NO316119B1 - Imidasopyrimidiner og imidasopyridiner, farmasöytisk sammensetning inneholdende samme og anvendelse av samme for fremstilling av medikamentet - Google Patents
Imidasopyrimidiner og imidasopyridiner, farmasöytisk sammensetning inneholdende samme og anvendelse av samme for fremstilling av medikamentet Download PDFInfo
- Publication number
- NO316119B1 NO316119B1 NO19996483A NO996483A NO316119B1 NO 316119 B1 NO316119 B1 NO 316119B1 NO 19996483 A NO19996483 A NO 19996483A NO 996483 A NO996483 A NO 996483A NO 316119 B1 NO316119 B1 NO 316119B1
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- ethyl
- group
- substituted
- hexane
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims description 17
- 229940079593 drug Drugs 0.000 title claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title description 26
- 150000005232 imidazopyridines Chemical class 0.000 title 1
- 150000005237 imidazopyrimidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 138
- -1 1-piperazinyl Chemical group 0.000 claims description 62
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 150000003839 salts Chemical group 0.000 claims description 19
- 125000003282 alkyl amino group Chemical group 0.000 claims description 18
- 208000035475 disorder Diseases 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 229910052740 iodine Inorganic materials 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 229910052685 Curium Inorganic materials 0.000 claims description 12
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 10
- 208000019901 Anxiety disease Diseases 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 230000036506 anxiety Effects 0.000 claims description 9
- 208000019022 Mood disease Diseases 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 208000024891 symptom Diseases 0.000 claims description 8
- 208000030814 Eating disease Diseases 0.000 claims description 7
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 235000014632 disordered eating Nutrition 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 6
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 6
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 5
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 5
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 5
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 4
- 206010048327 Supranuclear palsy Diseases 0.000 claims description 4
- 208000029650 alcohol withdrawal Diseases 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 208000011906 peptic ulcer disease Diseases 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 3
- 206010013654 Drug abuse Diseases 0.000 claims description 3
- 206010019233 Headaches Diseases 0.000 claims description 3
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 231100000869 headache Toxicity 0.000 claims description 3
- 230000002008 hemorrhagic effect Effects 0.000 claims description 3
- 208000000509 infertility Diseases 0.000 claims description 3
- 230000036512 infertility Effects 0.000 claims description 3
- 231100000535 infertility Toxicity 0.000 claims description 3
- 208000014674 injury Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 210000000278 spinal cord Anatomy 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- 230000008733 trauma Effects 0.000 claims description 3
- 201000001421 hyperglycemia Diseases 0.000 claims description 2
- 230000008629 immune suppression Effects 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 230000003595 spectral effect Effects 0.000 description 198
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 169
- 238000005481 NMR spectroscopy Methods 0.000 description 168
- 238000004809 thin layer chromatography Methods 0.000 description 163
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 152
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 94
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 83
- 239000000243 solution Substances 0.000 description 68
- 235000019439 ethyl acetate Nutrition 0.000 description 59
- 239000000203 mixture Substances 0.000 description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
- 238000000034 method Methods 0.000 description 49
- 229910001868 water Inorganic materials 0.000 description 45
- 239000000047 product Substances 0.000 description 42
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 39
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 38
- 239000003153 chemical reaction reagent Substances 0.000 description 38
- 102100021752 Corticoliberin Human genes 0.000 description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- 239000012267 brine Substances 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- 238000010992 reflux Methods 0.000 description 27
- 239000007787 solid Substances 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 239000000284 extract Substances 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- 238000004458 analytical method Methods 0.000 description 19
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 238000004440 column chromatography Methods 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 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 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 230000004048 modification Effects 0.000 description 12
- 238000012986 modification Methods 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- NEURYOYRKPFLKH-UHFFFAOYSA-N 2-chloro-1-isocyanato-4-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC=C(N=C=O)C(Cl)=C1 NEURYOYRKPFLKH-UHFFFAOYSA-N 0.000 description 7
- 206010020751 Hypersensitivity Diseases 0.000 description 7
- 229940049706 benzodiazepine Drugs 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 208000026935 allergic disease Diseases 0.000 description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 230000000112 colonic effect Effects 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 230000009610 hypersensitivity Effects 0.000 description 6
- 230000001900 immune effect Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 208000012902 Nervous system disease Diseases 0.000 description 5
- 208000025966 Neurological disease Diseases 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 239000001273 butane Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000002769 corticotropin releasing factor antagonist Substances 0.000 description 5
- 238000006352 cycloaddition reaction Methods 0.000 description 5
- 150000004985 diamines Chemical class 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 208000020016 psychiatric disease Diseases 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 4
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000003542 behavioural effect Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 229940125904 compound 1 Drugs 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 150000002828 nitro derivatives Chemical class 0.000 description 4
- 125000002524 organometallic group Chemical group 0.000 description 4
- 150000002905 orthoesters Chemical class 0.000 description 4
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 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 4
- 239000008188 pellet Substances 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 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
- ZEZJPIDPVXJEME-UHFFFAOYSA-N 2,4-Dihydroxypyridine Chemical compound OC=1C=CNC(=O)C=1 ZEZJPIDPVXJEME-UHFFFAOYSA-N 0.000 description 3
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- 101800000414 Corticotropin Proteins 0.000 description 3
- 229940122010 Corticotropin releasing factor antagonist Drugs 0.000 description 3
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 229910019213 POCl3 Inorganic materials 0.000 description 3
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 230000000338 anxiogenic effect Effects 0.000 description 3
- 239000002249 anxiolytic agent Substances 0.000 description 3
- 230000000949 anxiolytic effect Effects 0.000 description 3
- 229940005530 anxiolytics Drugs 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 238000004587 chromatography analysis Methods 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
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 3
- 229960000258 corticotropin Drugs 0.000 description 3
- VXVVUHQULXCUPF-UHFFFAOYSA-N cycloheptanamine Chemical compound NC1CCCCCC1 VXVVUHQULXCUPF-UHFFFAOYSA-N 0.000 description 3
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 150000002923 oximes Chemical class 0.000 description 3
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 125000002577 pseudohalo group Chemical group 0.000 description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
- ZGJWSJXILFPHDI-UHFFFAOYSA-N 1-(1-cyclopropylpropyl)-4-(2,4-dichlorophenyl)-2-ethylimidazo[4,5-c]pyridine Chemical compound CCC1=NC2=C(C=3C(=CC(Cl)=CC=3)Cl)N=CC=C2N1C(CC)C1CC1 ZGJWSJXILFPHDI-UHFFFAOYSA-N 0.000 description 2
- PEQIXJICXMPXKH-UHFFFAOYSA-N 1-(methoxymethoxy)-3-methylbenzene Chemical compound COCOC1=CC=CC(C)=C1 PEQIXJICXMPXKH-UHFFFAOYSA-N 0.000 description 2
- KTMLAWBZUWUSDP-UHFFFAOYSA-N 1-cyclopropylpropylazanium;chloride Chemical compound Cl.CCC(N)C1CC1 KTMLAWBZUWUSDP-UHFFFAOYSA-N 0.000 description 2
- SVPKNMBRVBMTLB-UHFFFAOYSA-N 2,3-dichloronaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(Cl)=C(Cl)C(=O)C2=C1 SVPKNMBRVBMTLB-UHFFFAOYSA-N 0.000 description 2
- PAXQXJDYVORMOO-UHFFFAOYSA-N 2-methyl-4-(trifluoromethyl)aniline Chemical group CC1=CC(C(F)(F)F)=CC=C1N PAXQXJDYVORMOO-UHFFFAOYSA-N 0.000 description 2
- FMBDGKGJYMSJKF-UHFFFAOYSA-N 2-phenylmethoxypyridine Chemical compound C=1C=CC=CC=1COC1=CC=CC=N1 FMBDGKGJYMSJKF-UHFFFAOYSA-N 0.000 description 2
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 2
- OZUXGFRLSKQVMI-UHFFFAOYSA-N 4-chloro-1h-pyridin-2-one Chemical compound OC1=CC(Cl)=CC=N1 OZUXGFRLSKQVMI-UHFFFAOYSA-N 0.000 description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 2
- DLAKMTRCKQTTJK-UHFFFAOYSA-N 7-(2-chloro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-ethylimidazo[4,5-b]pyridine Chemical compound CCC1=NC2=C(C=3C(=CC(OC)=CC=3)Cl)C=CN=C2N1C(CC)C1CC1 DLAKMTRCKQTTJK-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 102400000739 Corticotropin Human genes 0.000 description 2
- 102100038018 Corticotropin-releasing factor receptor 1 Human genes 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 206010013883 Dwarfism Diseases 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- RZKSECIXORKHQS-UHFFFAOYSA-N Heptan-3-ol Chemical compound CCCCC(O)CC RZKSECIXORKHQS-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010062767 Hypophysitis Diseases 0.000 description 2
- 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 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 108010069820 Pro-Opiomelanocortin Proteins 0.000 description 2
- 239000000683 Pro-Opiomelanocortin Substances 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 208000001871 Tachycardia Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 102000030621 adenylate cyclase Human genes 0.000 description 2
- 108060000200 adenylate cyclase Proteins 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000001543 aryl boronic acids Chemical class 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 239000010779 crude oil Substances 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 2
- ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical group O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 2
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- LTFTWJYRQNTCHI-UHFFFAOYSA-N hex-1-yn-3-ol Chemical compound CCCC(O)C#C LTFTWJYRQNTCHI-UHFFFAOYSA-N 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 150000007857 hydrazones Chemical class 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- JOWQNXIISCPKBK-UHFFFAOYSA-M magnesium;1,3,5-trimethylbenzene-6-ide;bromide Chemical compound [Mg+2].[Br-].CC1=CC(C)=[C-]C(C)=C1 JOWQNXIISCPKBK-UHFFFAOYSA-M 0.000 description 2
- 208000024714 major depressive disease Diseases 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000003961 neuronal insult Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000003182 parenteral nutrition solution Substances 0.000 description 2
- 210000003635 pituitary gland Anatomy 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 201000009032 substance abuse Diseases 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000006794 tachycardia Effects 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 229910052718 tin Inorganic materials 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- LOCGPWGCRVKCFN-UHFFFAOYSA-N (2-chloro-4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C(Cl)=C1 LOCGPWGCRVKCFN-UHFFFAOYSA-N 0.000 description 1
- XDIYNQZUNSSENW-UUBOPVPUSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 description 1
- WJHCQAYQFVWNSV-UHFFFAOYSA-N (6-methyl-2,3-dihydro-1-benzofuran-5-yl)boronic acid Chemical compound C1=C(B(O)O)C(C)=CC2=C1CCO2 WJHCQAYQFVWNSV-UHFFFAOYSA-N 0.000 description 1
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 1
- 125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 description 1
- FZENGILVLUJGJX-NSCUHMNNSA-N (E)-acetaldehyde oxime Chemical compound C\C=N\O FZENGILVLUJGJX-NSCUHMNNSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
- CWZUTHDJLNZLCM-DFBGVHRSSA-N 1-[2-[(1r,3s,5r)-3-[(6-bromopyridin-2-yl)carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]indazole-3-carboxamide Chemical compound O=C([C@@H]1C[C@H]2C[C@H]2N1C(=O)CN1N=C(C2=CC=CC=C21)C(=O)N)NC1=CC=CC(Br)=N1 CWZUTHDJLNZLCM-DFBGVHRSSA-N 0.000 description 1
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 1
- ACCAFIJEIFZRAO-UHFFFAOYSA-N 1-benzyl-4-chloro-2-ethyl-6-methylimidazo[4,5-c]pyridine Chemical compound CCC1=NC2=C(Cl)N=C(C)C=C2N1CC1=CC=CC=C1 ACCAFIJEIFZRAO-UHFFFAOYSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- NFQRIJRWUCDRPN-UHFFFAOYSA-N 1-cyclopropylprop-2-yn-1-ol Chemical compound C#CC(O)C1CC1 NFQRIJRWUCDRPN-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- KQCMTOWTPBNWDB-UHFFFAOYSA-N 2,4-dichloroaniline Chemical compound NC1=CC=C(Cl)C=C1Cl KQCMTOWTPBNWDB-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
- BQMNYXSBLZROPA-UHFFFAOYSA-N 2-(2-hydroxyethyl)-5-methylphenol Chemical compound CC1=CC=C(CCO)C(O)=C1 BQMNYXSBLZROPA-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- HJCYBCNHVJSQRX-UHFFFAOYSA-N 2-[2-(methoxymethoxy)-4-methylphenyl]ethanol Chemical compound COCOC1=CC(C)=CC=C1CCO HJCYBCNHVJSQRX-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- MGBVHCKCKXFVLF-UHFFFAOYSA-N 2-chloro-1-iodo-4-methoxybenzene Chemical compound COC1=CC=C(I)C(Cl)=C1 MGBVHCKCKXFVLF-UHFFFAOYSA-N 0.000 description 1
- UDSPOUFDXJYPPP-UHFFFAOYSA-N 2-chloro-6-methyl-3-nitro-4-(2,4,6-trimethylphenyl)pyridine Chemical compound CC1=CC(C)=CC(C)=C1C1=CC(C)=NC(Cl)=C1[N+]([O-])=O UDSPOUFDXJYPPP-UHFFFAOYSA-N 0.000 description 1
- VDOXMHLUNYHXNC-UHFFFAOYSA-N 2-cyclopropyl-N'-[4-(2,4-dichlorophenyl)pyridin-2-yl]propane-1,3-diamine Chemical compound NCC(CNC1=NC=CC(=C1)C1=C(C=C(C=C1)Cl)Cl)C1CC1 VDOXMHLUNYHXNC-UHFFFAOYSA-N 0.000 description 1
- XBZCNJVSUTYCIA-UHFFFAOYSA-N 2-ethyl-1-(1-methoxybutan-2-yl)-4-(2,5,6-trimethylpyridin-3-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(COC)CC)C(CC)=NC2=C1C1=CC(C)=C(C)N=C1C XBZCNJVSUTYCIA-UHFFFAOYSA-N 0.000 description 1
- LRLOPKDQTHLYGS-UHFFFAOYSA-N 2-ethyl-1-(1-methoxybutan-2-yl)-4-(4-methoxy-2,5-dimethylphenyl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(COC)CC)C(CC)=NC2=C1C1=CC(C)=C(OC)C=C1C LRLOPKDQTHLYGS-UHFFFAOYSA-N 0.000 description 1
- RSGFXXDWJKSKRS-UHFFFAOYSA-N 2-ethyl-1-(1-methoxypentan-3-yl)-4-(2,5,6-trimethylpyridin-3-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CCOC)CC)C(CC)=NC2=C1C1=CC(C)=C(C)N=C1C RSGFXXDWJKSKRS-UHFFFAOYSA-N 0.000 description 1
- TURWUUTXXSVCLC-UHFFFAOYSA-N 2-ethyl-3-(1-methoxybutan-2-yl)-7-(4-methoxy-2,5-dimethylphenyl)imidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(COC)CC)C(CC)=NC2=C1C1=CC(C)=C(OC)C=C1C TURWUUTXXSVCLC-UHFFFAOYSA-N 0.000 description 1
- BAHNSGSCOVMVBU-UHFFFAOYSA-N 2-ethyl-3-(1-methoxypentan-3-yl)-7-(2,5,6-trimethylpyridin-3-yl)imidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(CCOC)CC)C(CC)=NC2=C1C1=CC(C)=C(C)N=C1C BAHNSGSCOVMVBU-UHFFFAOYSA-N 0.000 description 1
- RIOIUHCWAGQTOY-UHFFFAOYSA-N 2-ethyl-4-(5-fluoro-4-methoxy-2-methylphenyl)-1-(1-methoxypentan-3-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CCOC)CC)C(CC)=NC2=C1C1=CC(F)=C(OC)C=C1C RIOIUHCWAGQTOY-UHFFFAOYSA-N 0.000 description 1
- AECCVOFWYNFBLH-UHFFFAOYSA-N 2-ethyl-7-(4-methoxy-2,5-dimethylphenyl)-3-(1-methoxypentan-3-yl)imidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(CCOC)CC)C(CC)=NC2=C1C1=CC(C)=C(OC)C=C1C AECCVOFWYNFBLH-UHFFFAOYSA-N 0.000 description 1
- VINMFFYDHNBLHT-UHFFFAOYSA-N 2-ethyl-7-(5-fluoro-4-methoxy-2-methylphenyl)-3-pentan-3-ylimidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(CC)CC)C(CC)=NC2=C1C1=CC(F)=C(OC)C=C1C VINMFFYDHNBLHT-UHFFFAOYSA-N 0.000 description 1
- OLTSPVSNBDERSN-UHFFFAOYSA-N 2-ethyl-7-[4-methoxy-2-(trifluoromethyl)phenyl]-3-pentan-3-ylimidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(CC)CC)C(CC)=NC2=C1C1=CC=C(OC)C=C1C(F)(F)F OLTSPVSNBDERSN-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- WEOMCNQGKJRVRH-UHFFFAOYSA-N 2-methoxy-1-(1-methoxybutan-2-yl)-4-(6-methoxy-2-methylpyridin-3-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(COC)CC)C(OC)=NC2=C1C1=CC=C(OC)N=C1C WEOMCNQGKJRVRH-UHFFFAOYSA-N 0.000 description 1
- YFJBBUPZMSBYLN-UHFFFAOYSA-N 2-methoxy-3-(1-methoxybutan-2-yl)-7-(4-methoxy-2,5-dimethylphenyl)imidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(COC)CC)C(OC)=NC2=C1C1=CC(C)=C(OC)C=C1C YFJBBUPZMSBYLN-UHFFFAOYSA-N 0.000 description 1
- JWGIOVIIXBRBIZ-UHFFFAOYSA-N 2-methoxy-4-(4-methoxy-2,5-dimethylphenyl)-1-pentan-3-ylimidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CC)CC)C(OC)=NC2=C1C1=CC(C)=C(OC)C=C1C JWGIOVIIXBRBIZ-UHFFFAOYSA-N 0.000 description 1
- DEMPQPVDOMDOHK-UHFFFAOYSA-N 2-methoxy-4-(6-methoxy-2-methylpyridin-3-yl)-1-(1-methoxypentan-3-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CCOC)CC)C(OC)=NC2=C1C1=CC=C(OC)N=C1C DEMPQPVDOMDOHK-UHFFFAOYSA-N 0.000 description 1
- UCNFAPAGGGELDL-UHFFFAOYSA-N 2-methoxy-4-[4-methoxy-2-(trifluoromethyl)phenyl]-1-pentan-3-ylimidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CC)CC)C(OC)=NC2=C1C1=CC=C(OC)C=C1C(F)(F)F UCNFAPAGGGELDL-UHFFFAOYSA-N 0.000 description 1
- TXTYUVJHBSFZIU-UHFFFAOYSA-N 2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)-3-(1-methoxypentan-3-yl)imidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(CCOC)CC)C(OC)=NC2=C1C1=CC(C)=C(OC)C=C1C TXTYUVJHBSFZIU-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
- HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical class [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 description 1
- QOEQGSBZVOHUGJ-UHFFFAOYSA-N 3-(1-cyclopropylpropyl)-2-ethyl-7-(2,4,5-trimethylphenyl)imidazo[4,5-b]pyridine Chemical compound CCC1=NC2=C(C=3C(=CC(C)=C(C)C=3)C)C=CN=C2N1C(CC)C1CC1 QOEQGSBZVOHUGJ-UHFFFAOYSA-N 0.000 description 1
- QOZKMWCLZFOTMM-UHFFFAOYSA-N 3-(1-cyclopropylpropyl)-2-ethyl-7-(4-methoxy-2,5-dimethylphenyl)imidazo[4,5-b]pyridine Chemical compound CCC1=NC2=C(C=3C(=CC(OC)=C(C)C=3)C)C=CN=C2N1C(CC)C1CC1 QOZKMWCLZFOTMM-UHFFFAOYSA-N 0.000 description 1
- KLSGZRXSZYISIB-UHFFFAOYSA-N 3-(1-cyclopropylpropyl)-2-methoxy-7-(2,4,5-trimethylphenyl)imidazo[4,5-b]pyridine Chemical compound COC1=NC2=C(C=3C(=CC(C)=C(C)C=3)C)C=CN=C2N1C(CC)C1CC1 KLSGZRXSZYISIB-UHFFFAOYSA-N 0.000 description 1
- SVDORZAAEFJOBO-UHFFFAOYSA-N 3-(1-cyclopropylpropyl)-2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)imidazo[4,5-b]pyridine Chemical compound COC1=NC2=C(C=3C(=CC(OC)=C(C)C=3)C)C=CN=C2N1C(CC)C1CC1 SVDORZAAEFJOBO-UHFFFAOYSA-N 0.000 description 1
- ZFEOFCQPJMXUNV-UHFFFAOYSA-N 3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-ethylimidazo[4,5-b]pyridine Chemical compound CCC1=NC2=C(C=3C(=CC(Cl)=CC=3)Cl)C=CN=C2N1C(CC)C1CC1 ZFEOFCQPJMXUNV-UHFFFAOYSA-N 0.000 description 1
- IUYUAVKFWKJGSE-UHFFFAOYSA-N 3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-methoxyimidazo[4,5-b]pyridine Chemical compound COC1=NC2=C(C=3C(=CC(Cl)=CC=3)Cl)C=CN=C2N1C(CC)C1CC1 IUYUAVKFWKJGSE-UHFFFAOYSA-N 0.000 description 1
- BYMGANFIZGPNPM-UHFFFAOYSA-N 3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-methylsulfanylimidazo[4,5-b]pyridine Chemical compound CSC1=NC2=C(C=3C(=CC(Cl)=CC=3)Cl)C=CN=C2N1C(CC)C1CC1 BYMGANFIZGPNPM-UHFFFAOYSA-N 0.000 description 1
- HKMVLTIGXZYHDS-UHFFFAOYSA-N 3-(1-cyclopropylpropyl)-7-(2,6-dimethylpyridin-3-yl)-2-ethylimidazo[4,5-b]pyridine Chemical compound CCC1=NC2=C(C=3C(=NC(C)=CC=3)C)C=CN=C2N1C(CC)C1CC1 HKMVLTIGXZYHDS-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- BFJMHTOBRRZELQ-UHFFFAOYSA-N 3-iodo-2h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C(I)=NNC2=C1 BFJMHTOBRRZELQ-UHFFFAOYSA-N 0.000 description 1
- UBOOKRVGOBKDMM-UHFFFAOYSA-N 3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=C2NC=NC2=C1 UBOOKRVGOBKDMM-UHFFFAOYSA-N 0.000 description 1
- NIGDWBHWHVHOAD-UHFFFAOYSA-N 4,6-dichloropyrimidin-5-amine Chemical compound NC1=C(Cl)N=CN=C1Cl NIGDWBHWHVHOAD-UHFFFAOYSA-N 0.000 description 1
- YJSYBGMGUWRVAM-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-2-ethyl-1-(1-methoxybutan-2-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(COC)CC)C(CC)=NC2=C1C1=CC=C(Cl)C=C1Cl YJSYBGMGUWRVAM-UHFFFAOYSA-N 0.000 description 1
- RWRLJALVGHABKM-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-2-ethyl-1-(1-methoxypentan-3-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CCOC)CC)C(CC)=NC2=C1C1=CC=C(Cl)C=C1Cl RWRLJALVGHABKM-UHFFFAOYSA-N 0.000 description 1
- KTZUYLZJXFMIAT-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-2-ethyl-1-pentan-3-ylimidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CC)CC)C(CC)=NC2=C1C1=CC=C(Cl)C=C1Cl KTZUYLZJXFMIAT-UHFFFAOYSA-N 0.000 description 1
- GHXCUZWPQQFECJ-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-2-methoxy-1-(1-methoxybutan-2-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(COC)CC)C(OC)=NC2=C1C1=CC=C(Cl)C=C1Cl GHXCUZWPQQFECJ-UHFFFAOYSA-N 0.000 description 1
- XEZWJLVIVCOEKE-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-2-methoxy-1-pentan-3-ylimidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CC)CC)C(OC)=NC2=C1C1=CC=C(Cl)C=C1Cl XEZWJLVIVCOEKE-UHFFFAOYSA-N 0.000 description 1
- KGJMLFLYMTWODX-UHFFFAOYSA-N 4-(2,6-dimethoxypyridin-3-yl)-2-methoxy-1-(1-methoxypentan-3-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CCOC)CC)C(OC)=NC2=C1C1=CC=C(OC)N=C1OC KGJMLFLYMTWODX-UHFFFAOYSA-N 0.000 description 1
- ILWGETWNYLUZQB-UHFFFAOYSA-N 4-(2,6-dimethylpyridin-3-yl)-2-ethyl-1-(1-methoxypentan-3-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CCOC)CC)C(CC)=NC2=C1C1=CC=C(C)N=C1C ILWGETWNYLUZQB-UHFFFAOYSA-N 0.000 description 1
- YHGUZJLWCAZCEC-UHFFFAOYSA-N 4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-ethylimidazo[4,5-c]pyridine Chemical compound CCC1=NC2=C(C=3C(=CC(OC)=CC=3)Cl)N=CC=C2N1C(CC)C1CC1 YHGUZJLWCAZCEC-UHFFFAOYSA-N 0.000 description 1
- XNRQEEFNCOZBOV-UHFFFAOYSA-N 4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-methoxyimidazo[4,5-c]pyridine Chemical compound COC1=NC2=C(C=3C(=CC(OC)=CC=3)Cl)N=CC=C2N1C(CC)C1CC1 XNRQEEFNCOZBOV-UHFFFAOYSA-N 0.000 description 1
- NVKPDRYBDRZIKI-UHFFFAOYSA-N 4-(2-chloro-4-methoxyphenyl)-1-(dicyclopropylmethyl)-2-methoxyimidazo[4,5-c]pyridine Chemical compound COC1=NC2=C(C=3C(=CC(OC)=CC=3)Cl)N=CC=C2N1C(C1CC1)C1CC1 NVKPDRYBDRZIKI-UHFFFAOYSA-N 0.000 description 1
- HDQUHRWBRVFSFU-UHFFFAOYSA-N 4-(2-chloro-4-methoxyphenyl)-2-ethyl-1-(1-methoxypentan-3-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CCOC)CC)C(CC)=NC2=C1C1=CC=C(OC)C=C1Cl HDQUHRWBRVFSFU-UHFFFAOYSA-N 0.000 description 1
- DCHWLIGWAXZITF-UHFFFAOYSA-N 4-(2-chloro-4-methoxyphenyl)-2-ethyl-1-pentan-3-ylimidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CC)CC)C(CC)=NC2=C1C1=CC=C(OC)C=C1Cl DCHWLIGWAXZITF-UHFFFAOYSA-N 0.000 description 1
- CXXCMQAJLGDBKQ-UHFFFAOYSA-N 4-(2-chloro-4-methoxyphenyl)-2-methoxy-1-pentan-3-ylimidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CC)CC)C(OC)=NC2=C1C1=CC=C(OC)C=C1Cl CXXCMQAJLGDBKQ-UHFFFAOYSA-N 0.000 description 1
- HBMJFWKGHFCERY-UHFFFAOYSA-N 4-(2-chloro-4-methylsulfonylphenyl)-2-methoxy-1-(1-methoxypentan-3-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CCOC)CC)C(OC)=NC2=C1C1=CC=C(S(C)(=O)=O)C=C1Cl HBMJFWKGHFCERY-UHFFFAOYSA-N 0.000 description 1
- JIDKRFCFYGEZRR-UHFFFAOYSA-N 4-(2-chloro-5-fluoro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-ethylimidazo[4,5-c]pyridine Chemical compound CCC1=NC2=C(C=3C(=CC(OC)=C(F)C=3)Cl)N=CC=C2N1C(CC)C1CC1 JIDKRFCFYGEZRR-UHFFFAOYSA-N 0.000 description 1
- IAQSCJFVIGRVCG-UHFFFAOYSA-N 4-(2-chloro-5-fluoro-4-methoxyphenyl)-2-methoxy-1-(1-methoxypentan-3-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CCOC)CC)C(OC)=NC2=C1C1=CC(F)=C(OC)C=C1Cl IAQSCJFVIGRVCG-UHFFFAOYSA-N 0.000 description 1
- LSTVGHBWKQWLHW-UHFFFAOYSA-N 4-(2-chloro-5-fluoro-4-methylphenyl)-2-methoxy-1-(1-methoxybutan-2-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(COC)CC)C(OC)=NC2=C1C1=CC(F)=C(C)C=C1Cl LSTVGHBWKQWLHW-UHFFFAOYSA-N 0.000 description 1
- HSEPABHFIGLZGZ-UHFFFAOYSA-N 4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1-(1-methoxybutan-2-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(COC)CC)C(OC)=NC2=C1C1=CC(F)=C(OC)C=C1C HSEPABHFIGLZGZ-UHFFFAOYSA-N 0.000 description 1
- IEQACZYTKLOVPQ-UHFFFAOYSA-N 4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1-pentan-3-ylimidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CC)CC)C(OC)=NC2=C1C1=CC(F)=C(OC)C=C1C IEQACZYTKLOVPQ-UHFFFAOYSA-N 0.000 description 1
- MCGSWJCPHLRFJD-UHFFFAOYSA-N 4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-cyclopropylpropyl)-2-methoxyimidazo[4,5-c]pyridine Chemical compound COC1=NC2=C(C=3C(=CC(=CC=3)C(F)(F)F)Cl)N=CC=C2N1C(CC)C1CC1 MCGSWJCPHLRFJD-UHFFFAOYSA-N 0.000 description 1
- WDAJNNWYQBKNJX-UHFFFAOYSA-N 4-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-1-(1-methoxybutan-2-yl)imidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(COC)CC)C(CC)=NC2=C1C1=CC=C(C(F)(F)F)C=C1Cl WDAJNNWYQBKNJX-UHFFFAOYSA-N 0.000 description 1
- JIOAMLXSOPAXFI-UHFFFAOYSA-N 4-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-1-pentan-3-ylimidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CC)CC)C(CC)=NC2=C1C1=CC=C(C(F)(F)F)C=C1Cl JIOAMLXSOPAXFI-UHFFFAOYSA-N 0.000 description 1
- WZPDFBKZSSQGBM-UHFFFAOYSA-N 4-[2-chloro-4-(trifluoromethyl)phenyl]-2-methoxy-1-pentan-3-ylimidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C(CC)CC)C(OC)=NC2=C1C1=CC=C(C(F)(F)F)C=C1Cl WZPDFBKZSSQGBM-UHFFFAOYSA-N 0.000 description 1
- MQEMNXCYMRUDGK-UHFFFAOYSA-N 4-n-benzyl-2-chloro-6-methylpyridine-3,4-diamine Chemical compound ClC1=NC(C)=CC(NCC=2C=CC=CC=2)=C1N MQEMNXCYMRUDGK-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- FOWAAUYNAZZPIZ-UHFFFAOYSA-N 5-bromo-6-methyl-1-benzofuran Chemical compound C1=C(Br)C(C)=CC2=C1C=CO2 FOWAAUYNAZZPIZ-UHFFFAOYSA-N 0.000 description 1
- VSXYEQNLRXXOAJ-UHFFFAOYSA-N 5-bromo-6-methyl-2,3-dihydro-1-benzofuran Chemical compound C1=C(Br)C(C)=CC2=C1CCO2 VSXYEQNLRXXOAJ-UHFFFAOYSA-N 0.000 description 1
- KMKKSWMYWITNTR-UHFFFAOYSA-N 6-(4-chloro-2-methylphenyl)-9-(dicyclopropylmethyl)-8-ethylpurine Chemical compound CCC1=NC2=C(C=3C(=CC(Cl)=CC=3)C)N=CN=C2N1C(C1CC1)C1CC1 KMKKSWMYWITNTR-UHFFFAOYSA-N 0.000 description 1
- UKOYHKIBNVQDPF-UHFFFAOYSA-N 6-[4-chloro-2-(trifluoromethyl)phenyl]-9-(1-cyclopropylethyl)-8-ethylpurine Chemical compound CCC1=NC2=C(C=3C(=CC(Cl)=CC=3)C(F)(F)F)N=CN=C2N1C(C)C1CC1 UKOYHKIBNVQDPF-UHFFFAOYSA-N 0.000 description 1
- XVUOLHQHLMXCCX-UHFFFAOYSA-N 6-methyl-2,3-dihydro-1-benzofuran Chemical compound CC1=CC=C2CCOC2=C1 XVUOLHQHLMXCCX-UHFFFAOYSA-N 0.000 description 1
- ZSAUNFMTNWOJOR-UHFFFAOYSA-N 7-(2,4-dichlorophenyl)-2-ethyl-3-(1-methoxybutan-2-yl)imidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(COC)CC)C(CC)=NC2=C1C1=CC=C(Cl)C=C1Cl ZSAUNFMTNWOJOR-UHFFFAOYSA-N 0.000 description 1
- OBCIACTZSKCORZ-UHFFFAOYSA-N 7-(2,4-dichlorophenyl)-2-ethyl-3-pentan-3-ylimidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(CC)CC)C(CC)=NC2=C1C1=CC=C(Cl)C=C1Cl OBCIACTZSKCORZ-UHFFFAOYSA-N 0.000 description 1
- XWZPSCUJIBARQW-UHFFFAOYSA-N 7-(2,4-dichlorophenyl)-2-methoxy-3-(1-methoxypentan-3-yl)imidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(CCOC)CC)C(OC)=NC2=C1C1=CC=C(Cl)C=C1Cl XWZPSCUJIBARQW-UHFFFAOYSA-N 0.000 description 1
- KZVLSWGOBGTBJU-UHFFFAOYSA-N 7-(2,4-dichlorophenyl)-3-(dicyclopropylmethyl)-2-ethylimidazo[4,5-b]pyridine Chemical compound CCC1=NC2=C(C=3C(=CC(Cl)=CC=3)Cl)C=CN=C2N1C(C1CC1)C1CC1 KZVLSWGOBGTBJU-UHFFFAOYSA-N 0.000 description 1
- RXYHTGOBRMFWIL-UHFFFAOYSA-N 7-(2-chloro-4-methoxyphenyl)-2-ethyl-3-(1-methoxypentan-3-yl)imidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(CCOC)CC)C(CC)=NC2=C1C1=CC=C(OC)C=C1Cl RXYHTGOBRMFWIL-UHFFFAOYSA-N 0.000 description 1
- VKWJFXMOJUFCTR-UHFFFAOYSA-N 7-(2-chloro-4-methoxyphenyl)-3-(dicyclopropylmethyl)-2-ethylimidazo[4,5-b]pyridine Chemical compound CCC1=NC2=C(C=3C(=CC(OC)=CC=3)Cl)C=CN=C2N1C(C1CC1)C1CC1 VKWJFXMOJUFCTR-UHFFFAOYSA-N 0.000 description 1
- ZQGXEMMFOVKVEL-UHFFFAOYSA-N 7-(2-chloro-4-methylsulfonylphenyl)-2-ethyl-3-pentan-3-ylimidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(CC)CC)C(CC)=NC2=C1C1=CC=C(S(C)(=O)=O)C=C1Cl ZQGXEMMFOVKVEL-UHFFFAOYSA-N 0.000 description 1
- XBPREEUPCRKTNF-UHFFFAOYSA-N 7-(2-chloro-4-methylsulfonylphenyl)-2-methoxy-3-(1-methoxybutan-2-yl)imidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(COC)CC)C(OC)=NC2=C1C1=CC=C(S(C)(=O)=O)C=C1Cl XBPREEUPCRKTNF-UHFFFAOYSA-N 0.000 description 1
- NBFIABXZJUDQJW-UHFFFAOYSA-N 7-(2-chloro-5-fluoro-4-methylphenyl)-2-methoxy-3-(1-methoxybutan-2-yl)imidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(COC)CC)C(OC)=NC2=C1C1=CC(F)=C(C)C=C1Cl NBFIABXZJUDQJW-UHFFFAOYSA-N 0.000 description 1
- UCGWPWPBIYQFFP-UHFFFAOYSA-N 7-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-3-(1-methoxypentan-3-yl)imidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(CCOC)CC)C(OC)=NC2=C1C1=CC(F)=C(OC)C=C1C UCGWPWPBIYQFFP-UHFFFAOYSA-N 0.000 description 1
- ZUWDZQGAAIBDGC-UHFFFAOYSA-N 7-(6-chloro-6-fluoro-4-methoxycyclohexa-2,4-dien-1-yl)-3-(1-cyclopropylpropyl)-2-methoxyimidazo[4,5-b]pyridine Chemical compound ClC1(C(C=CC(=C1)OC)C1=C2C(=NC=C1)N(C(=N2)OC)C(CC)C1CC1)F ZUWDZQGAAIBDGC-UHFFFAOYSA-N 0.000 description 1
- MUKKVYNYGMUILS-UHFFFAOYSA-N 7-(6-chloro-6-fluoro-4-methylcyclohexa-2,4-dien-1-yl)-3-(1-cyclopropylpropyl)-2-methoxyimidazo[4,5-b]pyridine Chemical compound ClC1(C(C=CC(=C1)C)C1=C2C(=NC=C1)N(C(=N2)OC)C(CC)C1CC1)F MUKKVYNYGMUILS-UHFFFAOYSA-N 0.000 description 1
- SQTWFTOTWYCLIW-UHFFFAOYSA-N 7-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-3-pentan-3-ylimidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(CC)CC)C(CC)=NC2=C1C1=CC=C(C(F)(F)F)C=C1Cl SQTWFTOTWYCLIW-UHFFFAOYSA-N 0.000 description 1
- NHNQHPMKBHFNLV-UHFFFAOYSA-N 7-[2-chloro-4-(trifluoromethyl)phenyl]-2-methoxy-3-(1-methoxybutan-2-yl)imidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(COC)CC)C(OC)=NC2=C1C1=CC=C(C(F)(F)F)C=C1Cl NHNQHPMKBHFNLV-UHFFFAOYSA-N 0.000 description 1
- MXHVPWCNVKXVHX-UHFFFAOYSA-N 7-[2-chloro-4-(trifluoromethyl)phenyl]-2-methoxy-3-pentan-3-ylimidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C(CC)CC)C(OC)=NC2=C1C1=CC=C(C(F)(F)F)C=C1Cl MXHVPWCNVKXVHX-UHFFFAOYSA-N 0.000 description 1
- XPAGCCOTCLHANN-UHFFFAOYSA-N 7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-cyclopropylpropyl)-2-ethylimidazo[4,5-b]pyridine Chemical compound CCC1=NC2=C(C=3C(=CC(=CC=3)C(F)(F)F)Cl)C=CN=C2N1C(CC)C1CC1 XPAGCCOTCLHANN-UHFFFAOYSA-N 0.000 description 1
- OIILAXLKKDULGU-UHFFFAOYSA-N 7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-cyclopropylpropyl)-2-methoxyimidazo[4,5-b]pyridine Chemical compound COC1=NC2=C(C=3C(=CC(=CC=3)C(F)(F)F)Cl)C=CN=C2N1C(CC)C1CC1 OIILAXLKKDULGU-UHFFFAOYSA-N 0.000 description 1
- PICGLEOOUWTXOA-UHFFFAOYSA-N 7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-cyclopropylpropyl)-2-methylsulfanylimidazo[4,5-b]pyridine Chemical compound CSC1=NC2=C(C=3C(=CC(=CC=3)C(F)(F)F)Cl)C=CN=C2N1C(CC)C1CC1 PICGLEOOUWTXOA-UHFFFAOYSA-N 0.000 description 1
- XTEYKDBNVQVHTH-UHFFFAOYSA-N 8-ethyl-9-hexan-2-yl-6-[4-methoxy-2-(trifluoromethyl)phenyl]purine Chemical compound N1=CN=C2N(C(C)CCCC)C(CC)=NC2=C1C1=CC=C(OC)C=C1C(F)(F)F XTEYKDBNVQVHTH-UHFFFAOYSA-N 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- 208000017194 Affective disease Diseases 0.000 description 1
- 229940110385 Benzodiazepine receptor antagonist Drugs 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- BNZLTPCWOLWBNJ-UHFFFAOYSA-M Br[Mg] Chemical group Br[Mg] BNZLTPCWOLWBNJ-UHFFFAOYSA-M 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 125000006519 CCH3 Chemical group 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010008583 Chloroma Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 101710198652 Corticotropin-releasing factor receptor 1 Proteins 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 241000283073 Equus caballus Species 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 241000736355 Euthyroides Species 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000011688 Generalised anxiety disease Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- 101000878678 Homo sapiens Corticotropin-releasing factor receptor 1 Proteins 0.000 description 1
- 101100084403 Homo sapiens PRODH gene Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 206010053198 Inappropriate antidiuretic hormone secretion Diseases 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000005314 Multi-Infarct Dementia Diseases 0.000 description 1
- 208000007101 Muscle Cramp Diseases 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
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 229910004878 Na2S2O4 Inorganic materials 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 101150059359 POX2 gene Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 208000008939 Pneumonic Pasteurellosis Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 201000009916 Postpartum depression Diseases 0.000 description 1
- 208000005107 Premature Birth Diseases 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 102100028772 Proline dehydrogenase 1, mitochondrial Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 101100029251 Zea mays PER2 gene Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- GPRDHQSAXBLERL-UHFFFAOYSA-M [Cl-].CC1=CC(C)=C([Zn+])C(C)=C1 Chemical compound [Cl-].CC1=CC(C)=C([Zn+])C(C)=C1 GPRDHQSAXBLERL-UHFFFAOYSA-M 0.000 description 1
- GELXFVQAWNTGPQ-UHFFFAOYSA-N [N].C1=CNC=N1 Chemical group [N].C1=CNC=N1 GELXFVQAWNTGPQ-UHFFFAOYSA-N 0.000 description 1
- CZCSLHYZEQSUNV-UHFFFAOYSA-N [Na].OB(O)O Chemical compound [Na].OB(O)O CZCSLHYZEQSUNV-UHFFFAOYSA-N 0.000 description 1
- ZXYNGLRGFYLTQZ-UHFFFAOYSA-M [Zn]Cl Chemical group [Zn]Cl ZXYNGLRGFYLTQZ-UHFFFAOYSA-M 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- JOBBRIRILCAFIA-UHFFFAOYSA-N ac1l9md0 Chemical compound O.O.O.O.O.O.O.O.O JOBBRIRILCAFIA-UHFFFAOYSA-N 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000005233 alkylalcohol group Chemical group 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- SVEIXENKLWYGIZ-UHFFFAOYSA-J aluminum;sodium;tetrahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[Na+].[Al+3] SVEIXENKLWYGIZ-UHFFFAOYSA-J 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000003927 aminopyridines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 239000000749 benzodiazepine receptor blocking agent Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- FOHGPRAJGVHHFX-UHFFFAOYSA-M bis(2-methylpropyl)alumanylium;hydroxide Chemical compound [OH-].CC(C)C[Al+]CC(C)C FOHGPRAJGVHHFX-UHFFFAOYSA-M 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- HRQGCQVOJVTVLU-UHFFFAOYSA-N bis(chloromethyl) ether Chemical compound ClCOCCl HRQGCQVOJVTVLU-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 230000008859 change Effects 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
- 235000013330 chicken meat Nutrition 0.000 description 1
- 150000001805 chlorine compounds Chemical group 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 108010050742 corticotropin releasing hormone (9-41) Proteins 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 150000004292 cyclic ethers Chemical class 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
- 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
- 208000026725 cyclothymic disease Diseases 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 229960003887 dichlorophen Drugs 0.000 description 1
- BIPUHAHGLJKIPK-UHFFFAOYSA-N dicyclopropylmethanone Chemical compound C1CC1C(=O)C1CC1 BIPUHAHGLJKIPK-UHFFFAOYSA-N 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- SURBAJYBTYLRMQ-UHFFFAOYSA-N dioxido(propan-2-yloxy)borane Chemical compound CC(C)OB([O-])[O-] SURBAJYBTYLRMQ-UHFFFAOYSA-N 0.000 description 1
- JZBWUTVDIDNCMW-UHFFFAOYSA-L dipotassium;oxido sulfate Chemical compound [K+].[K+].[O-]OS([O-])(=O)=O JZBWUTVDIDNCMW-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 231100000318 excitotoxic Toxicity 0.000 description 1
- 230000003492 excitotoxic effect Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011850 initial investigation Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 125000005322 morpholin-1-yl group Chemical group 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- CDGZSMOCDYNULJ-UHFFFAOYSA-N n-(2-chloro-4-hydroxyphenyl)acetamide Chemical compound CC(=O)NC1=CC=C(O)C=C1Cl CDGZSMOCDYNULJ-UHFFFAOYSA-N 0.000 description 1
- JMASXNZVWWFJRF-UHFFFAOYSA-N n-(2-chloroethylidene)hydroxylamine Chemical compound ON=CCCl JMASXNZVWWFJRF-UHFFFAOYSA-N 0.000 description 1
- RIVIDPPYRINTTH-UHFFFAOYSA-N n-ethylpropan-2-amine Chemical compound CCNC(C)C RIVIDPPYRINTTH-UHFFFAOYSA-N 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000009251 neurologic dysfunction Effects 0.000 description 1
- 230000007658 neurological function Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000001272 nitrous oxide Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- AOCUKGFDRUSDQH-PIKKTMSISA-N ocrf Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CO)[C@@H](C)CC)C(C)CC)[C@@H](C)O)C(C)C)C(C)O)C1=CNC=N1 AOCUKGFDRUSDQH-PIKKTMSISA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002734 organomagnesium group Chemical group 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- BHIIWXJHALLFBD-UHFFFAOYSA-N oxolane;propan-2-ol Chemical compound CC(C)O.C1CCOC1 BHIIWXJHALLFBD-UHFFFAOYSA-N 0.000 description 1
- 150000002926 oxygen Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000037324 pain perception Effects 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- QJPQVXSHYBGQGM-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 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- 208000021090 palsy Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 229950007002 phosphocreatine Drugs 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000020685 sleep-wake disease Diseases 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 229940062627 tribasic potassium phosphate Drugs 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-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
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- MMSLSKDMIZOHRX-WYDAWZGFSA-N α-helical crf(9-41) Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(N)=O MMSLSKDMIZOHRX-WYDAWZGFSA-N 0.000 description 1
Classifications
-
- 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
-
- 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
- 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
- A61P25/22—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
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Addiction (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US5162897P | 1997-07-03 | 1997-07-03 | |
US8066598P | 1998-04-03 | 1998-04-03 | |
PCT/US1998/013913 WO1999001454A1 (en) | 1997-07-03 | 1998-07-02 | Imidazopyrimidines and imidazopyridines for the treatment of neurological disorders |
Publications (3)
Publication Number | Publication Date |
---|---|
NO996483D0 NO996483D0 (no) | 1999-12-27 |
NO996483L NO996483L (no) | 2000-03-02 |
NO316119B1 true NO316119B1 (no) | 2003-12-15 |
Family
ID=26729655
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19996483A NO316119B1 (no) | 1997-07-03 | 1999-12-27 | Imidasopyrimidiner og imidasopyridiner, farmasöytisk sammensetning inneholdende samme og anvendelse av samme for fremstilling av medikamentet |
Country Status (20)
Country | Link |
---|---|
US (3) | US6143743A (zh) |
EP (1) | EP0994877A1 (zh) |
JP (1) | JP2002507996A (zh) |
KR (1) | KR20010014431A (zh) |
CN (1) | CN1268137A (zh) |
AR (1) | AR016307A1 (zh) |
AU (1) | AU746706B2 (zh) |
BR (1) | BR9810508A (zh) |
CA (1) | CA2294117A1 (zh) |
EE (1) | EE04280B1 (zh) |
HR (1) | HRP980375A2 (zh) |
HU (1) | HUP0100179A3 (zh) |
IL (1) | IL133800A0 (zh) |
MY (1) | MY132871A (zh) |
NO (1) | NO316119B1 (zh) |
NZ (1) | NZ502642A (zh) |
PL (1) | PL337888A1 (zh) |
SK (1) | SK179899A3 (zh) |
TW (1) | TW589309B (zh) |
WO (1) | WO1999001454A1 (zh) |
Families Citing this family (74)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MXPA03006730A (es) * | 1996-12-11 | 2003-10-24 | Aventis Pharma Inc | Preparacion de 4-hidroxi-3-nitro-2(1h)-piridona. |
US6124463A (en) * | 1998-07-02 | 2000-09-26 | Dupont Pharmaceuticals | Benzimidazoles as corticotropin release factor antagonists |
US6365589B1 (en) * | 1998-07-02 | 2002-04-02 | Bristol-Myers Squibb Pharma Company | Imidazo-pyridines, -pyridazines, and -triazines as corticotropin releasing factor antagonists |
ATE280171T1 (de) * | 1998-12-23 | 2004-11-15 | Bristol Myers Squibb Pharma Co | Stickstoffhaltige heterobicyclen als faktor-xa- hemmer |
US6271380B1 (en) * | 1998-12-30 | 2001-08-07 | Dupont Pharmaceuticals Company | 1H-imidazo[4,5-d]pyridazin-7-ones, 3H-imidazo-[4,5-c]pyridin-4-ones and corresponding thiones as corticotropin releasing factor (CRF) receptor ligands |
AU4331500A (en) | 1999-04-06 | 2000-10-23 | Du Pont Pharmaceuticals Company | Pyrazolotriazines as crf antagonists |
WO2000059908A2 (en) | 1999-04-06 | 2000-10-12 | Du Pont Pharmaceuticals Company | Pyrazolopyrimidines as crf antagonists |
US6432989B1 (en) * | 1999-08-27 | 2002-08-13 | Pfizer Inc | Use of CRF antagonists to treat circadian rhythm disorders |
US7045529B2 (en) * | 1999-12-17 | 2006-05-16 | Bristol-Myers Squibb Company | Imidazopyrimidinyl and imidazopyri dinyl derivatives |
CA2398956A1 (en) * | 2000-02-14 | 2001-08-16 | Japan Tobacco Inc. | A pharmaceutical composition for prophylaxis or therapy of a postoperative stress |
US20040077605A1 (en) * | 2001-06-20 | 2004-04-22 | Salvati Mark E. | Fused heterocyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function |
AR028782A1 (es) | 2000-07-05 | 2003-05-21 | Taisho Pharmaceutical Co Ltd | Derivados heterociclicos tetrahidropiridino o piperidino |
CA2419626A1 (en) | 2000-07-14 | 2002-01-24 | Rajagopal Bakthavatachalam | Imidazo¬1,2-a|pyrazines for the treatment of neurological disorders |
EP1854798A3 (en) | 2000-09-19 | 2007-11-28 | Bristol-Myers Squibb Company | Fused heterocyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function |
GB0100623D0 (en) | 2001-01-10 | 2001-02-21 | Vernalis Res Ltd | Chemical compounds IV |
CN1499972A (zh) | 2001-01-26 | 2004-05-26 | ����˹�ж�-����˹˹������˾ | 用作促肾上腺皮质激素释放因子抑制剂的咪唑基衍生物 |
TWI312347B (en) | 2001-02-08 | 2009-07-21 | Eisai R&D Man Co Ltd | Bicyclic nitrogen-containing condensed ring compounds |
US20040087548A1 (en) | 2001-02-27 | 2004-05-06 | Salvati Mark E. | Fused cyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function |
WO2002072202A1 (en) | 2001-03-13 | 2002-09-19 | Bristol-Myers Squibb Pharma Company | 4-(2-butylamino)-2,7-dimethyl-8-(2-methyl-6-methoxypyrid-3-yl) pyrazolo-[1,5-a]-1,3,5-triazine, its enantiomers and pharmaceutically acceptable salts as corticotropin releasing factor receptor ligands |
PL214231B1 (pl) | 2001-04-27 | 2013-07-31 | Eisai R & D Man Co | Pochodne pirazolo [1,5-a] pirydyny, kompozycje je zawierajace oraz zastosowanie |
RU2003135424A (ru) | 2001-05-14 | 2005-05-20 | Бристол-Маерс Сквибб Фарма Компани (Us) | Замещенные пиразиноны, пиридины и пиримидины в качестве лигандов кортикотропин высвобождающего фактора |
US6894045B2 (en) | 2001-07-12 | 2005-05-17 | Bristol-Myers Squibb Pharma Company | Tetrahydropurinones and derivatives thereof as corticotropin releasing factor receptor ligands |
WO2003006015A1 (en) | 2001-07-13 | 2003-01-23 | Bristol-Myers Squibb Pharma Company | Substituted thiazoles and oxazoles as corticotropin releasing hormone ligands |
US20070129334A1 (en) * | 2001-10-30 | 2007-06-07 | Conforma Therapeutics Corporation | Orally Active Purine-Based Inhibitors of Heat Shock Protein 90 |
EP2336133A1 (en) * | 2001-10-30 | 2011-06-22 | Conforma Therapeutics Corporation | Purine analogs having HSP90-inhibiting activity |
US20030119831A1 (en) | 2001-11-20 | 2003-06-26 | Hartz Richard A. | 3,7-dihydro-purine-2,6-dione derivatives as CRF receptor ligands |
MXPA04006614A (es) * | 2002-01-07 | 2004-10-04 | Eisai Co Ltd | Deazapurinas y usos de las mismas. |
EP1485384A1 (en) | 2002-03-13 | 2004-12-15 | Pharmacia & Upjohn Company LLC | Pyrazolo(1,5-a)pyridine derivatives as neurotransmitter modulators |
US6884880B2 (en) * | 2002-08-21 | 2005-04-26 | Ash Stevens, Inc. | Process for the preparation of 9-β-anomeric nucleoside analogs |
US7067658B2 (en) | 2002-09-30 | 2006-06-27 | Bristol-Myers Squibb Company | Pyridino and pyrimidino pyrazinones |
US7176216B2 (en) | 2002-10-22 | 2007-02-13 | Eisai Co., Ltd. | 7-phenylpyrazolopyridine compounds |
US7323569B2 (en) | 2002-10-22 | 2008-01-29 | Eisai R&D Management Co., Ltd. | 7-phenylpyrazolopyridine compounds |
US7332508B2 (en) * | 2002-12-18 | 2008-02-19 | Novo Nordisk A/S | Substituted homopiperidine, piperidine or pyrrolidine derivatives |
EP1633756B1 (en) | 2003-04-09 | 2008-12-24 | Biogen Idec MA Inc. | A2a adenosine receptor antagonists |
US7674791B2 (en) | 2003-04-09 | 2010-03-09 | Biogen Idec Ma Inc. | Triazolopyrazines and methods of making and using the same |
WO2004092170A2 (en) | 2003-04-09 | 2004-10-28 | Biogen Idec Ma Inc. | Triazolotriazines and pyrazolotriazines useful as a2a adenosine receptor antagon ists |
EA010160B1 (ru) | 2003-09-18 | 2008-06-30 | Конформа Терапьютикс Корпорейшн | Новые гетероциклические соединения - ингибиторы hsp90 и способы их получения |
US7459562B2 (en) * | 2004-04-23 | 2008-12-02 | Bristol-Myers Squibb Company | Monocyclic heterocycles as kinase inhibitors |
TW200538453A (en) | 2004-04-26 | 2005-12-01 | Bristol Myers Squibb Co | Bicyclic heterocycles as kinase inhibitors |
US7173031B2 (en) | 2004-06-28 | 2007-02-06 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
US7439246B2 (en) * | 2004-06-28 | 2008-10-21 | Bristol-Myers Squibb Company | Fused heterocyclic kinase inhibitors |
US7432373B2 (en) * | 2004-06-28 | 2008-10-07 | Bristol-Meyers Squibb Company | Processes and intermediates useful for preparing fused heterocyclic kinase inhibitors |
US7572805B2 (en) | 2004-07-14 | 2009-08-11 | Bristol-Myers Squibb Company | Pyrrolo(oxo)isoquinolines as 5HT ligands |
DE102004037554A1 (de) * | 2004-08-03 | 2006-03-16 | Sanofi-Aventis Deutschland Gmbh | Substituierte 8-Aminoalkylthio-xanthine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
DE102004039507A1 (de) * | 2004-08-14 | 2006-03-02 | Sanofi-Aventis Deutschland Gmbh | Substituierte 8-Aminoalkoxi-xanthine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
EP1846410B1 (en) * | 2005-02-10 | 2009-01-21 | Bristol-Myers Squibb Company | Dihydroquinazolinones as 5ht modulators |
NZ561939A (en) * | 2005-03-30 | 2011-03-31 | Conforma Therapeutics Corp | Alkynyl pyrrolopyrimidines and related analogs as HSP90-inhibitors |
BRPI0614485A2 (pt) * | 2005-07-28 | 2011-03-29 | Bristol-Myers Squibb Company | tetrahidro-1h-pirido [4, 3, b] indóis substituìdos como agonistas e antagonistas receptores de serotonina |
US7795436B2 (en) * | 2005-08-24 | 2010-09-14 | Bristol-Myers Squibb Company | Substituted tricyclic heterocycles as serotonin receptor agonists and antagonists |
GB0519245D0 (en) * | 2005-09-20 | 2005-10-26 | Vernalis R&D Ltd | Purine compounds |
EP1937258A2 (en) * | 2005-09-23 | 2008-07-02 | Conforma Therapeutics Corporation | Anti-tumor methods using multi drug resistance independent synthetic hsp90 inhibitors |
EA026126B1 (ru) * | 2006-11-22 | 2017-03-31 | Инсайт Холдингс Корпорейшн | Имидазотриазины и имидазопиримидины в качестве ингибиторов киназы |
WO2008127584A1 (en) * | 2007-04-11 | 2008-10-23 | Merck & Co., Inc. | Cgrp receptor antagonists with tertiary amide, sulfonamide, carbamate and urea end groups |
RU2681081C2 (ru) | 2007-10-05 | 2019-03-04 | Верастэм, Инк. | Пиримидинзамещенные производные пурина, фармацевтическая композиция на их основе, способ ингибирования протеинкиназ, способ лечения или профилактики заболеваний, чувствительных к ингибированию протеинкиназ, и способ лечения пролиферативных заболеваний |
SI2266990T1 (sl) | 2008-04-15 | 2013-01-31 | Eisai R&D Management Co. Ltd. | Spojina 3-fenilpirazolo(5,1-b)tiazola |
WO2009152584A1 (en) * | 2008-06-20 | 2009-12-23 | Macquarie University | Synthesis of ageladine a and analogs thereof |
FR2933982A1 (fr) * | 2008-07-18 | 2010-01-22 | Sanofi Aventis | Nouveaux derives imidazo°1,2-a!pyrimidine, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilisation notamment comme inhibiteurs de met |
CA2738429C (en) * | 2008-09-26 | 2016-10-25 | Intellikine, Inc. | Heterocyclic kinase inhibitors |
RU2506264C2 (ru) | 2009-04-03 | 2014-02-10 | Вэрастэм, Инк. | Пиримидин-замещенные пуриновые соединения в качестве ингибиторов киназы (или киназ) |
AR078521A1 (es) | 2009-10-08 | 2011-11-16 | Eisai R&D Man Co Ltd | Compuesto pirazolotiazol |
JP2013520502A (ja) | 2010-02-25 | 2013-06-06 | メルク・シャープ・エンド・ドーム・コーポレイション | 有用な抗糖尿病薬である新規な環状ベンズイミダゾール誘導体 |
JP2013542202A (ja) | 2010-10-01 | 2013-11-21 | ブリストル−マイヤーズ スクイブ カンパニー | Cyp17修飾因子として有用である置換ベンゾイミダゾールおよびイミダゾピリジン化合物 |
EP2638041B1 (en) | 2010-11-12 | 2015-07-22 | Bristol-Myers Squibb Company | Substituted azaindazole compounds |
US8969586B2 (en) | 2011-09-27 | 2015-03-03 | Bristol-Myers Squibb Company | Substituted bicyclic heteroaryl compounds |
KR20150007300A (ko) * | 2012-05-08 | 2015-01-20 | 머크 샤프 앤드 돔 코포레이션 | Ror감마 활성의 억제를 위한 테트라히드로나프티리딘 및 관련 비시클릭 화합물 및 질환의 치료 |
EP2818472A1 (en) * | 2013-06-27 | 2014-12-31 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Imidazo[4,5-c]pyridine and pyrrolo[3,2-c]pyridine compounds as G-protein-coupled receptor kinase 5 (GRK5) modulators |
BR112016012243A2 (pt) * | 2013-12-09 | 2017-08-08 | Ucb Biopharma Sprl | Derivados de imidazopiridina como moduladores de atividade de tnf |
TWI731317B (zh) * | 2013-12-10 | 2021-06-21 | 美商健臻公司 | 原肌球蛋白相關之激酶(trk)抑制劑 |
WO2015088885A1 (en) * | 2013-12-11 | 2015-06-18 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
JP6645695B2 (ja) * | 2014-10-14 | 2020-02-14 | 中尾 洋一 | イミダゾピリジンアミン化合物、その製造方法及び用途 |
KR102561692B1 (ko) | 2014-12-18 | 2023-07-28 | 젠자임 코포레이션 | 트로포미오신-관련 키나제(trk) 억제제의 약제학적 제형 |
KR102665765B1 (ko) * | 2015-07-20 | 2024-05-10 | 젠자임 코포레이션 | 콜로니 자극 인자-1 수용체(csf-1r) 저해제 |
US11168082B2 (en) * | 2017-05-15 | 2021-11-09 | The Regents Of The University Of Michigan | Pyrrolo[2,3-C]pyridines and related analogs as LSD-1 inhibitors |
JP2024500919A (ja) | 2020-12-23 | 2024-01-10 | ジェンザイム・コーポレーション | 重水素化コロニー刺激因子-1受容体(csf-1r)阻害剤 |
Family Cites Families (89)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5015473A (en) * | 1984-01-30 | 1991-05-14 | Pfizer Inc. | 6-(substituted)methylenepenicillanic and 6-(substituted)hydroxymethylpenicillanic acids and derivatives thereof |
GB8601160D0 (en) * | 1986-01-17 | 1986-02-19 | Fujisawa Pharmaceutical Co | Heterocyclic compounds |
US4859672A (en) * | 1986-10-29 | 1989-08-22 | Rorer Pharmaceutical Corporation | Pyrido[2,3-d]pyrimidinone and imidazo[4,5-b]pyrimidinone |
US5495010A (en) * | 1987-04-17 | 1996-02-27 | The United States Of America As Represented By The Department Of Health And Human Services | Acid stable purine dideoxynucleosides |
US4999363A (en) * | 1988-06-09 | 1991-03-12 | Kyowa Hakko Kogyo Co., Ltd. | Tricyclic compounds |
KR900701787A (ko) * | 1988-07-19 | 1990-12-04 | 제임스 제이. 플린 | 치환된 페닐트리아졸로피리미딘 제초제 |
AU618158B2 (en) * | 1989-01-07 | 1991-12-12 | Bayer Aktiengesellschaft | New substituted pyrido(2,3-d)pyrimidines |
FR2643903A1 (fr) * | 1989-03-03 | 1990-09-07 | Union Pharma Scient Appl | Nouveaux derives de benzimidazole, leurs procedes de preparation, intermediaires de synthese, compositions pharmaceutiques les contenant, utiles notamment pour le traitement des maladies cardiovasculaires, et des ulceres duodenaux |
GB8906168D0 (en) * | 1989-03-17 | 1989-05-04 | Pfizer Ltd | Therapeutic agents |
DE3916469A1 (de) * | 1989-05-20 | 1990-11-22 | Basf Ag | Sulfonamide |
IE64514B1 (en) * | 1989-05-23 | 1995-08-09 | Zeneca Ltd | Azaindenes |
US5102880A (en) * | 1989-05-30 | 1992-04-07 | Merck & Co., Inc. | Substituted imidazo-fused 6-membered heterocycles as angiotensin II antagonists |
US5157026A (en) * | 1989-05-30 | 1992-10-20 | Merck & Co., Inc. | Oxo-purines as angiotensin II antagonists |
IL94390A (en) * | 1989-05-30 | 1996-03-31 | Merck & Co Inc | The 6-membered trans-nitrogen-containing heterocycles are compressed with imidazo and pharmaceutical preparations containing them |
DE3921271A1 (de) * | 1989-06-29 | 1991-01-03 | Basf Ag | Purinsulfonamide |
US5145959A (en) * | 1989-07-18 | 1992-09-08 | Bayer Aktiengesellschaft | Substituted pyrido (2,3-d) pyrimidines as intermediates |
EP0416740A3 (en) * | 1989-08-08 | 1991-08-28 | Beecham Group P.L.C. | Novel compounds with renin-inhibiting activity |
EP0415886A3 (en) * | 1989-08-30 | 1991-10-23 | Ciba-Geigy Ag | Aza compounds |
GB8927872D0 (en) * | 1989-12-08 | 1990-02-14 | Beecham Group Plc | Pharmaceuticals |
EP0434038A1 (en) * | 1989-12-22 | 1991-06-26 | Takeda Chemical Industries, Ltd. | Fused imidazole derivatives, their production and use |
US5587470A (en) * | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
AU653524B2 (en) * | 1990-06-08 | 1994-10-06 | Roussel-Uclaf | New imidazole derivatives, their preparation process, the new intermediates obtained, their use as medicaments and the pharmaceutical compositions containing them |
WO1991019715A1 (en) * | 1990-06-15 | 1991-12-26 | G.D. Searle & Co. | 1H-SUBSTITUTED-IMIDAZO[4,5-d]PYRIDAZINE COMPOUNDS FOR TREATMENT OF CARDIOVASCULAR DISORDERS |
DE4023369A1 (de) * | 1990-07-23 | 1992-01-30 | Thomae Gmbh Dr K | Benzimidazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
US5210092A (en) * | 1990-09-25 | 1993-05-11 | Fujisawa Pharmaceutical Co., Ltd. | Angiotensin ii antagonizing heterocyclic derivatives |
US5260322A (en) * | 1990-10-08 | 1993-11-09 | Merck & Co., Inc. | Angiotension II antagonists in the treatment of hyperuricemia |
CA2062558A1 (en) * | 1991-03-08 | 1992-09-09 | Prasun K. Chakravarty | Heterocyclic compounds bearing acidic functional groups as angiotensin ii antagonists |
CH681806A5 (zh) * | 1991-03-19 | 1993-05-28 | Ciba Geigy Ag | |
US5128327A (en) * | 1991-03-25 | 1992-07-07 | Merck & Co., Inc. | Angiotensin II antagonists incorporating a nitrogen containing six membered ring heterocycle |
TW274551B (zh) * | 1991-04-16 | 1996-04-21 | Takeda Pharm Industry Co Ltd | |
US5332820A (en) * | 1991-05-20 | 1994-07-26 | E. I. Du Pont De Nemours And Company | Dibenzobicyclo(2.2.2) octane angiotensin II antagonists |
KR100207360B1 (ko) * | 1991-06-14 | 1999-07-15 | 돈 더블유. 슈미츠 | 이미다조[1,5,-a]퀸옥살린 |
IL102183A (en) * | 1991-06-27 | 1999-11-30 | Takeda Chemical Industries Ltd | The heterocyclic compounds are converted into biphenyl groups, their production and the pharmaceutical compositions containing them |
AU2338992A (en) * | 1991-07-26 | 1993-03-02 | G.D. Searle & Co. | Carbonate-substituted imidazo(4,5-d) pyridazine compounds for treatment of cardiovascular disorders |
DE4129603A1 (de) * | 1991-09-06 | 1993-03-11 | Thomae Gmbh Dr K | Kondensierte 5-gliedrige heterocyclen, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
TW300219B (zh) * | 1991-09-14 | 1997-03-11 | Hoechst Ag | |
US5178997A (en) * | 1991-09-20 | 1993-01-12 | Eastman Kodak Company | Process for the preparation of high chloride tabular grain emulsions (II) |
US5187159A (en) * | 1991-10-07 | 1993-02-16 | Merck & Co., Inc. | Angiotensin II antagonists incorporating a substituted 1,3-benzodioxole or 1,3-benzodithiole |
US5330989A (en) * | 1991-10-24 | 1994-07-19 | American Home Products Corporation | Heterocycles substituted with biphenyl-3-cyclobutene-1,2-dione derivatives |
US5332814A (en) * | 1991-11-12 | 1994-07-26 | Ciba-Geigy Corporation | Process for the preparation of carbacyclic nucleosides, and intermediates |
US5176991A (en) * | 1992-01-27 | 1993-01-05 | Eastman Kodak Company | Process of preparing for photographic use high chloride tabular grain emulsion |
GB2263637A (en) * | 1992-01-28 | 1993-08-04 | Merck & Co Inc | Substituted imidazo-fused 6-membered carbocycle or heterocycle as neurotensin antagonists |
JPH05213754A (ja) * | 1992-02-03 | 1993-08-24 | Kyowa Hakko Kogyo Co Ltd | 抗潰瘍剤 |
IT1254798B (it) * | 1992-02-18 | 1995-10-11 | Snam Progetti | Procedimento per il riavviamento dell'esercizio di una condotta contente fluidi ad alto valore di sforzo sterile e dispositivi per la sua realizzazione. |
DE4207904A1 (de) * | 1992-03-12 | 1993-09-16 | Thomae Gmbh Dr K | Substituierte benzimidazolylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
JPH05287209A (ja) * | 1992-04-09 | 1993-11-02 | Hitachi Chem Co Ltd | 蛍光標識用色素、蛍光標識用色素で標識された生物由来物質、及びそれらを含有する試薬 |
GB9210400D0 (en) * | 1992-05-15 | 1992-07-01 | Merck Sharp & Dohme | Therapeutic agents |
CA2113561C (en) * | 1992-05-21 | 1999-09-14 | Kazuyoshi Miyata | Phosphonic diester derivative |
US5612360A (en) * | 1992-06-03 | 1997-03-18 | Eli Lilly And Company | Angiotensin II antagonists |
EP0577558A2 (de) * | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
EP0662078B1 (en) * | 1992-09-28 | 2003-05-02 | Research Corporation Technologies, Inc. | Reagents for peptide couplings |
TW251284B (zh) * | 1992-11-02 | 1995-07-11 | Pfizer | |
GB2272899A (en) * | 1992-11-30 | 1994-06-01 | Du Pont Merck Pharma | Angiotensin-11 receptor blocking cycloalkylbenzylimidazoles |
US5376666A (en) * | 1992-11-30 | 1994-12-27 | The Du Pont Merck Pharmaceutical Company | Angiotension-II receptor blocking, azacycloalkyl or azacycloalkenyl |
DE69332762T2 (de) * | 1992-12-02 | 2003-08-14 | Pfizer Inc., New York | Cathecoldiether als selektive pde iv hemmungsmittel |
CA2154681A1 (en) * | 1993-02-03 | 1994-08-18 | Mark David Erion | Adenosine kinase inhibitors comprising lyxofuranosyl derivatives |
DE4304455A1 (de) * | 1993-02-15 | 1994-08-18 | Bayer Ag | Heterocyclisch substituierte Phenyl-cyclohexan-carbonsäurederivate |
US5374638A (en) * | 1993-03-19 | 1994-12-20 | Merck & Co., Inc. | Six membered ring fused imidazoles substituted with phenoxyphenylacetic acid derivatives used to treat asthma |
DE4309969A1 (de) * | 1993-03-26 | 1994-09-29 | Bayer Ag | Substituierte heteroanellierte Imidazole |
US5338740A (en) * | 1993-07-13 | 1994-08-16 | Pfizer Inc. | Angiotensin II receptor antagonists |
CA2131134A1 (en) * | 1993-09-17 | 1995-03-18 | Gerhard Stucky | Process for preparing imidazopyridine derivatives |
CA2131680C (en) * | 1993-09-17 | 2006-11-07 | Gerhard Stucky | Process for preparing imidazopyridine derivatives |
WO1995010506A1 (en) * | 1993-10-12 | 1995-04-20 | The Du Pont Merck Pharmaceutical Company | 1n-alkyl-n-arylpyrimidinamines and derivatives thereof |
CA2136885A1 (en) * | 1993-12-01 | 1995-06-02 | David L. Kuo | Process for preparing imidazopyridine derivatives |
HU220423B (hu) * | 1994-01-26 | 2002-01-28 | Novartis Ag. | Módosított oligonukleotidok |
KR0151816B1 (ko) * | 1994-02-08 | 1998-10-15 | 강박광 | 신규의 치환된 피리딜 이미다졸 유도체 및 그의 제조방법 |
NZ276172A (en) * | 1994-02-10 | 1998-02-26 | Pfizer | 5-heteroarylindole derivatives as benzodiazepine receptor site agonists and antagonists, 5-(hetero)arylaminoindole intermediates |
ES2203635T3 (es) * | 1994-04-27 | 2004-04-16 | Novartis Ag | Nucleosidos y oligonucleotidos con grupos 2'-eter. |
US5424432A (en) * | 1994-05-26 | 1995-06-13 | Merck & Co., Inc. | Process for the preparation of imidazolutidine |
KR100263429B1 (ko) * | 1994-06-06 | 2000-08-01 | 디. 제이. 우드 | 코르티코트로핀-방출 인자(crf) 길항 활성을 갖는 치환된 피라졸 |
TW574214B (en) * | 1994-06-08 | 2004-02-01 | Pfizer | Corticotropin releasing factor antagonists |
KR0151819B1 (ko) * | 1994-06-11 | 1998-10-15 | 강박광 | 신규의 피리딜 n-옥사이드로 치환된 피디딜이미다졸 유도체 및 그의 제조방법 |
CZ287613B6 (en) * | 1994-06-16 | 2001-01-17 | Pfizer | Pyrazolo- and pyrrolopyridines and pharmaceutical preparations based thereon |
SE9402431D0 (sv) * | 1994-07-08 | 1994-07-08 | Astra Ab | New tablet formulation |
SE504459C2 (sv) * | 1994-07-15 | 1997-02-17 | Astra Ab | Förfarande för framställning av substituerade sulfoxider |
US5597826A (en) * | 1994-09-14 | 1997-01-28 | Pfizer Inc. | Compositions containing sertraline and a 5-HT1D receptor agonist or antagonist |
US5563143A (en) * | 1994-09-21 | 1996-10-08 | Pfizer Inc. | Catechol diether compounds as inhibitors of TNF release |
GB9423970D0 (en) * | 1994-11-28 | 1995-01-11 | Astra Ab | Oxidation |
GB9423968D0 (en) * | 1994-11-28 | 1995-01-11 | Astra Ab | Resolution |
AU4303996A (en) * | 1994-12-19 | 1996-07-10 | Novartis Ag | 6'-substituted carbocyclic nucleosides |
SE9500422D0 (sv) * | 1995-02-06 | 1995-02-06 | Astra Ab | New oral pharmaceutical dosage forms |
SE9500478D0 (sv) * | 1995-02-09 | 1995-02-09 | Astra Ab | New pharmaceutical formulation and process |
US6403599B1 (en) * | 1995-11-08 | 2002-06-11 | Pfizer Inc | Corticotropin releasing factor antagonists |
WO1997008150A1 (en) * | 1995-08-22 | 1997-03-06 | The Du Pont Merck Pharmaceutical Company | Substituted cyclic ureas and derivatives thereof useful as retroviral protease inhibitors |
DE19536891A1 (de) * | 1995-10-04 | 1997-04-10 | Basf Ag | Neue Aminosäurederivate, ihre Herstellung und Verwendung |
DE19614533A1 (de) * | 1996-04-12 | 1997-10-16 | Basf Ag | Neue alpha-Hydroxysäurederivate, ihre Herstellung und Verwendung |
US6022978A (en) * | 1996-06-11 | 2000-02-08 | Pfizer Inc. | Benzimidazole derivatives |
EP0923582B1 (en) * | 1996-08-28 | 2006-09-20 | Pfizer Inc. | Substituted 6,5-hetero-bicyclic derivatives |
WO1998035967A2 (en) | 1997-02-18 | 1998-08-20 | Neurocrine Biosciences, Inc. | Biazacyclic crf antagonists |
-
1998
- 1998-07-02 HR HR60/080,665A patent/HRP980375A2/hr not_active Application Discontinuation
- 1998-07-02 HU HU0100179A patent/HUP0100179A3/hu unknown
- 1998-07-02 AU AU81819/98A patent/AU746706B2/en not_active Ceased
- 1998-07-02 WO PCT/US1998/013913 patent/WO1999001454A1/en not_active Application Discontinuation
- 1998-07-02 CN CN98808584A patent/CN1268137A/zh active Pending
- 1998-07-02 EP EP98931795A patent/EP0994877A1/en not_active Withdrawn
- 1998-07-02 JP JP50744099A patent/JP2002507996A/ja active Pending
- 1998-07-02 KR KR1019997012619A patent/KR20010014431A/ko not_active Application Discontinuation
- 1998-07-02 PL PL98337888A patent/PL337888A1/xx unknown
- 1998-07-02 MY MYPI98003027A patent/MY132871A/en unknown
- 1998-07-02 SK SK1798-99A patent/SK179899A3/sk unknown
- 1998-07-02 CA CA002294117A patent/CA2294117A1/en not_active Abandoned
- 1998-07-02 IL IL13380098A patent/IL133800A0/xx unknown
- 1998-07-02 TW TW087110857A patent/TW589309B/zh active
- 1998-07-02 BR BR9810508-6A patent/BR9810508A/pt not_active IP Right Cessation
- 1998-07-02 US US09/109,877 patent/US6143743A/en not_active Expired - Lifetime
- 1998-07-02 NZ NZ502642A patent/NZ502642A/en unknown
- 1998-07-02 EE EEP199900607A patent/EE04280B1/xx not_active IP Right Cessation
- 1998-07-03 AR ARP980103234A patent/AR016307A1/es not_active Application Discontinuation
- 1998-12-10 US US09/208,778 patent/US6362180B1/en not_active Expired - Lifetime
-
1999
- 1999-12-27 NO NO19996483A patent/NO316119B1/no not_active IP Right Cessation
-
2001
- 2001-11-07 US US10/053,475 patent/US6642230B2/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
HUP0100179A2 (hu) | 2001-11-28 |
BR9810508A (pt) | 2000-09-05 |
US6362180B1 (en) | 2002-03-26 |
HRP980375A2 (en) | 1999-04-30 |
MY132871A (en) | 2007-10-31 |
NO996483L (no) | 2000-03-02 |
EE9900607A (et) | 2000-08-15 |
SK179899A3 (en) | 2001-12-03 |
CA2294117A1 (en) | 1999-01-14 |
CN1268137A (zh) | 2000-09-27 |
IL133800A0 (en) | 2001-04-30 |
AU746706B2 (en) | 2002-05-02 |
NO996483D0 (no) | 1999-12-27 |
HUP0100179A3 (en) | 2002-12-28 |
WO1999001454A1 (en) | 1999-01-14 |
NZ502642A (en) | 2002-06-28 |
AU8181998A (en) | 1999-01-25 |
AR016307A1 (es) | 2001-07-04 |
US6642230B2 (en) | 2003-11-04 |
TW589309B (en) | 2004-06-01 |
US20030114468A1 (en) | 2003-06-19 |
JP2002507996A (ja) | 2002-03-12 |
US6143743A (en) | 2000-11-07 |
EP0994877A1 (en) | 2000-04-26 |
EE04280B1 (et) | 2004-04-15 |
KR20010014431A (ko) | 2001-02-26 |
PL337888A1 (en) | 2000-09-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO316119B1 (no) | Imidasopyrimidiner og imidasopyridiner, farmasöytisk sammensetning inneholdende samme og anvendelse av samme for fremstilling av medikamentet | |
EP1238979B1 (en) | Fused heterotricyclic compounds, process for preparing the compounds and drugs containing the same | |
US20040082784A1 (en) | Pyridino and pyrimidino pyrazinones | |
EP1344779B1 (en) | Azolo-pyrimidines | |
US20060211696A1 (en) | IMIDAZO[1,2-b]PYRIDAZINE COMPOUND | |
US20050197352A1 (en) | Imidazo-substituted compounds as p38 kinase inhibitors | |
JP2002515032A (ja) | アリールアミノ縮合ピリジンおよびアリールアミノ縮合ピリミジン | |
WO1999011643A1 (en) | Heterocyclyl-substituted ring-fused pyridines and pyrimidines as corticotropin releasing hormone (crh) antagonists, useful for treating cns and stress-related disorders | |
TW201118096A (en) | CGRP receptor antagonists | |
EP1140929B1 (en) | 1h-imidazo 4,5-d]pyridazin-7-ones, 3h-imidazo 4,5-c]pyridin-4-ones and corresponding thiones as corticotropin releasing factor (crf) receptor ligands | |
EP1091961A1 (en) | Imidazo-pyridines, -pyridazines, and -triazines as corticotropin releasing factor antagonists | |
US6174912B1 (en) | Nitrogen substituted imidazo[4,5-C]pyrazoles as corticotropin releasing hormone antagonists | |
US20100056491A1 (en) | 4'-amino cyclic compounds having 5-ht6 receptor affinity | |
JP4704521B2 (ja) | アゾロトリアジン類およびアゾロピリミジン類 | |
US7045529B2 (en) | Imidazopyrimidinyl and imidazopyri dinyl derivatives | |
AU9021598A (en) | Nitrogen substituted imidazo{4,5-c}pyrazoles as corticotropin relea sing hormone antagonists | |
AU2011279722A1 (en) | Novel tetrahydropyrazolo[3,4-B]azepine derivatives and their use as allosteric modulators of metabotropic glutamate receptors | |
CZ453799A3 (cs) | Imidazopyrimidiny a imidazopyridiny pro léčení neurologických poruch | |
WO2003018546A2 (en) | Tricyclic pyridin-2-one analogues as ligands for gaba-a receptors |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |