KR20060006031A - 염증 질환 치료에 유용한 베타-카르볼린 - Google Patents
염증 질환 치료에 유용한 베타-카르볼린 Download PDFInfo
- Publication number
- KR20060006031A KR20060006031A KR1020057019268A KR20057019268A KR20060006031A KR 20060006031 A KR20060006031 A KR 20060006031A KR 1020057019268 A KR1020057019268 A KR 1020057019268A KR 20057019268 A KR20057019268 A KR 20057019268A KR 20060006031 A KR20060006031 A KR 20060006031A
- Authority
- KR
- South Korea
- Prior art keywords
- aliphatic
- hydrogen
- halo
- ring
- carboline
- 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.)
- Ceased
Links
- AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical compound N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 208000027866 inflammatory disease Diseases 0.000 title claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 195
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 52
- 201000010099 disease Diseases 0.000 claims abstract description 44
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 15
- 201000011510 cancer Diseases 0.000 claims abstract description 13
- 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 5
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims abstract description 5
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 5
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims abstract description 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims abstract description 5
- 230000001404 mediated effect Effects 0.000 claims abstract description 4
- 125000001931 aliphatic group Chemical group 0.000 claims description 176
- 238000000034 method Methods 0.000 claims description 158
- 229910052739 hydrogen Inorganic materials 0.000 claims description 156
- 239000001257 hydrogen Substances 0.000 claims description 149
- -1 hydroxy, amino Chemical group 0.000 claims description 129
- 201000006417 multiple sclerosis Diseases 0.000 claims description 90
- 125000005843 halogen group Chemical group 0.000 claims description 82
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 77
- 150000002431 hydrogen Chemical class 0.000 claims description 71
- 229910052757 nitrogen Inorganic materials 0.000 claims description 63
- 125000000623 heterocyclic group Chemical group 0.000 claims description 56
- 125000001072 heteroaryl group Chemical group 0.000 claims description 53
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 38
- 125000003118 aryl group Chemical group 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 33
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 32
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 125000004043 oxo group Chemical group O=* 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 17
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000011593 sulfur Substances 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 206010025323 Lymphomas Diseases 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 125000006244 carboxylic acid protecting group Chemical group 0.000 claims description 5
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 4
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 3
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 3
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 3
- 206010027476 Metastases Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 230000009401 metastasis Effects 0.000 claims description 2
- 230000000010 osteolytic effect Effects 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 208000014829 head and neck neoplasm Diseases 0.000 claims 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 208000026037 malignant tumor of neck Diseases 0.000 claims 1
- 150000003464 sulfur compounds Chemical class 0.000 claims 1
- 229940122296 IKK2 inhibitor Drugs 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 219
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 163
- 239000000243 solution Substances 0.000 description 143
- 239000007787 solid Substances 0.000 description 134
- 238000005160 1H NMR spectroscopy Methods 0.000 description 131
- 239000000203 mixture Substances 0.000 description 105
- 239000000543 intermediate Substances 0.000 description 103
- 230000014759 maintenance of location Effects 0.000 description 82
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 79
- 239000005695 Ammonium acetate Substances 0.000 description 78
- 235000019257 ammonium acetate Nutrition 0.000 description 78
- 229940043376 ammonium acetate Drugs 0.000 description 78
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 70
- 235000019439 ethyl acetate Nutrition 0.000 description 70
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- 239000011541 reaction mixture Substances 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 53
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 46
- 238000006243 chemical reaction Methods 0.000 description 44
- HHZQETZZACUFHE-UHFFFAOYSA-N 6-chloro-9h-pyrido[3,4-b]indol-8-amine Chemical compound C12=CC=NC=C2NC2=C1C=C(Cl)C=C2N HHZQETZZACUFHE-UHFFFAOYSA-N 0.000 description 40
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 39
- 239000012267 brine Substances 0.000 description 38
- 210000004027 cell Anatomy 0.000 description 38
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 239000000047 product Substances 0.000 description 34
- 238000001914 filtration Methods 0.000 description 32
- 238000010561 standard procedure Methods 0.000 description 32
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 30
- 239000010410 layer Substances 0.000 description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 239000012044 organic layer Substances 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- 235000019253 formic acid Nutrition 0.000 description 23
- 239000000725 suspension Substances 0.000 description 23
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 22
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 22
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 22
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 22
- 239000003921 oil Substances 0.000 description 22
- 235000019198 oils Nutrition 0.000 description 22
- 229920006395 saturated elastomer Polymers 0.000 description 22
- 208000024891 symptom Diseases 0.000 description 21
- 230000002829 reductive effect Effects 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 239000011734 sodium Substances 0.000 description 19
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 17
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 17
- HNTZKNJGAFJMHQ-UHFFFAOYSA-N 2-methylpyridine-3-carboxylic acid Chemical compound CC1=NC=CC=C1C(O)=O HNTZKNJGAFJMHQ-UHFFFAOYSA-N 0.000 description 16
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 16
- 102000001284 I-kappa-B kinase Human genes 0.000 description 16
- 108060006678 I-kappa-B kinase Proteins 0.000 description 16
- 108010057466 NF-kappa B Proteins 0.000 description 16
- 239000002002 slurry Substances 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000003458 I kappa b kinase inhibitor Substances 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- 239000012458 free base Substances 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000000843 powder Substances 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 13
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 13
- 238000003556 assay Methods 0.000 description 13
- 239000003814 drug Substances 0.000 description 13
- 150000003840 hydrochlorides Chemical class 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- GGFMPVNNFQUOMK-UHFFFAOYSA-N 6-chloro-7-fluoro-8-nitro-9h-pyrido[3,4-b]indole Chemical compound N1C2=CN=CC=C2C2=C1C([N+](=O)[O-])=C(F)C(Cl)=C2 GGFMPVNNFQUOMK-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 206010035226 Plasma cell myeloma Diseases 0.000 description 11
- 229910052786 argon Inorganic materials 0.000 description 11
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 125000001188 haloalkyl group Chemical group 0.000 description 10
- 201000000050 myeloid neoplasm Diseases 0.000 description 10
- 125000006574 non-aromatic ring group Chemical group 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- 229910052708 sodium Inorganic materials 0.000 description 10
- DFHOVKRFNRGDMK-INIZCTEOSA-N 2-[(5s)-5-[(6-chloro-9h-pyrido[3,4-b]indol-8-yl)carbamoyl]-2,2-dimethylmorpholin-4-yl]acetic acid Chemical compound C1OC(C)(C)CN(CC(O)=O)[C@@H]1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 DFHOVKRFNRGDMK-INIZCTEOSA-N 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 9
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 238000000967 suction filtration Methods 0.000 description 9
- DFHOVKRFNRGDMK-UHFFFAOYSA-N 2-[5-[(6-chloro-9h-pyrido[3,4-b]indol-8-yl)carbamoyl]-2,2-dimethylmorpholin-4-yl]acetic acid Chemical compound C1OC(C)(C)CN(CC(O)=O)C1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 DFHOVKRFNRGDMK-UHFFFAOYSA-N 0.000 description 8
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 206010003246 arthritis Diseases 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 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 8
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 229910052693 Europium Inorganic materials 0.000 description 7
- 208000001132 Osteoporosis Diseases 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 6
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 6
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 6
- GNGXTWQIBWAVCJ-UHFFFAOYSA-N 6,6-dimethylmorpholine-3-carboxylic acid Chemical compound CC1(C)CNC(C(O)=O)CO1 GNGXTWQIBWAVCJ-UHFFFAOYSA-N 0.000 description 6
- KLNYXHBKTSSUMT-UHFFFAOYSA-N 6-chloro-4-methyl-9h-pyrido[3,4-b]indol-8-amine Chemical compound N1C2=C(N)C=C(Cl)C=C2C2=C1C=NC=C2C KLNYXHBKTSSUMT-UHFFFAOYSA-N 0.000 description 6
- BRLSNUXWHXOFPO-UHFFFAOYSA-N 6-chloro-7-methoxy-9h-pyrido[3,4-b]indole Chemical compound N1C2=CN=CC=C2C2=C1C=C(OC)C(Cl)=C2 BRLSNUXWHXOFPO-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 238000009739 binding Methods 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 6
- 125000005647 linker group Chemical group 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- YLZBIUIUXVYRRQ-UHFFFAOYSA-N 1-[2-(dimethylazaniumyl)ethyl]-5-oxopyrrolidine-3-carboxylate Chemical compound CN(C)CCN1CC(C(O)=O)CC1=O YLZBIUIUXVYRRQ-UHFFFAOYSA-N 0.000 description 5
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 5
- 235000011054 acetic acid Nutrition 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 239000012300 argon atmosphere Substances 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 210000000988 bone and bone Anatomy 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 125000004438 haloalkoxy group Chemical group 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- JUNOWSHJELIDQP-UHFFFAOYSA-N morpholin-4-ium-3-carboxylate Chemical compound OC(=O)C1COCCN1 JUNOWSHJELIDQP-UHFFFAOYSA-N 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 5
- 229910052697 platinum Inorganic materials 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000003765 sweetening agent Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- QPMCUNAXNMSGTK-UHFFFAOYSA-N 2-aminopropanal Chemical compound CC(N)C=O QPMCUNAXNMSGTK-UHFFFAOYSA-N 0.000 description 4
- JWYOAMOZLZXDER-UHFFFAOYSA-N 2-azaniumylcyclopentane-1-carboxylate Chemical compound NC1CCCC1C(O)=O JWYOAMOZLZXDER-UHFFFAOYSA-N 0.000 description 4
- VZBGRLPHMCTXFX-UHFFFAOYSA-N 4,6,6-trimethylmorpholine-3-carboxylic acid Chemical compound CN1CC(C)(C)OCC1C(O)=O VZBGRLPHMCTXFX-UHFFFAOYSA-N 0.000 description 4
- CNBFPSXUMQDGPJ-UHFFFAOYSA-N 6-chloro-4-methyl-9h-pyrido[3,4-b]indole Chemical compound N1C2=CC=C(Cl)C=C2C2=C1C=NC=C2C CNBFPSXUMQDGPJ-UHFFFAOYSA-N 0.000 description 4
- XWHCUKZNPUPEHS-UHFFFAOYSA-N 6-chloro-7-fluoro-9h-pyrido[3,4-b]indole Chemical compound N1C2=CN=CC=C2C2=C1C=C(F)C(Cl)=C2 XWHCUKZNPUPEHS-UHFFFAOYSA-N 0.000 description 4
- SSJXCZMMXHUVFW-UHFFFAOYSA-N 6-chloro-7-methoxy-9h-pyrido[3,4-b]indol-8-amine Chemical compound C1=NC=C2NC3=C(N)C(OC)=C(Cl)C=C3C2=C1 SSJXCZMMXHUVFW-UHFFFAOYSA-N 0.000 description 4
- YAZGVGNTWXKUPG-UHFFFAOYSA-N 6-chloro-9h-pyrido[3,4-b]indol-4-amine Chemical compound N1C2=CC=C(Cl)C=C2C2=C1C=NC=C2N YAZGVGNTWXKUPG-UHFFFAOYSA-N 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 238000008157 ELISA kit Methods 0.000 description 4
- 208000009386 Experimental Arthritis Diseases 0.000 description 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
- 102000018745 NF-KappaB Inhibitor alpha Human genes 0.000 description 4
- 108010052419 NF-KappaB Inhibitor alpha Proteins 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 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 4
- 239000012317 TBTU Substances 0.000 description 4
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 150000001413 amino acids Chemical group 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 235000008504 concentrate Nutrition 0.000 description 4
- 239000013058 crude material Substances 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 229960004679 doxorubicin Drugs 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000000105 evaporative light scattering detection Methods 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- XKFFWDOSZUVXNP-UHFFFAOYSA-N n-(8-amino-6-chloro-9h-pyrido[3,4-b]indol-4-yl)-2,2,2-trifluoroacetamide Chemical compound N1C2=CN=CC(NC(=O)C(F)(F)F)=C2C2=C1C(N)=CC(Cl)=C2 XKFFWDOSZUVXNP-UHFFFAOYSA-N 0.000 description 4
- GQQAUZKXIXGTEC-UHFFFAOYSA-N n-[[4-(2-aminopropyl)-6,6-dimethylmorpholin-3-yl]methyl]-6-chloro-9h-pyrido[3,4-b]indol-8-amine Chemical compound CC(N)CN1CC(C)(C)OCC1CNC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 GQQAUZKXIXGTEC-UHFFFAOYSA-N 0.000 description 4
- 201000008482 osteoarthritis Diseases 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 238000011552 rat model Methods 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- PYIUHCZICWLNCG-YUMQZZPRSA-N (3s)-4-[(2s)-2-aminopropyl]-6,6-dimethylmorpholine-3-carboxylic acid Chemical compound C[C@H](N)CN1CC(C)(C)OC[C@H]1C(O)=O PYIUHCZICWLNCG-YUMQZZPRSA-N 0.000 description 3
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 3
- UZBOWOQARWWIER-UHFFFAOYSA-N 2,2-dimethyl-5-oxooxolane-3-carboxylic acid Chemical compound CC1(C)OC(=O)CC1C(O)=O UZBOWOQARWWIER-UHFFFAOYSA-N 0.000 description 3
- LVLAJMZZLUHIDL-UHFFFAOYSA-N 2-benzoyl-6-chloro-3,9-dihydro-1h-pyrido[3,4-b]indol-4-one Chemical compound C1C(=O)C=2C3=CC(Cl)=CC=C3NC=2CN1C(=O)C1=CC=CC=C1 LVLAJMZZLUHIDL-UHFFFAOYSA-N 0.000 description 3
- USEGQJLHQSTGHW-UHFFFAOYSA-N 3-bromo-2-methylprop-1-ene Chemical compound CC(=C)CBr USEGQJLHQSTGHW-UHFFFAOYSA-N 0.000 description 3
- TUBAMTLKNXGLDC-UHFFFAOYSA-N 4-(2-aminopropyl)-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethylmorpholine-3-carboxamide Chemical compound CC(N)CN1CC(C)(C)OCC1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 TUBAMTLKNXGLDC-UHFFFAOYSA-N 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- SNBAOJLDRWLIMF-UHFFFAOYSA-N 4-methyl-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole Chemical compound N1C2=CC=CC=C2C2=C1CNCC2C SNBAOJLDRWLIMF-UHFFFAOYSA-N 0.000 description 3
- UMWBOJUUVNTCMM-UHFFFAOYSA-N 4-methyl-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-1-carboxylic acid Chemical compound N1C2=CC=CC=C2C2=C1C(C(O)=O)NCC2C UMWBOJUUVNTCMM-UHFFFAOYSA-N 0.000 description 3
- DKEYKFSKWICGPE-UHFFFAOYSA-N 4-methyl-9h-pyrido[3,4-b]indole Chemical compound N1C2=CC=CC=C2C2=C1C=NC=C2C DKEYKFSKWICGPE-UHFFFAOYSA-N 0.000 description 3
- MGRYVXAAUYHOSI-UHFFFAOYSA-N 4-methylpyrimidine-5-carboxylic acid Chemical compound CC1=NC=NC=C1C(O)=O MGRYVXAAUYHOSI-UHFFFAOYSA-N 0.000 description 3
- AAEZKWUAXIQWAS-UHFFFAOYSA-N 6,6-dimethyl-4-[(2-methylpropan-2-yl)oxycarbonyl]morpholine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CC(C)(C)OCC1C(O)=O AAEZKWUAXIQWAS-UHFFFAOYSA-N 0.000 description 3
- SXHJWBRJNQZWBI-UHFFFAOYSA-N 6-chloro-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole Chemical compound C1NCCC2=C1NC1=CC=C(Cl)C=C12 SXHJWBRJNQZWBI-UHFFFAOYSA-N 0.000 description 3
- ZZZGTAMRJWTZQR-UHFFFAOYSA-N 6-chloro-4-methyl-8-nitro-9h-pyrido[3,4-b]indole Chemical compound N1C2=C([N+]([O-])=O)C=C(Cl)C=C2C2=C1C=NC=C2C ZZZGTAMRJWTZQR-UHFFFAOYSA-N 0.000 description 3
- BEFPNCDSYSEDHA-UHFFFAOYSA-N 6-chloro-7-(4-methylpiperazin-1-yl)-8-nitro-9h-pyrido[3,4-b]indole Chemical compound C1CN(C)CCN1C1=C(Cl)C=C(C=2C(=CN=CC=2)N2)C2=C1[N+]([O-])=O BEFPNCDSYSEDHA-UHFFFAOYSA-N 0.000 description 3
- RZFYGSJSQGTDBY-UHFFFAOYSA-N 6-chloro-7-(4-methylpiperazin-1-yl)-9h-pyrido[3,4-b]indol-8-amine Chemical compound C1CN(C)CCN1C1=C(Cl)C=C(C=2C(=CN=CC=2)N2)C2=C1N RZFYGSJSQGTDBY-UHFFFAOYSA-N 0.000 description 3
- VCGIIEJPYBEKAX-UHFFFAOYSA-N 6-chloro-7-(cyclopropylmethoxy)-8-nitro-9h-pyrido[3,4-b]indole Chemical compound ClC1=CC=2C3=CC=NC=C3NC=2C([N+](=O)[O-])=C1OCC1CC1 VCGIIEJPYBEKAX-UHFFFAOYSA-N 0.000 description 3
- DZHKDNVFKKYWAE-UHFFFAOYSA-N 6-chloro-7-(cyclopropylmethoxy)-9h-pyrido[3,4-b]indol-8-amine Chemical compound ClC1=CC=2C3=CC=NC=C3NC=2C(N)=C1OCC1CC1 DZHKDNVFKKYWAE-UHFFFAOYSA-N 0.000 description 3
- XCHVWCLDEKYPAS-UHFFFAOYSA-N 6-chloro-7-ethylsulfanyl-8-nitro-9h-pyrido[3,4-b]indole Chemical compound C1=NC=C2NC3=C([N+]([O-])=O)C(SCC)=C(Cl)C=C3C2=C1 XCHVWCLDEKYPAS-UHFFFAOYSA-N 0.000 description 3
- GBVJKSVYCWBPQL-UHFFFAOYSA-N 6-chloro-7-fluoro-9h-pyrido[3,4-b]indol-8-amine Chemical compound C12=CC=NC=C2NC2=C1C=C(Cl)C(F)=C2N GBVJKSVYCWBPQL-UHFFFAOYSA-N 0.000 description 3
- FHZDUYJUBFDYKO-UHFFFAOYSA-N 6-chloro-7-methoxy-8-nitro-9h-pyrido[3,4-b]indole Chemical compound C1=NC=C2NC3=C([N+]([O-])=O)C(OC)=C(Cl)C=C3C2=C1 FHZDUYJUBFDYKO-UHFFFAOYSA-N 0.000 description 3
- HVODJNJBOXNFRH-UHFFFAOYSA-N 6-chloro-7-methylsulfanyl-8-nitro-9h-pyrido[3,4-b]indole Chemical compound C1=NC=C2NC3=C([N+]([O-])=O)C(SC)=C(Cl)C=C3C2=C1 HVODJNJBOXNFRH-UHFFFAOYSA-N 0.000 description 3
- OTGGOPSBNVEBDA-UHFFFAOYSA-N 7-fluoro-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole Chemical compound C1CNCC2=C1C1=CC=C(F)C=C1N2 OTGGOPSBNVEBDA-UHFFFAOYSA-N 0.000 description 3
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 206010006895 Cachexia Diseases 0.000 description 3
- 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 3
- 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 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 206010040070 Septic Shock Diseases 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 3
- 125000005195 alkyl amino carbonyloxy group Chemical group 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 3
- 125000001118 alkylidene group Chemical group 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- NGKZRFZBVRGVJR-UHFFFAOYSA-N benzyl 4-benzyl-6,6-dimethylmorpholine-3-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)C1COC(C)(C)CN1CC1=CC=CC=C1 NGKZRFZBVRGVJR-UHFFFAOYSA-N 0.000 description 3
- PETWURBQGVEHKF-UHFFFAOYSA-N benzyl 4-benzyl-6-(iodomethyl)-6-methylmorpholine-3-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)C1COC(C)(CI)CN1CC1=CC=CC=C1 PETWURBQGVEHKF-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 125000004452 carbocyclyl group Chemical group 0.000 description 3
- 150000001721 carbon Chemical class 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 238000004296 chiral HPLC Methods 0.000 description 3
- 210000001612 chondrocyte Anatomy 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 235000015165 citric acid Nutrition 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 3
- 125000005202 dialkylaminocarbonyloxy group Chemical group 0.000 description 3
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 208000024908 graft versus host disease Diseases 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- AZHVGGHWMKRNTI-UHFFFAOYSA-N n-(6-chloro-8-nitro-9h-pyrido[3,4-b]indol-4-yl)-2,2,2-trifluoroacetamide Chemical compound N1C2=CN=CC(NC(=O)C(F)(F)F)=C2C2=C1C([N+](=O)[O-])=CC(Cl)=C2 AZHVGGHWMKRNTI-UHFFFAOYSA-N 0.000 description 3
- ONCJWBZCRIFBPB-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-4-yl)-2,2,2-trifluoroacetamide Chemical compound N1C2=CC=C(Cl)C=C2C2=C1C=NC=C2NC(=O)C(F)(F)F ONCJWBZCRIFBPB-UHFFFAOYSA-N 0.000 description 3
- OWAQAOYCQXVHPG-UHFFFAOYSA-N n-[6-chloro-4-[(2,2,2-trifluoroacetyl)amino]-9h-pyrido[3,4-b]indol-8-yl]pyridine-3-carboxamide Chemical compound C1=C(Cl)C=C2C=3C(NC(=O)C(F)(F)F)=CN=CC=3NC2=C1NC(=O)C1=CC=CN=C1 OWAQAOYCQXVHPG-UHFFFAOYSA-N 0.000 description 3
- 239000011570 nicotinamide Substances 0.000 description 3
- 229960003966 nicotinamide Drugs 0.000 description 3
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 239000000049 pigment Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 3
- 229940069328 povidone Drugs 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 235000015424 sodium Nutrition 0.000 description 3
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- OVDVEVYAICRSNM-UHFFFAOYSA-N tert-butyl 3-(1-cyanoethyl)indole-1-carboxylate Chemical compound C1=CC=C2C(C(C#N)C)=CN(C(=O)OC(C)(C)C)C2=C1 OVDVEVYAICRSNM-UHFFFAOYSA-N 0.000 description 3
- YCQLNYZZVFUWIZ-UHFFFAOYSA-N tert-butyl 3-(cyanomethyl)indole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C=C(CC#N)C2=C1 YCQLNYZZVFUWIZ-UHFFFAOYSA-N 0.000 description 3
- YVCLHJRHJPVCEK-UHFFFAOYSA-N tert-butyl 5-[(6-chloro-9h-pyrido[3,4-b]indol-8-yl)carbamoyl]-2,2-dimethylmorpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(C)(C)OCC1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 YVCLHJRHJPVCEK-UHFFFAOYSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
- JUNOWSHJELIDQP-BYPYZUCNSA-N (3s)-morpholin-4-ium-3-carboxylate Chemical compound OC(=O)[C@@H]1COCCN1 JUNOWSHJELIDQP-BYPYZUCNSA-N 0.000 description 2
- LUFITPGRMPLUOU-UHFFFAOYSA-N (6-chloro-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl)-phenylmethanone Chemical compound C1CC=2C3=CC(Cl)=CC=C3NC=2CN1C(=O)C1=CC=CC=C1 LUFITPGRMPLUOU-UHFFFAOYSA-N 0.000 description 2
- RRHNHROUKUVAHR-UHFFFAOYSA-N 1,2,2-trimethyl-5-oxopyrrolidine-3-carboxylic acid Chemical compound CN1C(=O)CC(C(O)=O)C1(C)C RRHNHROUKUVAHR-UHFFFAOYSA-N 0.000 description 2
- 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 2
- UFLFSJVTFSZTKX-UHFFFAOYSA-N 2,2-dimethylmorpholine Chemical group CC1(C)CNCCO1 UFLFSJVTFSZTKX-UHFFFAOYSA-N 0.000 description 2
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 2
- JIILUWWXYBUTPB-UHFFFAOYSA-N 2-[(6-chloro-8-nitro-9h-pyrido[3,4-b]indol-7-yl)sulfanyl]-n,n-dimethylethanamine Chemical compound C1=NC=C2NC3=C([N+]([O-])=O)C(SCCN(C)C)=C(Cl)C=C3C2=C1 JIILUWWXYBUTPB-UHFFFAOYSA-N 0.000 description 2
- 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 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- AHLHQTSLLAXDQT-UHFFFAOYSA-N 4-(2-amino-3-methylbutyl)-6,6-dimethylmorpholine-3-carboxylic acid Chemical compound CC(C)C(N)CN1CC(C)(C)OCC1C(O)=O AHLHQTSLLAXDQT-UHFFFAOYSA-N 0.000 description 2
- ALJDUXLUIHQXQO-UHFFFAOYSA-N 4-(2-aminobutyl)-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethylmorpholine-3-carboxamide Chemical compound CCC(N)CN1CC(C)(C)OCC1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 ALJDUXLUIHQXQO-UHFFFAOYSA-N 0.000 description 2
- MVAIQODSRXKFRD-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonyl]-1,1-dioxo-1,4-thiazinane-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCS(=O)(=O)CC1C(O)=O MVAIQODSRXKFRD-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- FLEJOBRWKBPUOX-UHFFFAOYSA-N 4-chloro-2-iodoaniline Chemical compound NC1=CC=C(Cl)C=C1I FLEJOBRWKBPUOX-UHFFFAOYSA-N 0.000 description 2
- GXEDMZQPADTRGS-UHFFFAOYSA-N 6-chloro-4-fluoro-8-nitro-9h-pyrido[3,4-b]indole Chemical compound N1C2=CN=CC(F)=C2C2=C1C([N+](=O)[O-])=CC(Cl)=C2 GXEDMZQPADTRGS-UHFFFAOYSA-N 0.000 description 2
- PLUJCXMMYZUSOP-UHFFFAOYSA-N 6-chloro-4-fluoro-9h-pyrido[3,4-b]indol-8-amine Chemical compound N1C2=CN=CC(F)=C2C2=C1C(N)=CC(Cl)=C2 PLUJCXMMYZUSOP-UHFFFAOYSA-N 0.000 description 2
- QBOMANJQBZTOES-UHFFFAOYSA-N 6-chloro-4-fluoro-9h-pyrido[3,4-b]indole Chemical compound N1C2=CC=C(Cl)C=C2C2=C1C=NC=C2F QBOMANJQBZTOES-UHFFFAOYSA-N 0.000 description 2
- TXTHBSWZFXMWKR-UHFFFAOYSA-N 6-chloro-7-(cyclopropylmethoxy)-9H-pyrido[3,4-b]indole Chemical compound ClC=1C=C2C=3C=CN=CC=3NC2=CC=1OCC1CC1 TXTHBSWZFXMWKR-UHFFFAOYSA-N 0.000 description 2
- PPSJVMCQQWJZBS-UHFFFAOYSA-N 6-chloro-7-[2-(dimethylamino)ethylsulfanyl]-9h-pyrido[3,4-b]indol-8-amine Chemical compound C1=NC=C2NC3=C(N)C(SCCN(C)C)=C(Cl)C=C3C2=C1 PPSJVMCQQWJZBS-UHFFFAOYSA-N 0.000 description 2
- VJYLKKYJEUNEFL-UHFFFAOYSA-N 6-chloro-7-ethoxy-8-nitro-9h-pyrido[3,4-b]indole Chemical compound C1=NC=C2NC3=C([N+]([O-])=O)C(OCC)=C(Cl)C=C3C2=C1 VJYLKKYJEUNEFL-UHFFFAOYSA-N 0.000 description 2
- PQDJNDAUIAVBTD-UHFFFAOYSA-N 6-chloro-7-ethoxy-9H-pyrido[3,4-b]indole Chemical compound ClC=1C=C2C=3C=CN=CC3NC2=CC1OCC PQDJNDAUIAVBTD-UHFFFAOYSA-N 0.000 description 2
- DNXLWUHVMXFUMA-UHFFFAOYSA-N 6-chloro-7-ethylsulfanyl-9H-pyrido[3,4-b]indole Chemical compound CCSC1=C(C=C2C3=C(C=NC=C3)NC2=C1)Cl DNXLWUHVMXFUMA-UHFFFAOYSA-N 0.000 description 2
- PHYZXFIBPLHHDC-UHFFFAOYSA-N 6-chloro-7-ethylsulfanyl-9h-pyrido[3,4-b]indol-8-amine Chemical compound C1=NC=C2NC3=C(N)C(SCC)=C(Cl)C=C3C2=C1 PHYZXFIBPLHHDC-UHFFFAOYSA-N 0.000 description 2
- AOQURXPIMQFREQ-UHFFFAOYSA-N 6-chloro-7-methylsulfanyl-9H-pyrido[3,4-b]indole Chemical compound CSC1=C(C=C2C3=C(C=NC=C3)NC2=C1)Cl AOQURXPIMQFREQ-UHFFFAOYSA-N 0.000 description 2
- VVDCWTOHRVSIIE-UHFFFAOYSA-N 6-chloro-7-methylsulfanyl-9h-pyrido[3,4-b]indol-8-amine Chemical compound C1=NC=C2NC3=C(N)C(SC)=C(Cl)C=C3C2=C1 VVDCWTOHRVSIIE-UHFFFAOYSA-N 0.000 description 2
- AUPDLGPLWDFZFL-UHFFFAOYSA-N 7-fluoro-9h-pyrido[3,4-b]indole Chemical compound N1=CC=C2C3=CC=C(F)C=C3NC2=C1 AUPDLGPLWDFZFL-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 208000012124 AIDS-related disease Diseases 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 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
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 108010039627 Aprotinin Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 2
- 206010065687 Bone loss Diseases 0.000 description 2
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 description 2
- QBXVUKUGWLSDRO-VHPWLNBFSA-N C=1C(Cl)=CC=2C3=CC=NC=C3NC=2C=1NC(=O)C1COC(C)(C)CN1CC(=O)N[C@H]1CC[C@H](O)CC1 Chemical compound C=1C(Cl)=CC=2C3=CC=NC=C3NC=2C=1NC(=O)C1COC(C)(C)CN1CC(=O)N[C@H]1CC[C@H](O)CC1 QBXVUKUGWLSDRO-VHPWLNBFSA-N 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- 241000701022 Cytomegalovirus Species 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
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010017533 Fungal infection Diseases 0.000 description 2
- 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 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 2
- 201000005569 Gout Diseases 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- 229920002907 Guar gum Polymers 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 230000004950 I-kappaB phosphorylation Effects 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 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
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 102000005741 Metalloproteases Human genes 0.000 description 2
- 108010006035 Metalloproteases Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
- RIYCRKQLTRWKNZ-UHFFFAOYSA-N N-(6-chloro-7-fluoro-9H-pyrido[3,4-b]indol-8-yl)-2-methylpyridine-3-carboxamide dihydrochloride Chemical compound Cl.Cl.ClC=1C=C2C=3C=CN=CC3NC2=C(C1F)NC(C1=C(N=CC=C1)C)=O RIYCRKQLTRWKNZ-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 229940123237 Taxane Drugs 0.000 description 2
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 206010044248 Toxic shock syndrome Diseases 0.000 description 2
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 229940045799 anthracyclines and related substance Drugs 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 229960004405 aprotinin Drugs 0.000 description 2
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- KVKCAARWJKEXLZ-INIZCTEOSA-N benzyl (2s)-2-(benzylamino)-3-hydroxypropanoate Chemical compound N([C@@H](CO)C(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 KVKCAARWJKEXLZ-INIZCTEOSA-N 0.000 description 2
- 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 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 230000024279 bone resorption Effects 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 208000029028 brain injury Diseases 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229960001631 carbomer Drugs 0.000 description 2
- 229960004562 carboplatin Drugs 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 238000003570 cell viability assay Methods 0.000 description 2
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 2
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 2
- 229960004630 chlorambucil Drugs 0.000 description 2
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 239000002254 cytotoxic agent Substances 0.000 description 2
- 231100000599 cytotoxic agent Toxicity 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 229950006137 dexfosfoserine Drugs 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 229960000390 fludarabine Drugs 0.000 description 2
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 235000010417 guar gum Nutrition 0.000 description 2
- 239000000665 guar gum Substances 0.000 description 2
- 229960002154 guar gum Drugs 0.000 description 2
- 229940022353 herceptin Drugs 0.000 description 2
- 125000005114 heteroarylalkoxy group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- DMCPFOBLJMLSNX-UHFFFAOYSA-N indole-3-acetonitrile Chemical compound C1=CC=C2C(CC#N)=CNC2=C1 DMCPFOBLJMLSNX-UHFFFAOYSA-N 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 2
- 229960004768 irinotecan Drugs 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229960001924 melphalan Drugs 0.000 description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 229960001156 mitoxantrone Drugs 0.000 description 2
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- QIQKUHQPLGQZFX-UHFFFAOYSA-N n-(4-amino-6-chloro-9h-pyrido[3,4-b]indol-8-yl)-2-methylpyridine-3-carboxamide Chemical compound CC1=NC=CC=C1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC(N)=C21 QIQKUHQPLGQZFX-UHFFFAOYSA-N 0.000 description 2
- XSBVTRUKELZUEJ-UHFFFAOYSA-N n-(4-amino-6-chloro-9h-pyrido[3,4-b]indol-8-yl)pyridine-3-carboxamide Chemical compound C1=C(Cl)C=C2C=3C(N)=CN=CC=3NC2=C1NC(=O)C1=CC=CN=C1 XSBVTRUKELZUEJ-UHFFFAOYSA-N 0.000 description 2
- SCTYMLLSXJQHJB-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-4-[2-[4-(hydroxymethyl)piperidin-1-yl]-2-oxoethyl]-6,6-dimethylmorpholine-3-carboxamide Chemical compound C=1C(Cl)=CC=2C3=CC=NC=C3NC=2C=1NC(=O)C1COC(C)(C)CN1CC(=O)N1CCC(CO)CC1 SCTYMLLSXJQHJB-UHFFFAOYSA-N 0.000 description 2
- XDHCEURKBDDLSU-UHFFFAOYSA-N n-[6-chloro-4-[(2,2,2-trifluoroacetyl)amino]-9h-pyrido[3,4-b]indol-8-yl]-2-methylpyridine-3-carboxamide Chemical compound CC1=NC=CC=C1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC(NC(=O)C(F)(F)F)=C21 XDHCEURKBDDLSU-UHFFFAOYSA-N 0.000 description 2
- 235000005152 nicotinamide Nutrition 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 210000002997 osteoclast Anatomy 0.000 description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
- 229960001756 oxaliplatin Drugs 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 208000028169 periodontal disease Diseases 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 229960004618 prednisone Drugs 0.000 description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 230000010349 pulsation Effects 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000005932 reductive alkylation reaction Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- 235000019204 saccharin Nutrition 0.000 description 2
- 229940081974 saccharin Drugs 0.000 description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 229960004964 temozolomide Drugs 0.000 description 2
- JVHMAVNINUKKSX-KRWDZBQOSA-N tert-butyl (3s)-3-[(6-chloro-9h-pyrido[3,4-b]indol-8-yl)carbamoyl]morpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOC[C@H]1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 JVHMAVNINUKKSX-KRWDZBQOSA-N 0.000 description 2
- YVCLHJRHJPVCEK-SFHVURJKSA-N tert-butyl (5s)-5-[(6-chloro-9h-pyrido[3,4-b]indol-8-yl)carbamoyl]-2,2-dimethylmorpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(C)(C)OC[C@H]1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 YVCLHJRHJPVCEK-SFHVURJKSA-N 0.000 description 2
- MXCAGVCUIHYAGH-UHFFFAOYSA-N tert-butyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)C(C)(C)C1 MXCAGVCUIHYAGH-UHFFFAOYSA-N 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
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 2
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 2
- 229960003433 thalidomide Drugs 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- ITBMRVUPEVXILF-UHFFFAOYSA-N tributyl-(3,5-difluoropyridin-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=C(F)C=NC=C1F ITBMRVUPEVXILF-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical class C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
- QJEQJDJFJWWURK-BDAKNGLRSA-N (1r,2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)N[C@H]1CCCC[C@H]1C(O)=O QJEQJDJFJWWURK-BDAKNGLRSA-N 0.000 description 1
- JWYOAMOZLZXDER-UHNVWZDZSA-N (1r,2s)-2-azaniumylcyclopentane-1-carboxylate Chemical compound N[C@H]1CCC[C@H]1C(O)=O JWYOAMOZLZXDER-UHNVWZDZSA-N 0.000 description 1
- SMZPWUUYPYYHIV-HNJRGHQBSA-N (2r,3s)-3-[formyl(hydroxy)amino]-4-methyl-n-[(2s,3s)-3-methyl-1-oxo-1-(pyridin-2-ylamino)pentan-2-yl]-2-(2-methylpropyl)pentanamide Chemical compound O=CN(O)[C@@H](C(C)C)[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NC1=CC=CC=N1 SMZPWUUYPYYHIV-HNJRGHQBSA-N 0.000 description 1
- AFHNFHHYTYQLIO-KGZKBUQUSA-N (2r,5r)-2,5-dimethylpyrrolidine;hydrochloride Chemical compound Cl.C[C@@H]1CC[C@@H](C)N1 AFHNFHHYTYQLIO-KGZKBUQUSA-N 0.000 description 1
- SJADBRRVMVKDLY-APPDUMDISA-N (3r)-4-[(2s)-2-aminopropyl]-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)morpholine-3-carboxamide Chemical compound C[C@H](N)CN1CCOC[C@@H]1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 SJADBRRVMVKDLY-APPDUMDISA-N 0.000 description 1
- KVXXEKIGMOEPSA-ZETCQYMHSA-N (3s)-4-[(2-methylpropan-2-yl)oxycarbonyl]morpholine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCOC[C@H]1C(O)=O KVXXEKIGMOEPSA-ZETCQYMHSA-N 0.000 description 1
- ZOONHKLFCIXUJO-OLZOCXBDSA-N (3s)-4-[(2r)-2-amino-3-phenylpropyl]morpholine-3-carboxylic acid Chemical compound C([C@H](N)CC=1C=CC=CC=1)N1CCOC[C@H]1C(O)=O ZOONHKLFCIXUJO-OLZOCXBDSA-N 0.000 description 1
- HJEQMNMGEMLIHV-RQJHMYQMSA-N (3s)-4-[(2r)-2-aminopropyl]morpholine-3-carboxylic acid Chemical compound C[C@@H](N)CN1CCOC[C@H]1C(O)=O HJEQMNMGEMLIHV-RQJHMYQMSA-N 0.000 description 1
- SJADBRRVMVKDLY-GTNSWQLSSA-N (3s)-4-[(2s)-2-aminopropyl]-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)morpholine-3-carboxamide Chemical compound C[C@H](N)CN1CCOC[C@H]1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 SJADBRRVMVKDLY-GTNSWQLSSA-N 0.000 description 1
- PJCXUSBLNCTAJP-YFKPBYRVSA-N (3s)-4-methylmorpholine-3-carboxylic acid Chemical compound CN1CCOC[C@H]1C(O)=O PJCXUSBLNCTAJP-YFKPBYRVSA-N 0.000 description 1
- XUKNUEKHEPJITM-QWRGUYRKSA-N (3s)-6,6-dimethyl-4-[(2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]morpholine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C)CN1CC(C)(C)OC[C@H]1C(O)=O XUKNUEKHEPJITM-QWRGUYRKSA-N 0.000 description 1
- GNGXTWQIBWAVCJ-YFKPBYRVSA-N (3s)-6,6-dimethylmorpholine-3-carboxylic acid Chemical compound CC1(C)CN[C@H](C(O)=O)CO1 GNGXTWQIBWAVCJ-YFKPBYRVSA-N 0.000 description 1
- WOJNVGOKIPXUAF-XDHUDOTRSA-N (3s)-n-(6-chloro-4-methyl-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethyl-4-[(2s)-2-[(2-methylpyridine-3-carbonyl)amino]propyl]morpholine-3-carboxamide Chemical compound N([C@H](CN1[C@@H](COC(C)(C)C1)C(=O)NC=1C2=C(C3=C(C)C=NC=C3N2)C=C(Cl)C=1)C)C(=O)C1=CC=CN=C1C WOJNVGOKIPXUAF-XDHUDOTRSA-N 0.000 description 1
- VNWFZUOVGFIHGU-FGJQBABTSA-N (3s)-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-4-[2-(3,3-dimethylmorpholin-4-yl)-2-oxoethyl]-6,6-dimethylmorpholine-3-carboxamide;dihydrochloride Chemical compound Cl.Cl.C([C@H]1C(=O)NC=2C=3NC4=CN=CC=C4C=3C=C(Cl)C=2)OC(C)(C)CN1CC(=O)N1CCOCC1(C)C VNWFZUOVGFIHGU-FGJQBABTSA-N 0.000 description 1
- OVNWAYSGZNZAOU-FEAODWGOSA-N (3s)-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-4-[2-[(2r,5r)-2,5-dimethylpyrrolidin-1-yl]-2-oxoethyl]-6,6-dimethylmorpholine-3-carboxamide;dihydrochloride Chemical compound Cl.Cl.C[C@@H]1CC[C@@H](C)N1C(=O)CN1[C@H](C(=O)NC=2C=3NC4=CN=CC=C4C=3C=C(Cl)C=2)COC(C)(C)C1 OVNWAYSGZNZAOU-FEAODWGOSA-N 0.000 description 1
- XIEUUJLWUPMKDF-IBGZPJMESA-N (3s)-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-4-[2-[2-hydroxyethyl(methyl)amino]-2-oxoethyl]-6,6-dimethylmorpholine-3-carboxamide Chemical compound OCCN(C)C(=O)CN1CC(C)(C)OC[C@H]1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 XIEUUJLWUPMKDF-IBGZPJMESA-N 0.000 description 1
- NGPSUPKCYOXPGQ-KUHUBIRLSA-N (3s)-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-4-[[(2r)-pyrrolidin-2-yl]methyl]morpholine-3-carboxamide Chemical compound C([C@H]1C(=O)NC=2C=C(C=C3C4=CC=NC=C4NC3=2)Cl)OCCN1C[C@H]1CCCN1 NGPSUPKCYOXPGQ-KUHUBIRLSA-N 0.000 description 1
- CYHIFUWMKOQOAL-FQEVSTJZSA-N (3s)-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethyl-4-(2-morpholin-4-yl-2-oxoethyl)morpholine-3-carboxamide Chemical compound C([C@H]1C(=O)NC=2C=3NC4=CN=CC=C4C=3C=C(Cl)C=2)OC(C)(C)CN1CC(=O)N1CCOCC1 CYHIFUWMKOQOAL-FQEVSTJZSA-N 0.000 description 1
- WTVIWHFMHDFLCB-NRFANRHFSA-N (3s)-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethyl-4-(2-oxo-2-piperidin-1-ylethyl)morpholine-3-carboxamide Chemical compound C([C@H]1C(=O)NC=2C=3NC4=CN=CC=C4C=3C=C(Cl)C=2)OC(C)(C)CN1CC(=O)N1CCCCC1 WTVIWHFMHDFLCB-NRFANRHFSA-N 0.000 description 1
- GXVJNIMBOAMEPI-FQEVSTJZSA-N (3s)-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethyl-4-(2-oxo-2-pyrrolidin-1-ylethyl)morpholine-3-carboxamide Chemical compound C([C@H]1C(=O)NC=2C=3NC4=CN=CC=C4C=3C=C(Cl)C=2)OC(C)(C)CN1CC(=O)N1CCCC1 GXVJNIMBOAMEPI-FQEVSTJZSA-N 0.000 description 1
- KQWKQNIAMJHDHJ-FYSMJZIKSA-N (3s)-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethyl-4-[(2s)-2-[(2-methylpyridine-3-carbonyl)amino]propyl]morpholine-3-carboxamide Chemical compound N([C@H](CN1[C@@H](COC(C)(C)C1)C(=O)NC=1C=2NC3=CN=CC=C3C=2C=C(Cl)C=1)C)C(=O)C1=CC=CN=C1C KQWKQNIAMJHDHJ-FYSMJZIKSA-N 0.000 description 1
- WEGJDCJTFBXXTH-NRFANRHFSA-N (3s)-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethyl-4-[2-oxo-2-(pyridin-3-ylamino)ethyl]morpholine-3-carboxamide Chemical class C([C@H]1C(=O)NC=2C=3NC4=CN=CC=C4C=3C=C(Cl)C=2)OC(C)(C)CN1CC(=O)NC1=CC=CN=C1 WEGJDCJTFBXXTH-NRFANRHFSA-N 0.000 description 1
- WSAYCJCSEVCNQP-QFIPXVFZSA-N (3s)-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethyl-4-[2-oxo-2-(pyridin-4-ylmethylamino)ethyl]morpholine-3-carboxamide Chemical compound C([C@H]1C(=O)NC=2C=3NC4=CN=CC=C4C=3C=C(Cl)C=2)OC(C)(C)CN1CC(=O)NCC1=CC=NC=C1 WSAYCJCSEVCNQP-QFIPXVFZSA-N 0.000 description 1
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RBNPOMFGQQGHHO-UHFFFAOYSA-N -2,3-Dihydroxypropanoic acid Natural products OCC(O)C(O)=O RBNPOMFGQQGHHO-UHFFFAOYSA-N 0.000 description 1
- PPAKHTONXJJHHK-UHFFFAOYSA-N 1,1-dioxo-1,4-thiazinane-3-carboxylic acid Chemical compound OC(=O)C1CS(=O)(=O)CCN1 PPAKHTONXJJHHK-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- KDKGWGUUUVROTO-UHFFFAOYSA-N 1-hydroxypiperazine Chemical compound ON1CCNCC1 KDKGWGUUUVROTO-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- JAHNSTQSQJOJLO-UHFFFAOYSA-N 2-(3-fluorophenyl)-1h-imidazole Chemical compound FC1=CC=CC(C=2NC=CN=2)=C1 JAHNSTQSQJOJLO-UHFFFAOYSA-N 0.000 description 1
- ODVDIBHWTMTHOS-UHFFFAOYSA-N 2-(6-fluoro-1h-indol-3-yl)ethanamine;hydron;chloride Chemical compound Cl.FC1=CC=C2C(CCN)=CNC2=C1 ODVDIBHWTMTHOS-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- CLQDUOCCOCSMNY-UHFFFAOYSA-N 2-amino-n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)cyclohexane-1-carboxamide Chemical compound NC1CCCCC1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 CLQDUOCCOCSMNY-UHFFFAOYSA-N 0.000 description 1
- LYIIBVSRGJSHAV-UHFFFAOYSA-N 2-aminoacetaldehyde Chemical compound NCC=O LYIIBVSRGJSHAV-UHFFFAOYSA-N 0.000 description 1
- USQHEVWOPJDAAX-UHFFFAOYSA-N 2-azaniumylcyclohexane-1-carboxylate Chemical compound NC1CCCCC1C(O)=O USQHEVWOPJDAAX-UHFFFAOYSA-N 0.000 description 1
- WWFXNTQTTXCMRG-UHFFFAOYSA-N 2-bromo-1-(3,3-dimethylmorpholin-4-yl)ethanone Chemical compound CC1(C)COCCN1C(=O)CBr WWFXNTQTTXCMRG-UHFFFAOYSA-N 0.000 description 1
- SYZRZLUNWVNNNV-UHFFFAOYSA-N 2-bromoacetyl chloride Chemical compound ClC(=O)CBr SYZRZLUNWVNNNV-UHFFFAOYSA-N 0.000 description 1
- IZEGJNWOOPXVJG-RNFRBKRXSA-N 2-chloro-1-[(2r,5r)-2,5-dimethylpyrrolidin-1-yl]ethanone Chemical compound C[C@@H]1CC[C@@H](C)N1C(=O)CCl IZEGJNWOOPXVJG-RNFRBKRXSA-N 0.000 description 1
- IBRSSZOHCGUTHI-UHFFFAOYSA-N 2-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1Cl IBRSSZOHCGUTHI-UHFFFAOYSA-N 0.000 description 1
- 125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- UBPDKIDWEADHPP-UHFFFAOYSA-N 2-iodoaniline Chemical compound NC1=CC=CC=C1I UBPDKIDWEADHPP-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- KXBPUMSPCLLXRZ-UHFFFAOYSA-N 3,3-dimethylpiperidin-4-one Chemical compound CC1(C)CNCCC1=O KXBPUMSPCLLXRZ-UHFFFAOYSA-N 0.000 description 1
- PLYTVAFAKDFFKM-UHFFFAOYSA-N 3,4-dimethylmorpholine Chemical compound CC1COCCN1C PLYTVAFAKDFFKM-UHFFFAOYSA-N 0.000 description 1
- WRXAZPPGFLETFR-UHFFFAOYSA-N 3,5-difluoropyridine Chemical compound FC1=CN=CC(F)=C1 WRXAZPPGFLETFR-UHFFFAOYSA-N 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- PWMHJYUCYRPQOW-UHFFFAOYSA-N 4-(2-acetamidopropyl)-n-(6-chloro-4-fluoro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethylmorpholine-3-carboxamide Chemical compound CC(=O)NC(C)CN1CC(C)(C)OCC1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC(F)=C21 PWMHJYUCYRPQOW-UHFFFAOYSA-N 0.000 description 1
- PULYXVNUBZMHMS-UHFFFAOYSA-N 4-(2-aminoethyl)morpholine-3-carboxylic acid Chemical compound NCCN1CCOCC1C(O)=O PULYXVNUBZMHMS-UHFFFAOYSA-N 0.000 description 1
- PYIUHCZICWLNCG-UHFFFAOYSA-N 4-(2-aminopropyl)-6,6-dimethylmorpholine-3-carboxylic acid Chemical compound CC(N)CN1CC(C)(C)OCC1C(O)=O PYIUHCZICWLNCG-UHFFFAOYSA-N 0.000 description 1
- CTDIKDIZNAGMFK-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonyl]thiomorpholine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCSCC1C(O)=O CTDIKDIZNAGMFK-UHFFFAOYSA-N 0.000 description 1
- FKZMQZYUBDCDCO-UHFFFAOYSA-N 4-[2-(3,3-dimethyl-4-oxopiperidin-1-yl)-2-oxoethyl]-6,6-dimethylmorpholine-3-carboxylic acid Chemical compound OC(=O)C1COC(C)(C)CN1CC(=O)N1CC(C)(C)C(=O)CC1 FKZMQZYUBDCDCO-UHFFFAOYSA-N 0.000 description 1
- ULXDWTIHCJPKEI-UHFFFAOYSA-N 4-[2-[(2,4-dimethylpyridine-3-carbonyl)amino]propyl]-6,6-dimethylmorpholine-3-carboxylic acid Chemical compound CC=1C=CN=C(C)C=1C(=O)NC(C)CN1CC(C)(C)OCC1C(O)=O ULXDWTIHCJPKEI-UHFFFAOYSA-N 0.000 description 1
- KSTORQPYNQHKOI-UHFFFAOYSA-N 4-[2-[(4,6-dimethylpyrimidine-5-carbonyl)amino]propyl]-6,6-dimethylmorpholine-3-carboxylic acid Chemical compound CC=1N=CN=C(C)C=1C(=O)NC(C)CN1CC(C)(C)OCC1C(O)=O KSTORQPYNQHKOI-UHFFFAOYSA-N 0.000 description 1
- RKTQEVMZBCBOSB-UHFFFAOYSA-N 4-aminocyclohexan-1-ol;hydron;chloride Chemical compound Cl.NC1CCC(O)CC1 RKTQEVMZBCBOSB-UHFFFAOYSA-N 0.000 description 1
- PJDXPAYJDDQOGU-UHFFFAOYSA-N 4-chloro-2-(3,5-difluoropyridin-4-yl)aniline Chemical compound NC1=CC=C(Cl)C=C1C1=C(F)C=NC=C1F PJDXPAYJDDQOGU-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- ZKUZSTXNVMIDCY-UHFFFAOYSA-N 4-methylpyridine-3-carboxylic acid Chemical compound CC1=CC=NC=C1C(O)=O ZKUZSTXNVMIDCY-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- UYHITMNUZIKNIN-UHFFFAOYSA-N 6,6-dimethyl-4-(2-oxo-2-pyrrolidin-1-ylethyl)morpholine-3-carboxylic acid Chemical compound OC(=O)C1COC(C)(C)CN1CC(=O)N1CCCC1 UYHITMNUZIKNIN-UHFFFAOYSA-N 0.000 description 1
- QPGFBVOHCGDKPO-UHFFFAOYSA-N 6,6-dimethyl-4-[2-(pyrazine-2-carbonylamino)propyl]morpholine-3-carboxylic acid Chemical compound C=1N=CC=NC=1C(=O)NC(C)CN1CC(C)(C)OCC1C(O)=O QPGFBVOHCGDKPO-UHFFFAOYSA-N 0.000 description 1
- VVTCZBMNWZJMDF-UHFFFAOYSA-N 6,6-dimethyl-4-[3-methyl-2-[(2-methylpyridine-3-carbonyl)amino]butyl]morpholine-3-carboxylic acid Chemical compound C=1C=CN=C(C)C=1C(=O)NC(C(C)C)CN1CC(C)(C)OCC1C(O)=O VVTCZBMNWZJMDF-UHFFFAOYSA-N 0.000 description 1
- CIKAESZSRYLUGR-UHFFFAOYSA-N 6-chloro-7-ethoxy-9h-pyrido[3,4-b]indol-8-amine Chemical compound C1=NC=C2NC3=C(N)C(OCC)=C(Cl)C=C3C2=C1 CIKAESZSRYLUGR-UHFFFAOYSA-N 0.000 description 1
- OIVJKYMIBKPOHU-UHFFFAOYSA-N 6-chloro-8-nitro-9h-pyrido[3,4-b]indole Chemical compound N1C2=CN=CC=C2C2=C1C([N+](=O)[O-])=CC(Cl)=C2 OIVJKYMIBKPOHU-UHFFFAOYSA-N 0.000 description 1
- UKENNFIRYSNSHX-UHFFFAOYSA-N 6-chloro-9H-pyrido[3,4-b]indol-8-amine 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=NC=C2NC2=C1C=C(Cl)C=C2N UKENNFIRYSNSHX-UHFFFAOYSA-N 0.000 description 1
- YOYDGKNKZANQBG-UHFFFAOYSA-N 6-chloro-9h-pyrido[3,4-b]indole Chemical compound N1=CC=C2C3=CC(Cl)=CC=C3NC2=C1 YOYDGKNKZANQBG-UHFFFAOYSA-N 0.000 description 1
- RXXMVVVZCLUPAQ-UHFFFAOYSA-N 7-fluoro-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-1-carboxylic acid Chemical compound N1C2=CC(F)=CC=C2C2=C1C(C(=O)O)NCC2 RXXMVVVZCLUPAQ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- BPMFPOGUJAAYHL-UHFFFAOYSA-N 9H-Pyrido[2,3-b]indole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=N1 BPMFPOGUJAAYHL-UHFFFAOYSA-N 0.000 description 1
- CTVJIUHXFMNMFP-UHFFFAOYSA-N 9h-pyrido[3,4-b]indol-1-amine Chemical compound C12=CC=CC=C2NC2=C1C=CN=C2N CTVJIUHXFMNMFP-UHFFFAOYSA-N 0.000 description 1
- 108010022579 ATP dependent 26S protease Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- LCSNMPNLALNZEL-UHFFFAOYSA-N CCC(C)OC(=O)NC1CCCC1C(=O)O Chemical compound CCC(C)OC(=O)NC1CCCC1C(=O)O LCSNMPNLALNZEL-UHFFFAOYSA-N 0.000 description 1
- 0 CN(C)CCN(CC(C1)C(Nc2cc(Cl)cc3c2[n]c2c3C=C*=C=C2)=O)C1=O Chemical compound CN(C)CCN(CC(C1)C(Nc2cc(Cl)cc3c2[n]c2c3C=C*=C=C2)=O)C1=O 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ILCVYWBYVFZKLQ-UHFFFAOYSA-N Cc(nccc1)c1C(Nc(c1c(cc2Cl)c3ccncc3[nH]1)c2F)=O Chemical compound Cc(nccc1)c1C(Nc(c1c(cc2Cl)c3ccncc3[nH]1)c2F)=O ILCVYWBYVFZKLQ-UHFFFAOYSA-N 0.000 description 1
- RHPQSVRHOOMIIG-UHFFFAOYSA-N Cc1ncccc1C(Nc(c1c(cc2Cl)c3ccncc3[nH]1)c2SCCN(C)C)=O Chemical compound Cc1ncccc1C(Nc(c1c(cc2Cl)c3ccncc3[nH]1)c2SCCN(C)C)=O RHPQSVRHOOMIIG-UHFFFAOYSA-N 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000000503 Collagen Type II Human genes 0.000 description 1
- 108010041390 Collagen Type II Proteins 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- RBNPOMFGQQGHHO-UWTATZPHSA-N D-glyceric acid Chemical compound OC[C@@H](O)C(O)=O RBNPOMFGQQGHHO-UWTATZPHSA-N 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 208000015872 Gaucher disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018634 Gouty Arthritis Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 206010058359 Hypogonadism Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 101710110357 Inhibitor of nuclear factor kappa-B kinase subunit alpha Proteins 0.000 description 1
- 102100021892 Inhibitor of nuclear factor kappa-B kinase subunit alpha Human genes 0.000 description 1
- 101710205525 Inhibitor of nuclear factor kappa-B kinase subunit beta Proteins 0.000 description 1
- 102100021854 Inhibitor of nuclear factor kappa-B kinase subunit beta Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 206010027236 Meningitis fungal Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 206010028570 Myelopathy Diseases 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- WLEFGJJSAVVCGI-UHFFFAOYSA-N OC(=O)C(F)(F)F.CC1(C)CNCCC1=O Chemical compound OC(=O)C(F)(F)F.CC1(C)CNCCC1=O WLEFGJJSAVVCGI-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 208000003076 Osteolysis Diseases 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 108010001441 Phosphopeptides Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 201000010001 Silicosis Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- DBGUUPDUZXSAJF-UHFFFAOYSA-N [Cu+].[I+] Chemical compound [Cu+].[I+] DBGUUPDUZXSAJF-UHFFFAOYSA-N 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- QTBSBXVTEAMEQO-GUEYOVJQSA-N acetic acid-d4 Chemical compound [2H]OC(=O)C([2H])([2H])[2H] QTBSBXVTEAMEQO-GUEYOVJQSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 150000001346 alkyl aryl ethers Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 150000007860 aryl ester derivatives Chemical class 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- CKNWWFLJDPCURW-UHFFFAOYSA-N benzoic acid;2-phenylphenol Chemical compound OC(=O)C1=CC=CC=C1.OC1=CC=CC=C1C1=CC=CC=C1 CKNWWFLJDPCURW-UHFFFAOYSA-N 0.000 description 1
- 125000005872 benzooxazolyl group Chemical group 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- MGZWCDQAKCHOBX-FVGYRXGTSA-N benzyl (2s)-2-amino-3-hydroxypropanoate;hydrochloride Chemical compound Cl.OC[C@H](N)C(=O)OCC1=CC=CC=C1 MGZWCDQAKCHOBX-FVGYRXGTSA-N 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 102000043871 biotin binding protein Human genes 0.000 description 1
- 108700021042 biotin binding protein Proteins 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 208000019664 bone resorption disease Diseases 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
- 229960001467 bortezomib Drugs 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 229940095672 calcium sulfate Drugs 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- IDTRHAOWFLXAET-UHFFFAOYSA-N chlorosyl 2-chloroacetate Chemical compound ClCC(=O)OCl=O IDTRHAOWFLXAET-UHFFFAOYSA-N 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- MUYSADWCWFFZKR-UHFFFAOYSA-N cinchomeronic acid Chemical compound OC(=O)C1=CC=NC=C1C(O)=O MUYSADWCWFFZKR-UHFFFAOYSA-N 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000011382 collagen catabolic process Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentane carboxylic acid Natural products OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 1
- GUDMZGLFZNLYEY-UHFFFAOYSA-N cyclopropylmethanol Chemical compound OCC1CC1 GUDMZGLFZNLYEY-UHFFFAOYSA-N 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 229940125436 dual inhibitor Drugs 0.000 description 1
- 230000007368 endocrine function Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 201000010056 fungal meningitis Diseases 0.000 description 1
- KFKMGUPDWTWQFM-UHFFFAOYSA-N furo[3,4-c]pyridine-1,3-dione Chemical compound N1=CC=C2C(=O)OC(=O)C2=C1 KFKMGUPDWTWQFM-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000000262 haloalkenyl group Chemical group 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- MSYBLBLAMDYKKZ-UHFFFAOYSA-N hydron;pyridine-3-carbonyl chloride;chloride Chemical compound Cl.ClC(=O)C1=CC=CN=C1 MSYBLBLAMDYKKZ-UHFFFAOYSA-N 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 208000003532 hypothyroidism Diseases 0.000 description 1
- 230000002989 hypothyroidism Effects 0.000 description 1
- 201000000916 idiopathic juvenile osteoporosis Diseases 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 108091006086 inhibitor proteins Proteins 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 235000014705 isoleucine Nutrition 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 208000018937 joint inflammation Diseases 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229910052747 lanthanoid Inorganic materials 0.000 description 1
- 150000002602 lanthanoids Chemical class 0.000 description 1
- 235000005772 leucine Nutrition 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 208000022766 lymph node neoplasm Diseases 0.000 description 1
- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- NRVFDGZJTPCULU-UHFFFAOYSA-N meda Chemical compound Cl.CN(C)CCS NRVFDGZJTPCULU-UHFFFAOYSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- BUTPBERGMJVRBM-UHFFFAOYSA-N methanol;methylsulfinylmethane Chemical compound OC.CS(C)=O BUTPBERGMJVRBM-UHFFFAOYSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- RZVWBASHHLFBJF-UHFFFAOYSA-N methyl piperidine-4-carboxylate Chemical compound COC(=O)C1CCNCC1 RZVWBASHHLFBJF-UHFFFAOYSA-N 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- LVHBHZANLOWSRM-UHFFFAOYSA-N methylenebutanedioic acid Natural products OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
- XMWFMEYDRNJSOO-UHFFFAOYSA-N morpholine-4-carbonyl chloride Chemical compound ClC(=O)N1CCOCC1 XMWFMEYDRNJSOO-UHFFFAOYSA-N 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
- PZKXTTZFVZZJQX-UHFFFAOYSA-N n,n-diethylethanamine;(2,2,2-trifluoroacetyl) 2,2,2-trifluoroacetate Chemical compound CCN(CC)CC.FC(F)(F)C(=O)OC(=O)C(F)(F)F PZKXTTZFVZZJQX-UHFFFAOYSA-N 0.000 description 1
- HMROVXFWHOHCBQ-UHFFFAOYSA-N n-(6-chloro-4-fluoro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethyl-4-[2-[(2-methylpyridine-3-carbonyl)amino]propyl]morpholine-3-carboxamide Chemical compound C1C(C)(C)OCC(C(=O)NC=2C3=C(C4=C(F)C=NC=C4N3)C=C(Cl)C=2)N1CC(C)NC(=O)C1=CC=CN=C1C HMROVXFWHOHCBQ-UHFFFAOYSA-N 0.000 description 1
- VQYFIXOEGWXDGI-UHFFFAOYSA-N n-(6-chloro-4-methyl-9h-pyrido[3,4-b]indol-8-yl)pyridine-3-carboxamide Chemical compound C1=C(Cl)C=C2C=3C(C)=CN=CC=3NC2=C1NC(=O)C1=CC=CN=C1 VQYFIXOEGWXDGI-UHFFFAOYSA-N 0.000 description 1
- KUBIRPSTEODLSB-UHFFFAOYSA-N n-(6-chloro-7-ethylsulfanyl-9h-pyrido[3,4-b]indol-8-yl)-2-methylpyridine-3-carboxamide Chemical compound CCSC1=C(Cl)C=C2C3=CC=NC=C3NC2=C1NC(=O)C1=CC=CN=C1C KUBIRPSTEODLSB-UHFFFAOYSA-N 0.000 description 1
- MNZORSMJAFQOFK-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-1,1-dioxo-1,4-thiazinane-3-carboxamide Chemical compound C=12NC3=CN=CC=C3C2=CC(Cl)=CC=1NC(=O)C1CS(=O)(=O)CCN1 MNZORSMJAFQOFK-UHFFFAOYSA-N 0.000 description 1
- BQBAVNBXWBYXIF-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-4-[2-(2,6-dimethylmorpholin-4-yl)-2-oxoethyl]-6,6-dimethylmorpholine-3-carboxamide Chemical compound C1C(C)OC(C)CN1C(=O)CN1C(C(=O)NC=2C=3NC4=CN=CC=C4C=3C=C(Cl)C=2)COC(C)(C)C1 BQBAVNBXWBYXIF-UHFFFAOYSA-N 0.000 description 1
- CGKCMWALAYUKEE-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-4-[2-(3,3-dimethyl-4-oxopiperidin-1-yl)-2-oxoethyl]-6,6-dimethylmorpholine-3-carboxamide Chemical compound C=1C(Cl)=CC=2C3=CC=NC=C3NC=2C=1NC(=O)C1COC(C)(C)CN1CC(=O)N1CCC(=O)C(C)(C)C1 CGKCMWALAYUKEE-UHFFFAOYSA-N 0.000 description 1
- KXNBWCQLHYDGPZ-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-4-[2-(4-hydroxypiperidin-1-yl)-2-oxoethyl]-6,6-dimethylmorpholine-3-carboxamide Chemical compound C=1C(Cl)=CC=2C3=CC=NC=C3NC=2C=1NC(=O)C1COC(C)(C)CN1CC(=O)N1CCC(O)CC1 KXNBWCQLHYDGPZ-UHFFFAOYSA-N 0.000 description 1
- GPODVZCSWGZWNE-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-4-[2-(diethylamino)-2-oxoethyl]-6,6-dimethylmorpholine-3-carboxamide Chemical compound CCN(CC)C(=O)CN1CC(C)(C)OCC1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 GPODVZCSWGZWNE-UHFFFAOYSA-N 0.000 description 1
- UYEXDTNPNBSPFN-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-4-[2-[4-(2-hydroxypropan-2-yl)piperidin-1-yl]-2-oxoethyl]-6,6-dimethylmorpholine-3-carboxamide Chemical compound C1CC(C(C)(O)C)CCN1C(=O)CN1C(C(=O)NC=2C=3NC4=CN=CC=C4C=3C=C(Cl)C=2)COC(C)(C)C1 UYEXDTNPNBSPFN-UHFFFAOYSA-N 0.000 description 1
- KRWHEIRFRMHJDQ-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethyl-4-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]morpholine-3-carboxamide Chemical compound C1CN(C)CCN1C(=O)CN1C(C(=O)NC=2C=3NC4=CN=CC=C4C=3C=C(Cl)C=2)COC(C)(C)C1 KRWHEIRFRMHJDQ-UHFFFAOYSA-N 0.000 description 1
- OCHNKNXQGYDGBQ-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethyl-4-[2-(methylcarbamoylamino)propyl]morpholine-3-carboxamide Chemical class CNC(=O)NC(C)CN1CC(C)(C)OCC1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 OCHNKNXQGYDGBQ-UHFFFAOYSA-N 0.000 description 1
- XPPPOILXFJKBQU-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethyl-4-[2-[(2,2,2-trifluoroacetyl)amino]propyl]morpholine-3-carboxamide Chemical class FC(F)(F)C(=O)NC(C)CN1CC(C)(C)OCC1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 XPPPOILXFJKBQU-UHFFFAOYSA-N 0.000 description 1
- HXRBFZXEAJGEQU-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethyl-4-[2-[(2-methylpyridine-3-carbonyl)amino]butyl]morpholine-3-carboxamide Chemical compound C1C(C)(C)OCC(C(=O)NC=2C=3NC4=CN=CC=C4C=3C=C(Cl)C=2)N1CC(CC)NC(=O)C1=CC=CN=C1C HXRBFZXEAJGEQU-UHFFFAOYSA-N 0.000 description 1
- XFXJTXQXTCFLBH-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethyl-4-[3-methyl-2-[(2-methylpyridine-3-carbonyl)amino]butyl]morpholine-3-carboxamide Chemical compound C1C(C)(C)OCC(C(=O)NC=2C=3NC4=CN=CC=C4C=3C=C(Cl)C=2)N1CC(C(C)C)NC(=O)C1=CC=CN=C1C XFXJTXQXTCFLBH-UHFFFAOYSA-N 0.000 description 1
- QLPKCLIYOWKCRT-UHFFFAOYSA-N n-(6-chloro-9h-pyrido[3,4-b]indol-8-yl)-6,6-dimethylmorpholine-3-carboxamide Chemical compound C1OC(C)(C)CNC1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 QLPKCLIYOWKCRT-UHFFFAOYSA-N 0.000 description 1
- WYNOYHFTNSJNGD-UHFFFAOYSA-N n-[6-chloro-7-[2-(dimethylamino)ethylsulfanyl]-9h-pyrido[3,4-b]indol-8-yl]-2-methylpyridine-3-carboxamide;trihydrochloride Chemical compound Cl.Cl.Cl.CN(C)CCSC1=C(Cl)C=C2C3=CC=NC=C3NC2=C1NC(=O)C1=CC=CN=C1C WYNOYHFTNSJNGD-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 108010087904 neutravidin Proteins 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N nicotinic acid Natural products OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- UEHLXXJAWYWUGI-UHFFFAOYSA-M nitromersol Chemical compound CC1=CC=C([N+]([O-])=O)C2=C1O[Hg]2 UEHLXXJAWYWUGI-UHFFFAOYSA-M 0.000 description 1
- 229940118238 nitromersol Drugs 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 235000008729 phenylalanine Nutrition 0.000 description 1
- XEBWQGVWTUSTLN-UHFFFAOYSA-M phenylmercury acetate Chemical compound CC(=O)O[Hg]C1=CC=CC=C1 XEBWQGVWTUSTLN-UHFFFAOYSA-M 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 201000003651 pulmonary sarcoidosis Diseases 0.000 description 1
- NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- YDBPZCVWPFMBDH-MRVPVSSYSA-N tert-butyl (2r)-2-formylpyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@@H]1C=O YDBPZCVWPFMBDH-MRVPVSSYSA-N 0.000 description 1
- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- NBDAUFXJXMBQRC-UHFFFAOYSA-N tert-butyl n-(1-oxobutan-2-yl)carbamate Chemical compound CCC(C=O)NC(=O)OC(C)(C)C NBDAUFXJXMBQRC-UHFFFAOYSA-N 0.000 description 1
- YMNBXYLOSIKZGL-UHFFFAOYSA-N tert-butyl n-(3-methyl-1-oxobutan-2-yl)carbamate Chemical compound CC(C)C(C=O)NC(=O)OC(C)(C)C YMNBXYLOSIKZGL-UHFFFAOYSA-N 0.000 description 1
- OEQRZPWMXXJEKU-LURJTMIESA-N tert-butyl n-[(2s)-1-oxopropan-2-yl]carbamate Chemical compound O=C[C@H](C)NC(=O)OC(C)(C)C OEQRZPWMXXJEKU-LURJTMIESA-N 0.000 description 1
- RHTNIIWWVYQJSH-UHFFFAOYSA-N tert-butyl n-[2-[(6-chloro-9h-pyrido[3,4-b]indol-8-yl)carbamoyl]cyclopentyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1CCCC1C(=O)NC1=CC(Cl)=CC2=C1NC1=CN=CC=C12 RHTNIIWWVYQJSH-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 238000001685 time-resolved fluorescence spectroscopy Methods 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000005068 transpiration Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 235000002374 tyrosine Nutrition 0.000 description 1
- 230000006663 ubiquitin-proteasome pathway Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 235000014393 valine Nutrition 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- 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
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46146803P | 2003-04-09 | 2003-04-09 | |
| US60/461,468 | 2003-04-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20060006031A true KR20060006031A (ko) | 2006-01-18 |
Family
ID=33299818
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020057019268A Ceased KR20060006031A (ko) | 2003-04-09 | 2004-04-09 | 염증 질환 치료에 유용한 베타-카르볼린 |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US7727985B2 (enExample) |
| EP (1) | EP1611134A1 (enExample) |
| JP (1) | JP2006522824A (enExample) |
| KR (1) | KR20060006031A (enExample) |
| CN (1) | CN1802375A (enExample) |
| AU (1) | AU2004230952A1 (enExample) |
| BR (1) | BRPI0409263A (enExample) |
| CA (1) | CA2521300A1 (enExample) |
| CO (1) | CO5700746A2 (enExample) |
| CR (1) | CR8042A (enExample) |
| EA (1) | EA009121B1 (enExample) |
| EC (1) | ECSP056145A (enExample) |
| HR (1) | HRP20050926A2 (enExample) |
| MA (1) | MA27837A1 (enExample) |
| MX (1) | MXPA05010793A (enExample) |
| NI (1) | NI200500174A (enExample) |
| NO (1) | NO20054598L (enExample) |
| OA (1) | OA13115A (enExample) |
| RS (1) | RS20050832A (enExample) |
| TN (1) | TNSN05257A1 (enExample) |
| WO (1) | WO2004092167A1 (enExample) |
| ZA (1) | ZA200508198B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101646916B1 (ko) | 2015-07-13 | 2016-08-09 | 강원대학교산학협력단 | 베타-카르볼린 알칼로이드 화합물을 함유하는 염증성 질환의 예방 또는 치료용 조성물 |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006522824A (ja) | 2003-04-09 | 2006-10-05 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | 炎症性疾患を処置するために有用なβ−カルボリン |
| BRPI0509660A (pt) * | 2004-04-09 | 2007-10-09 | Millennium Pharm Inc | compostos de beta-carbolina de utilidade no tratamento de doenças inflamatórias |
| US8119655B2 (en) * | 2005-10-07 | 2012-02-21 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
| AU2006316322B2 (en) * | 2005-11-22 | 2011-08-25 | Merck Canada Inc. | Tricyclic compounds useful as inhibitors of kinases |
| US8426355B2 (en) * | 2006-03-15 | 2013-04-23 | Theralogics, Inc. | Methods of treating muscular wasting diseases using NF-κB activation inhibitors |
| WO2008002246A1 (en) * | 2006-06-28 | 2008-01-03 | Astrazeneca Ab | A pharmaceutical composition comprising an ikk2 inhibitor and a second active ingrdient. |
| AU2007334541A1 (en) * | 2006-12-13 | 2008-06-26 | Gilead Sciences, Inc. | Monophosphates as mutual prodrugs of anti-inflammatory signal transduction modulators (AISTM's) and beta-agonists for the treatment of pulmonary inflammation and bronchoconstriction |
| WO2009054970A1 (en) * | 2007-10-23 | 2009-04-30 | Millennium Pharmaceuticals, Inc. | Mesylate salt of an ikk inhibitor |
| WO2009054965A1 (en) * | 2007-10-23 | 2009-04-30 | Millennium Pharmaceuticals, Inc. | Salts of n- (6-chloro-9h-pyrido [3,4-b] ind0l-8-yl) -4- [2- (2, 6-dimethyl-4-morpholinyl) -2-0x0e thyl] -6, 6-dimethyl-morpholinecarboxamide |
| EP2297347B1 (en) | 2008-05-14 | 2017-03-08 | Millennium Pharmaceuticals, Inc. | Methods and kits for monitoring the effects of immunomodulators on adaptive immunity |
| CN102171204B (zh) | 2008-10-02 | 2014-08-20 | 旭化成制药株式会社 | 8位取代异喹啉衍生物及其用途 |
| WO2011120911A1 (en) | 2010-03-30 | 2011-10-06 | Novartis Ag | Pkc inhibitors for the treatment of b-cell lymphoma having chronic active b-cell-receptor signalling |
| US9440966B2 (en) * | 2011-03-28 | 2016-09-13 | Sjt Molecular Research, S.L. | Compounds for treatment of metabolic syndrome |
| CN102416014B (zh) * | 2011-09-13 | 2012-11-21 | 河南中医学院 | 一种生物碱类成分组合物在制备抗甲型h1n1流感病毒药物中的应用 |
| CN102391323B (zh) * | 2011-10-18 | 2013-09-25 | 首都医科大学 | 四氢-β-咔啉衍生物、其制备方法及其用途 |
| CN108271369A (zh) | 2015-10-23 | 2018-07-10 | 法尔玛赞公司 | 用于制备色胺及其衍生物的新工艺 |
| CN109593089B (zh) * | 2019-01-24 | 2022-01-28 | 西南大学 | 二氮杂螺癸烷哌啶甲酰胺类化合物制备和应用 |
| CN112824387B (zh) * | 2019-11-21 | 2023-03-21 | 济南尚博生物科技有限公司 | 一种2-甲基烟酸酯及其制备方法和应用 |
| CN117510494B (zh) * | 2023-11-07 | 2024-04-19 | 桂林医学院附属医院 | β-咔啉-沙利度胺偶联物及其在制备逆转ABT-199耐药的药物中的应用 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE297908T1 (de) * | 1998-08-12 | 2005-07-15 | Pfizer Prod Inc | Tace inhibitoren |
| DE19951360A1 (de) | 1999-10-26 | 2001-05-03 | Aventis Pharma Gmbh | Substituierte Indole |
| EP1268477B1 (en) | 2000-03-15 | 2010-04-21 | Sanofi-Aventis Deutschland GmbH | Substituted beta-carbolines with ikb-kinase inhibiting activity |
| MXPA02007981A (es) | 2000-03-15 | 2004-04-05 | Aventis Pharma Gmbh | Beta-carbolinas sustituidas con actividad que inhibe la ikb-cinasa. |
| BR0212617A (pt) * | 2001-09-19 | 2005-02-09 | Pharmacia Corp | Compostos de pirazolila substituìdo para o tratamento de inflamação |
| AU2002352498A1 (en) * | 2001-11-07 | 2003-05-19 | Millennium Pharmaceuticals, Inc. | Carboline derivatives as inhibitors of ikb in the treatment of multiple myeloma and others cancers |
| WO2004080996A1 (en) * | 2003-03-07 | 2004-09-23 | Eli Lilly And Company | Opioid receptor antagonists |
| JP2006522824A (ja) | 2003-04-09 | 2006-10-05 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | 炎症性疾患を処置するために有用なβ−カルボリン |
-
2004
- 2004-04-09 JP JP2006509889A patent/JP2006522824A/ja active Pending
- 2004-04-09 OA OA1200500279A patent/OA13115A/en unknown
- 2004-04-09 WO PCT/US2004/011080 patent/WO2004092167A1/en not_active Ceased
- 2004-04-09 HR HR20050926A patent/HRP20050926A2/hr not_active Application Discontinuation
- 2004-04-09 CA CA002521300A patent/CA2521300A1/en not_active Abandoned
- 2004-04-09 EA EA200501584A patent/EA009121B1/ru not_active IP Right Cessation
- 2004-04-09 CN CNA2004800160170A patent/CN1802375A/zh active Pending
- 2004-04-09 RS YUP-2005/0832A patent/RS20050832A/sr unknown
- 2004-04-09 BR BRPI0409263-5A patent/BRPI0409263A/pt not_active IP Right Cessation
- 2004-04-09 EP EP04759390A patent/EP1611134A1/en not_active Withdrawn
- 2004-04-09 MX MXPA05010793A patent/MXPA05010793A/es active IP Right Grant
- 2004-04-09 AU AU2004230952A patent/AU2004230952A1/en not_active Abandoned
- 2004-04-09 US US10/821,545 patent/US7727985B2/en active Active
- 2004-04-09 KR KR1020057019268A patent/KR20060006031A/ko not_active Ceased
-
2005
- 2005-10-06 NO NO20054598A patent/NO20054598L/no not_active Application Discontinuation
- 2005-10-07 NI NI200500174A patent/NI200500174A/es unknown
- 2005-10-07 TN TNP2005000257A patent/TNSN05257A1/en unknown
- 2005-10-11 ZA ZA200508198A patent/ZA200508198B/xx unknown
- 2005-10-12 CR CR8042A patent/CR8042A/es not_active Application Discontinuation
- 2005-11-04 CO CO05113041A patent/CO5700746A2/es not_active Application Discontinuation
- 2005-11-07 EC EC2005006145A patent/ECSP056145A/es unknown
- 2005-11-09 MA MA28592A patent/MA27837A1/fr unknown
-
2009
- 2009-12-17 US US12/640,335 patent/US20100093713A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101646916B1 (ko) | 2015-07-13 | 2016-08-09 | 강원대학교산학협력단 | 베타-카르볼린 알칼로이드 화합물을 함유하는 염증성 질환의 예방 또는 치료용 조성물 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004092167A1 (en) | 2004-10-28 |
| OA13115A (en) | 2006-11-10 |
| HRP20050926A2 (en) | 2006-06-30 |
| AU2004230952A1 (en) | 2004-10-28 |
| NO20054598L (no) | 2005-10-27 |
| MXPA05010793A (es) | 2005-12-05 |
| US20100093713A1 (en) | 2010-04-15 |
| ECSP056145A (es) | 2006-04-19 |
| EP1611134A1 (en) | 2006-01-04 |
| RS20050832A (sr) | 2007-12-31 |
| US20040235839A1 (en) | 2004-11-25 |
| ZA200508198B (en) | 2007-01-31 |
| EA200501584A1 (ru) | 2006-06-30 |
| MA27837A1 (fr) | 2006-04-03 |
| WO2004092167A8 (en) | 2006-01-05 |
| JP2006522824A (ja) | 2006-10-05 |
| EA009121B1 (ru) | 2007-10-26 |
| CO5700746A2 (es) | 2006-11-30 |
| US7727985B2 (en) | 2010-06-01 |
| CR8042A (es) | 2006-05-30 |
| TNSN05257A1 (en) | 2007-07-10 |
| CN1802375A (zh) | 2006-07-12 |
| BRPI0409263A (pt) | 2006-03-28 |
| NI200500174A (es) | 2006-04-17 |
| NO20054598D0 (no) | 2005-10-06 |
| CA2521300A1 (en) | 2004-10-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20100093713A1 (en) | Beta-carbolines useful for treating inflammatory disease | |
| JP7679173B2 (ja) | Ｒａｆ（急速進行性線維肉腫）ポリペプチドの標的分解のための化合物および方法 | |
| CA2693182C (en) | Pyrimidine compounds, methods of synthesis thereof, and use thereof in the treatment of raf kinase-mediated disorders | |
| EP1735311B1 (en) | Beta-carbolines useful for treating inflammatory disease | |
| KR20190113842A (ko) | 에스트로겐 수용체 단백질 분해 조절제 및 관련 사용 방법 | |
| KR20190101406A (ko) | Egfr 단백질분해 표적화 키메라 분자 및 관련 사용 방법 | |
| KR20180029061A (ko) | 단백질 분해의 알라닌계 조절인자 및 관련된 이용 방법 | |
| CN108137507A (zh) | 基于mdm2的蛋白水解调节剂和相关的使用方法 | |
| JP2006528702A (ja) | グリコーゲンホスホリラーゼのピロロピリジン−２−カルボン酸アミドインヒビター | |
| EP1819332B1 (en) | Pyrrolopyridine-2-carboxylic acid amides | |
| WO2005118583A1 (en) | 2, 5-dihydro-pyrazolo`4, 3-c!quinolin-4-ones as chk-1 inhibitors | |
| WO2009067233A1 (en) | Beta carbolines and uses thereof | |
| CN101432278B (zh) | 作为抗病毒剂的二酮基哌嗪和哌啶衍生物 | |
| JP2023537586A (ja) | Ｃｄｋ９阻害剤およびその使用 | |
| AU2014200030A1 (en) | Pyrimidine Derivatives Useful as Raf Kinase Inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20051010 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20090408 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20110318 Patent event code: PE09021S01D |
|
| E601 | Decision to refuse application | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 20111017 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 20110318 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |