CA2372743A1 - New pharmaceutically active compounds - Google Patents
New pharmaceutically active compounds Download PDFInfo
- Publication number
- CA2372743A1 CA2372743A1 CA002372743A CA2372743A CA2372743A1 CA 2372743 A1 CA2372743 A1 CA 2372743A1 CA 002372743 A CA002372743 A CA 002372743A CA 2372743 A CA2372743 A CA 2372743A CA 2372743 A1 CA2372743 A1 CA 2372743A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- indol
- compound
- fluoro
- optionally substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 407
- 238000000034 method Methods 0.000 claims abstract description 100
- 150000003839 salts Chemical class 0.000 claims abstract description 49
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 41
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 35
- 239000012453 solvate Substances 0.000 claims abstract description 31
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 7
- 238000013160 medical therapy Methods 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 367
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 152
- -1 3,4-methylenedioxyphenyl Chemical group 0.000 claims description 148
- 125000000217 alkyl group Chemical group 0.000 claims description 94
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 75
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 49
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 26
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 16
- 230000008569 process Effects 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 102000003923 Protein Kinase C Human genes 0.000 claims description 12
- 108090000315 Protein Kinase C Proteins 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 10
- 238000010992 reflux Methods 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 229910021529 ammonia Inorganic materials 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 239000007858 starting material Substances 0.000 claims description 7
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000000524 functional group Chemical group 0.000 claims description 5
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 5
- 230000001900 immune effect Effects 0.000 claims description 5
- 230000002757 inflammatory effect Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 150000004702 methyl esters Chemical class 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 150000002825 nitriles Chemical class 0.000 claims description 4
- 230000000771 oncological effect Effects 0.000 claims description 4
- MIZCFULWBDXIJS-UHFFFAOYSA-O (3,5-dimethylpyrazole-1-carboximidoyl)azanium;nitrate Chemical compound [O-][N+]([O-])=O.CC=1C=C(C)N(C(N)=[NH2+])N=1 MIZCFULWBDXIJS-UHFFFAOYSA-O 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 claims description 2
- 159000000021 acetate salts Chemical class 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000002168 alkylating agent Substances 0.000 claims description 2
- 229940100198 alkylating agent Drugs 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- XJHABGPPCLHLLV-UHFFFAOYSA-N benzo[de]isoquinoline-1,3-dione Chemical compound C1=CC(C(=O)NC2=O)=C3C2=CC=CC3=C1 XJHABGPPCLHLLV-UHFFFAOYSA-N 0.000 claims description 2
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 208000015114 central nervous system disease Diseases 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000005270 trialkylamine group Chemical group 0.000 claims description 2
- 125000004954 trialkylamino group Chemical group 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 13
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 6
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 1
- 125000005265 dialkylamine group Chemical group 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 4
- 229940123924 Protein kinase C inhibitor Drugs 0.000 abstract description 2
- 239000003881 protein kinase C inhibitor Substances 0.000 abstract description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 300
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 220
- 238000005481 NMR spectroscopy Methods 0.000 description 150
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 145
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 140
- 239000000203 mixture Substances 0.000 description 138
- 239000000243 solution Substances 0.000 description 101
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 84
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 79
- 229940093499 ethyl acetate Drugs 0.000 description 74
- 239000000047 product Substances 0.000 description 74
- 235000019439 ethyl acetate Nutrition 0.000 description 73
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 60
- 238000005160 1H NMR spectroscopy Methods 0.000 description 58
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 52
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
- 239000007787 solid Substances 0.000 description 50
- 239000012267 brine Substances 0.000 description 44
- 239000012074 organic phase Substances 0.000 description 44
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 44
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 44
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 43
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 42
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- 239000000377 silicon dioxide Substances 0.000 description 33
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 30
- 239000002904 solvent Substances 0.000 description 30
- 101150041968 CDC13 gene Proteins 0.000 description 29
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 25
- 239000003921 oil Substances 0.000 description 25
- 235000019198 oils Nutrition 0.000 description 25
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 23
- 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 22
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 21
- 238000001704 evaporation Methods 0.000 description 21
- 230000008020 evaporation Effects 0.000 description 21
- 238000003756 stirring Methods 0.000 description 19
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- 229960000583 acetic acid Drugs 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 229940086542 triethylamine Drugs 0.000 description 17
- 238000002953 preparative HPLC Methods 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 239000012043 crude product Substances 0.000 description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 15
- 238000010898 silica gel chromatography Methods 0.000 description 15
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- 238000000746 purification Methods 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 238000004108 freeze drying Methods 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 11
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 239000012071 phase Substances 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 8
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 8
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 8
- ODFFPRGJZRXNHZ-UHFFFAOYSA-N 5-fluoroindole Chemical compound FC1=CC=C2NC=CC2=C1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 229940126062 Compound A Drugs 0.000 description 7
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 7
- 239000000908 ammonium hydroxide Substances 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- KMYZDVOJRUTMEA-UHFFFAOYSA-N 1-methylindole-3-carbohydrazide Chemical compound C1=CC=C2N(C)C=C(C(=O)NN)C2=C1 KMYZDVOJRUTMEA-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-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
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- CELPHAGZKFMOMR-UHFFFAOYSA-N azanium;dichloromethane;methanol;hydroxide Chemical compound [NH4+].[OH-].OC.ClCCl CELPHAGZKFMOMR-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 239000003039 volatile agent Substances 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 5
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 5
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 4
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 229940043355 kinase inhibitor Drugs 0.000 description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
- PUCISIFGLFZMSB-UHFFFAOYSA-N 1-methylindole-3-carbonyl azide Chemical compound C1=CC=C2N(C)C=C(C(=O)N=[N+]=[N-])C2=C1 PUCISIFGLFZMSB-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- CWOKQKQGNWNVJC-UHFFFAOYSA-N O=c1nc[nH][nH]1.OC(=O)C(F)(F)F Chemical compound O=c1nc[nH][nH]1.OC(=O)C(F)(F)F CWOKQKQGNWNVJC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 3
- QXAUTQFAWKKNLM-UHFFFAOYSA-N methyl indole-3-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)=CNC2=C1 QXAUTQFAWKKNLM-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- IOHBREAOIKFHPN-UHFFFAOYSA-N 1-[2-(1-benzylpyrrolidin-3-yl)ethyl]-5-fluoroindole Chemical compound C1=CC2=CC(F)=CC=C2N1CCC(C1)CCN1CC1=CC=CC=C1 IOHBREAOIKFHPN-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 2
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 2
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- CPLMHIJMVZAVPK-UHFFFAOYSA-N 5-fluoro-1-methylindole-3-carbohydrazide Chemical compound FC1=CC=C2N(C)C=C(C(=O)NN)C2=C1 CPLMHIJMVZAVPK-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- XCOBLONWWXQEBS-KPKJPENVSA-N N,O-bis(trimethylsilyl)trifluoroacetamide Chemical compound C[Si](C)(C)O\C(C(F)(F)F)=N\[Si](C)(C)C XCOBLONWWXQEBS-KPKJPENVSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 2
- CXVDLYHQAQWYEV-NEPJUHHUSA-N [(1s,4r)-4-[tert-butyl(dimethyl)silyl]oxycyclopent-2-en-1-yl] acetate Chemical compound CC(=O)O[C@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)C=C1 CXVDLYHQAQWYEV-NEPJUHHUSA-N 0.000 description 2
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 2
- SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000003924 bisindolylmaleimides Chemical class 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 239000012351 deprotecting agent Substances 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229940112141 dry powder inhaler Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- HNRKAVGCIXAWFB-UHFFFAOYSA-N ethyl acetate;heptane;methanol Chemical compound OC.CCOC(C)=O.CCCCCCC HNRKAVGCIXAWFB-UHFFFAOYSA-N 0.000 description 2
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000008241 heterogeneous mixture Substances 0.000 description 2
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- VVVPGLRKXQSQSZ-UHFFFAOYSA-N indolo[3,2-c]carbazole Chemical class C1=CC=CC2=NC3=C4C5=CC=CC=C5N=C4C=CC3=C21 VVVPGLRKXQSQSZ-UHFFFAOYSA-N 0.000 description 2
- 229960005544 indolocarbazole Drugs 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 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 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- VEPTXBCIDSFGBF-UHFFFAOYSA-M tetrabutylazanium;fluoride;trihydrate Chemical compound O.O.O.[F-].CCCC[N+](CCCC)(CCCC)CCCC VEPTXBCIDSFGBF-UHFFFAOYSA-M 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 1
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- FLQPYEOKVZYXRL-UHFFFAOYSA-N (1-benzylpiperidin-4-yl)methanol Chemical compound C1CC(CO)CCN1CC1=CC=CC=C1 FLQPYEOKVZYXRL-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- 0 *C(N1C[Al]I)=NN(*)C1=* Chemical compound *C(N1C[Al]I)=NN(*)C1=* 0.000 description 1
- MDTUWBLTRPRXBX-UHFFFAOYSA-N 1,2,4-triazol-3-one Chemical compound O=C1N=CN=N1 MDTUWBLTRPRXBX-UHFFFAOYSA-N 0.000 description 1
- CYKFUIIKIBJQDI-UHFFFAOYSA-N 1,2,4-triazol-3-one 2,2,2-trifluoroacetic acid Chemical compound O=C1N=CN=N1.OC(=O)C(F)(F)F CYKFUIIKIBJQDI-UHFFFAOYSA-N 0.000 description 1
- YTBYMCDIVMHTPV-UHFFFAOYSA-N 1,2,4-triazol-3-one triphenylphosphane Chemical compound C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.N1=NC(N=C1)=O YTBYMCDIVMHTPV-UHFFFAOYSA-N 0.000 description 1
- FANQZVHDXNGXSI-UHFFFAOYSA-N 1,2,4-triazol-3-one;hydrochloride Chemical compound Cl.O=C1N=CN=N1 FANQZVHDXNGXSI-UHFFFAOYSA-N 0.000 description 1
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- UHSHMGGJKMOJIA-UHFFFAOYSA-N 1,6-dimethylindole-3-carbohydrazide Chemical compound CC1=CC=C2C(C(=O)NN)=CN(C)C2=C1 UHSHMGGJKMOJIA-UHFFFAOYSA-N 0.000 description 1
- URHJYXLATLWPRN-UHFFFAOYSA-N 1-(3-azidopropyl)-5-fluoroindole-3-carbonyl azide Chemical compound FC1=CC=C2N(CCCN=[N+]=[N-])C=C(C(=O)N=[N+]=[N-])C2=C1 URHJYXLATLWPRN-UHFFFAOYSA-N 0.000 description 1
- LVSUNWRKBYLQDU-UHFFFAOYSA-N 1-(3-azidopropyl)indole-3-carbonyl azide Chemical compound C1=CC=C2N(CCCN=[N+]=[N-])C=C(C(=O)N=[N+]=[N-])C2=C1 LVSUNWRKBYLQDU-UHFFFAOYSA-N 0.000 description 1
- DCAHAWBGNCTCNH-UHFFFAOYSA-N 1-[(3-cyanophenyl)methyl]-5-fluoroindole-3-carbohydrazide Chemical compound C12=CC=C(F)C=C2C(C(=O)NN)=CN1CC1=CC=CC(C#N)=C1 DCAHAWBGNCTCNH-UHFFFAOYSA-N 0.000 description 1
- CDMOTFBQZUYKAC-UHFFFAOYSA-N 1-[(3-cyanophenyl)methyl]-5-fluoroindole-3-carbonyl azide Chemical compound C1=C(C(=O)N=[N+]=[N-])C2=CC(F)=CC=C2N1CC1=CC=CC(C#N)=C1 CDMOTFBQZUYKAC-UHFFFAOYSA-N 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- NEUPKPZUVBWGJX-UHFFFAOYSA-N 1-[(5-fluoro-1-methylindole-3-carbonyl)amino]-3-(5-fluoro-1-methylindol-3-yl)urea Chemical compound C12=CC(F)=CC=C2N(C)C=C1NC(=O)NNC(=O)C1=CN(C)C2=CC=C(F)C=C12 NEUPKPZUVBWGJX-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- DHTLWOMYRJWRKV-UHFFFAOYSA-N 1-[3-(azidomethyl)phenyl]-5-fluoroindole-3-carbonyl azide Chemical compound C1=C(C(=O)N=[N+]=[N-])C2=CC(F)=CC=C2N1C1=CC=CC(CN=[N+]=[N-])=C1 DHTLWOMYRJWRKV-UHFFFAOYSA-N 0.000 description 1
- UCADSCXOJWCXPJ-UHFFFAOYSA-N 1-[3-(dimethylamino)propyl]-5-fluoroindole-3-carbonyl azide Chemical compound FC1=CC=C2N(CCCN(C)C)C=C(C(=O)N=[N+]=[N-])C2=C1 UCADSCXOJWCXPJ-UHFFFAOYSA-N 0.000 description 1
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 1
- UAXNXOMKCGKNCI-UHFFFAOYSA-N 1-diphenylphosphanylethyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)P(C=1C=CC=CC=1)C1=CC=CC=C1 UAXNXOMKCGKNCI-UHFFFAOYSA-N 0.000 description 1
- BDQNKCYCTYYMAA-UHFFFAOYSA-N 1-isocyanatonaphthalene Chemical compound C1=CC=C2C(N=C=O)=CC=CC2=C1 BDQNKCYCTYYMAA-UHFFFAOYSA-N 0.000 description 1
- OTESFSDCTOGGRY-UHFFFAOYSA-N 1-methylindazole-3-carbohydrazide Chemical compound C1=CC=C2N(C)N=C(C(=O)NN)C2=C1 OTESFSDCTOGGRY-UHFFFAOYSA-N 0.000 description 1
- BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical compound C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- JBDOSUUXMYMWQH-UHFFFAOYSA-N 1-naphthyl isothiocyanate Chemical compound C1=CC=C2C(N=C=S)=CC=CC2=C1 JBDOSUUXMYMWQH-UHFFFAOYSA-N 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- QHUYDKZSGDJDSC-UHFFFAOYSA-N 1h-indole-3-carbohydrazide Chemical compound C1=CC=C2C(C(=O)NN)=CNC2=C1 QHUYDKZSGDJDSC-UHFFFAOYSA-N 0.000 description 1
- IUMFFGBZQDGHEM-UHFFFAOYSA-N 1h-indole-6-carbohydrazide Chemical compound NNC(=O)C1=CC=C2C=CNC2=C1 IUMFFGBZQDGHEM-UHFFFAOYSA-N 0.000 description 1
- QLPZEDHKVHQPAD-UHFFFAOYSA-N 2,2,2-trifluoro-n-trimethylsilylacetamide Chemical compound C[Si](C)(C)NC(=O)C(F)(F)F QLPZEDHKVHQPAD-UHFFFAOYSA-N 0.000 description 1
- NDVMCQUOSYOQMZ-UHFFFAOYSA-N 2,2-bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)C(C(N)=O)[Si](C)(C)C NDVMCQUOSYOQMZ-UHFFFAOYSA-N 0.000 description 1
- XZRHNAFEYMSXRG-UHFFFAOYSA-N 2,5-dimethylbenzoic acid Chemical compound CC1=CC=C(C)C(C(O)=O)=C1 XZRHNAFEYMSXRG-UHFFFAOYSA-N 0.000 description 1
- FGBGOYAWNBDXCH-UHFFFAOYSA-N 2,6-bis(chloromethyl)pyridine;hydrochloride Chemical compound Cl.ClCC1=CC=CC(CCl)=N1 FGBGOYAWNBDXCH-UHFFFAOYSA-N 0.000 description 1
- HNVIQLPOGUDBSU-UHFFFAOYSA-N 2,6-dimethylmorpholine Chemical compound CC1CNCC(C)O1 HNVIQLPOGUDBSU-UHFFFAOYSA-N 0.000 description 1
- IFNWESYYDINUHV-UHFFFAOYSA-N 2,6-dimethylpiperazine Chemical compound CC1CNCC(C)N1 IFNWESYYDINUHV-UHFFFAOYSA-N 0.000 description 1
- MXIIGARCOMRJNX-UHFFFAOYSA-N 2-[3-[5-fluoro-3-[3-(5-fluoro-1-methylindol-3-yl)-5-oxo-1h-1,2,4-triazol-4-yl]indol-1-yl]propyl]guanidine Chemical compound C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCN=C(N)N)C2=CC=C(F)C=C12 MXIIGARCOMRJNX-UHFFFAOYSA-N 0.000 description 1
- SGIKHNDGGGZRQK-UHFFFAOYSA-N 2-[[3-(bromomethyl)phenyl]methyl]isoindole-1,3-dione Chemical compound BrCC1=CC=CC(CN2C(C3=CC=CC=C3C2=O)=O)=C1 SGIKHNDGGGZRQK-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- YWBNEGVZAUBGKR-UHFFFAOYSA-N 2-methyl-1H-indole-6-carbonitrile 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.CC=1NC2=CC(=CC=C2C1)C#N YWBNEGVZAUBGKR-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- ZMQVYNIOQCGXGR-UHFFFAOYSA-N 3,4-bis(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(C)C2=CC=C(F)C=C12 ZMQVYNIOQCGXGR-UHFFFAOYSA-N 0.000 description 1
- WLGBNJMELJITAN-UHFFFAOYSA-N 3,4-bis[1-(3-aminopropyl)-5-fluoroindol-3-yl]-1h-1,2,4-triazol-5-one;dihydrochloride Chemical compound Cl.Cl.C12=CC(F)=CC=C2N(CCCN)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=C(F)C=C12 WLGBNJMELJITAN-UHFFFAOYSA-N 0.000 description 1
- DNISXKBKTSHNKL-UHFFFAOYSA-N 3,5-dichlorobenzohydrazide Chemical compound NNC(=O)C1=CC(Cl)=CC(Cl)=C1 DNISXKBKTSHNKL-UHFFFAOYSA-N 0.000 description 1
- YGUOEYBSIVPOFN-UHFFFAOYSA-N 3-(1-methylindol-3-yl)-4-[1-(2-pyrrolidin-3-ylethyl)indol-3-yl]-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC=CC=C11)=CN1CCC1CCNC1 YGUOEYBSIVPOFN-UHFFFAOYSA-N 0.000 description 1
- WPUGRIOWYOMMFW-UHFFFAOYSA-N 3-(1-methylindol-3-yl)-4-[1-(piperidin-4-ylmethyl)indol-3-yl]-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC=CC=C11)=CN1CC1CCNCC1 WPUGRIOWYOMMFW-UHFFFAOYSA-N 0.000 description 1
- QHYDFNIXJFQESU-UHFFFAOYSA-N 3-(1H-indol-3-yl)-4-(1-methylindol-3-yl)-1H-1,2,4-triazol-5-one Chemical compound C12=CC=CC=C2N(C)C=C1N1C(=O)NN=C1C1=CNC2=CC=CC=C12 QHYDFNIXJFQESU-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- ISHPTGUXPSLOFA-UHFFFAOYSA-N 3-(5-fluoro-1-methylindol-3-yl)-4-[5-fluoro-1-(3-morpholin-4-ylpropyl)indol-3-yl]-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC(F)=CC=C11)=CN1CCCN1CCOCC1 ISHPTGUXPSLOFA-UHFFFAOYSA-N 0.000 description 1
- BDAMPZXXBISCIU-UHFFFAOYSA-N 3-(5-fluoro-1-methylindol-3-yl)-4-[5-fluoro-1-[3-(4-methylpiperazin-1-yl)propyl]indol-3-yl]-1h-1,2,4-triazol-5-one Chemical compound C1CN(C)CCN1CCCN1C2=CC=C(F)C=C2C(N2C(NN=C2C=2C3=CC(F)=CC=C3N(C)C=2)=O)=C1 BDAMPZXXBISCIU-UHFFFAOYSA-N 0.000 description 1
- FNCMSIDQGGZIOV-UHFFFAOYSA-N 3-(5-fluoro-1-methylindol-3-yl)-4-[5-fluoro-1-[4-(4-methylpiperazin-1-yl)butyl]indol-3-yl]-1h-1,2,4-triazol-5-one;dihydrochloride Chemical compound Cl.Cl.C1CN(C)CCN1CCCCN1C2=CC=C(F)C=C2C(N2C(NN=C2C=2C3=CC(F)=CC=C3N(C)C=2)=O)=C1 FNCMSIDQGGZIOV-UHFFFAOYSA-N 0.000 description 1
- WWGHHBGGZOKBDD-UHFFFAOYSA-N 3-(5-fluoro-1-methylindol-3-yl)-4-[5-fluoro-1-[[3-(morpholine-4-carboximidoyl)phenyl]methyl]indol-3-yl]-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC(F)=CC=C11)=CN1CC(C=1)=CC=CC=1C(=N)N1CCOCC1 WWGHHBGGZOKBDD-UHFFFAOYSA-N 0.000 description 1
- QWRRSNUIGJIBBM-UHFFFAOYSA-N 3-(5-fluoroindol-1-yl)benzamide Chemical compound NC(=O)C1=CC=CC(N2C3=CC=C(F)C=C3C=C2)=C1 QWRRSNUIGJIBBM-UHFFFAOYSA-N 0.000 description 1
- CVKOOKPNCVYHNY-UHFFFAOYSA-N 3-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=CC(C#N)=C1 CVKOOKPNCVYHNY-UHFFFAOYSA-N 0.000 description 1
- JXEWSFVECIGYIT-UHFFFAOYSA-N 3-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-4-naphthalen-1-yl-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(CCCN)C=C1C1=NNC(=O)N1C1=CC=CC2=CC=CC=C12 JXEWSFVECIGYIT-UHFFFAOYSA-N 0.000 description 1
- QDFSMTKDDAJSIV-UHFFFAOYSA-N 3-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-4-naphthalen-1-yl-1h-1,2,4-triazole-5-thione;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(CCCN)C=C1C1=NNC(=S)N1C1=CC=CC2=CC=CC=C12 QDFSMTKDDAJSIV-UHFFFAOYSA-N 0.000 description 1
- DMIGAYOYBPCUMA-UHFFFAOYSA-N 3-[1-(3-aminopropyl)indol-3-yl]-4-(1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=CC=C2N(C)C=C1N1C(=O)NN=C1C1=CN(CCCN)C2=CC=CC=C12 DMIGAYOYBPCUMA-UHFFFAOYSA-N 0.000 description 1
- LWCWCXLJXOGGNF-UHFFFAOYSA-N 3-[5-fluoro-3-[3-(5-fluoro-1-methylindol-3-yl)-5-oxo-1h-1,2,4-triazol-4-yl]indol-1-yl]propyl carbamimidothioate;hydrobromide Chemical compound Br.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCSC(N)=N)C2=CC=C(F)C=C12 LWCWCXLJXOGGNF-UHFFFAOYSA-N 0.000 description 1
- MALYQGXPJLBJIH-UHFFFAOYSA-N 3-[8-(aminomethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-methylindol-3-yl)-1H-1,2,4-triazol-5-one hydrochloride Chemical compound Cl.CN1C=C(C2=CC=CC=C12)N1C(NN=C1C1=C2N(C3=CC=CC=C13)CCC(C2)CN)=O MALYQGXPJLBJIH-UHFFFAOYSA-N 0.000 description 1
- LBBYRRUKGSBAJG-UHFFFAOYSA-N 3-[8-(aminomethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C12=CC=CC=C2N(C)C=C1N1C(=O)NN=C1C(C1=CC=CC=C11)=C2N1CCC(CN)C2 LBBYRRUKGSBAJG-UHFFFAOYSA-N 0.000 description 1
- RHIPONUMEUMUCA-UHFFFAOYSA-N 3-[[5-fluoro-3-[3-(5-fluoro-1-methylindol-3-yl)-5-oxo-1h-1,2,4-triazol-4-yl]indol-1-yl]methyl]-n'-propan-2-ylbenzenecarboximidamide;hydrochloride Chemical compound Cl.CC(C)NC(=N)C1=CC=CC(CN2C3=CC=C(F)C=C3C(N3C(NN=C3C=3C4=CC(F)=CC=C4N(C)C=3)=O)=C2)=C1 RHIPONUMEUMUCA-UHFFFAOYSA-N 0.000 description 1
- GHQRSGUMWMEVNK-UHFFFAOYSA-N 3-[[5-fluoro-3-[3-(5-fluoro-1-methylindol-3-yl)-5-oxo-1h-1,2,4-triazol-4-yl]indol-1-yl]methyl]benzenecarboximidamide;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC(F)=CC=C11)=CN1CC1=CC=CC(C(N)=N)=C1 GHQRSGUMWMEVNK-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- BNAQRAZIPAHWAR-UHFFFAOYSA-N 3-bromobenzohydrazide Chemical compound NNC(=O)C1=CC=CC(Br)=C1 BNAQRAZIPAHWAR-UHFFFAOYSA-N 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- PSUXTZLDBVEZTD-UHFFFAOYSA-N 3-bromopropoxymethylbenzene Chemical compound BrCCCOCC1=CC=CC=C1 PSUXTZLDBVEZTD-UHFFFAOYSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
- KIQZVIYRELYCOO-UHFFFAOYSA-N 4-(8-amino-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC=CC=C11)=C2N1CCC(N)C2 KIQZVIYRELYCOO-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- RXSGFTJEEOETIA-UHFFFAOYSA-N 4-[1-(2-aminoethyl)-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCN)C2=CC=C(F)C=C12 RXSGFTJEEOETIA-UHFFFAOYSA-N 0.000 description 1
- KGSLJMJZRZKGOT-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-chloroindol-3-yl]-3-(5-chloro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C12=CC(Cl)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=C(Cl)C=C12 KGSLJMJZRZKGOT-UHFFFAOYSA-N 0.000 description 1
- MMZSECAMNSYLMN-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-chloroindol-3-yl]-3-(5-chloro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(Cl)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=C(Cl)C=C12 MMZSECAMNSYLMN-UHFFFAOYSA-N 0.000 description 1
- OUUKCMXGIFXOPW-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(1,2-dimethylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=CC=C2N(C)C(C)=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=C(F)C=C12 OUUKCMXGIFXOPW-UHFFFAOYSA-N 0.000 description 1
- ADHOSNNRWQLFNR-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(1,5-dimethylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C1=C(F)C=C2C(N3C(=O)NN=C3C3=CN(C)C4=CC=C(C=C43)C)=CN(CCCN)C2=C1 ADHOSNNRWQLFNR-UHFFFAOYSA-N 0.000 description 1
- WLEHYGHOTLEEPN-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(1-ethylindol-3-yl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC=CC=C2N(CC)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=C(F)C=C12 WLEHYGHOTLEEPN-UHFFFAOYSA-N 0.000 description 1
- HAXKLRKESAFOIN-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(1-methyl-4-phenylpyrrol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1N(C)C=C(C=2N(C(=O)NN=2)C=2C3=CC(F)=CC=C3N(CCCN)C=2)C=1C1=CC=CC=C1 HAXKLRKESAFOIN-UHFFFAOYSA-N 0.000 description 1
- WQMVJDCSSOJAEL-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(1-methyl-6-phenylmethoxyindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C2N(C)C=C(C=3N(C(=O)NN=3)C=3C4=CC(F)=CC=C4N(CCCN)C=3)C2=CC=C1OCC1=CC=CC=C1 WQMVJDCSSOJAEL-UHFFFAOYSA-N 0.000 description 1
- RFUAFAKZJPTAOK-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=C(F)C=C12 RFUAFAKZJPTAOK-UHFFFAOYSA-N 0.000 description 1
- NZESXUMKGHEFTF-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(1-propylindol-3-yl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC=CC=C2N(CCC)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=C(F)C=C12 NZESXUMKGHEFTF-UHFFFAOYSA-N 0.000 description 1
- DTTGDGRVYLFBMI-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(3,5-dichlorophenyl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(CCCN)C=C1N(C(NN=1)=O)C=1C1=CC(Cl)=CC(Cl)=C1 DTTGDGRVYLFBMI-UHFFFAOYSA-N 0.000 description 1
- IRHONFRDLQVEAC-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(3-bromophenyl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(CCCN)C=C1N(C(NN=1)=O)C=1C1=CC=CC(Br)=C1 IRHONFRDLQVEAC-UHFFFAOYSA-N 0.000 description 1
- GQDZUDPRTQSUDM-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(4-bromophenyl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(CCCN)C=C1N(C(NN=1)=O)C=1C1=CC=C(Br)C=C1 GQDZUDPRTQSUDM-UHFFFAOYSA-N 0.000 description 1
- OUOQHBOBSYSHQW-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(4-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=C(F)C=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=C(F)C=C12 OUOQHBOBSYSHQW-UHFFFAOYSA-N 0.000 description 1
- GYOCZIOEVZKPMG-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(4-phenoxyphenyl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(CCCN)C=C1N(C(NN=1)=O)C=1C(C=C1)=CC=C1OC1=CC=CC=C1 GYOCZIOEVZKPMG-UHFFFAOYSA-N 0.000 description 1
- YOFSNWCZCIQTMW-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(5-chloro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C12=CC(Cl)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=C(F)C=C12 YOFSNWCZCIQTMW-UHFFFAOYSA-N 0.000 description 1
- OAZMHAPHMSGKEZ-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=C(F)C=C12 OAZMHAPHMSGKEZ-UHFFFAOYSA-N 0.000 description 1
- VLUOLVPIMQUAOT-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=C(F)C=C12 VLUOLVPIMQUAOT-UHFFFAOYSA-N 0.000 description 1
- XQHBKVJEFACHNN-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(5-methoxy-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(F)C=C2C(N3C(=O)NN=C3C3=CN(C)C4=CC=C(C=C43)OC)=CN(CCCN)C2=C1 XQHBKVJEFACHNN-UHFFFAOYSA-N 0.000 description 1
- NGQZPJKXITVKTC-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(6-chloro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=C(Cl)C=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=C(F)C=C12 NGQZPJKXITVKTC-UHFFFAOYSA-N 0.000 description 1
- JUZMUNRCYNEHPZ-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(6-hydroxy-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=C(O)C=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=C(F)C=C12 JUZMUNRCYNEHPZ-UHFFFAOYSA-N 0.000 description 1
- FIDBDSXBZXNQCW-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(6-methoxy-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(F)C=C2C(N3C(=O)NN=C3C=3C4=CC=C(C=C4N(C)C=3)OC)=CN(CCCN)C2=C1 FIDBDSXBZXNQCW-UHFFFAOYSA-N 0.000 description 1
- QWYCYXNSCLBQRZ-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(9h-pyrido[3,4-b]indol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(CCCN)C=C1N1C(=O)NN=C1C1=CC(C2=CC=CC=C2N2)=C2C=N1 QWYCYXNSCLBQRZ-UHFFFAOYSA-N 0.000 description 1
- AYVHCHBYVZCIRJ-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-[1-(2-hydroxyethyl)indol-3-yl]-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(CCCN)C=C1N1C(=O)NN=C1C1=CN(CCO)C2=CC=CC=C12 AYVHCHBYVZCIRJ-UHFFFAOYSA-N 0.000 description 1
- CBDMQLPXJKHFTL-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-phenyl-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(CCCN)C=C1N(C(NN=1)=O)C=1C1=CC=CC=C1 CBDMQLPXJKHFTL-UHFFFAOYSA-N 0.000 description 1
- BVLCEJBQCZBBGQ-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-quinolin-2-yl-1h-1,2,4-triazol-5-one;dihydrochloride Chemical compound Cl.Cl.C12=CC(F)=CC=C2N(CCCN)C=C1N1C(=O)NN=C1C1=CC=C(C=CC=C2)C2=N1 BVLCEJBQCZBBGQ-UHFFFAOYSA-N 0.000 description 1
- VPDFGMJMMJWKQD-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-methoxyindol-3-yl]-3-(1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=C2C(C=3N(C(NN=3)=O)C3=CN(CCCN)C4=CC=C(C=C43)OC)=CN(C)C2=C1 VPDFGMJMMJWKQD-UHFFFAOYSA-N 0.000 description 1
- RPCUDWLJIZLVSL-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-5-methylindol-3-yl]-3-(1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=C2C(C=3N(C(NN=3)=O)C3=CN(CCCN)C4=CC=C(C=C43)C)=CN(C)C2=C1 RPCUDWLJIZLVSL-UHFFFAOYSA-N 0.000 description 1
- CYZAHMHNVIIMRX-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-6-fluoroindol-3-yl]-3-(6-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=C(F)C=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC(F)=CC=C12 CYZAHMHNVIIMRX-UHFFFAOYSA-N 0.000 description 1
- PJYZWPSNYJQDDH-UHFFFAOYSA-N 4-[1-(3-aminopropyl)-6-methylindol-3-yl]-3-(1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=C2C(C=3N(C(NN=3)=O)C=3C4=CC=C(C=C4N(CCCN)C=3)C)=CN(C)C2=C1 PJYZWPSNYJQDDH-UHFFFAOYSA-N 0.000 description 1
- NTLIEQHMMMZVTH-UHFFFAOYSA-N 4-[1-(3-aminopropyl)indol-3-yl]-3-(1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=CC=C12 NTLIEQHMMMZVTH-UHFFFAOYSA-N 0.000 description 1
- HXTVSGVKKNPSAM-UHFFFAOYSA-N 4-[1-(3-aminopropyl)indol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCN)C2=CC=CC=C12 HXTVSGVKKNPSAM-UHFFFAOYSA-N 0.000 description 1
- RHGOZJMATZGHMQ-UHFFFAOYSA-N 4-[1-(3-bromobutyl)-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C12=CC(F)=CC=C2N(CCC(Br)C)C=C1N1C(=O)NN=C1C1=CN(C)C2=CC=C(F)C=C12 RHGOZJMATZGHMQ-UHFFFAOYSA-N 0.000 description 1
- CMCJVMVHWLRDSB-UHFFFAOYSA-N 4-[1-(4-aminobutyl)-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCCN)C2=CC=C(F)C=C12 CMCJVMVHWLRDSB-UHFFFAOYSA-N 0.000 description 1
- GMMOMOORVZUQJD-UHFFFAOYSA-N 4-[1-(5-aminopentyl)-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCCCN)C2=CC=C(F)C=C12 GMMOMOORVZUQJD-UHFFFAOYSA-N 0.000 description 1
- RELYDMCRJDCNGM-UHFFFAOYSA-N 4-[1-[(1-benzylpiperidin-4-yl)methyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC(F)=CC=C11)=CN1CC(CC1)CCN1CC1=CC=CC=C1 RELYDMCRJDCNGM-UHFFFAOYSA-N 0.000 description 1
- VTYOJTJKKABQMG-UHFFFAOYSA-N 4-[1-[(1-benzylpiperidin-4-yl)methyl]indol-3-yl]-3-(1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC=CC=C11)=CN1CC(CC1)CCN1CC1=CC=CC=C1 VTYOJTJKKABQMG-UHFFFAOYSA-N 0.000 description 1
- AHNJYHWMVKSKMI-CVLQQERVSA-N 4-[1-[(1S,3R)-3-(aminomethyl)cyclopentyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1H-1,2,4-triazol-5-one 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.NC[C@H]1C[C@H](CC1)N1C=C(C2=CC(=CC=C12)F)N1C(NN=C1C1=CN(C2=CC=C(C=C12)F)C)=O AHNJYHWMVKSKMI-CVLQQERVSA-N 0.000 description 1
- GHYQOQXKQYZUBF-QNBGGDODSA-N 4-[1-[(1r,3r)-3-aminocyclopentyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC(F)=CC=C11)=CN1[C@@H]1CC[C@@H](N)C1 GHYQOQXKQYZUBF-QNBGGDODSA-N 0.000 description 1
- GHYQOQXKQYZUBF-IDVLALEDSA-N 4-[1-[(1r,3s)-3-aminocyclopentyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC(F)=CC=C11)=CN1[C@@H]1CC[C@H](N)C1 GHYQOQXKQYZUBF-IDVLALEDSA-N 0.000 description 1
- BGDSDQHZCLRHBB-PBHICJAKSA-N 4-[1-[(1s,3r)-3-(aminomethyl)cyclopentyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC(F)=CC=C11)=CN1[C@H]1CC[C@@H](CN)C1 BGDSDQHZCLRHBB-PBHICJAKSA-N 0.000 description 1
- HQMQNUKTIFTLGJ-APWZRJJASA-N 4-[1-[(1s,3r)-3-[(dimethylamino)methyl]cyclopentyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C1[C@H](CN(C)C)CC[C@@H]1N1C2=CC=C(F)C=C2C(N2C(NN=C2C=2C3=CC(F)=CC=C3N(C)C=2)=O)=C1 HQMQNUKTIFTLGJ-APWZRJJASA-N 0.000 description 1
- IWZJPXDQWRFGHM-VWJDFLIZSA-N 4-[1-[(1s,3r)-3-[(dimethylamino)methyl]cyclopentyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1[C@H](CN(C)C)CC[C@@H]1N1C2=CC=C(F)C=C2C(N2C(NN=C2C=2C3=CC(F)=CC=C3N(C)C=2)=O)=C1 IWZJPXDQWRFGHM-VWJDFLIZSA-N 0.000 description 1
- JCBGOGOMFOAFLR-XLCHORMMSA-N 4-[1-[(1s,3r)-3-[(dimethylamino)methyl]cyclopentyl]-5-fluoroindol-3-yl]-5-(5-fluoro-1-methylindol-3-yl)-2-(hydroxymethyl)-1,2,4-triazol-3-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1[C@H](CN(C)C)CC[C@@H]1N1C2=CC=C(F)C=C2C(N2C(N(CO)N=C2C=2C3=CC(F)=CC=C3N(C)C=2)=O)=C1 JCBGOGOMFOAFLR-XLCHORMMSA-N 0.000 description 1
- XWJSSXQWQZXIOR-CVEARBPZSA-N 4-[1-[(1s,3r)-3-aminocyclopentyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC(F)=CC=C11)=CN1[C@H]1CC[C@@H](N)C1 XWJSSXQWQZXIOR-CVEARBPZSA-N 0.000 description 1
- VURYZHMNBKFMRP-JKSUJKDBSA-N 4-[1-[(1s,3r)-3-hydroxycyclopentyl]indol-3-yl]-3-(1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C12=CC=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC=CC=C11)=CN1[C@H]1CC[C@@H](O)C1 VURYZHMNBKFMRP-JKSUJKDBSA-N 0.000 description 1
- FKSWECLKHIACLV-PMACEKPBSA-N 4-[1-[(1s,3s)-3-(diethylamino)cyclopentyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C1[C@@H](N(CC)CC)CC[C@@H]1N1C2=CC=C(F)C=C2C(N2C(NN=C2C=2C3=CC(F)=CC=C3N(C)C=2)=O)=C1 FKSWECLKHIACLV-PMACEKPBSA-N 0.000 description 1
- GRHLSAFFQDUYCU-APTPAJQOSA-N 4-[1-[(1s,3s)-3-(dimethylamino)cyclopentyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1[C@@H](N(C)C)CC[C@@H]1N1C2=CC=C(F)C=C2C(N2C(NN=C2C=2C3=CC(F)=CC=C3N(C)C=2)=O)=C1 GRHLSAFFQDUYCU-APTPAJQOSA-N 0.000 description 1
- USLMWYYAKQRJTA-MOGJOVFKSA-N 4-[1-[(1s,3s)-3-aminocyclopentyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC(F)=CC=C11)=CN1[C@H]1CC[C@H](N)C1 USLMWYYAKQRJTA-MOGJOVFKSA-N 0.000 description 1
- QEEPKFXKPKUAAF-MOGJOVFKSA-N 4-[1-[(1s,3s)-3-aminocyclopentyl]indol-3-yl]-3-(1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC=CC=C11)=CN1[C@H]1CC[C@H](N)C1 QEEPKFXKPKUAAF-MOGJOVFKSA-N 0.000 description 1
- WYAKRKGBSXYOAL-UHFFFAOYSA-N 4-[1-[2-(1-benzylpyrrolidin-3-yl)ethyl]indol-3-yl]-3-(1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC=CC=C11)=CN1CCC(C1)CCN1CC1=CC=CC=C1 WYAKRKGBSXYOAL-UHFFFAOYSA-N 0.000 description 1
- TWEUKRKIWATVPT-UHFFFAOYSA-N 4-[1-[2-(2-aminoethoxy)ethyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCOCCN)C2=CC=C(F)C=C12 TWEUKRKIWATVPT-UHFFFAOYSA-N 0.000 description 1
- HVTISWMYPBUUCJ-UHFFFAOYSA-N 4-[1-[3-(4-benzylpiperazin-1-yl)propyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;dihydrochloride Chemical compound Cl.Cl.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC(F)=CC=C11)=CN1CCCN(CC1)CCN1CC1=CC=CC=C1 HVTISWMYPBUUCJ-UHFFFAOYSA-N 0.000 description 1
- BRODJSCHXPCAGR-UHFFFAOYSA-N 4-[1-[3-(dimethylamino)propyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(CCCN(C)C)C=C1N1C(=O)NN=C1C1=CN(C)C2=CC=C(F)C=C12 BRODJSCHXPCAGR-UHFFFAOYSA-N 0.000 description 1
- ZGZYSRUKTBMDFI-UHFFFAOYSA-N 4-[1-[3-(ethylamino)propyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(CCCNCC)C=C1N1C(=O)NN=C1C1=CN(C)C2=CC=C(F)C=C12 ZGZYSRUKTBMDFI-UHFFFAOYSA-N 0.000 description 1
- XFAVFTSDONUGTK-UHFFFAOYSA-N 4-[1-[[6-(aminomethyl)pyridin-2-yl]methyl]-5-fluoroindol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC(F)=CC=C11)=CN1CC1=CC=CC(CN)=N1 XFAVFTSDONUGTK-UHFFFAOYSA-N 0.000 description 1
- YMLFKNAZZHGFBG-UHFFFAOYSA-N 4-[2-(aminomethyl)-2,3-dihydro-1h-pyrrolo[1,2-a]indol-4-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC=CC=C11)=C2N1CC(CN)C2 YMLFKNAZZHGFBG-UHFFFAOYSA-N 0.000 description 1
- MCZHOJKLCIWEDU-UHFFFAOYSA-N 4-[5-fluoro-1-(3-hydroxypropyl)indol-3-yl]-3-(1-propan-2-ylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C12=CC=CC=C2N(C(C)C)C=C1C1=NNC(=O)N1C1=CN(CCCO)C2=CC=C(F)C=C12 MCZHOJKLCIWEDU-UHFFFAOYSA-N 0.000 description 1
- QEELXJKABYIVBN-UHFFFAOYSA-N 4-[5-fluoro-1-(3-hydroxypropyl)indol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCO)C2=CC=C(F)C=C12 QEELXJKABYIVBN-UHFFFAOYSA-N 0.000 description 1
- IJPSWTODBALAJI-UHFFFAOYSA-N 4-[5-fluoro-1-(4-hydroxybutyl)indol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCCO)C2=CC=C(F)C=C12 IJPSWTODBALAJI-UHFFFAOYSA-N 0.000 description 1
- OMQCFDRUAOYQNC-UHFFFAOYSA-N 4-[5-fluoro-1-[3-(2-hydroxyethylamino)propyl]indol-3-yl]-3-(5-fluoro-1-methylindol-3-yl)-1h-1,2,4-triazol-5-one;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCNCCO)C2=CC=C(F)C=C12 OMQCFDRUAOYQNC-UHFFFAOYSA-N 0.000 description 1
- LWFSKUXXILQXII-UHFFFAOYSA-N 4-[8-(aminomethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-3-(1-methylindazol-3-yl)-1h-1,2,4-triazol-5-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=CC=C2N(C)N=C1C1=NNC(=O)N1C(C1=CC=CC=C11)=C2N1CCC(CN)C2 LWFSKUXXILQXII-UHFFFAOYSA-N 0.000 description 1
- UYIMBYKIIMYFPS-UHFFFAOYSA-N 4-bromobenzohydrazide Chemical compound NNC(=O)C1=CC=C(Br)C=C1 UYIMBYKIIMYFPS-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- VERXTAUONOFMLH-UHFFFAOYSA-N 5-bromopyridine-3-carbohydrazide Chemical compound NNC(=O)C1=CN=CC(Br)=C1 VERXTAUONOFMLH-UHFFFAOYSA-N 0.000 description 1
- PHPZYBWYMSGCDU-UHFFFAOYSA-N 5-chloro-1-methylindole-3-carbohydrazide Chemical compound ClC1=CC=C2N(C)C=C(C(=O)NN)C2=C1 PHPZYBWYMSGCDU-UHFFFAOYSA-N 0.000 description 1
- DLJKNBXHOSLOLL-UHFFFAOYSA-N 5-cyano-1-methylindole-3-carbohydrazide Chemical compound N#CC1=CC=C2N(C)C=C(C(=O)NN)C2=C1 DLJKNBXHOSLOLL-UHFFFAOYSA-N 0.000 description 1
- QLKSDNORPWTATO-UHFFFAOYSA-N 5-fluoro-1-(1-methylpiperidin-4-yl)indole Chemical compound C1CN(C)CCC1N1C2=CC=C(F)C=C2C=C1 QLKSDNORPWTATO-UHFFFAOYSA-N 0.000 description 1
- VVTGVLXHFMKPSO-UHFFFAOYSA-N 5-fluoro-1-(3-phenylmethoxypropyl)indole-3-carbohydrazide Chemical compound C12=CC=C(F)C=C2C(C(=O)NN)=CN1CCCOCC1=CC=CC=C1 VVTGVLXHFMKPSO-UHFFFAOYSA-N 0.000 description 1
- WRKAUQVCURXQRT-UHFFFAOYSA-N 5-fluoro-1-methylindole-3-carbonyl azide Chemical compound FC1=CC=C2N(C)C=C(C(=O)N=[N+]=[N-])C2=C1 WRKAUQVCURXQRT-UHFFFAOYSA-N 0.000 description 1
- DYVWOGCIQANCRE-UHFFFAOYSA-N 5-fluoro-1-methylindole-3-carboxylic acid Chemical compound FC1=CC=C2N(C)C=C(C(O)=O)C2=C1 DYVWOGCIQANCRE-UHFFFAOYSA-N 0.000 description 1
- SAGHJOVKZGHFJR-UHFFFAOYSA-N 5-fluoro-3-isocyanato-1-(3-phenylmethoxypropyl)indole Chemical compound C1=C(N=C=O)C2=CC(F)=CC=C2N1CCCOCC1=CC=CC=C1 SAGHJOVKZGHFJR-UHFFFAOYSA-N 0.000 description 1
- DWAQDRSOVMLGRQ-UHFFFAOYSA-N 5-methoxyindole Chemical compound COC1=CC=C2NC=CC2=C1 DWAQDRSOVMLGRQ-UHFFFAOYSA-N 0.000 description 1
- TZNAHYKFVSHGDA-UHFFFAOYSA-N 5-methyl-1h-indole-3-carboxylic acid Chemical compound CC1=CC=C2NC=C(C(O)=O)C2=C1 TZNAHYKFVSHGDA-UHFFFAOYSA-N 0.000 description 1
- WPNLWBKLLWLXHK-UHFFFAOYSA-N 6-chloro-1-methylindole-3-carbohydrazide Chemical compound C1=C(Cl)C=C2N(C)C=C(C(=O)NN)C2=C1 WPNLWBKLLWLXHK-UHFFFAOYSA-N 0.000 description 1
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
- RDSVSEFWZUWZHW-UHFFFAOYSA-N 7-bromo-1h-indole Chemical compound BrC1=CC=CC2=C1NC=C2 RDSVSEFWZUWZHW-UHFFFAOYSA-N 0.000 description 1
- OOYRZDRJOQXMLF-UHFFFAOYSA-N 8-(azidomethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indole Chemical compound C1=CC=C2N3CCC(CN=[N+]=[N-])CC3=CC2=C1 OOYRZDRJOQXMLF-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 229920000945 Amylopectin Polymers 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000012657 Atopic disease Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- OKNGHYMKAJHCID-UHFFFAOYSA-N C12=CC=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCCN)C2=CC=CC=C12 Chemical compound C12=CC=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCCN)C2=CC=CC=C12 OKNGHYMKAJHCID-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 208000014997 Crohn colitis Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- QWIZNVHXZXRPDR-UHFFFAOYSA-N D-melezitose Natural products O1C(CO)C(O)C(O)C(O)C1OC1C(O)C(CO)OC1(CO)OC1OC(CO)C(O)C(O)C1O QWIZNVHXZXRPDR-UHFFFAOYSA-N 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 244000165918 Eucalyptus papuana Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000001344 Macular Edema Diseases 0.000 description 1
- 206010025415 Macular oedema Diseases 0.000 description 1
- 101100537948 Mus musculus Trir gene Proteins 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- MLMJGMHUNYTLQX-RCPFAERMSA-N OC(=O)C(F)(F)F.Cn1cc(-c2n[nH]c(=O)n2-c2cn([C@@H]3C[C@H](N)C=C3)c3ccc(F)cc23)c2cc(F)ccc12 Chemical compound OC(=O)C(F)(F)F.Cn1cc(-c2n[nH]c(=O)n2-c2cn([C@@H]3C[C@H](N)C=C3)c3ccc(F)cc23)c2cc(F)ccc12 MLMJGMHUNYTLQX-RCPFAERMSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- OTMZKAWXPIKBIY-UHFFFAOYSA-N acetic acid;4-[1-(3-aminopropyl)-5-fluoroindol-3-yl]-3-(1-benzylindol-3-yl)-1h-1,2,4-triazol-5-one Chemical compound CC(O)=O.C12=CC(F)=CC=C2N(CCCN)C=C1N(C(NN=1)=O)C=1C(C1=CC=CC=C11)=CN1CC1=CC=CC=C1 OTMZKAWXPIKBIY-UHFFFAOYSA-N 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910000091 aluminium hydride Inorganic materials 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
- UZXHZRFWCCZBDW-UHFFFAOYSA-O aminoazanium;azide Chemical compound [NH3+]N.[N-]=[N+]=[N-] UZXHZRFWCCZBDW-UHFFFAOYSA-O 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000947 anti-immunosuppressive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- ZTZTWQPPCCBBML-UHFFFAOYSA-N azane;ethyl acetate;methanol Chemical compound N.OC.CCOC(C)=O ZTZTWQPPCCBBML-UHFFFAOYSA-N 0.000 description 1
- GHQPBDDZGPAVJP-UHFFFAOYSA-N azanium;methanol;hydroxide Chemical compound N.O.OC GHQPBDDZGPAVJP-UHFFFAOYSA-N 0.000 description 1
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- VQXINLNPICQTLR-UHFFFAOYSA-N carbonyl diazide Chemical compound [N-]=[N+]=NC(=O)N=[N+]=[N-] VQXINLNPICQTLR-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003610 charcoal Substances 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
- DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- AASUFOVSZUIILF-UHFFFAOYSA-N diphenylmethanone;sodium Chemical compound [Na].C=1C=CC=CC=1C(=O)C1=CC=CC=C1 AASUFOVSZUIILF-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- UZXHZRFWCCZBDW-UHFFFAOYSA-N hydrazine;azide Chemical compound NN.[N-]=[N+]=[N-] UZXHZRFWCCZBDW-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000001871 ion mobility spectroscopy Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 150000003925 isoquinoline sulfonamides Chemical class 0.000 description 1
- 239000000832 lactitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
- 235000010448 lactitol Nutrition 0.000 description 1
- 229960003451 lactitol Drugs 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 201000010230 macular retinal edema Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- QWIZNVHXZXRPDR-WSCXOGSTSA-N melezitose Chemical compound O([C@@]1(O[C@@H]([C@H]([C@@H]1O[C@@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O)CO)CO)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O QWIZNVHXZXRPDR-WSCXOGSTSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- HRNWNLYNQWLBIW-QWHCGFSZSA-N methyl 1-[(1r,4s)-4-acetyloxycyclopent-2-en-1-yl]-5-fluoroindole-3-carboxylate Chemical compound C12=CC=C(F)C=C2C(C(=O)OC)=CN1[C@@H]1C[C@H](OC(C)=O)C=C1 HRNWNLYNQWLBIW-QWHCGFSZSA-N 0.000 description 1
- PVIUEMJJVQYNDZ-UHFFFAOYSA-N methyl 1-[3-(dimethylamino)propyl]-3-[3-(5-fluoro-1-methylindol-3-yl)-5-oxo-1h-1,2,4-triazol-4-yl]indole-5-carboxylate;hydrochloride Chemical compound Cl.C1=C(F)C=C2C(C=3N(C(NN=3)=O)C3=CN(CCCN(C)C)C4=CC=C(C=C43)C(=O)OC)=CN(C)C2=C1 PVIUEMJJVQYNDZ-UHFFFAOYSA-N 0.000 description 1
- AYYOZKHMSABVRP-UHFFFAOYSA-N methyl 1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=CNC2=C1 AYYOZKHMSABVRP-UHFFFAOYSA-N 0.000 description 1
- QAYBGHPEUMGKSN-UHFFFAOYSA-N methyl 2-[3-[5-fluoro-3-[3-(5-fluoro-1-methylindol-3-yl)-5-oxo-1h-1,2,4-triazol-4-yl]indol-1-yl]propylamino]acetate;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(CCCNCC(=O)OC)C=C1N1C(=O)NN=C1C1=CN(C)C2=CC=C(F)C=C12 QAYBGHPEUMGKSN-UHFFFAOYSA-N 0.000 description 1
- VGDAUIWXRPCQTO-UHFFFAOYSA-N methyl 3-(5-fluoroindol-1-yl)benzoate Chemical compound COC(=O)C1=CC=CC(N2C3=CC=C(F)C=C3C=C2)=C1 VGDAUIWXRPCQTO-UHFFFAOYSA-N 0.000 description 1
- YHEFQTTVPQMMBW-UHFFFAOYSA-N methyl 3-[3-[5-fluoro-3-[3-(5-fluoro-1-methylindol-3-yl)-5-oxo-1h-1,2,4-triazol-4-yl]indol-1-yl]propylamino]propanoate;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(CCCNCCC(=O)OC)C=C1N1C(=O)NN=C1C1=CN(C)C2=CC=C(F)C=C12 YHEFQTTVPQMMBW-UHFFFAOYSA-N 0.000 description 1
- MKGGMZPOQNWIPZ-UHFFFAOYSA-N methyl 3-[[5-fluoro-3-[3-(5-fluoro-1-methylindol-3-yl)-5-oxo-1h-1,2,4-triazol-4-yl]indol-1-yl]methyl]benzenecarboximidate;hydrochloride Chemical compound Cl.COC(=N)C1=CC=CC(CN2C3=CC=C(F)C=C3C(N3C(NN=C3C=3C4=CC(F)=CC=C4N(C)C=3)=O)=C2)=C1 MKGGMZPOQNWIPZ-UHFFFAOYSA-N 0.000 description 1
- XVUFOQCWNNLYRZ-UHFFFAOYSA-N methyl 3-carbonazidoyl-1-[3-(dimethylamino)propyl]indole-5-carboxylate Chemical compound COC(=O)C1=CC=C2N(CCCN(C)C)C=C(C(=O)N=[N+]=[N-])C2=C1 XVUFOQCWNNLYRZ-UHFFFAOYSA-N 0.000 description 1
- FVCOPMDCKPXHDZ-UHFFFAOYSA-N methyl 5-fluoro-1h-indole-3-carboxylate Chemical compound C1=C(F)C=C2C(C(=O)OC)=CNC2=C1 FVCOPMDCKPXHDZ-UHFFFAOYSA-N 0.000 description 1
- UXOQQUHZHRSERD-UHFFFAOYSA-N methyl 6-cyano-1h-indole-3-carboxylate Chemical compound N#CC1=CC=C2C(C(=O)OC)=CNC2=C1 UXOQQUHZHRSERD-UHFFFAOYSA-N 0.000 description 1
- NJLDFQYDDBCJGG-UHFFFAOYSA-N methyl 6-methyl-1h-indole-3-carboxylate Chemical compound CC1=CC=C2C(C(=O)OC)=CNC2=C1 NJLDFQYDDBCJGG-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- SUSLKWIXQLFQSB-UHFFFAOYSA-N n'-[3-[5-chloro-3-[3-(5-chloro-1-methylindol-3-yl)-5-oxo-1h-1,2,4-triazol-4-yl]indol-1-yl]propyl]-n,n-dimethylmethanimidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(Cl)=CC=C2N(CCCN=CN(C)C)C=C1N1C(=O)NN=C1C1=CN(C)C2=CC=C(Cl)C=C12 SUSLKWIXQLFQSB-UHFFFAOYSA-N 0.000 description 1
- ZVMRHEIFHOBNNN-UHFFFAOYSA-N n'-[3-[5-fluoro-3-[3-(4-fluoro-1-methylindol-3-yl)-5-oxo-1h-1,2,4-triazol-4-yl]indol-1-yl]propyl]-n,n-dimethylmethanimidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC(F)=CC=C2N(CCCN=CN(C)C)C=C1N1C(=O)NN=C1C1=CN(C)C2=CC=CC(F)=C12 ZVMRHEIFHOBNNN-UHFFFAOYSA-N 0.000 description 1
- YOJSBIFLICLAKM-UHFFFAOYSA-N n'-benzyl-3-[[5-fluoro-3-[3-(5-fluoro-1-methylindol-3-yl)-5-oxo-1h-1,2,4-triazol-4-yl]indol-1-yl]methyl]benzenecarboximidamide;hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2N(C)C=C1C1=NNC(=O)N1C(C1=CC(F)=CC=C11)=CN1CC(C=1)=CC=CC=1C(=N)NCC1=CC=CC=C1 YOJSBIFLICLAKM-UHFFFAOYSA-N 0.000 description 1
- GJEJKUBQFYUSCU-UHFFFAOYSA-N n,n-dimethylformamide;trimethoxymethane Chemical compound CN(C)C=O.COC(OC)OC GJEJKUBQFYUSCU-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- RMUYDDKCUZHVHY-UHFFFAOYSA-N n-(4-tert-butylphenyl)acetamide Chemical compound CC(=O)NC1=CC=C(C(C)(C)C)C=C1 RMUYDDKCUZHVHY-UHFFFAOYSA-N 0.000 description 1
- YNTOKMNHRPSGFU-UHFFFAOYSA-N n-Propyl carbamate Chemical compound CCCOC(N)=O YNTOKMNHRPSGFU-UHFFFAOYSA-N 0.000 description 1
- INVLPYICFQWYLZ-UHFFFAOYSA-N n-[3-[5-fluoro-3-[3-(4-fluoro-1-methylindol-3-yl)-5-oxo-1h-1,2,4-triazol-4-yl]indol-1-yl]propyl]formamide Chemical compound C12=C(F)C=CC=C2N(C)C=C1C1=NNC(=O)N1C1=CN(CCCNC=O)C2=CC=C(F)C=C12 INVLPYICFQWYLZ-UHFFFAOYSA-N 0.000 description 1
- VMFUMDXVTKTZQY-UHFFFAOYSA-N naphthalene-1-carbohydrazide Chemical compound C1=CC=C2C(C(=O)NN)=CC=CC2=C1 VMFUMDXVTKTZQY-UHFFFAOYSA-N 0.000 description 1
- VMHBEYZHHMKZQD-UHFFFAOYSA-N naphthalene-1-carbonyl azide Chemical compound C1=CC=C2C(C(=O)N=[N+]=[N-])=CC=CC2=C1 VMHBEYZHHMKZQD-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- ZLELDFZZMFTDAO-UHFFFAOYSA-N potassium cyanide hydrochloride Chemical compound Cl.[C-]#N.[K+] ZLELDFZZMFTDAO-UHFFFAOYSA-N 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 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
- 239000012265 solid product Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 150000003408 sphingolipids Chemical class 0.000 description 1
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 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
- IOKGWQZQCNXXLD-UHFFFAOYSA-N tert-butyl n-(3-bromopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCBr IOKGWQZQCNXXLD-UHFFFAOYSA-N 0.000 description 1
- NFSFIFHYJTYGHC-UHFFFAOYSA-N tert-butyl n-(6,7,8,9-tetrahydropyrido[1,2-a]indol-8-yl)carbamate Chemical compound C1=CC=C2N3CCC(NC(=O)OC(C)(C)C)CC3=CC2=C1 NFSFIFHYJTYGHC-UHFFFAOYSA-N 0.000 description 1
- NXJBBBMRHKBFEV-UHFFFAOYSA-N tert-butyl n-[3-(3-carbonazidoyl-5-methoxyindol-1-yl)propyl]carbamate Chemical compound COC1=CC=C2N(CCCNC(=O)OC(C)(C)C)C=C(C(=O)N=[N+]=[N-])C2=C1 NXJBBBMRHKBFEV-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 150000003573 thiols Chemical group 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 229940074410 trehalose Drugs 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
- AAPLIUHOKVUFCC-UHFFFAOYSA-N trimethylsilanol Chemical compound C[Si](C)(C)O AAPLIUHOKVUFCC-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- 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
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
-
- 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
- A61P11/16—Central respiratory analeptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Nutrition Science (AREA)
- Pulmonology (AREA)
- Reproductive Health (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Gynecology & Obstetrics (AREA)
- Psychology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9901854-1 | 1999-05-21 | ||
| SE9901854A SE9901854D0 (sv) | 1999-05-21 | 1999-05-21 | New pharmaceutically active compounds |
| SE0000645A SE0000645D0 (sv) | 2000-02-28 | 2000-02-28 | New pharmaceutically active compounds |
| SE0000645-2 | 2000-02-28 | ||
| PCT/SE2000/001009 WO2000071537A1 (en) | 1999-05-21 | 2000-05-19 | New pharmaceutically active compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2372743A1 true CA2372743A1 (en) | 2000-11-30 |
Family
ID=26655003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002372743A Abandoned CA2372743A1 (en) | 1999-05-21 | 2000-05-19 | New pharmaceutically active compounds |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US6492406B1 (enExample) |
| EP (1) | EP1183252B1 (enExample) |
| JP (1) | JP4796698B2 (enExample) |
| KR (1) | KR20010113829A (enExample) |
| CN (1) | CN1351602A (enExample) |
| AR (1) | AR024060A1 (enExample) |
| AT (1) | ATE259798T1 (enExample) |
| AU (1) | AU4968600A (enExample) |
| BR (1) | BR0010520A (enExample) |
| CA (1) | CA2372743A1 (enExample) |
| DE (1) | DE60008372T2 (enExample) |
| IL (1) | IL146117A0 (enExample) |
| MX (1) | MXPA01011884A (enExample) |
| NO (1) | NO20015664L (enExample) |
| NZ (1) | NZ515281A (enExample) |
| WO (1) | WO2000071537A1 (enExample) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2842525B1 (fr) | 2002-07-16 | 2005-05-13 | Aventis Pharma Sa | Derives de 3-guanidinocarbonyl-1-heteroaryl-indole, procede de preparation a titre de medicaments et compositions pharmaceutiques les renfermant |
| FR2842526B1 (fr) | 2002-07-16 | 2007-07-13 | Aventis Pharma Sa | Compositions pharmaceutiques contenant un derive de 3-guanidinocarbonyl-1-heteroaryl-indole, procede de preparation a titre de medicaments |
| AR045595A1 (es) * | 2003-09-04 | 2005-11-02 | Vertex Pharma | Composiciones utiles como inhibidores de proteinas quinasas |
| PT1696920E (pt) | 2003-12-19 | 2015-01-14 | Plexxikon Inc | Compostos e métodos para o desenvolvimento de moduladores de ret |
| GB0330043D0 (en) | 2003-12-24 | 2004-01-28 | Pharmacia Italia Spa | Pyrrolo [2,3-b] pyridine derivatives active as kinase inhibitors process for their preparation and pharmaceutical compositions comprising them |
| GB0330042D0 (en) | 2003-12-24 | 2004-01-28 | Pharmacia Italia Spa | Pyrrolo [2,3-b] pyridine derivatives active as kinase inhibitors process for their preparation and pharmaceutical compositions them |
| US7498342B2 (en) | 2004-06-17 | 2009-03-03 | Plexxikon, Inc. | Compounds modulating c-kit activity |
| JP2008508304A (ja) | 2004-07-27 | 2008-03-21 | エスジーエックス ファーマシューティカルズ、インコーポレイテッド | 縮合環ヘテロ環キナーゼ調節因子 |
| US7361764B2 (en) | 2004-07-27 | 2008-04-22 | Sgx Pharmaceuticals, Inc. | Pyrrolo-pyridine kinase modulators |
| JP2008508303A (ja) | 2004-07-27 | 2008-03-21 | エスジーエックス ファーマシューティカルズ、インコーポレイテッド | ピロロ−ピリジンキナーゼモジュレーター |
| US7626021B2 (en) | 2004-07-27 | 2009-12-01 | Sgx Pharmaceuticals, Inc. | Fused ring heterocycle kinase modulators |
| SE0402591D0 (sv) * | 2004-10-25 | 2004-10-25 | Astrazeneca Ab | Novel use |
| ME01498B (me) | 2004-11-18 | 2014-04-20 | Synta Pharmaceuticals Corp | Jedinjenja triazola koja modulišu aktivnost hsp90 |
| WO2006117657A1 (en) * | 2005-05-03 | 2006-11-09 | Ranbaxy Laboratories Limited | Triazolone derivatives as anti-inflammatory agents |
| EP1928846B1 (en) * | 2005-08-18 | 2014-06-04 | Synta Pharmaceuticals Corp. | Triazole compounds that modulate hsp90 activity |
| US20080027047A1 (en) * | 2006-05-25 | 2008-01-31 | Weiwen Ying | Compounds that modulate HSP90 activity and methods for identifying same |
| WO2007139955A2 (en) * | 2006-05-25 | 2007-12-06 | Synta Pharmaceuticals Corp. | Triazole compounds that modulate hsp90 activity |
| EP2038262B1 (en) * | 2006-05-25 | 2014-11-12 | Synta Pharmaceuticals Corp. | Triazole compounds that modulate hsp90 activity |
| AU2007267859B2 (en) | 2006-05-25 | 2012-04-12 | Synta Pharmaceuticals Corp. | Triazole compounds that modulate Hsp90 activity |
| WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
| CA2695004C (en) | 2007-07-17 | 2016-01-19 | Plexxikon, Inc. | Compounds and methods for kinase modulation, and indications therefor |
| US8076491B2 (en) | 2007-08-21 | 2011-12-13 | Senomyx, Inc. | Compounds that inhibit (block) bitter taste in composition and use thereof |
| AU2008289485B2 (en) * | 2007-08-21 | 2014-08-14 | Senomyx, Inc. | Human T2R bitterness receptors and uses thereof |
| MX349923B (es) | 2009-04-03 | 2017-08-21 | Hoffmann La Roche | Composiciones del ácido propano-1-sulfónico {3-[5-(4-cloro-fenil)- 1h-pirrolo [2,3-b]-piridina-3-carbonil]-2,4-difluoro-fenil]-amida y el uso de las mismas. |
| ES2633317T3 (es) | 2009-11-06 | 2017-09-20 | Plexxikon, Inc. | Compuestos y métodos para la modulación de quinasas, e indicaciones para ello |
| FR2953838B1 (fr) * | 2009-12-10 | 2012-02-24 | Sanofi Aventis | Derives de 9h-beta-carboline (ou 9h-pyridino[3,4-b]indole) trisubstitues, leur preparation et leur utilisation therapeutique |
| FR2953837B1 (fr) * | 2009-12-10 | 2012-03-09 | Sanofi Aventis | Derives 9h-pyridino[3,4-b]indole disubstitues, leur preparation et leur utilisation therapeutique |
| US9205086B2 (en) | 2010-04-19 | 2015-12-08 | Synta Pharmaceuticals Corp. | Cancer therapy using a combination of a Hsp90 inhibitory compounds and a EGFR inhibitor |
| TR201816421T4 (tr) | 2011-02-07 | 2018-11-21 | Plexxikon Inc | Kinaz modülasyonu için bileşikler ve metotlar ve bunların endikasyonları. |
| TWI558702B (zh) | 2011-02-21 | 2016-11-21 | 普雷辛肯公司 | 醫藥活性物質的固態形式 |
| EP2776025A1 (en) | 2011-11-02 | 2014-09-17 | Synta Pharmaceuticals Corp. | Combination therapy of hsp90 inhibitors with platinum-containing agents |
| JP2014532712A (ja) | 2011-11-02 | 2014-12-08 | シンタ ファーマシューティカルズ コーポレーション | トポイソメラーゼｉ阻害剤とｈｓｐ９０阻害剤の組合せを使用する癌療法 |
| EP2780010A1 (en) | 2011-11-14 | 2014-09-24 | Synta Pharmaceuticals Corp. | Combination therapy of hsp90 inhibitors with braf inhibitors |
| US9150570B2 (en) | 2012-05-31 | 2015-10-06 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| CN107235966B (zh) * | 2017-05-04 | 2019-12-03 | 浙江工业大学 | 一类3,4-双吲哚-1,2,4-三氮唑酮类化合物及其制备方法和应用 |
| CN116199687B (zh) * | 2023-03-10 | 2024-04-19 | 石河子大学 | 一种β-咔啉-3位连接1,2,3-三氮唑类化合物及其制备方法、应用 |
| CN116462623A (zh) * | 2023-03-30 | 2023-07-21 | 南京神奇科技开发有限公司 | 一种吲哚-5-甲酸甲酯的制备方法 |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL34898C (enExample) * | 1931-08-18 | |||
| USRE28973E (en) | 1965-10-23 | 1976-09-21 | A. H. Robins Company, Incorporated | 3-(Omega-substituted alkyl)-indoles |
| US3821387A (en) | 1965-10-23 | 1974-06-28 | Robins Co Inc A H | The treatment of parkinsonism with 3-(omega-substituted alkyl)-indoles |
| US3821389A (en) | 1969-10-31 | 1974-06-28 | Sherwin Williams Co | Microbiocidal use of 1,2-benzisothiazolin-3-ones |
| SU389096A1 (enExample) | 1971-07-01 | 1973-07-05 | ||
| FR2182915A1 (en) | 1972-03-30 | 1973-12-14 | Nelson Res & Dev | Substd indoles, benzimidazoles - as anti-immune agents , antitumour agents, serotonin inhibitors, hypnotics |
| US4031221A (en) | 1974-06-17 | 1977-06-21 | American Hoechst Corporation | Method of treating pain and hypertension |
| GB1500176A (en) | 1975-06-03 | 1978-02-08 | Wyeth John & Brother Ltd | Reduction process for the preparation of 1-unsubstituted 3-(2-hydroxyethyl)-indole derivatives |
| GB2090826B (en) | 1981-01-09 | 1985-06-12 | Usv Pharma Corp | New heterocyclic compounds useful as anti-allergie agents |
| DE3132882A1 (de) | 1981-08-20 | 1983-03-03 | Cassella Ag, 6000 Frankfurt | Neue piperazinone, ihre herstellung und verwendung |
| DE3141063A1 (de) | 1981-10-13 | 1983-04-28 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Neue imidazol-derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate |
| US4532250A (en) | 1983-11-23 | 1985-07-30 | American Hospital Supply Corporation | 5-Heteroarylimidazol-2-ones having cardiotonic activity |
| US4912125A (en) | 1985-09-03 | 1990-03-27 | Ciba-Geigy Corporation | 2,3-dihydro-2-(4,5-dihydroimidazol-2-yl)-indoles for reducing intraocular pressure |
| SK75289A3 (en) | 1988-02-10 | 1998-05-06 | Hoffmann La Roche | Substituted pyrroles, their use for producing a drug, and the drug on their base |
| US5380746A (en) | 1989-05-05 | 1995-01-10 | Goedecke Aktiengesellschaft | Bis-(1H-indol-3-YL)-maleinimide derivatives, processes for the preparation thereof and pharmaceutical compositions containing them |
| GB9413975D0 (en) | 1994-07-11 | 1994-08-31 | Fujisawa Pharmaceutical Co | New heterobicyclic derivatives |
| DE69132691T2 (de) | 1990-06-07 | 2002-06-20 | Astrazeneca Ab, Soedertaelje | Indolderivate als 5-HT1-like Agonisten |
| US5077293A (en) | 1990-06-29 | 1991-12-31 | Bristol-Myers Squibb Co. | 1-indolyalkyl-4-(alkoxypyrimidinyl)piperazines |
| JPH04187686A (ja) * | 1990-11-20 | 1992-07-06 | Meiji Seika Kaisha Ltd | インドロカルバゾール誘導体 |
| US5192770A (en) | 1990-12-07 | 1993-03-09 | Syntex (U.S.A.) Inc. | Serotonergic alpha-oxoacetamides |
| GB9123396D0 (en) | 1991-11-04 | 1991-12-18 | Hoffmann La Roche | A process for the manufacture of substituted maleimides |
| EP0630241A1 (en) | 1992-03-20 | 1994-12-28 | The Wellcome Foundation Limited | Indole derivatives with antiviral activity |
| DE4237656A1 (de) | 1992-06-13 | 1993-12-16 | Merck Patent Gmbh | Benzimidazolderivate |
| GB9222262D0 (en) | 1992-10-23 | 1992-12-09 | Merck Sharp & Dohme | Therapeutic agents |
| DE4332168A1 (de) * | 1993-02-22 | 1995-03-23 | Thomae Gmbh Dr K | Cyclische Derivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| US5290777A (en) | 1993-02-24 | 1994-03-01 | Regents Of The Univ. Of California | Use for topsentin compounds and pharmaceutical compositions containing same |
| YU49200B (sh) * | 1993-12-07 | 2004-09-03 | Eli Lilly And Company | Inhibitori proteinske kinaze c |
| DK0817627T3 (da) | 1993-12-23 | 2005-06-06 | Lilly Co Eli | Inhibitorer af proteinkinase C |
| US5545636A (en) | 1993-12-23 | 1996-08-13 | Eli Lilly And Company | Protein kinase C inhibitors |
| CA2144940A1 (en) | 1994-03-18 | 1995-09-19 | Chikara Murakata | Therapeutic agent for thrombocytopenia and indolocarbazole derivatives |
| US5491242A (en) * | 1994-06-22 | 1996-02-13 | Eli Lilly And Company | Protein kinase C inhibitors |
| DK0776895T3 (da) | 1995-11-20 | 1999-06-23 | Lilly Co Eli | Proteinkinase C inhibitor |
| KR20000068323A (ko) | 1996-08-23 | 2000-11-25 | 피터 지. 스트링거 | 비스인돌릴말리미드의 합성 |
| SE9603283D0 (sv) | 1996-09-10 | 1996-09-10 | Astra Ab | New compounds |
| TW472045B (en) | 1996-09-25 | 2002-01-11 | Astra Ab | Protein kinase C inhibitor compounds, method for their preparation, pharmaceutical composition thereof and intermediate used for their preparation |
| US5854285A (en) | 1997-04-03 | 1998-12-29 | Natpro, Inc. | Protein kinase inhibitor |
| AR017200A1 (es) | 1997-12-23 | 2001-08-22 | Astrazeneca Ab | Compuestos inhibidores de la proteina cinasa c, sales farmaceuticamente aceptables de los mismos, formulaciones farmaceuitcas que los comprenden, usode las mismas y proceso para la sintesis de dichos compuestos |
| US6103712A (en) | 1998-03-05 | 2000-08-15 | Eli Lilly And Company | Therapeutic treatment for asthma |
| AU757290B2 (en) | 1998-03-25 | 2003-02-13 | Bristol-Myers Squibb Company | Imidazolone anorectic agents: II. phenyl derivatives |
-
2000
- 2000-03-19 US US09/646,972 patent/US6492406B1/en not_active Expired - Fee Related
- 2000-05-19 KR KR1020017014805A patent/KR20010113829A/ko not_active Withdrawn
- 2000-05-19 CN CN00807844A patent/CN1351602A/zh active Pending
- 2000-05-19 WO PCT/SE2000/001009 patent/WO2000071537A1/en not_active Ceased
- 2000-05-19 MX MXPA01011884A patent/MXPA01011884A/es unknown
- 2000-05-19 JP JP2000619794A patent/JP4796698B2/ja not_active Expired - Fee Related
- 2000-05-19 AU AU49686/00A patent/AU4968600A/en not_active Abandoned
- 2000-05-19 CA CA002372743A patent/CA2372743A1/en not_active Abandoned
- 2000-05-19 BR BR0010520-1A patent/BR0010520A/pt not_active IP Right Cessation
- 2000-05-19 EP EP00931873A patent/EP1183252B1/en not_active Expired - Lifetime
- 2000-05-19 DE DE60008372T patent/DE60008372T2/de not_active Expired - Lifetime
- 2000-05-19 AT AT00931873T patent/ATE259798T1/de not_active IP Right Cessation
- 2000-05-19 IL IL14611700A patent/IL146117A0/xx unknown
- 2000-05-19 NZ NZ515281A patent/NZ515281A/en unknown
- 2000-05-22 AR ARP000102486A patent/AR024060A1/es not_active Application Discontinuation
-
2001
- 2001-11-20 NO NO20015664A patent/NO20015664L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CN1351602A (zh) | 2002-05-29 |
| NO20015664D0 (no) | 2001-11-20 |
| AU4968600A (en) | 2000-12-12 |
| JP2003500404A (ja) | 2003-01-07 |
| NZ515281A (en) | 2003-08-29 |
| NO20015664L (no) | 2002-01-21 |
| WO2000071537A1 (en) | 2000-11-30 |
| EP1183252B1 (en) | 2004-02-18 |
| EP1183252A1 (en) | 2002-03-06 |
| JP4796698B2 (ja) | 2011-10-19 |
| DE60008372T2 (de) | 2005-05-19 |
| US6492406B1 (en) | 2002-12-10 |
| AR024060A1 (es) | 2002-09-04 |
| ATE259798T1 (de) | 2004-03-15 |
| MXPA01011884A (es) | 2002-05-06 |
| KR20010113829A (ko) | 2001-12-28 |
| DE60008372D1 (de) | 2004-03-25 |
| IL146117A0 (en) | 2002-07-25 |
| BR0010520A (pt) | 2002-02-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6492406B1 (en) | Pharmaceutically active compounds | |
| CN109153663B (zh) | 作为rock抑制剂的三唑酮类化合物和四唑酮类化合物 | |
| US11028071B2 (en) | Indazole derivatives as alpha v integrin antagonists | |
| JP6896113B2 (ja) | ジアザ二環式置換イミダゾピリミジンおよび呼吸障害を治療するためのその使用 | |
| JP6181862B2 (ja) | ピラゾロピロリジン誘導体および疾患の処置におけるその使用 | |
| US10717736B2 (en) | Pyrrole amides as alpha V integrin inhibitors | |
| JP2001505193A (ja) | ベンズアミド誘導体 | |
| EA004989B1 (ru) | Трициклические ингибиторы поли(adp-рибозо)полимераз | |
| AU2022240688B2 (en) | Furan fused ring-substituted glutarimide compound | |
| CN115443276A (zh) | 吡啶并嘧啶酮衍生物及其作为芳烃受体调节剂的应用 | |
| EP1042317B1 (en) | Indole derivatives as PKC-inhiboitors | |
| US6492409B1 (en) | Kinase inhibitors | |
| US6346625B1 (en) | Protein kinase inhibitors | |
| EP1095039B1 (en) | New pharmaceutically active compounds | |
| US6458792B1 (en) | Compounds | |
| JPH09136889A (ja) | ５‐ｈｔ３レセプターにおいて５‐ｈｔの作用に拮抗するラクタム誘導体を含む医薬組成物 | |
| JP7231610B2 (ja) | インドール誘導体及びその使用 | |
| WO2023001045A9 (zh) | 一种外用消炎偶联化合物药物及其制法和应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |