Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Dermatology (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Hospice & Palliative Care (AREA)
- Hematology (AREA)
- Psychiatry (AREA)
- Emergency Medicine (AREA)
- Otolaryngology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0103836A SE0103836D0 (sv) | 2001-11-16 | 2001-11-16 | Novel compounds |
| PCT/SE2002/002057 WO2003041707A1 (en) | 2001-11-16 | 2002-11-12 | N-adamantylmethyl derivates and intermediates as pharmaceutical compositions and processes for their preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ532755A true NZ532755A (en) | 2005-11-25 |
Family
ID=20286020
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ532755A NZ532755A (en) | 2001-11-16 | 2002-11-12 | N-adamantylmethyl derivates and intermediates as pharmaceutical compositions and processes for their preparation |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US7129246B2 (enExample) |
| EP (1) | EP1448195B1 (enExample) |
| JP (1) | JP4559077B2 (enExample) |
| KR (1) | KR20040058290A (enExample) |
| CN (1) | CN1585640B (enExample) |
| AR (1) | AR037534A1 (enExample) |
| AT (1) | ATE344034T1 (enExample) |
| AU (1) | AU2002347741B2 (enExample) |
| BR (1) | BR0214142A (enExample) |
| CA (1) | CA2464863A1 (enExample) |
| CO (1) | CO5580747A2 (enExample) |
| DE (1) | DE60215851T2 (enExample) |
| DK (1) | DK1448195T3 (enExample) |
| ES (1) | ES2274110T3 (enExample) |
| HU (1) | HUP0402560A3 (enExample) |
| IL (1) | IL161693A0 (enExample) |
| IS (1) | IS7261A (enExample) |
| MX (1) | MXPA04004498A (enExample) |
| MY (1) | MY136430A (enExample) |
| NO (1) | NO20042155L (enExample) |
| NZ (1) | NZ532755A (enExample) |
| PL (1) | PL370855A1 (enExample) |
| PT (1) | PT1448195E (enExample) |
| RU (1) | RU2300525C2 (enExample) |
| SE (1) | SE0103836D0 (enExample) |
| TW (1) | TW200407297A (enExample) |
| UA (1) | UA77978C2 (enExample) |
| WO (1) | WO2003041707A1 (enExample) |
| ZA (1) | ZA200403682B (enExample) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI258462B (en) * | 1999-12-17 | 2006-07-21 | Astrazeneca Ab | Adamantane derivative compounds, process for preparing the same and pharmaceutical composition comprising the same |
| GB0013737D0 (en) | 2000-06-07 | 2000-07-26 | Astrazeneca Ab | Novel compounds |
| SE0200920D0 (sv) * | 2002-03-25 | 2002-03-25 | Astrazeneca Ab | Novel compounds |
| SE0300480D0 (sv) * | 2003-02-21 | 2003-02-21 | Astrazeneca Ab | Novel compounds |
| WO2004105797A1 (en) * | 2003-05-29 | 2004-12-09 | Astrazeneca Ab | A pharmaceutical composition comprising a p2x7 antagonist and sulfasalazine |
| KR20060037258A (ko) * | 2003-05-29 | 2006-05-03 | 아스트라제네카 아베 | Ｐ2Ｘ7-수용체 길항제 및 종양 괴사 인자 α를 포함하는제약 조성물 |
| WO2004105796A1 (en) * | 2003-05-29 | 2004-12-09 | Astrazeneca Ab | A pharmaceutical composition containing a p2x7 receptor antagonist and methotrexate |
| GB0312609D0 (en) * | 2003-06-02 | 2003-07-09 | Astrazeneca Ab | Novel compounds |
| KR100554155B1 (ko) * | 2003-06-09 | 2006-02-22 | 학교법인 포항공과대학교 | 금속/반도체 나노막대 이종구조를 이용한 전극 구조물 및그 제조 방법 |
| SE0302139D0 (sv) * | 2003-07-28 | 2003-07-28 | Astrazeneca Ab | Novel compounds |
| SE0302192D0 (sv) * | 2003-08-08 | 2003-08-08 | Astrazeneca Ab | Novel compounds |
| SE0302488D0 (sv) * | 2003-09-18 | 2003-09-18 | Astrazeneca Ab | New combination |
| SA05260265A (ar) * | 2004-08-30 | 2005-12-03 | استرازينيكا ايه بي | مركبات جديدة |
| SE0402925D0 (sv) * | 2004-11-30 | 2004-11-30 | Astrazeneca Ab | Novel Compounds |
| KR20090094336A (ko) | 2006-11-27 | 2009-09-04 | 하. 룬트벡 아크티에 셀스카브 | 헤테로아릴 아미드 유도체 |
| ES2388454T3 (es) * | 2007-03-22 | 2012-10-15 | Astrazeneca Ab | Derivados de quinolina para el tratamiento de enfermedades inflamatorias |
| EP2155744A1 (en) | 2007-04-10 | 2010-02-24 | Lundbeck, H., A/S | Heteroaryl amide analogues as p2x7 antagonists |
| PE20091036A1 (es) | 2007-11-30 | 2009-08-15 | Astrazeneca Ab | Derivado de quinolina como antagonista del receptor p2x7 |
| NZ587799A (en) | 2008-03-25 | 2012-06-29 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| BRPI1014902A2 (pt) | 2009-04-14 | 2016-04-19 | Affectis Pharmaceuticals Ag | composto antagonista de p2x7r, sua composição e seus usos |
| MX2012013075A (es) | 2010-05-14 | 2012-12-17 | Affectis Pharmaceuticals Ag | Metodos novedosos para preparacion de antagonistas p2x7r. |
| WO2012110190A1 (en) | 2011-02-17 | 2012-08-23 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| WO2012163792A1 (en) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| WO2012163456A1 (en) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| RU2014106611A (ru) | 2011-07-22 | 2015-08-27 | Актелион Фармасьютиклз Лтд | Производные гетероциклических амидов в качестве антагонистов р2х7 рецептора |
| NZ628910A (en) | 2012-01-20 | 2016-02-26 | Actelion Pharmaceuticals Ltd | Heterocyclic amide derivatives as p2x7 receptor antagonists |
| KR101576235B1 (ko) | 2012-11-30 | 2015-12-11 | 한국생명공학연구원 | 신규한 이치환 아다만틸 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 함유하는 암 전이 억제용 약학적 조성물 |
| PL2931717T3 (pl) | 2012-12-12 | 2017-05-31 | Actelion Pharmaceuticals Ltd. | Pochodne indolokarboksyamidu jako antagoniści receptora p2x7 |
| AR094053A1 (es) | 2012-12-18 | 2015-07-08 | Actelion Pharmaceuticals Ltd | Derivados de indol carboxamida como antagonistas del receptor p2x₇ |
| EP2956457B1 (en) | 2013-01-22 | 2016-11-23 | Actelion Pharmaceuticals Ltd | Heterocyclic amide derivatives as p2x7 receptor antagonists |
| ES2616114T3 (es) | 2013-01-22 | 2017-06-09 | Actelion Pharmaceuticals Ltd. | Derivados de amida heterocíclica como antagonistas del receptor P2X7 |
| CN104163795B (zh) * | 2014-08-19 | 2016-02-03 | 四川大学 | 盐酸烟酰美金刚胺溶剂合物、其制备方法和用途 |
| CN104628615B (zh) * | 2015-02-12 | 2016-04-06 | 佛山市赛维斯医药科技有限公司 | 含卤代苯的n-金刚烷酰胺类化合物、其制备方法及其用途 |
| CN104628616B (zh) * | 2015-02-12 | 2016-06-01 | 佛山市赛维斯医药科技有限公司 | 含对硝基苯基的n-金刚烷酰胺类化合物、其制备方法及用途 |
| CN104628617B (zh) * | 2015-02-12 | 2016-04-06 | 佛山市赛维斯医药科技有限公司 | N-金刚烷酰胺类葡萄糖激酶活化剂、制备方法及其用途 |
| CN104693084B (zh) * | 2015-02-12 | 2016-03-16 | 佛山市赛维斯医药科技有限公司 | 含腈基苯基的n-金刚烷酰胺类化合物、其制备方法及用途 |
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| US3352912A (en) * | 1963-07-24 | 1967-11-14 | Du Pont | Adamantanes and tricyclo[4. 3. 1. 1 3.8] undecanes |
| US3471491A (en) * | 1967-08-28 | 1969-10-07 | Squibb & Sons Inc | Adamantyl-s-triazines |
| US3464998A (en) | 1968-03-04 | 1969-09-02 | Searle & Co | Adamantyl esters and amides of pyridinecarboxylic acids |
| GB1274652A (en) * | 1968-08-27 | 1972-05-17 | Lilly Industries Ltd | Adamantanyl-alkylamine derivatives and their preparation |
| US4027035A (en) * | 1968-08-27 | 1977-05-31 | Eli Lilly And Company | Therapeutic uses of adamantanealkylamine compounds |
| IL53441A0 (en) * | 1977-11-22 | 1978-01-31 | Teva Pharma | Methyladamantyl hydrazines their preparation and pharmaceutical compositions containing them |
| US4751292A (en) * | 1985-07-02 | 1988-06-14 | The Plant Cell Research Institute, Inc. | Adamantyl purines |
| AU5177390A (en) * | 1989-03-10 | 1990-10-09 | Idemitsu Kosan Company Limited | Pyridine derivatives and their salts, and insecticidal/acaricidal agent containing the same as active ingredient |
| AU682051B2 (en) | 1993-08-10 | 1997-09-18 | James Black Foundation Limited | Gastrin and CCK receptor ligands |
| US6034136A (en) * | 1997-03-20 | 2000-03-07 | Novartis Ag | Certain cyclic thio substituted acylaminoacid amide derivatives |
| FR2761358B1 (fr) * | 1997-03-27 | 1999-05-07 | Adir | Nouveaux composes de n-aryl piperidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| SE9704545D0 (sv) | 1997-12-05 | 1997-12-05 | Astra Pharma Prod | Novel compounds |
| SE9704544D0 (sv) | 1997-12-05 | 1997-12-05 | Astra Pharma Prod | Novel compounds |
| WO2000061569A1 (en) | 1999-04-09 | 2000-10-19 | Astrazeneca Ab | Adamantane derivatives |
| GB0013737D0 (en) | 2000-06-07 | 2000-07-26 | Astrazeneca Ab | Novel compounds |
| SE0200920D0 (sv) | 2002-03-25 | 2002-03-25 | Astrazeneca Ab | Novel compounds |
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