NO333647B1 - Triazolderivater, farmasoytiske sammensetninger som innbefatter nevnte derivater, samt anvendelse av derivatene til fremstilling av medikament - Google Patents
Triazolderivater, farmasoytiske sammensetninger som innbefatter nevnte derivater, samt anvendelse av derivatene til fremstilling av medikament Download PDFInfo
- Publication number
- NO333647B1 NO333647B1 NO20045120A NO20045120A NO333647B1 NO 333647 B1 NO333647 B1 NO 333647B1 NO 20045120 A NO20045120 A NO 20045120A NO 20045120 A NO20045120 A NO 20045120A NO 333647 B1 NO333647 B1 NO 333647B1
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- trifluoromethyl
- bis
- benzyl
- chloro
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 14
- 239000003814 drug Substances 0.000 title claims description 12
- 238000004519 manufacturing process Methods 0.000 title description 55
- 229940042055 systemic antimycotics triazole derivative Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 429
- 238000002360 preparation method Methods 0.000 claims abstract description 78
- 150000003839 salts Chemical class 0.000 claims abstract description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 146
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 110
- -1 cyano, difluoromethyl Chemical group 0.000 claims description 84
- 229910052757 nitrogen Inorganic materials 0.000 claims description 59
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 58
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- 239000001257 hydrogen Substances 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 17
- 208000019901 Anxiety disease Diseases 0.000 claims description 17
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 230000036506 anxiety Effects 0.000 claims description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 12
- 102000003141 Tachykinin Human genes 0.000 claims description 11
- 108060008037 tachykinin Proteins 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 239000011593 sulfur Substances 0.000 claims description 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
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- 208000020401 Depressive disease Diseases 0.000 claims description 6
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000005554 pyridyloxy group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 101100379079 Emericella variicolor andA gene Proteins 0.000 claims description 3
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- 101150115538 nero gene Proteins 0.000 claims description 3
- 240000001987 Pyrus communis Species 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- YONKORPAAADXNO-UHFFFAOYSA-N N'-[(2-chlorophenyl)methyl]ethane-1,2-diamine dihydrochloride Chemical compound Cl.Cl.NCCNCC1=CC=CC=C1Cl YONKORPAAADXNO-UHFFFAOYSA-N 0.000 claims 1
- WDWKUSVIIQGHQR-UHFFFAOYSA-N [2-[1-[[3,5-bis(trifluoromethyl)phenyl]methyl]-5-pyrazin-2-yltriazol-4-yl]pyridin-3-yl]-(2-chlorophenyl)methanone Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CN2C(=C(N=N2)C=2C(=CC=CN=2)C(=O)C=2C(=CC=CC=2)Cl)C=2N=CC=NC=2)=C1 WDWKUSVIIQGHQR-UHFFFAOYSA-N 0.000 claims 1
- CAVRKWRKTNINFF-UHFFFAOYSA-N [2-[1-[[3,5-bis(trifluoromethyl)phenyl]methyl]-5-pyridin-4-yltriazol-4-yl]pyridin-3-yl]-(2-chlorophenyl)methanone Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CN2C(=C(N=N2)C=2C(=CC=CN=2)C(=O)C=2C(=CC=CC=2)Cl)C=2C=CN=CC=2)=C1 CAVRKWRKTNINFF-UHFFFAOYSA-N 0.000 claims 1
- SJMNZGLLWWUYIN-UHFFFAOYSA-N [3-[1-[[3,5-bis(trifluoromethyl)phenyl]methyl]-5-pyridin-4-yltriazol-4-yl]-5-(2-hydroxypropan-2-yl)-1,2-oxazol-4-yl]-(2-chlorophenyl)methanone Chemical compound C=1C=CC=C(Cl)C=1C(=O)C1=C(C(C)(O)C)ON=C1C(=C1C=2C=CN=CC=2)N=NN1CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 SJMNZGLLWWUYIN-UHFFFAOYSA-N 0.000 claims 1
- 229910052614 beryl Inorganic materials 0.000 claims 1
- 125000000068 chlorophenyl group Chemical group 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- RCRKCUFVQRCCSF-UHFFFAOYSA-N tert-butyl n-[2-[[1-[[3,5-bis(trifluoromethyl)phenyl]methyl]-5-morpholin-4-yltriazole-4-carbonyl]-[1-(2-chlorophenyl)ethyl]amino]ethyl]carbamate Chemical compound C=1C=CC=C(Cl)C=1C(C)N(CCNC(=O)OC(C)(C)C)C(=O)C(=C1N2CCOCC2)N=NN1CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 RCRKCUFVQRCCSF-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 128
- 239000000543 intermediate Substances 0.000 abstract description 15
- 102000007124 Tachykinin Receptors Human genes 0.000 abstract description 6
- 108010072901 Tachykinin Receptors Proteins 0.000 abstract description 6
- 230000008569 process Effects 0.000 abstract description 2
- 239000003112 inhibitor Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 403
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 337
- 239000000243 solution Substances 0.000 description 191
- 235000019439 ethyl acetate Nutrition 0.000 description 187
- 235000008504 concentrate Nutrition 0.000 description 164
- 239000012141 concentrate Substances 0.000 description 164
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 144
- 238000003756 stirring Methods 0.000 description 138
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 134
- 239000000203 mixture Substances 0.000 description 123
- 238000006243 chemical reaction Methods 0.000 description 96
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 92
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 92
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 86
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 84
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
- 229910001868 water Inorganic materials 0.000 description 72
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 71
- 239000000284 extract Substances 0.000 description 70
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- 229910002027 silica gel Inorganic materials 0.000 description 63
- 239000002904 solvent Substances 0.000 description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 62
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 54
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 52
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 52
- 238000003818 flash chromatography Methods 0.000 description 50
- 229920006395 saturated elastomer Polymers 0.000 description 50
- 239000000460 chlorine Substances 0.000 description 46
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 45
- 239000012267 brine Substances 0.000 description 45
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 45
- 238000004587 chromatography analysis Methods 0.000 description 44
- 208000035475 disorder Diseases 0.000 description 44
- 239000012044 organic layer Substances 0.000 description 44
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
- 239000007858 starting material Substances 0.000 description 38
- 150000001299 aldehydes Chemical class 0.000 description 35
- 238000005160 1H NMR spectroscopy Methods 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 31
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- 238000004809 thin layer chromatography Methods 0.000 description 30
- 238000010992 reflux Methods 0.000 description 28
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
- 239000000047 product Substances 0.000 description 25
- 150000003254 radicals Chemical class 0.000 description 25
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
- 229960000583 acetic acid Drugs 0.000 description 20
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- 238000005481 NMR spectroscopy Methods 0.000 description 19
- 150000001345 alkine derivatives Chemical class 0.000 description 19
- 150000001412 amines Chemical class 0.000 description 19
- 239000013058 crude material Substances 0.000 description 19
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 description 18
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 description 18
- 125000005843 halogen group Chemical group 0.000 description 18
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 18
- 239000000463 material Substances 0.000 description 18
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
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- 235000019341 magnesium sulphate Nutrition 0.000 description 16
- 238000001819 mass spectrum Methods 0.000 description 16
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 16
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 15
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- 239000002585 base Substances 0.000 description 14
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 14
- 239000007787 solid Substances 0.000 description 13
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
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- TWJIMGNLEFJLDH-UHFFFAOYSA-N (2-bromopyridin-3-yl)-(2-chlorophenyl)methanone Chemical compound ClC1=CC=CC=C1C(=O)C1=CC=CN=C1Br TWJIMGNLEFJLDH-UHFFFAOYSA-N 0.000 description 5
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- IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 1
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- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
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- BHZSCNYTYGSATR-UHFFFAOYSA-N n-[[1-[[3,5-bis(trifluoromethyl)phenyl]methyl]-5-pyridin-3-yltriazol-4-yl]methylidene]hydroxylamine Chemical compound C=1C=CN=CC=1C1=C(C=NO)N=NN1CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 BHZSCNYTYGSATR-UHFFFAOYSA-N 0.000 description 1
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- 239000012038 nucleophile Substances 0.000 description 1
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- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
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- 125000004043 oxo group Chemical group O=* 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 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 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
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- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
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- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
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- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
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- LBKJNHPKYFYCLL-UHFFFAOYSA-N potassium;trimethyl(oxido)silane Chemical compound [K+].C[Si](C)(C)[O-] LBKJNHPKYFYCLL-UHFFFAOYSA-N 0.000 description 1
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- 150000003138 primary alcohols Chemical class 0.000 description 1
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
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- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
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- 239000000377 silicon dioxide Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
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- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
- VXEQUGMKLVUAPM-UHFFFAOYSA-N tert-butyl n-[2-(2-chlorobenzoyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC=C1C(=O)C1=CC=CC=C1Cl VXEQUGMKLVUAPM-UHFFFAOYSA-N 0.000 description 1
- OIGUUHQDFKRTHG-UHFFFAOYSA-N tert-butyl n-[2-[(2-chlorophenyl)-hydroxymethyl]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC=C1C(O)C1=CC=CC=C1Cl OIGUUHQDFKRTHG-UHFFFAOYSA-N 0.000 description 1
- KZZHPWMVEVZEFG-UHFFFAOYSA-N tert-butyl n-phenylcarbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC=C1 KZZHPWMVEVZEFG-UHFFFAOYSA-N 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
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- VTORJPDWMOIOIQ-UHFFFAOYSA-N tert-butyl(diphenyl)silane Chemical compound C=1C=CC=CC=1[SiH](C(C)(C)C)C1=CC=CC=C1 VTORJPDWMOIOIQ-UHFFFAOYSA-N 0.000 description 1
- ZYDKYFIXEYSNPO-UHFFFAOYSA-N tert-butyl-dimethyl-prop-2-ynoxysilane Chemical compound CC(C)(C)[Si](C)(C)OCC#C ZYDKYFIXEYSNPO-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- GMRIOAVKKGNMMV-UHFFFAOYSA-N tetrabutylazanium;azide Chemical compound [N-]=[N+]=[N-].CCCC[N+](CCCC)(CCCC)CCCC GMRIOAVKKGNMMV-UHFFFAOYSA-N 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 238000001149 thermolysis Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- LJJKNPQAGWVLDQ-SNVBAGLBSA-N thiorphan Chemical compound OC(=O)CNC(=O)[C@@H](CS)CC1=CC=CC=C1 LJJKNPQAGWVLDQ-SNVBAGLBSA-N 0.000 description 1
- XOLBLPGZBRYERU-UHFFFAOYSA-N tin dioxide Chemical compound O=[Sn]=O XOLBLPGZBRYERU-UHFFFAOYSA-N 0.000 description 1
- 229910001887 tin oxide Inorganic materials 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
- NDLIRBZKZSDGSO-UHFFFAOYSA-N tosyl azide Chemical compound CC1=CC=C(S(=O)(=O)[N-][N+]#N)C=C1 NDLIRBZKZSDGSO-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- PYICBYXAIVIUQH-UHFFFAOYSA-N tributyl(2-cyclopropylethynyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C#CC1CC1 PYICBYXAIVIUQH-UHFFFAOYSA-N 0.000 description 1
- FRCSTQBKEPXWPO-UHFFFAOYSA-N tributyl(2-morpholin-4-ylethynyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C#CN1CCOCC1 FRCSTQBKEPXWPO-UHFFFAOYSA-N 0.000 description 1
- UPIWXVYQSVXLIA-UHFFFAOYSA-N tributyl(2-pyridin-2-ylethynyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C#CC1=CC=CC=N1 UPIWXVYQSVXLIA-UHFFFAOYSA-N 0.000 description 1
- OFZQLPFIDGYEDE-UHFFFAOYSA-N tributyl(2-pyridin-4-ylethynyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C#CC1=CC=NC=C1 OFZQLPFIDGYEDE-UHFFFAOYSA-N 0.000 description 1
- KCQJLTOSSVXOCC-UHFFFAOYSA-N tributyl(prop-1-ynyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C#CC KCQJLTOSSVXOCC-UHFFFAOYSA-N 0.000 description 1
- JNRUXZIXAXHXTN-UHFFFAOYSA-N trimethyl(2-methylbut-3-yn-2-yloxy)silane Chemical compound C#CC(C)(C)O[Si](C)(C)C JNRUXZIXAXHXTN-UHFFFAOYSA-N 0.000 description 1
- BESYUGWNHQDZIK-UHFFFAOYSA-N trimethyl(2-pyrimidin-5-ylethynyl)silane Chemical compound C[Si](C)(C)C#CC1=CN=CN=C1 BESYUGWNHQDZIK-UHFFFAOYSA-N 0.000 description 1
- XFMVJXSNKUYCHF-UHFFFAOYSA-N trimethyl-(2-methyl-1-nitropropan-2-yl)oxysilane Chemical compound [O-][N+](=O)CC(C)(C)O[Si](C)(C)C XFMVJXSNKUYCHF-UHFFFAOYSA-N 0.000 description 1
- DNRFJJMFYWJGIY-UHFFFAOYSA-N trimethyl-[2-(pyridin-3-yloxymethoxy)ethyl]silane Chemical compound C[Si](C)(C)CCOCOC1=CC=CN=C1 DNRFJJMFYWJGIY-UHFFFAOYSA-N 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- NYVOYAFUSJONHU-UHFFFAOYSA-K trisodium;1,3,5-triazine-2,4,6-trithiolate Chemical compound [Na+].[Na+].[Na+].[S-]C1=NC([S-])=NC([S-])=N1 NYVOYAFUSJONHU-UHFFFAOYSA-K 0.000 description 1
- 230000002455 vasospastic effect Effects 0.000 description 1
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- 238000005303 weighing Methods 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
-
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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US37612102P | 2002-04-26 | 2002-04-26 | |
PCT/US2003/010681 WO2003091226A1 (en) | 2002-04-26 | 2003-04-22 | Triazole derivatives as tachykinin receptor antagonists |
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NO20045120L NO20045120L (no) | 2004-12-07 |
NO333647B1 true NO333647B1 (no) | 2013-07-29 |
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EP (1) | EP1501809B1 (es) |
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CN (1) | CN1312136C (es) |
AR (1) | AR039329A1 (es) |
AT (1) | ATE384053T1 (es) |
AU (1) | AU2003230829B8 (es) |
BR (1) | BRPI0309534B8 (es) |
CA (1) | CA2483159C (es) |
CR (1) | CR7548A (es) |
CY (1) | CY1107221T1 (es) |
DE (1) | DE60318697T2 (es) |
DK (1) | DK1501809T3 (es) |
EA (1) | EA007720B1 (es) |
EC (1) | ECSP045391A (es) |
ES (1) | ES2298513T3 (es) |
HK (1) | HK1073304A1 (es) |
HR (1) | HRP20041008B1 (es) |
IL (2) | IL164675A0 (es) |
MX (1) | MXPA04010622A (es) |
MY (1) | MY141559A (es) |
NO (1) | NO333647B1 (es) |
NZ (1) | NZ535886A (es) |
PE (1) | PE20040600A1 (es) |
PL (1) | PL212090B1 (es) |
PT (1) | PT1501809E (es) |
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UA (1) | UA79113C2 (es) |
WO (1) | WO2003091226A1 (es) |
ZA (1) | ZA200408670B (es) |
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WO2006083711A1 (en) * | 2005-02-01 | 2006-08-10 | Eli Lilly And Company | Tachykinin receptor antagonists |
WO2006106711A1 (ja) | 2005-03-30 | 2006-10-12 | Eisai R & D Management Co., Ltd. | ピリジン誘導体を含有する抗真菌剤 |
EP1894919B1 (en) * | 2005-06-07 | 2012-03-28 | Shionogi & Co., Ltd. | Heterocyclic compound having type i 11 beta hydroxysteroid dehydrogenase inhibitory activity |
ATE487704T1 (de) * | 2005-07-25 | 2010-11-15 | Hoffmann La Roche | Substituierte triazolderivate und ihre verwendung als antagonisten des neurokinin-3-rezeptors |
TWI385169B (zh) | 2005-10-31 | 2013-02-11 | Eisai R&D Man Co Ltd | 經雜環取代之吡啶衍生物及含有彼之抗真菌劑 |
AU2006347397A1 (en) * | 2006-08-18 | 2008-02-21 | Syngenta Limited | Use of HPPD inhibitors in the treatment of depression and/or withdrawal symptoms associated with addictive drugs |
US8183264B2 (en) | 2006-09-21 | 2012-05-22 | Eisai R&D Managment Co., Ltd. | Pyridine derivative substituted by heteroaryl ring, and antifungal agent comprising the same |
WO2008079600A1 (en) * | 2006-12-20 | 2008-07-03 | Eli Lilly And Company | Novel intermediate and process useful in the preparation of {2-[1-(3,5-bis-trifluoromethyl-benzyl)-5-pyridin-4-yl-1h-[1,2,3]triazol-4-yl]-pyridin-3-yl}-(2-chlorophenyl)-methanone |
US8110588B2 (en) | 2007-08-08 | 2012-02-07 | Neurosearch A/S | 1,2,3-triazole derivatives useful as modulators of nicotinic acetylcholine receptors |
GB0722077D0 (en) * | 2007-11-09 | 2007-12-19 | Smithkline Beecham Corp | Compounds |
US8513287B2 (en) | 2007-12-27 | 2013-08-20 | Eisai R&D Management Co., Ltd. | Heterocyclic ring and phosphonoxymethyl group substituted pyridine derivatives and antifungal agent containing same |
MX2010013920A (es) * | 2008-06-26 | 2011-02-21 | Amgen Inc | Alcoholes alquinilicos como inhibidores de cinasas. |
GB0823002D0 (en) * | 2008-12-17 | 2009-01-28 | Syngenta Participations Ag | Isoxazoles derivatives with plant growth regulating properties |
ES2672099T3 (es) | 2011-07-04 | 2018-06-12 | Irbm - Science Park S.P.A. | Antagonistas del receptor NK-1 para el tratamiento de la neovascularización corneal |
TWI636047B (zh) | 2013-08-14 | 2018-09-21 | 英商卡爾維斯塔製藥有限公司 | 雜環衍生物 |
GB201421085D0 (en) | 2014-11-27 | 2015-01-14 | Kalvista Pharmaceuticals Ltd | New enzyme inhibitors |
GB201421083D0 (en) | 2014-11-27 | 2015-01-14 | Kalvista Pharmaceuticals Ltd | Enzyme inhibitors |
US10463655B2 (en) * | 2015-03-04 | 2019-11-05 | Vanda Pharmaceuticals Inc. | Method of treatment with tradipitant |
WO2017031215A1 (en) * | 2015-08-17 | 2017-02-23 | Eli Lilly And Company | Process development of a pyridine-containing nk-1 receptor antagonist |
US11180484B2 (en) | 2016-05-31 | 2021-11-23 | Kalvista Pharmaceuticals Limited | Pyrazole derivatives as plasma kallikrein inhibitors |
GB201609603D0 (en) | 2016-06-01 | 2016-07-13 | Kalvista Pharmaceuticals Ltd | Polymorphs of N-[(6-cyano-2-fluoro-3-methoxyphenyl)Methyl]-3-(methoxymethyl)-1-({4-[(2-ox opyridin-1-YL)Methyl]phenyl}methyl)pyrazole-4-carboxamide |
GB201609607D0 (en) | 2016-06-01 | 2016-07-13 | Kalvista Pharmaceuticals Ltd | Polymorphs of N-(3-Fluoro-4-methoxypyridin-2-yl)methyl)-3-(methoxymethyl)-1-({4-((2-oxopy ridin-1-yl)methyl)phenyl}methyl)pyrazole-4-carboxamide and salts |
CA3073998A1 (en) | 2017-09-13 | 2019-03-21 | Vanda Pharmaceuticals Inc. | Improved treatment of atopic dermatitis with tradipitant |
KR20200088346A (ko) | 2017-11-17 | 2020-07-22 | 반다 파마슈티칼즈, 인코퍼레이티드. | 트라디피탄트를 이용한 위장 질환의 치료 방법 |
SI3716952T1 (sl) | 2017-11-29 | 2022-04-29 | Kalvista Pharmaceuticals Limited | Farmacevtske oblike, ki obsegajo zaviralec plazemskega kalikreina |
GB201719881D0 (en) | 2017-11-29 | 2018-01-10 | Kalvista Pharmaceuticals Ltd | Solid forms of plasma kallikrein inhibitor and salts thereof |
AU2019223237A1 (en) | 2018-02-26 | 2020-09-03 | Ospedale San Raffaele S.R.L. | NK-1 antagonists for use in the treatment of ocular pain |
CN112218636A (zh) * | 2018-06-08 | 2021-01-12 | 万达制药公司 | 使用川地匹坦进行治疗的方法 |
KR20210067980A (ko) * | 2018-09-28 | 2021-06-08 | 반다 파마슈티칼즈, 인코퍼레이티드. | 멀미에서의 트라디피탄트의 용도 |
US10821099B2 (en) | 2018-09-28 | 2020-11-03 | Vanda Pharmaceuticals Inc. | Use of tradipitant in motion sickness |
US20220096449A1 (en) | 2018-12-03 | 2022-03-31 | Vanda Pharmaceuticals Inc. | Method of treatment with tradipitant |
WO2020132513A1 (en) | 2018-12-21 | 2020-06-25 | Vanda Pharmaceuticals Inc. | Improved treatment of atopic dermatitis with tradipitant |
EP4010333A1 (en) | 2019-08-09 | 2022-06-15 | Kalvista Pharmaceuticals Limited | Plasma kallikrein inhibitors |
WO2021173641A1 (en) | 2020-02-25 | 2021-09-02 | Vanda Pharmaceuticals Inc. | Improved treatment of atopic dermatitis with tradipitant |
WO2021180885A1 (en) | 2020-03-11 | 2021-09-16 | Ospedale San Raffaele S.R.L. | Treatment of stem cell deficiency |
US20230145932A1 (en) | 2020-03-26 | 2023-05-11 | Vanda Pharmaceuticals Inc. | Treatment of lower respiratory tract infection with tradipitant |
MX2022011545A (es) | 2020-04-03 | 2022-11-09 | Nerre Therapeutics Ltd | Un antagonista de receptor de nk-1 para tratar una enfermedad que se selecciona de sepsis, choque septico, síndrome de dificultad respiratoria aguda (ards) 0 síndrome de disfunción orgánica múltiple (mcds). |
CN113563306B (zh) * | 2020-04-28 | 2022-07-01 | 新发药业有限公司 | 一种2-(4-苯氧基苯基)-6-(哌啶-4-)基烟酰胺的制备方法 |
CN115697332A (zh) | 2020-06-02 | 2023-02-03 | 尼尔医疗有限公司 | 用于治疗由肺的机械损伤促进的肺纤维化状况的神经激肽(nk)-1受体拮抗剂 |
CN111662235B (zh) * | 2020-06-23 | 2023-12-22 | 黄淮学院 | 一种苯甲酰基哒嗪衍生物及其制备方法 |
WO2023019084A1 (en) | 2021-08-12 | 2023-02-16 | Vanda Pharmaceuticals Inc. | Treatment of gastric accommodation with tradipitant |
EP4395778A1 (en) | 2021-08-31 | 2024-07-10 | Vanda Pharmaceuticals Inc. | Treatment of lower respiratory tract infection with tradipitant |
WO2024138040A1 (en) | 2022-12-21 | 2024-06-27 | Vanda Pharmaceuticals Inc. | Methods of treatment with tradipitant |
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IL50699A0 (en) | 1975-10-28 | 1976-12-31 | Ici America Inc | Triazole derivatives |
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AU2633897A (en) | 1996-04-19 | 1997-11-12 | Novo Nordisk A/S | Solid phase and combinatorial synthesis of substituted 1,2,3-triazoles and of arrays of substituted 1,2,3-triazoles |
HU229024B1 (en) | 1996-07-24 | 2013-07-29 | Bristol Myers Squibb Pharma Co | Azolo-pyridimidines, pharmaceutical compositions containing the same and use thereof |
US6060478A (en) * | 1996-07-24 | 2000-05-09 | Dupont Pharmaceuticals | Azolo triazines and pyrimidines |
TR200000291T2 (tr) | 1997-08-06 | 2000-07-21 | Eli Lilly And Company | Taşikinin reseptör antagonistleri olarak 2-asilaminopropanaminler. |
CA2393672A1 (en) * | 1999-12-17 | 2001-06-21 | Schering Corporation | Selective neurokinin antagonists |
TWI287003B (en) | 2000-07-24 | 2007-09-21 | Hoffmann La Roche | 4-phenyl-pyridine derivatives |
DE10036818A1 (de) * | 2000-07-28 | 2002-02-07 | Solvay Pharm Gmbh | Neue N-Triazolylmethyl-Piperazinderivate als Neurokininrezeptor-Antagonisten |
JP2002123925A (ja) | 2000-10-13 | 2002-04-26 | Fuji Photo Film Co Ltd | 磁気記録媒体 |
DE60321907D1 (de) * | 2002-04-26 | 2008-08-14 | Lilly Co Eli | Tachykininrezeptorantagonisten |
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