HRP20030074A2 - Tetrahydropyridino heterocyclic derivatives - Google Patents
Tetrahydropyridino heterocyclic derivatives Download PDFInfo
- Publication number
- HRP20030074A2 HRP20030074A2 HR20030074A HRP20030074A HRP20030074A2 HR P20030074 A2 HRP20030074 A2 HR P20030074A2 HR 20030074 A HR20030074 A HR 20030074A HR P20030074 A HRP20030074 A HR P20030074A HR P20030074 A2 HRP20030074 A2 HR P20030074A2
- Authority
- HR
- Croatia
- Prior art keywords
- group
- formula
- cycloalkyl
- compound
- represented
- Prior art date
Links
- 125000000623 heterocyclic group Chemical group 0.000 title claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 133
- -1 C1-5alkyl group Chemical group 0.000 claims description 44
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 39
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 21
- 125000006843 cycloalkyl-C1-5-alkyl Chemical group 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 239000002769 corticotropin releasing factor antagonist Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000002464 receptor antagonist Substances 0.000 claims description 2
- 229940044551 receptor antagonist Drugs 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 131
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 87
- 239000002904 solvent Substances 0.000 description 80
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 76
- 238000002425 crystallisation Methods 0.000 description 60
- 230000008025 crystallization Effects 0.000 description 60
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
- 239000000203 mixture Substances 0.000 description 46
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 238000002844 melting Methods 0.000 description 40
- 230000008018 melting Effects 0.000 description 40
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- 239000011541 reaction mixture Substances 0.000 description 37
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 34
- 239000012442 inert solvent Substances 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 30
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 29
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 28
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 28
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- 239000000706 filtrate Substances 0.000 description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 25
- 239000002274 desiccant Substances 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 239000012044 organic layer Substances 0.000 description 22
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 20
- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 description 19
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 239000003480 eluent Substances 0.000 description 19
- 239000000499 gel Substances 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- 238000010898 silica gel chromatography Methods 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 17
- 238000000034 method Methods 0.000 description 17
- 239000002244 precipitate Substances 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 15
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
- 229930195733 hydrocarbon Natural products 0.000 description 14
- 150000002430 hydrocarbons Chemical class 0.000 description 14
- 239000012312 sodium hydride Substances 0.000 description 14
- 229910000104 sodium hydride Inorganic materials 0.000 description 14
- 150000001408 amides Chemical class 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- MHNNAWXXUZQSNM-UHFFFAOYSA-N methylethylethylene Natural products CCC(C)=C MHNNAWXXUZQSNM-UHFFFAOYSA-N 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 229910000029 sodium carbonate Inorganic materials 0.000 description 10
- 235000017550 sodium carbonate Nutrition 0.000 description 10
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000012046 mixed solvent Substances 0.000 description 9
- 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 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 206010008118 cerebral infarction Diseases 0.000 description 8
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 8
- 150000002170 ethers Chemical class 0.000 description 8
- 150000007529 inorganic bases Chemical class 0.000 description 8
- 239000004533 oil dispersion Substances 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 235000011181 potassium carbonates Nutrition 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- GMUZQONFKJHOEY-UHFFFAOYSA-N 1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]-3,6-dihydro-2h-pyridine-4-carboxamide Chemical compound C=12C=CC=C(C=3C(=CC(Cl)=CC=3)Cl)C2=NC(C)=CC=1N1CCC(C(N)=O)=CC1 GMUZQONFKJHOEY-UHFFFAOYSA-N 0.000 description 7
- 235000019270 ammonium chloride Nutrition 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000002184 metal Substances 0.000 description 7
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 7
- 235000011121 sodium hydroxide Nutrition 0.000 description 7
- DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 6
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
- 239000004215 Carbon black (E152) Substances 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 150000007530 organic bases Chemical class 0.000 description 6
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 6
- 229910000105 potassium hydride Inorganic materials 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 5
- 208000019901 Anxiety disease Diseases 0.000 description 5
- 235000011054 acetic acid Nutrition 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000036506 anxiety Effects 0.000 description 5
- 238000009739 binding Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 230000026030 halogenation Effects 0.000 description 5
- 238000005658 halogenation reaction Methods 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- KPKNTUUIEVXMOH-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane Chemical compound O1CCOC11CCNCC1 KPKNTUUIEVXMOH-UHFFFAOYSA-N 0.000 description 4
- FSBYWVGIAAGAPR-UHFFFAOYSA-N 2-[1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]-3,6-dihydro-2h-pyridin-4-yl]acetamide Chemical compound C=12C=CC=C(C=3C(=CC(Cl)=CC=3)Cl)C2=NC(C)=CC=1N1CCC(CC(N)=O)=CC1 FSBYWVGIAAGAPR-UHFFFAOYSA-N 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- 201000006474 Brain Ischemia Diseases 0.000 description 4
- 206010048962 Brain oedema Diseases 0.000 description 4
- 206010008120 Cerebral ischaemia Diseases 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- 208000030814 Eating disease Diseases 0.000 description 4
- 208000019454 Feeding and Eating disease Diseases 0.000 description 4
- 206010019196 Head injury Diseases 0.000 description 4
- 208000023105 Huntington disease Diseases 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000009435 amidation Effects 0.000 description 4
- 238000007112 amidation reaction Methods 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 208000006752 brain edema Diseases 0.000 description 4
- 208000026106 cerebrovascular disease Diseases 0.000 description 4
- 235000014632 disordered eating Nutrition 0.000 description 4
- 206010013663 drug dependence Diseases 0.000 description 4
- 150000002148 esters Chemical group 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 208000018556 stomach disease Diseases 0.000 description 4
- 208000011117 substance-related disease Diseases 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- QNEGDGPAXKYZHZ-UHFFFAOYSA-N (2,4-dichlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1Cl QNEGDGPAXKYZHZ-UHFFFAOYSA-N 0.000 description 3
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 3
- DQNRQBLSVNPIDU-UHFFFAOYSA-N 1-[1-(2,4-dichlorophenyl)-2,3,6-trimethylpyrrolo[2,3-b]pyridin-4-yl]piperidin-4-one Chemical compound CC1=C(C)C2=C(N3CCC(=O)CC3)C=C(C)N=C2N1C1=CC=C(Cl)C=C1Cl DQNRQBLSVNPIDU-UHFFFAOYSA-N 0.000 description 3
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- GUTKHRAMYLGCLQ-UHFFFAOYSA-N 8-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]-1,4-dioxa-8-azaspiro[4.5]decane Chemical compound C=12C=CC=C(C=3C(=CC(Cl)=CC=3)Cl)C2=NC(C)=CC=1N(CC1)CCC21OCCO2 GUTKHRAMYLGCLQ-UHFFFAOYSA-N 0.000 description 3
- VZEQVJZHDYRCBZ-UHFFFAOYSA-N 8-bromo-2-methyl-1h-quinolin-4-one Chemical compound C1=CC(Br)=C2NC(C)=CC(=O)C2=C1 VZEQVJZHDYRCBZ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 201000004384 Alopecia Diseases 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 3
- BYWBCSRCPLBDFU-CYBMUJFWSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[(3R)-3-aminopyrrolidin-1-yl]methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1C[C@@H](CC1)N BYWBCSRCPLBDFU-CYBMUJFWSA-N 0.000 description 3
- 231100000360 alopecia Toxicity 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 3
- 229910001863 barium hydroxide Inorganic materials 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 206010015037 epilepsy Diseases 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 230000002140 halogenating effect Effects 0.000 description 3
- 150000003840 hydrochlorides Chemical class 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 229910001415 sodium ion Inorganic materials 0.000 description 3
- FFRKSBLPSJYACR-UHFFFAOYSA-N 1,2,3,6-tetrahydropyridine-4-carboxamide;hydrochloride Chemical compound Cl.NC(=O)C1=CCNCC1 FFRKSBLPSJYACR-UHFFFAOYSA-N 0.000 description 2
- WDPKWTPGSJECAF-UHFFFAOYSA-N 1,2,3,6-tetrahydropyridine-5-carboxamide;hydrochloride Chemical compound Cl.NC(=O)C1=CCCNC1 WDPKWTPGSJECAF-UHFFFAOYSA-N 0.000 description 2
- CKVPLOWRBKWBIT-UHFFFAOYSA-N 1-(8-bromo-2-methylquinolin-4-yl)-3,6-dihydro-2h-pyridine-4-carboxamide Chemical compound C=12C=CC=C(Br)C2=NC(C)=CC=1N1CCC(C(N)=O)=CC1 CKVPLOWRBKWBIT-UHFFFAOYSA-N 0.000 description 2
- FWLIMFJWOTZSIO-UHFFFAOYSA-N 1-[1-(2,4-dichlorophenyl)-2,3,6-trimethylpyrrolo[2,3-b]pyridin-4-yl]-3,6-dihydro-2h-pyridine-4-carboxamide Chemical compound CC1=C(C)C2=C(N3CC=C(CC3)C(N)=O)C=C(C)N=C2N1C1=CC=C(Cl)C=C1Cl FWLIMFJWOTZSIO-UHFFFAOYSA-N 0.000 description 2
- VYGNNNOINUILJD-UHFFFAOYSA-N 1-[1-(2,4-dichlorophenyl)-2,3,6-trimethylpyrrolo[2,3-b]pyridin-4-yl]-3,6-dihydro-2h-pyridine-5-carboxamide Chemical compound CC1=C(C)C2=C(N3CC(=CCC3)C(N)=O)C=C(C)N=C2N1C1=CC=C(Cl)C=C1Cl VYGNNNOINUILJD-UHFFFAOYSA-N 0.000 description 2
- UITPLODTICJELE-UHFFFAOYSA-N 1-[2-(2,4-dichloro-n-ethylanilino)-4-methyl-1,3-thiazol-5-yl]-3,6-dihydro-2h-pyridine-4-carboxamide Chemical compound C=1C=C(Cl)C=C(Cl)C=1N(CC)C(S1)=NC(C)=C1N1CCC(C(N)=O)=CC1 UITPLODTICJELE-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
- NJVAGXZNZUXJJW-UHFFFAOYSA-N 2-[1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]-3,6-dihydro-2h-pyridin-4-yl]acetic acid Chemical compound C=12C=CC=C(C=3C(=CC(Cl)=CC=3)Cl)C2=NC(C)=CC=1N1CCC(CC(O)=O)=CC1 NJVAGXZNZUXJJW-UHFFFAOYSA-N 0.000 description 2
- MACHHFHQODDOPO-UHFFFAOYSA-N 2-[1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]piperidin-4-ylidene]acetic acid Chemical compound C=12C=CC=C(C=3C(=CC(Cl)=CC=3)Cl)C2=NC(C)=CC=1N1CCC(=CC(O)=O)CC1 MACHHFHQODDOPO-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- UIQXKVALFBWZGJ-UHFFFAOYSA-N 5-bromo-n-(2,4-dichlorophenyl)-n-ethyl-4-methyl-1,3-thiazol-2-amine Chemical compound C=1C=C(Cl)C=C(Cl)C=1N(CC)C1=NC(C)=C(Br)S1 UIQXKVALFBWZGJ-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- VYPXHRUYISNLQD-UHFFFAOYSA-N 8-(2,4-dichlorophenyl)-2-methyl-1h-quinolin-4-one Chemical compound C12=NC(C)=CC(O)=C2C=CC=C1C1=CC=C(Cl)C=C1Cl VYPXHRUYISNLQD-UHFFFAOYSA-N 0.000 description 2
- JNYYWEHCAFYHJW-UHFFFAOYSA-N 8-(8-bromo-2-methylquinolin-4-yl)-1,4-dioxa-8-azaspiro[4.5]decane Chemical compound C=12C=CC=C(Br)C2=NC(C)=CC=1N(CC1)CCC21OCCO2 JNYYWEHCAFYHJW-UHFFFAOYSA-N 0.000 description 2
- VCONPVJCNLLRSR-UHFFFAOYSA-N 8-[1-(2,4-dichlorophenyl)-2,3,6-trimethylpyrrolo[2,3-b]pyridin-4-yl]-1,4-dioxa-8-azaspiro[4.5]decane Chemical compound CC1=C(C)C2=C(N3CCC4(CC3)OCCO4)C=C(C)N=C2N1C1=CC=C(Cl)C=C1Cl VCONPVJCNLLRSR-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- MOOAHMCRPCTRLV-UHFFFAOYSA-N boron sodium Chemical compound [B].[Na] MOOAHMCRPCTRLV-UHFFFAOYSA-N 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 2
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
- KIXYFTIDLCBXGC-UHFFFAOYSA-N ethyl 1-[1-(2,4-dichlorophenyl)-2,3,6-trimethylpyrrolo[2,3-b]pyridin-4-yl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=CCCN1C1=CC(C)=NC2=C1C(C)=C(C)N2C1=CC=C(Cl)C=C1Cl KIXYFTIDLCBXGC-UHFFFAOYSA-N 0.000 description 2
- KLDVZHNQKMGKOY-UHFFFAOYSA-N ethyl 1-[1-(2,4-dichlorophenyl)-2,3,6-trimethylpyrrolo[2,3-b]pyridin-4-yl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1C1=CC(C)=NC2=C1C(C)=C(C)N2C1=CC=C(Cl)C=C1Cl KLDVZHNQKMGKOY-UHFFFAOYSA-N 0.000 description 2
- 210000005153 frontal cortex Anatomy 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 2
- AIKRYGDTVBUHJQ-UHFFFAOYSA-N propan-2-yl 1-(8-bromo-2-methylquinolin-4-yl)-3,6-dihydro-2h-pyridine-4-carboxylate Chemical compound C1CC(C(=O)OC(C)C)=CCN1C1=CC(C)=NC2=C(Br)C=CC=C12 AIKRYGDTVBUHJQ-UHFFFAOYSA-N 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical compound C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 238000006277 sulfonation reaction Methods 0.000 description 2
- 230000006103 sulfonylation Effects 0.000 description 2
- 238000005694 sulfonylation reaction Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- YPHWNNXCXAXUGY-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)-2,3,6-trimethyl-7h-pyrrolo[2,3-b]pyridin-4-one Chemical compound CC1=C(C)C2=C(O)C=C(C)N=C2N1C1=CC=C(Cl)C=C1Cl YPHWNNXCXAXUGY-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- YQLGOLYFJUTAPI-UHFFFAOYSA-N 1-[1-(2,4-dichlorophenyl)-2,3,6-trimethylpyrrolo[2,3-b]pyridin-4-yl]-3,6-dihydro-2h-pyridine-4-carbonitrile Chemical compound CC1=C(C)C2=C(N3CC=C(CC3)C#N)C=C(C)N=C2N1C1=CC=C(Cl)C=C1Cl YQLGOLYFJUTAPI-UHFFFAOYSA-N 0.000 description 1
- XWRYGIFJOWKXTR-UHFFFAOYSA-N 1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]-3,6-dihydro-2h-pyridine-4-carbonitrile Chemical compound C=12C=CC=C(C=3C(=CC(Cl)=CC=3)Cl)C2=NC(C)=CC=1N1CCC(C#N)=CC1 XWRYGIFJOWKXTR-UHFFFAOYSA-N 0.000 description 1
- KLEFSWLPKYEQNF-UHFFFAOYSA-N 1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]-3,6-dihydro-2h-pyridine-4-carboxylic acid Chemical compound C=12C=CC=C(C=3C(=CC(Cl)=CC=3)Cl)C2=NC(C)=CC=1N1CCC(C(O)=O)=CC1 KLEFSWLPKYEQNF-UHFFFAOYSA-N 0.000 description 1
- KJQVZKYNXDWTPL-UHFFFAOYSA-N 1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]-3,6-dihydro-2h-pyridine-5-carboxamide Chemical compound C=12C=CC=C(C=3C(=CC(Cl)=CC=3)Cl)C2=NC(C)=CC=1N1CCC=C(C(N)=O)C1 KJQVZKYNXDWTPL-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- VFTFKUDGYRBSAL-UHFFFAOYSA-N 15-crown-5 Chemical compound C1COCCOCCOCCOCCO1 VFTFKUDGYRBSAL-UHFFFAOYSA-N 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
- MLEPAUPTSOHLIA-UHFFFAOYSA-N 2-[1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]piperidin-4-ylidene]acetamide Chemical compound C=12C=CC=C(C=3C(=CC(Cl)=CC=3)Cl)C2=NC(C)=CC=1N1CCC(=CC(N)=O)CC1 MLEPAUPTSOHLIA-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- ZMCQQCBOZIGNRV-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(1,2,4-triazol-1-yl)ethyl]benzamide Chemical compound NCC1=CC(OC2=CC=CC(=C2)C(=O)NCCN2C=NC=N2)=NC(=C1)C(F)(F)F ZMCQQCBOZIGNRV-UHFFFAOYSA-N 0.000 description 1
- AJZDHLHTTJRNQJ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(tetrazol-1-yl)ethyl]benzamide Chemical compound N1(N=NN=C1)CCNC(C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)=O AJZDHLHTTJRNQJ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- BBNQCAXGODUUPF-UHFFFAOYSA-N 4-chloro-8-(2,4-dichlorophenyl)-2-methylquinoline Chemical compound C12=NC(C)=CC(Cl)=C2C=CC=C1C1=CC=C(Cl)C=C1Cl BBNQCAXGODUUPF-UHFFFAOYSA-N 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- HBBGRARXTFLTSG-UHFFFAOYSA-N Lithium ion Chemical compound [Li+] HBBGRARXTFLTSG-UHFFFAOYSA-N 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- YQYBUJYBXOVWQW-UHFFFAOYSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-(3,4-dihydro-1H-isoquinolin-2-yl)methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1CC2=CC=CC=C2CC1 YQYBUJYBXOVWQW-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- KTLFENNEPHBKJD-UHFFFAOYSA-K benzyl(trimethyl)azanium;tribromide Chemical compound [Br-].[Br-].[Br-].C[N+](C)(C)CC1=CC=CC=C1.C[N+](C)(C)CC1=CC=CC=C1.C[N+](C)(C)CC1=CC=CC=C1 KTLFENNEPHBKJD-UHFFFAOYSA-K 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 1
- 238000007333 cyanation reaction Methods 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004859 cyclopropyloxymethyl group Chemical group C1(CC1)OC* 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- MXOATMXKPSGVBM-UHFFFAOYSA-N ethyl 1-[1-(2,4-dichlorophenyl)-2,3,6-trimethylpyrrolo[2,3-b]pyridin-4-yl]-4-hydroxypiperidine-3-carboxylate Chemical compound C1CC(O)C(C(=O)OCC)CN1C1=CC(C)=NC2=C1C(C)=C(C)N2C1=CC=C(Cl)C=C1Cl MXOATMXKPSGVBM-UHFFFAOYSA-N 0.000 description 1
- ARXMHOIFDYIFLN-UHFFFAOYSA-N ethyl 1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]-2-methylidenepiperidine-4-carboxylate Chemical compound C=C1CC(C(=O)OCC)CCN1C1=CC(C)=NC2=C(C=3C(=CC(Cl)=CC=3)Cl)C=CC=C12 ARXMHOIFDYIFLN-UHFFFAOYSA-N 0.000 description 1
- MMZGJPTYWAUISQ-UHFFFAOYSA-N ethyl 2-[1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]piperidin-4-ylidene]acetate Chemical compound C1CC(=CC(=O)OCC)CCN1C1=CC(C)=NC2=C(C=3C(=CC(Cl)=CC=3)Cl)C=CC=C12 MMZGJPTYWAUISQ-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229910001416 lithium ion Inorganic materials 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- FYCXPOFJVJBYRQ-UHFFFAOYSA-N n-(2,4-dichlorophenyl)-n-ethyl-4-methyl-1,3-thiazol-2-amine;hydrochloride Chemical compound Cl.C=1C=C(Cl)C=C(Cl)C=1N(CC)C1=NC(C)=CS1 FYCXPOFJVJBYRQ-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 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
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- LKVYWSOUXPAASC-UHFFFAOYSA-N propan-2-yl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound CC(C)OC(=O)C1=CCNCC1 LKVYWSOUXPAASC-UHFFFAOYSA-N 0.000 description 1
- YSNWRAAJCSCDLM-UHFFFAOYSA-N propan-2-yl 1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]-3,6-dihydro-2h-pyridine-4-carboxylate Chemical compound C1CC(C(=O)OC(C)C)=CCN1C1=CC(C)=NC2=C(C=3C(=CC(Cl)=CC=3)Cl)C=CC=C12 YSNWRAAJCSCDLM-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 210000002820 sympathetic nervous system Anatomy 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- NZBUCABTIWJWAN-UHFFFAOYSA-N tetrabromomethane;triphenylphosphane Chemical compound BrC(Br)(Br)Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NZBUCABTIWJWAN-UHFFFAOYSA-N 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- C07D401/04—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A61P25/12—Antiepileptics; Anticonvulsants for grand-mal
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—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
-
- 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
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Nutrition Science (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Addiction (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000204021 | 2000-07-05 | ||
| JP2000270535 | 2000-09-06 | ||
| PCT/JP2001/005806 WO2002002549A1 (en) | 2000-07-05 | 2001-07-04 | Tetrahydropyridino or piperidino heterocyclic derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20030074A2 true HRP20030074A2 (en) | 2005-02-28 |
Family
ID=26595443
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20030074A HRP20030074A2 (en) | 2000-07-05 | 2003-02-05 | Tetrahydropyridino heterocyclic derivatives |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US6852732B2 (ru) |
| EP (1) | EP1299378B1 (ru) |
| JP (1) | JP2004502685A (ru) |
| KR (1) | KR20030015368A (ru) |
| CN (2) | CN1535968A (ru) |
| AR (1) | AR028782A1 (ru) |
| AT (1) | ATE353885T1 (ru) |
| AU (2) | AU6943701A (ru) |
| BG (1) | BG107374A (ru) |
| BR (1) | BR0112166A (ru) |
| CA (1) | CA2412287A1 (ru) |
| CZ (1) | CZ20024229A3 (ru) |
| DE (1) | DE60126616T2 (ru) |
| EA (1) | EA005289B1 (ru) |
| EE (1) | EE200300007A (ru) |
| HK (1) | HK1057042A1 (ru) |
| HR (1) | HRP20030074A2 (ru) |
| HU (1) | HUP0301165A2 (ru) |
| IL (1) | IL153718A0 (ru) |
| MX (1) | MXPA02012820A (ru) |
| NO (1) | NO20026125L (ru) |
| PL (1) | PL358411A1 (ru) |
| SK (1) | SK132003A3 (ru) |
| TW (1) | TW591022B (ru) |
| WO (1) | WO2002002549A1 (ru) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6900226B2 (en) * | 2000-09-06 | 2005-05-31 | Hoffman-La Roche Inc. | Neuropeptide Y antagonists |
| GB0117396D0 (en) | 2001-07-17 | 2001-09-05 | Glaxo Group Ltd | Chemical compounds |
| TWI270549B (en) * | 2002-12-26 | 2007-01-11 | Taisho Pharmaceutical Co Ltd | Pyrrolopyrimidine and pyrrolopyridine derivatives substituted with cyclic amino group |
| EP1927594A1 (en) * | 2003-01-14 | 2008-06-04 | Arena Pharmaceuticals, Inc. | 1,2,3-Trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto such as diabetes and hyperglycemia |
| ATE374766T1 (de) * | 2003-01-14 | 2007-10-15 | Arena Pharm Inc | 1,2,3-trisubstituierte aryl- und heteroarylderivate als modulatoren des metabolismus zur vorbeugung und behandlung von metabolismus-bedingten krankheiten wie diabetes oder hyperglykämie |
| GB0308208D0 (en) * | 2003-04-09 | 2003-05-14 | Glaxo Group Ltd | Chemical compounds |
| US7268133B2 (en) * | 2003-04-23 | 2007-09-11 | Pfizer, Inc. Patent Department | Cannabinoid receptor ligands and uses thereof |
| TWI287010B (en) * | 2003-06-12 | 2007-09-21 | Euro Celtique Sa | Therapeutic agents useful for treating pain |
| AU2004257267B2 (en) | 2003-07-14 | 2009-12-03 | Arena Pharmaceuticals,Inc | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
| MXPA06003762A (es) * | 2003-10-16 | 2006-06-14 | Boehringer Ingelheim Int | Composicion farmaceutica que comprende un inhibidor de recaptacion de neurotransmisor monoamina y un inhibidor de acetilcolinesterasa. |
| EP1697369A1 (en) * | 2003-12-22 | 2006-09-06 | SB Pharmco Puerto Rico Inc | Crf receptor antagonists and methods relating thereto |
| WO2005066182A1 (en) * | 2004-01-06 | 2005-07-21 | Taisho Pharmaceutical Co., Ltd. | Thienopyrimidine and thienopyridine derivatives substituted with cyclic amino group |
| RU2006128600A (ru) | 2004-01-06 | 2008-02-20 | Тайсо Фармасьютикал Ко., Лтд. (Jp) | ПРОИЗВОДНЫЕ ТРИАЗАЦИКЛОПЕНТА [cd] ИНДЕНА |
| CA2552503C (en) | 2004-01-06 | 2011-09-13 | Taisho Pharmaceutical Co., Ltd. | Pyrrolopyrimidine and pyrrolotriazine derivatives |
| EP1725562A1 (en) * | 2004-03-05 | 2006-11-29 | Taisho Pharmaceutical Co., Ltd | Pyrrolopyrimidine derivatives |
| WO2006001501A1 (en) * | 2004-06-25 | 2006-01-05 | Taisho Pharmaceutical Co., Ltd. | Pyrrolopyrimidine and pyrrolopyridine derivatives substituted with tetrahydropyridine as crf antagonists |
| JP2007161585A (ja) * | 2004-06-25 | 2007-06-28 | Taisho Pharmaceut Co Ltd | 環状アミノ基で置換されているピロロピリミジン及びピロロピリジン誘導体 |
| EP1814885A4 (en) * | 2004-11-23 | 2009-12-16 | Us Therapeutics Inc Reddy | NOVEL HETEROCYCLIC BICYCLIC COMPOUNDS, PROCESS FOR THEIR PREPARATION AND COMPOSITIONS CONTAINING SAME |
| AU2007221049A1 (en) * | 2006-02-28 | 2007-09-07 | Amgen Inc. | Cinnoline and quinazoline derivates as phosphodiesterase 10 inhibitors |
| ES2301380B1 (es) | 2006-08-09 | 2009-06-08 | Laboratorios Almirall S.A. | Nuevos derivados de 1,7-naftiridina. |
| US20100048633A1 (en) * | 2007-01-31 | 2010-02-25 | Philipp Lehr | Piperidine-4-acrylamides |
| ES2320955B1 (es) | 2007-03-02 | 2010-03-16 | Laboratorios Almirall S.A. | Nuevos derivados de 3-((1,2,4)triazolo(4,3-a)piridin-7-il)benzamida. |
| ES2329639B1 (es) | 2007-04-26 | 2010-09-23 | Laboratorios Almirall S.A. | Nuevos derivados de 4,8-difenilpoliazanaftaleno. |
| KR20090130422A (ko) | 2007-04-27 | 2009-12-23 | 퍼듀 퍼머 엘피 | 통증 치료에 유용한 치료제 |
| PL2142529T3 (pl) * | 2007-04-27 | 2014-06-30 | Purdue Pharma Lp | Antagoniści trpv1 i ich zastosowania |
| EP2108641A1 (en) | 2008-04-11 | 2009-10-14 | Laboratorios Almirall, S.A. | New substituted spiro[cycloalkyl-1,3'-indo]-2'(1'H)-one derivatives and their use as p38 mitogen-activated kinase inhibitors |
| EP2113503A1 (en) | 2008-04-28 | 2009-11-04 | Laboratorios Almirall, S.A. | New substituted indolin-2-one derivatives and their use as p39 mitogen-activated kinase inhibitors |
| CA2812061A1 (en) | 2010-09-22 | 2012-03-29 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| MX2013007937A (es) | 2011-01-07 | 2013-11-01 | Taiho Pharmaceutical Co Ltd | Nuevo derivado de indol o indazol o sal del mismo. |
| JP5792201B2 (ja) * | 2011-01-07 | 2015-10-07 | 大鵬薬品工業株式会社 | 新規二環式化合物又はその塩 |
| MY185061A (en) | 2011-06-22 | 2021-04-30 | Shionogi & Co | Trpv1 antagonists including dihydroxy substituent and uses thereof |
| CN107405332A (zh) | 2015-01-06 | 2017-11-28 | 艾尼纳制药公司 | 治疗与s1p1受体有关的病症的方法 |
| CA3002551A1 (en) | 2015-06-22 | 2016-12-29 | Arena Pharmaceuticals, Inc. | Crystalline l-arginine salt of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid(com pound 1)for use in s1p1 receptor-associated disorders |
| CN109311868B (zh) | 2015-12-22 | 2022-04-01 | 尚医治疗有限责任公司 | 用于治疗癌症和炎性疾病的化合物 |
| ES2849560T3 (es) * | 2016-05-04 | 2021-08-19 | Genoscience Pharma Sas | Derivados de 2,4-diamino-quinolina sustituidos para su uso en el tratamiento de enfermedades proliferativas |
| CN110520124A (zh) | 2017-02-16 | 2019-11-29 | 艾尼纳制药公司 | 用于治疗原发性胆汁性胆管炎的化合物和方法 |
| SG11201911929XA (en) | 2017-06-21 | 2020-01-30 | SHY Therapeutics LLC | Compounds that interact with the ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease |
| EP3838847B1 (en) | 2019-12-20 | 2024-04-17 | Industrial Technology Research Institute | Composite material and method of removing fluorine in waste liquid |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1293565A (en) * | 1969-05-03 | 1972-10-18 | Aspro Nicholas Ltd | Aminophthalazines and pharmaceutical compositions thereof |
| KR20010005568A (ko) | 1997-03-26 | 2001-01-15 | 우에하라 아끼라 | 4-테트라히드로피리딜피리미딘 유도체 |
| NZ335822A (en) | 1997-04-22 | 2001-05-25 | Neurocrine Biosciences Inc | Preparation and use of 2-methyl-4-dipropylamino-8(2',4'-dichlorophenyl)-quinoline and 2-methyl-4-(N-propyl-N-cyclopropanemethyl)amino-8(2',4'-dichlorophenyl)-quinoline for treating corticotropin-releasing factor related diseases |
| US6143743A (en) | 1997-07-03 | 2000-11-07 | Dupont Pharmaceuticals Company | Imidazopyrimidines and imidazopyridines for the treatment of neurological disorders |
| JPH11335376A (ja) | 1998-05-25 | 1999-12-07 | Taisho Pharmaceut Co Ltd | アリールテトラヒドロピリジン誘導体 |
| JPH11335373A (ja) | 1998-05-25 | 1999-12-07 | Taisho Pharmaceut Co Ltd | アリールメチレンピペリジノピリミジン誘導体 |
| JP2000086663A (ja) | 1998-09-09 | 2000-03-28 | Taisho Pharmaceut Co Ltd | アリールテトラヒドロピリジン誘導体 |
| EP1176146B1 (en) | 1999-03-11 | 2005-06-08 | Taisho Pharmaceutical Co., Ltd | Carbamoyl tetrahydropyridine derivatives |
-
2001
- 2001-07-03 AR ARP010103171A patent/AR028782A1/es unknown
- 2001-07-04 JP JP2002507801A patent/JP2004502685A/ja active Pending
- 2001-07-04 PL PL01358411A patent/PL358411A1/xx not_active Application Discontinuation
- 2001-07-04 DE DE60126616T patent/DE60126616T2/de not_active Expired - Fee Related
- 2001-07-04 MX MXPA02012820A patent/MXPA02012820A/es unknown
- 2001-07-04 IL IL15371801A patent/IL153718A0/xx unknown
- 2001-07-04 HU HU0301165A patent/HUP0301165A2/hu unknown
- 2001-07-04 CZ CZ20024229A patent/CZ20024229A3/cs unknown
- 2001-07-04 US US10/311,277 patent/US6852732B2/en not_active Expired - Fee Related
- 2001-07-04 SK SK13-2003A patent/SK132003A3/sk unknown
- 2001-07-04 TW TW090116391A patent/TW591022B/zh not_active IP Right Cessation
- 2001-07-04 AT AT01947819T patent/ATE353885T1/de not_active IP Right Cessation
- 2001-07-04 CN CNA2004100338762A patent/CN1535968A/zh active Pending
- 2001-07-04 CN CNB018120016A patent/CN1260225C/zh not_active Expired - Fee Related
- 2001-07-04 CA CA002412287A patent/CA2412287A1/en not_active Abandoned
- 2001-07-04 AU AU6943701A patent/AU6943701A/xx active Pending
- 2001-07-04 WO PCT/JP2001/005806 patent/WO2002002549A1/en active IP Right Grant
- 2001-07-04 EP EP01947819A patent/EP1299378B1/en not_active Expired - Lifetime
- 2001-07-04 AU AU2001269437A patent/AU2001269437B2/en not_active Ceased
- 2001-07-04 EE EEP200300007A patent/EE200300007A/xx unknown
- 2001-07-04 KR KR10-2003-7000112A patent/KR20030015368A/ko not_active Application Discontinuation
- 2001-07-04 EA EA200300118A patent/EA005289B1/ru not_active IP Right Cessation
- 2001-07-04 BR BR0112166-9A patent/BR0112166A/pt not_active IP Right Cessation
-
2002
- 2002-12-11 BG BG107374A patent/BG107374A/bg unknown
- 2002-12-19 NO NO20026125A patent/NO20026125L/no not_active Application Discontinuation
-
2003
- 2003-02-05 HR HR20030074A patent/HRP20030074A2/hr not_active Application Discontinuation
- 2003-12-23 HK HK03109322A patent/HK1057042A1/xx not_active IP Right Cessation
-
2004
- 2004-08-06 US US10/912,185 patent/US7160900B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20030074A2 (en) | Tetrahydropyridino heterocyclic derivatives | |
| AU2001269437A1 (en) | Tetrahydropyridino or piperidino heterocyclic derivatives | |
| DE60212968T2 (de) | N-aroyl-(cyclisches amin)-derivate als orexinrezeptor antagonisten | |
| JP4866722B2 (ja) | 縮合ｎ−ヘテロサイクリック化合物およびｃｒｆ受容体アンタゴニストとしてのその使用 | |
| CA2679530C (en) | Benzimidazole compound and pharmaceutical use thereof | |
| JPH11513679A (ja) | 薬剤活性キナゾリン化合物 | |
| JPWO2006051704A1 (ja) | イミン化合物 | |
| JP2004515544A (ja) | キナゾリノン誘導体 | |
| CA2607874A1 (en) | Quinoline derivatives as neurokinin receptor antagonists | |
| US7557111B2 (en) | Substituted thieno[3,2-d]pyrimidines as CRF receptor antagonists | |
| KR20010085898A (ko) | 도파민 ｄ3 수용체 조절제 (정신병 치료제)로서 유용한테트라히드로벤즈아제핀 유도체 | |
| MXPA06015002A (es) | Derivados de pirrolopirimidina y pirrolopiridina sustituidos con tetrahidropiridina como antagonistas de crf. | |
| JP2011516398A (ja) | Ｎｐｙ−ｙ５アンタゴニストとしてのヘテロスピロ−デカン残基を有するベンズイミダゾール誘導体 | |
| AU2013329097A1 (en) | Urea and amide derivatives of aminoalkylpiperazines and use thereof | |
| KR20180049056A (ko) | 삼환식 축합피리딘-2－온 유도체 및 이들의 brd4 저해제로서의 용도 | |
| JP3351748B2 (ja) | ２，３−ジ置換−（５，６）−ヘテロアリール縮合−ピリミジン−４−オンの新規なアトロプ異性体 | |
| TW202334167A (zh) | 作為ｅｒｂｂ２抑制劑之稠合四環喹唑啉衍生物 | |
| BG64989B1 (bg) | Заместено триазолопиридазиново производно фармацевтични състави, получени от него | |
| AU2008316895A1 (en) | (1,4-diaza-bicyclo[3.2.2]non-6-en-4-yl)-heterocyclyl-methanone ligands for nicotinic acetylcholine receptors, useful for the treatment of disease | |
| EP1176146B1 (en) | Carbamoyl tetrahydropyridine derivatives | |
| WO1997003986A1 (fr) | Composes fusionnes de triazole | |
| JP5225269B2 (ja) | 新規なｍｃｈ受容体アンタゴニスト | |
| JP2007517869A (ja) | 治療薬ｉｉ |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A1OB | Publication of a patent application | ||
| OBST | Application withdrawn |