MX2010011896A - Derivados de aminopiridina. - Google Patents
Derivados de aminopiridina.Info
- Publication number
- MX2010011896A MX2010011896A MX2010011896A MX2010011896A MX2010011896A MX 2010011896 A MX2010011896 A MX 2010011896A MX 2010011896 A MX2010011896 A MX 2010011896A MX 2010011896 A MX2010011896 A MX 2010011896A MX 2010011896 A MX2010011896 A MX 2010011896A
- Authority
- MX
- Mexico
- Prior art keywords
- amino
- pyridin
- ylmethyl
- ethyl
- carbamoyl
- Prior art date
Links
- 150000003927 aminopyridines Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 196
- 208000006673 asthma Diseases 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 27
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 3
- -1 6-amino-pyridin-3-ylmethyl Chemical group 0.000 claims description 762
- 239000002253 acid Substances 0.000 claims description 175
- 229940080818 propionamide Drugs 0.000 claims description 89
- 125000000217 alkyl group Chemical group 0.000 claims description 83
- 125000003118 aryl group Chemical group 0.000 claims description 62
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 56
- FRIVVXSYDCWJOW-ZDUSSCGKSA-N (2s)-2-amino-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)propanamide Chemical compound C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 FRIVVXSYDCWJOW-ZDUSSCGKSA-N 0.000 claims description 55
- CWLQUGTUXBXTLF-RXMQYKEDSA-N (2r)-1-methylpyrrolidine-2-carboxylic acid Chemical compound CN1CCC[C@@H]1C(O)=O CWLQUGTUXBXTLF-RXMQYKEDSA-N 0.000 claims description 50
- 125000003545 alkoxy group Chemical group 0.000 claims description 48
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 46
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 39
- 125000005843 halogen group Chemical group 0.000 claims description 38
- 125000001424 substituent group Chemical group 0.000 claims description 37
- MDJFUIWBWQEWFX-ZDUSSCGKSA-N (2s)-2-amino-n-[(6-aminopyridin-3-yl)methyl]-3-(4-fluorophenyl)propanamide Chemical compound C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C=C1 MDJFUIWBWQEWFX-ZDUSSCGKSA-N 0.000 claims description 35
- YTBBVDRTLFHSFZ-ZDUSSCGKSA-N (2s)-2-amino-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-dichlorophenyl)propanamide Chemical compound C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C(Cl)=C1 YTBBVDRTLFHSFZ-ZDUSSCGKSA-N 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 31
- XQGVQRPSTODODM-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrrole-2-carboxylic acid Chemical compound CC1=CC(C)=C(C(O)=O)N1 XQGVQRPSTODODM-UHFFFAOYSA-N 0.000 claims description 30
- 125000004429 atom Chemical group 0.000 claims description 30
- 229910052799 carbon Inorganic materials 0.000 claims description 29
- 125000001072 heteroaryl group Chemical group 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 24
- 230000000694 effects Effects 0.000 claims description 24
- 230000001575 pathological effect Effects 0.000 claims description 23
- CKPAOPWAVKSUPQ-SSDOTTSWSA-N (2r)-1-propan-2-ylpyrrolidine-2-carboxylic acid Chemical compound CC(C)N1CCC[C@@H]1C(O)=O CKPAOPWAVKSUPQ-SSDOTTSWSA-N 0.000 claims description 22
- 208000010668 atopic eczema Diseases 0.000 claims description 22
- 125000005842 heteroatom Chemical group 0.000 claims description 22
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 21
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
- 230000000172 allergic effect Effects 0.000 claims description 19
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 17
- 206010011224 Cough Diseases 0.000 claims description 17
- 239000012453 solvate Substances 0.000 claims description 17
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 16
- YIVHOQIKHMTVRG-UHFFFAOYSA-N 3-methyl-1h-pyrrole-2-carboxylic acid Chemical compound CC=1C=CNC=1C(O)=O YIVHOQIKHMTVRG-UHFFFAOYSA-N 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- IGERQMDMYFFQLC-RXMQYKEDSA-N (2r)-1-methylpyrrolidine-2-carboxamide Chemical compound CN1CCC[C@@H]1C(N)=O IGERQMDMYFFQLC-RXMQYKEDSA-N 0.000 claims description 14
- 206010061218 Inflammation Diseases 0.000 claims description 14
- 230000004054 inflammatory process Effects 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 13
- ILTPUGMAIWNEDF-ZDUSSCGKSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-(3-chlorophenyl)propanamide Chemical compound C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC(Cl)=C1 ILTPUGMAIWNEDF-ZDUSSCGKSA-N 0.000 claims description 12
- RHDULCDZXCAQBQ-ZDUSSCGKSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-(3-fluorophenyl)propanamide Chemical compound C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC(F)=C1 RHDULCDZXCAQBQ-ZDUSSCGKSA-N 0.000 claims description 12
- TZPYUTJMVLCBKD-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrrole-2-carboxamide Chemical compound CC1=CC(C)=C(C(N)=O)N1 TZPYUTJMVLCBKD-UHFFFAOYSA-N 0.000 claims description 12
- 125000002619 bicyclic group Chemical group 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 206010033645 Pancreatitis Diseases 0.000 claims description 10
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 201000010105 allergic rhinitis Diseases 0.000 claims description 10
- GYUFTOBBATZROT-ZDUSSCGKSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-(3,5-difluorophenyl)propanamide Chemical compound C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1=CC(F)=CC(F)=C1 GYUFTOBBATZROT-ZDUSSCGKSA-N 0.000 claims description 9
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 9
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 9
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 9
- 230000001684 chronic effect Effects 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 claims description 8
- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- 230000001613 neoplastic effect Effects 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- YNXFKYXSWNIWGO-ZCFIWIBFSA-N (2r)-1-ethylpyrrolidin-1-ium-2-carboxylate Chemical compound CCN1CCC[C@@H]1C(O)=O YNXFKYXSWNIWGO-ZCFIWIBFSA-N 0.000 claims description 7
- 101000605522 Homo sapiens Kallikrein-1 Proteins 0.000 claims description 7
- 206010033647 Pancreatitis acute Diseases 0.000 claims description 7
- 201000003229 acute pancreatitis Diseases 0.000 claims description 7
- 206010003246 arthritis Diseases 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 201000008482 osteoarthritis Diseases 0.000 claims description 7
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 6
- 206010010741 Conjunctivitis Diseases 0.000 claims description 6
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 6
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 claims description 6
- 230000005713 exacerbation Effects 0.000 claims description 6
- 230000002757 inflammatory effect Effects 0.000 claims description 6
- 210000002307 prostate Anatomy 0.000 claims description 6
- GLSAEEYATLRIKW-AWEZNQCLSA-N (2S)-2-amino-N-[(6-amino-2-methylpyridin-3-yl)methyl]-3-(4-fluorophenyl)propanamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@@H](N)CC1=CC=C(F)C=C1 GLSAEEYATLRIKW-AWEZNQCLSA-N 0.000 claims description 5
- MRBYGTPCMFIOHF-AWEZNQCLSA-N (2S)-2-amino-N-[(6-amino-2-methylpyridin-3-yl)methyl]-3-[3-(trifluoromethyl)phenyl]propanamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@@H](N)CC1=CC=CC(C(F)(F)F)=C1 MRBYGTPCMFIOHF-AWEZNQCLSA-N 0.000 claims description 5
- BPSLZWSRHTULGU-ZCFIWIBFSA-N (2r)-1-methylpiperidin-1-ium-2-carboxylate Chemical compound CN1CCCC[C@@H]1C(O)=O BPSLZWSRHTULGU-ZCFIWIBFSA-N 0.000 claims description 5
- HRJKYJQVBJYEBH-SSDOTTSWSA-N (2r)-1-propan-2-ylpyrrolidine-2-carboxamide Chemical compound CC(C)N1CCC[C@@H]1C(N)=O HRJKYJQVBJYEBH-SSDOTTSWSA-N 0.000 claims description 5
- CYXLHZVPLXEUPP-SSDOTTSWSA-N (2r)-1-propylpyrrolidin-1-ium-2-carboxylate Chemical compound CCCN1CCC[C@@H]1C(O)=O CYXLHZVPLXEUPP-SSDOTTSWSA-N 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- MWASWDHUXRVLEN-KRWDZBQOSA-N (2s)-2-amino-n-[(6-aminopyridin-3-yl)methyl]-3-naphthalen-1-ylpropanamide Chemical compound O=C([C@H](CC=1C2=CC=CC=C2C=CC=1)N)NCC1=CC=C(N)N=C1 MWASWDHUXRVLEN-KRWDZBQOSA-N 0.000 claims description 4
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- NBFVMBGIPAJCJQ-ZCFIWIBFSA-N (2r)-1-methylpiperidine-2-carboxamide Chemical compound CN1CCCC[C@@H]1C(N)=O NBFVMBGIPAJCJQ-ZCFIWIBFSA-N 0.000 claims description 3
- UMFBAWNSXKASMF-AZUAARDMSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-2-(dimethylamino)-3-methylbutanamide Chemical compound C([C@H](NC(=O)[C@H](N(C)C)C(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C(Cl)=C1 UMFBAWNSXKASMF-AZUAARDMSA-N 0.000 claims description 3
- SHHYWMRZINUSMU-PKOBYXMFSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-3-methyl-2-(methylamino)butanamide Chemical compound C([C@H](NC(=O)[C@@H](C(C)C)NC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C(Cl)=C1 SHHYWMRZINUSMU-PKOBYXMFSA-N 0.000 claims description 3
- ITCSRFRLSFJJOK-KXBFYZLASA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3-chlorophenyl)-2-[[(2s)-2-[methyl(propan-2-yl)amino]propanoyl]amino]propanamide Chemical compound C([C@H](NC(=O)[C@H](C)N(C)C(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC(Cl)=C1 ITCSRFRLSFJJOK-KXBFYZLASA-N 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 201000004624 Dermatitis Diseases 0.000 claims description 3
- 208000005615 Interstitial Cystitis Diseases 0.000 claims description 3
- 206010034038 Parotitis Diseases 0.000 claims description 3
- 208000036071 Rhinorrhea Diseases 0.000 claims description 3
- 206010039101 Rhinorrhoea Diseases 0.000 claims description 3
- 208000005392 Spasm Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 208000024780 Urticaria Diseases 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 208000028169 periodontal disease Diseases 0.000 claims description 3
- 230000000306 recurrent effect Effects 0.000 claims description 3
- 230000000241 respiratory effect Effects 0.000 claims description 3
- 206010039083 rhinitis Diseases 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 201000009890 sinusitis Diseases 0.000 claims description 3
- 208000017520 skin disease Diseases 0.000 claims description 3
- 210000002460 smooth muscle Anatomy 0.000 claims description 3
- ZBJBLJBCRBJSOH-LIRRHRJNSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[(2s)-2-(diethylamino)propanoyl]amino]-3-(3,4-difluorophenyl)propanamide Chemical compound C([C@H](NC(=O)[C@H](C)N(CC)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 ZBJBLJBCRBJSOH-LIRRHRJNSA-N 0.000 claims description 2
- FNBWXEBZXBEKQV-FQEVSTJZSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[2-[di(propan-2-yl)amino]acetyl]amino]propanamide Chemical compound C([C@H](NC(=O)CN(C(C)C)C(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 FNBWXEBZXBEKQV-FQEVSTJZSA-N 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 102100038297 Kallikrein-1 Human genes 0.000 claims 5
- LTFSFTYAXJRGHD-ICSRJNTNSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-difluorophenyl)-1-oxopropan-2-yl]-2-(dimethylamino)-3,3-dimethylbutanamide Chemical compound C([C@H](NC(=O)[C@H](N(C)C)C(C)(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 LTFSFTYAXJRGHD-ICSRJNTNSA-N 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- BPPVUXSMLBXYGG-UHFFFAOYSA-N 4-[3-(4,5-dihydro-1,2-oxazol-3-yl)-2-methyl-4-methylsulfonylbenzoyl]-2-methyl-1h-pyrazol-3-one Chemical compound CC1=C(C(=O)C=2C(N(C)NC=2)=O)C=CC(S(C)(=O)=O)=C1C1=NOCC1 BPPVUXSMLBXYGG-UHFFFAOYSA-N 0.000 claims 1
- 241001091551 Clio Species 0.000 claims 1
- 208000007101 Muscle Cramp Diseases 0.000 claims 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 28
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 125
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 96
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
- 108060005987 Kallikrein Proteins 0.000 description 45
- 102000001399 Kallikrein Human genes 0.000 description 44
- 239000000243 solution Substances 0.000 description 43
- 229910001868 water Inorganic materials 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
- 239000007787 solid Substances 0.000 description 32
- 239000002904 solvent Substances 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- 150000001412 amines Chemical class 0.000 description 27
- 239000003112 inhibitor Substances 0.000 description 25
- 239000011541 reaction mixture Substances 0.000 description 22
- 239000012267 brine Substances 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 21
- 125000006239 protecting group Chemical group 0.000 description 18
- 239000007832 Na2SO4 Substances 0.000 description 17
- 206010028980 Neoplasm Diseases 0.000 description 17
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- 229910052938 sodium sulfate Inorganic materials 0.000 description 17
- 235000011152 sodium sulphate Nutrition 0.000 description 17
- 238000003818 flash chromatography Methods 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 125000004212 difluorophenyl group Chemical group 0.000 description 15
- 239000003480 eluent Substances 0.000 description 15
- 238000009472 formulation Methods 0.000 description 15
- 239000000377 silicon dioxide Substances 0.000 description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 12
- YEBJVSLNUMZXRJ-UHFFFAOYSA-N 5-methoxyindole-2-carboxylic acid Chemical compound COC1=CC=C2NC(C(O)=O)=CC2=C1 YEBJVSLNUMZXRJ-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 208000024891 symptom Diseases 0.000 description 12
- ONIBWKKTOPOVIA-SCSAIBSYSA-N D-Proline Chemical compound OC(=O)[C@H]1CCCN1 ONIBWKKTOPOVIA-SCSAIBSYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- HXEACLLIILLPRG-RXMQYKEDSA-N D-pipecolic acid Chemical compound OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 10
- HPOUSMGVBCPKMF-GZUIOVLMSA-N (2S)-3-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl)-2-amino-N-[(6-aminopyridin-3-yl)methyl]propanamide Chemical compound O=C([C@H](CC1C2CCCCC2CCC1)N)NCC1=CC=C(N)N=C1 HPOUSMGVBCPKMF-GZUIOVLMSA-N 0.000 description 9
- 201000009030 Carcinoma Diseases 0.000 description 9
- 201000011510 cancer Diseases 0.000 description 9
- 150000001721 carbon Chemical group 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 210000004072 lung Anatomy 0.000 description 9
- AGPKZVBTJJNPAG-BRJRFNKRSA-N (2r)-2-amino-3-methylpentanoic acid Chemical compound CCC(C)[C@@H](N)C(O)=O AGPKZVBTJJNPAG-BRJRFNKRSA-N 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 8
- 229940024606 amino acid Drugs 0.000 description 8
- 230000033115 angiogenesis Effects 0.000 description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- 238000002953 preparative HPLC Methods 0.000 description 8
- ASKNSOHBVNDHER-ZDUSSCGKSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-[3-(trifluoromethyl)phenyl]propanamide Chemical compound C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC(C(F)(F)F)=C1 ASKNSOHBVNDHER-ZDUSSCGKSA-N 0.000 description 7
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 7
- HSHJMEDEJJTZND-UHFFFAOYSA-N 5-(aminomethyl)pyridin-2-amine;dihydrochloride Chemical compound Cl.Cl.NCC1=CC=C(N)N=C1 HSHJMEDEJJTZND-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 7
- 102000057032 Tissue Kallikreins Human genes 0.000 description 7
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 7
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 7
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 208000023504 respiratory system disease Diseases 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- IHUIMHAJYBRGHZ-ZDUSSCGKSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-(2,4,5-trifluorophenyl)propanamide Chemical compound C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1=CC(F)=C(F)C=C1F IHUIMHAJYBRGHZ-ZDUSSCGKSA-N 0.000 description 6
- ZBTIJKRAXCTPRJ-GXKRWWSZSA-N (2s)-2-amino-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)propanamide;dihydrochloride Chemical compound Cl.Cl.C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 ZBTIJKRAXCTPRJ-GXKRWWSZSA-N 0.000 description 6
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 6
- 241000157855 Cinchona Species 0.000 description 6
- 235000001258 Cinchona calisaya Nutrition 0.000 description 6
- 229930182820 D-proline Natural products 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000003102 growth factor Substances 0.000 description 6
- 150000002430 hydrocarbons Chemical group 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 238000005897 peptide coupling reaction Methods 0.000 description 6
- XNROFTAJEGCDCT-LLVKDONJSA-N (2r)-1-benzylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCN1CC1=CC=CC=C1 XNROFTAJEGCDCT-LLVKDONJSA-N 0.000 description 5
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 101710176219 Kallikrein-1 Proteins 0.000 description 5
- 102000003827 Plasma Kallikrein Human genes 0.000 description 5
- 108090000113 Plasma Kallikrein Proteins 0.000 description 5
- 108090000190 Thrombin Proteins 0.000 description 5
- 108090000631 Trypsin Proteins 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 5
- 208000009956 adenocarcinoma Diseases 0.000 description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 150000004702 methyl esters Chemical class 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 125000003410 quininyl group Chemical group 0.000 description 5
- 230000026267 regulation of growth Effects 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 229960004072 thrombin Drugs 0.000 description 5
- 229960001322 trypsin Drugs 0.000 description 5
- 239000012588 trypsin Substances 0.000 description 5
- XRTWQXKBNYKNFD-HNNXBMFYSA-N (2S)-2-amino-N-[(6-amino-2-methylpyridin-3-yl)methyl]-3-(1H-indol-3-yl)propanamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@@H](N)CC1=CNC2=CC=CC=C12 XRTWQXKBNYKNFD-HNNXBMFYSA-N 0.000 description 4
- AGOKIGHSAABERQ-AWEZNQCLSA-N (2S)-2-amino-N-[(6-amino-2-methylpyridin-3-yl)methyl]-3-(3,4-dichlorophenyl)propanamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@@H](N)CC1=CC=C(Cl)C(Cl)=C1 AGOKIGHSAABERQ-AWEZNQCLSA-N 0.000 description 4
- KOKUVDVUESFHOH-ZDUSSCGKSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-(4-hydroxyphenyl)propanamide Chemical compound C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(O)C=C1 KOKUVDVUESFHOH-ZDUSSCGKSA-N 0.000 description 4
- WBISTYPFBZZTJS-HXUWFJFHSA-N (2r)-2-amino-n-[(6-aminopyridin-3-yl)methyl]-3,3-dicyclohexylpropanamide Chemical compound C1CCCCC1C([C@@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1CCCCC1 WBISTYPFBZZTJS-HXUWFJFHSA-N 0.000 description 4
- KSPIYJQBLVDRRI-PRJDIBJQSA-N (2r)-3-methyl-2-(methylamino)pentanoic acid Chemical compound CCC(C)[C@@H](NC)C(O)=O KSPIYJQBLVDRRI-PRJDIBJQSA-N 0.000 description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 4
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 4
- GUGAOFSHCGOMMW-UHFFFAOYSA-N 5-(4-methylphenyl)-1h-pyrrole-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1C1=CC=C(C(O)=O)N1 GUGAOFSHCGOMMW-UHFFFAOYSA-N 0.000 description 4
- 206010006482 Bronchospasm Diseases 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- CWLQUGTUXBXTLF-YFKPBYRVSA-N N-methylproline Chemical compound CN1CCC[C@H]1C(O)=O CWLQUGTUXBXTLF-YFKPBYRVSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- KDPAWGWELVVRCH-UHFFFAOYSA-N bromoacetic acid Chemical class OC(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-N 0.000 description 4
- 230000007885 bronchoconstriction Effects 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 208000027866 inflammatory disease Diseases 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 206010061289 metastatic neoplasm Diseases 0.000 description 4
- 210000003800 pharynx Anatomy 0.000 description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 150000003431 steroids Chemical class 0.000 description 4
- 230000002459 sustained effect Effects 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- CWBXUAFZTBHDIT-AWEZNQCLSA-N (2S)-2-amino-N-[(6-amino-2-methylpyridin-3-yl)methyl]-3-[2-(trifluoromethyl)phenyl]propanamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@@H](N)CC1=CC=CC=C1C(F)(F)F CWBXUAFZTBHDIT-AWEZNQCLSA-N 0.000 description 3
- PLBKXFWFOBEYBB-SFHVURJKSA-N (2S)-2-amino-N-[(6-amino-2-methylpyridin-3-yl)methyl]-3-naphthalen-1-ylpropanamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@@H](N)CC1=CC=CC2=CC=CC=C12 PLBKXFWFOBEYBB-SFHVURJKSA-N 0.000 description 3
- DRGFRNRRBJZJBD-AWEZNQCLSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-(4-methoxyphenyl)propanamide Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)NCC1=CC=C(N)N=C1 DRGFRNRRBJZJBD-AWEZNQCLSA-N 0.000 description 3
- GKCYFPMWCTXULZ-INIZCTEOSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-(4-tert-butylphenyl)propanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1C[C@H](N)C(=O)NCC1=CC=C(N)N=C1 GKCYFPMWCTXULZ-INIZCTEOSA-N 0.000 description 3
- UBDPNUDSNBSUJJ-ZDUSSCGKSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-[2-(trifluoromethyl)phenyl]propanamide Chemical compound C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1C(F)(F)F UBDPNUDSNBSUJJ-ZDUSSCGKSA-N 0.000 description 3
- FVHTZNQHKOBGHA-MRVPVSSYSA-N (2r)-1-(2-methylpropyl)pyrrolidin-1-ium-2-carboxylate Chemical compound CC(C)CN1CCC[C@@H]1C(O)=O FVHTZNQHKOBGHA-MRVPVSSYSA-N 0.000 description 3
- LQOASEHNECNLNM-ZCFIWIBFSA-N (2r)-1-ethylpyrrolidine-2-carboxamide Chemical compound CCN1CCC[C@@H]1C(N)=O LQOASEHNECNLNM-ZCFIWIBFSA-N 0.000 description 3
- QFLCTAXQTJMMJD-MRVPVSSYSA-N (2r)-1-propan-2-ylpiperidine-2-carboxylic acid Chemical compound CC(C)N1CCCC[C@@H]1C(O)=O QFLCTAXQTJMMJD-MRVPVSSYSA-N 0.000 description 3
- AGPKZVBTJJNPAG-AKGZTFGVSA-N (2s)-2-amino-3-methylpentanoic acid Chemical compound CCC(C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-AKGZTFGVSA-N 0.000 description 3
- VIBCTULCDAYVMK-GXKRWWSZSA-N (2s)-2-amino-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-dichlorophenyl)propanamide;dihydrochloride Chemical compound Cl.Cl.C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C(Cl)=C1 VIBCTULCDAYVMK-GXKRWWSZSA-N 0.000 description 3
- AQYITCGWTVTHIU-RMRYJAPISA-N (2s)-2-amino-n-[(6-aminopyridin-3-yl)methyl]-3-naphthalen-1-ylpropanamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.O=C([C@H](CC=1C2=CC=CC=C2C=CC=1)N)NCC1=CC=C(N)N=C1 AQYITCGWTVTHIU-RMRYJAPISA-N 0.000 description 3
- 125000000301 2-(3-chlorophenyl)ethyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 3
- YXYAHRAFINYJPL-UHFFFAOYSA-N 4-methyl-1h-pyrrole-2-carboxylic acid Chemical compound CC1=CNC(C(O)=O)=C1 YXYAHRAFINYJPL-UHFFFAOYSA-N 0.000 description 3
- WTXBRZCVLDTWLP-UHFFFAOYSA-N 5-fluoro-1H-indole-2-carboxylic acid Chemical compound FC1=CC=C2NC(C(=O)O)=CC2=C1 WTXBRZCVLDTWLP-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- DZLNHFMRPBPULJ-GSVOUGTGSA-N D-thioproline Chemical compound OC(=O)[C@H]1CSCN1 DZLNHFMRPBPULJ-GSVOUGTGSA-N 0.000 description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 description 3
- 108010016626 Dipeptides Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- 102100035792 Kininogen-1 Human genes 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 235000019502 Orange oil Nutrition 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102000012479 Serine Proteases Human genes 0.000 description 3
- 108010022999 Serine Proteases Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000009285 allergic inflammation Effects 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 206010006451 bronchitis Diseases 0.000 description 3
- 125000004803 chlorobenzyl group Chemical group 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 125000004188 dichlorophenyl group Chemical group 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 238000000227 grinding Methods 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 239000003607 modifier Substances 0.000 description 3
- 230000009826 neoplastic cell growth Effects 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000010502 orange oil Substances 0.000 description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 3
- 210000000496 pancreas Anatomy 0.000 description 3
- 125000003386 piperidinyl group Chemical group 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000005932 reductive alkylation reaction Methods 0.000 description 3
- 210000002345 respiratory system Anatomy 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 229910052703 rhodium Inorganic materials 0.000 description 3
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- BAEXAYUOYXRHMY-WSXZXBBNSA-N tert-butyl n-[(2s)-3-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl)-1-[(6-aminopyridin-3-yl)methylamino]-1-oxopropan-2-yl]carbamate Chemical compound O=C([C@H](CC1C2CCCCC2CCC1)NC(=O)OC(C)(C)C)NCC1=CC=C(N)N=C1 BAEXAYUOYXRHMY-WSXZXBBNSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 108010036927 trypsin-like serine protease Proteins 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- GSFMVTZIMNGTRL-AWEZNQCLSA-N (2S)-2-amino-N-[(6-amino-2-methylpyridin-3-yl)methyl]-3-(3-chlorophenyl)propanamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@@H](N)CC1=CC=CC(Cl)=C1 GSFMVTZIMNGTRL-AWEZNQCLSA-N 0.000 description 2
- JZOAIMPVVPIYAU-AWEZNQCLSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-(1-benzothiophen-3-yl)propanamide Chemical compound O=C([C@H](CC=1C2=CC=CC=C2SC=1)N)NCC1=CC=C(N)N=C1 JZOAIMPVVPIYAU-AWEZNQCLSA-N 0.000 description 2
- XXJFNIJFDVOAIM-ZDUSSCGKSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-(2-fluorophenyl)propanamide Chemical compound C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1F XXJFNIJFDVOAIM-ZDUSSCGKSA-N 0.000 description 2
- QHUKZRWOUCJLLM-ZDUSSCGKSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-cyclohexylpropanamide Chemical compound C([C@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1CCCCC1 QHUKZRWOUCJLLM-ZDUSSCGKSA-N 0.000 description 2
- ZYBCTKJORPOWEA-LLVKDONJSA-N (2r)-1-[(3-chlorophenyl)methyl]pyrrolidin-1-ium-2-carboxylate Chemical compound OC(=O)[C@H]1CCCN1CC1=CC=CC(Cl)=C1 ZYBCTKJORPOWEA-LLVKDONJSA-N 0.000 description 2
- AFFQKOXRJTVUEF-LLVKDONJSA-N (2r)-1-[(4-chlorophenyl)methyl]pyrrolidin-1-ium-2-carboxylate Chemical compound [O-]C(=O)[C@H]1CCC[NH+]1CC1=CC=C(Cl)C=C1 AFFQKOXRJTVUEF-LLVKDONJSA-N 0.000 description 2
- OGVCJOXRWBEJDW-RXMQYKEDSA-N (2r)-1-methylsulfonylpyrrolidine-2-carboxylic acid Chemical compound CS(=O)(=O)N1CCC[C@@H]1C(O)=O OGVCJOXRWBEJDW-RXMQYKEDSA-N 0.000 description 2
- YHCRFKQBCIZJJV-RTWAWAEBSA-N (2r)-2-amino-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-1-oxo-3-[3-(trifluoromethyl)phenyl]propan-2-yl]-3-(4-chlorophenyl)propanamide Chemical compound C([C@@H](N)C(=O)N[C@@H](CC=1C=C(C=CC=1)C(F)(F)F)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C=C1 YHCRFKQBCIZJJV-RTWAWAEBSA-N 0.000 description 2
- NKLBBZPCXCCMOV-ZJLLDPBHSA-N (2r)-2-amino-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-1-oxo-3-[3-(trifluoromethyl)phenyl]propan-2-yl]-3-methylpentanamide Chemical compound C([C@H](NC(=O)[C@H](N)C(C)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC(C(F)(F)F)=C1 NKLBBZPCXCCMOV-ZJLLDPBHSA-N 0.000 description 2
- VCMISWMIIHDEQE-WMZOPIPTSA-N (2r)-2-amino-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-3,3-dimethylbutanamide Chemical compound C([C@H](NC(=O)[C@H](N)C(C)(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C(Cl)=C1 VCMISWMIIHDEQE-WMZOPIPTSA-N 0.000 description 2
- VJJVPORFFVTEEI-FAVHNTAZSA-N (2r)-2-amino-n-[(6-aminopyridin-3-yl)methyl]-3,3-dicyclohexylpropanamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C1CCCCC1C([C@@H](N)C(=O)NCC=1C=NC(N)=CC=1)C1CCCCC1 VJJVPORFFVTEEI-FAVHNTAZSA-N 0.000 description 2
- BQJKEMBUHUODKO-YADHBBJMSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-2-(methylamino)-3-phenylpropanamide Chemical compound C([C@@H](NC)C(=O)N[C@@H](CC=1C=C(Cl)C(Cl)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1 BQJKEMBUHUODKO-YADHBBJMSA-N 0.000 description 2
- LTTSUNQEJQITKP-YADHBBJMSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-difluorophenyl)-1-oxopropan-2-yl]-2-(methylamino)-3-phenylpropanamide Chemical compound C([C@@H](NC)C(=O)N[C@@H](CC=1C=C(F)C(F)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1 LTTSUNQEJQITKP-YADHBBJMSA-N 0.000 description 2
- WZMTUVTWZKVOMO-XMMPIXPASA-N (2r)-n-[(6-aminopyridin-3-yl)methyl]-3,3-dicyclohexyl-2-[[2-(dimethylamino)acetyl]amino]propanamide Chemical compound C1CCCCC1C([C@@H](NC(=O)CN(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1CCCCC1 WZMTUVTWZKVOMO-XMMPIXPASA-N 0.000 description 2
- ZZNYVUKMNKYRTR-HSZRJFAPSA-N (2r)-n-[(6-aminopyridin-3-yl)methyl]-3,3-dicyclohexyl-2-[[2-(methylamino)acetyl]amino]propanamide Chemical compound C1CCCCC1C([C@@H](NC(=O)CNC)C(=O)NCC=1C=NC(N)=CC=1)C1CCCCC1 ZZNYVUKMNKYRTR-HSZRJFAPSA-N 0.000 description 2
- QJCNLJWUIOIMMF-HTQZYQBOSA-N (2r,3r)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC[C@@H](C)[C@H](C(O)=O)NC(=O)OC(C)(C)C QJCNLJWUIOIMMF-HTQZYQBOSA-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
- JBULSURVMXPBNA-RXMQYKEDSA-N (2s)-2-amino-3,3-dimethylbutan-1-ol Chemical compound CC(C)(C)[C@H](N)CO JBULSURVMXPBNA-RXMQYKEDSA-N 0.000 description 2
- SKTNCXRWBPQRSO-NTEVMMBTSA-N (2s)-2-amino-n-[(6-amino-2-methylpyridin-3-yl)methyl]-3-naphthalen-1-ylpropanamide;dihydrochloride Chemical compound Cl.Cl.CC1=NC(N)=CC=C1CNC(=O)[C@@H](N)CC1=CC=CC2=CC=CC=C12 SKTNCXRWBPQRSO-NTEVMMBTSA-N 0.000 description 2
- FRXPDNYODKBYJA-HLYMMOCJSA-N (2s)-3-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl)-2-[(2-aminoacetyl)amino]-n-[(6-aminopyridin-3-yl)methyl]propanamide Chemical compound O=C([C@H](CC1C2CCCCC2CCC1)NC(=O)CN)NCC1=CC=C(N)N=C1 FRXPDNYODKBYJA-HLYMMOCJSA-N 0.000 description 2
- FHQFSCZWIZJLKX-LVRZERHZSA-N (2s)-3-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl)-2-[[(2r)-2-amino-3-(4-chlorophenyl)propanoyl]amino]-n-[(6-aminopyridin-3-yl)methyl]propanamide Chemical compound C([C@@H](N)C(=O)N[C@@H](CC1C2CCCCC2CCC1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C=C1 FHQFSCZWIZJLKX-LVRZERHZSA-N 0.000 description 2
- YFXRXXJBWUAVPY-SQGVNUKZSA-N (2s)-3-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl)-2-amino-n-[(6-aminopyridin-3-yl)methyl]propanamide;dihydrochloride Chemical compound Cl.Cl.O=C([C@H](CC1C2CCCCC2CCC1)N)NCC1=CC=C(N)N=C1 YFXRXXJBWUAVPY-SQGVNUKZSA-N 0.000 description 2
- QORVFNMGWOFDNM-LFVBFMBRSA-N (2s)-3-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl)-n-[(6-aminopyridin-3-yl)methyl]-2-[[2-(methylamino)acetyl]amino]propanamide Chemical compound O=C([C@H](CC1C2CCCCC2CCC1)NC(=O)CNC)NCC1=CC=C(N)N=C1 QORVFNMGWOFDNM-LFVBFMBRSA-N 0.000 description 2
- UEDIYMVBQLUMMW-GKAPJAKFSA-N (2s)-3-methyl-2-[methyl(propan-2-yl)amino]pentanoic acid Chemical compound CCC(C)[C@@H](C(O)=O)N(C)C(C)C UEDIYMVBQLUMMW-GKAPJAKFSA-N 0.000 description 2
- QQASLLRATBSGKR-SFHVURJKSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[2-(diethylamino)acetyl]amino]-3-(3,4-difluorophenyl)propanamide Chemical compound C([C@H](NC(=O)CN(CC)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 QQASLLRATBSGKR-SFHVURJKSA-N 0.000 description 2
- ZILARAYOAFBHDM-IBGZPJMESA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-dichlorophenyl)-2-[(2-piperidin-1-ylacetyl)amino]propanamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)CN1CCCCC1)CC1=CC=C(Cl)C(Cl)=C1 ZILARAYOAFBHDM-IBGZPJMESA-N 0.000 description 2
- BFNKXNXXAIJTQO-HNNXBMFYSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-dichlorophenyl)-2-[[2-(methylamino)acetyl]amino]propanamide Chemical compound C([C@H](NC(=O)CNC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C(Cl)=C1 BFNKXNXXAIJTQO-HNNXBMFYSA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 2
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 2
- MSCHSIGGQKWJIB-UHFFFAOYSA-N 3,4,5-trimethyl-1h-pyrrole-2-carboxylic acid Chemical compound CC=1NC(C(O)=O)=C(C)C=1C MSCHSIGGQKWJIB-UHFFFAOYSA-N 0.000 description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- PHBVTMQLXNCAQO-UHFFFAOYSA-N 5-(aminomethyl)pyridin-2-amine Chemical compound NCC1=CC=C(N)N=C1 PHBVTMQLXNCAQO-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 101800004538 Bradykinin Proteins 0.000 description 2
- 108050001736 Bradykinin receptor Proteins 0.000 description 2
- 102000010183 Bradykinin receptor Human genes 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 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 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
- 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 2
- 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 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- 108010088842 Fibrinolysin Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 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
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- 206010023232 Joint swelling Diseases 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 108010006035 Metalloproteases Proteins 0.000 description 2
- 102000005741 Metalloproteases Human genes 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 206010068319 Oropharyngeal pain Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 201000007100 Pharyngitis Diseases 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- 208000037656 Respiratory Sounds Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- 102000008847 Serpin Human genes 0.000 description 2
- 108050000761 Serpin Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 206010047924 Wheezing Diseases 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 208000037883 airway inflammation Diseases 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 235000008206 alpha-amino acids Nutrition 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 229960004405 aprotinin Drugs 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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 230000005907 cancer growth Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 229960000265 cromoglicic acid Drugs 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
- 229920006237 degradable polymer Polymers 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 208000010643 digestive system disease Diseases 0.000 description 2
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 206010022000 influenza 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
- 150000002576 ketones Chemical class 0.000 description 2
- 150000002617 leukotrienes Chemical class 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 229940125389 long-acting beta agonist Drugs 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 230000003843 mucus production Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 239000006199 nebulizer Substances 0.000 description 2
- 229960004398 nedocromil Drugs 0.000 description 2
- RQTOOFIXOKYGAN-UHFFFAOYSA-N nedocromil Chemical compound CCN1C(C(O)=O)=CC(=O)C2=C1C(CCC)=C1OC(C(O)=O)=CC(=O)C1=C2 RQTOOFIXOKYGAN-UHFFFAOYSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 239000012740 non-selective inhibitor Substances 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 206010033675 panniculitis Diseases 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N pentanoic acid group Chemical group C(CCCC)(=O)O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 125000003884 phenylalkyl group Chemical group 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 229940012957 plasmin Drugs 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 108010029690 procollagenase Proteins 0.000 description 2
- 108010067415 progelatinase Proteins 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000003001 serine protease inhibitor Substances 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 210000004304 subcutaneous tissue Anatomy 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 150000003890 succinate salts Chemical class 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 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 2
- DIBBBNBGHJDCSX-INIZCTEOSA-N tert-butyl n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-difluorophenyl)-1-oxopropan-2-yl]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 DIBBBNBGHJDCSX-INIZCTEOSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 2
- 229960000278 theophylline Drugs 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000005747 tumor angiogenesis Effects 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
- GSFMVTZIMNGTRL-CQSZACIVSA-N (2R)-2-amino-N-[(6-amino-2-methylpyridin-3-yl)methyl]-3-(3-chlorophenyl)propanamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@H](N)CC1=CC=CC(Cl)=C1 GSFMVTZIMNGTRL-CQSZACIVSA-N 0.000 description 1
- QXFROGNJVKLBDX-SJORKVTESA-N (2R)-N-[(2S)-1-[(6-aminopyridin-3-yl)methylamino]-3-(4-fluorophenyl)-1-oxopropan-2-yl]pyrrolidine-2-carboxamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)[C@@H]1NCCC1)CC1=CC=C(F)C=C1 QXFROGNJVKLBDX-SJORKVTESA-N 0.000 description 1
- DVJRGBYHFSYMKH-FVFODTBWSA-N (2R)-N-[(2S)-3-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl)-1-[(6-aminopyridin-3-yl)methylamino]-1-oxopropan-2-yl]pyrrolidine-2-carboxamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)[C@@H]1NCCC1)CC1C2CCCCC2CCC1 DVJRGBYHFSYMKH-FVFODTBWSA-N 0.000 description 1
- KMEAPWRFTOWONR-QHCPKHFHSA-N (2S)-2-[acetyl-(2-phenylethylamino)amino]-N-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)propanamide Chemical compound CC(=O)N([C@@H](CC=1C=C(F)C(F)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)NCCC1=CC=CC=C1 KMEAPWRFTOWONR-QHCPKHFHSA-N 0.000 description 1
- DEWHQYXTNDXFBH-AWEZNQCLSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-(3-methylphenyl)propanamide Chemical compound CC1=CC=CC(C[C@H](N)C(=O)NCC=2C=NC(N)=CC=2)=C1 DEWHQYXTNDXFBH-AWEZNQCLSA-N 0.000 description 1
- ZTVKVRVTFDLHBZ-HNNXBMFYSA-N (2S)-2-amino-N-[(6-aminopyridin-3-yl)methyl]-3-(4-ethoxyphenyl)propanamide Chemical compound C1=CC(OCC)=CC=C1C[C@H](N)C(=O)NCC1=CC=C(N)N=C1 ZTVKVRVTFDLHBZ-HNNXBMFYSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- ZQEBQGAAWMOMAI-SSDOTTSWSA-N (2r)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@@H]1C(O)=O ZQEBQGAAWMOMAI-SSDOTTSWSA-N 0.000 description 1
- OMGHIGVFLOPEHJ-SCSAIBSYSA-N (2r)-2,5-dihydro-1h-pyrrol-1-ium-2-carboxylate Chemical compound [O-]C(=O)[C@@H]1[NH2+]CC=C1 OMGHIGVFLOPEHJ-SCSAIBSYSA-N 0.000 description 1
- SCTZBZIJVJXCJE-JOCHJYFZSA-N (2r)-2-[(2-aminoacetyl)amino]-n-[(6-aminopyridin-3-yl)methyl]-3,3-dicyclohexylpropanamide Chemical compound C1CCCCC1C([C@@H](NC(=O)CN)C(=O)NCC=1C=NC(N)=CC=1)C1CCCCC1 SCTZBZIJVJXCJE-JOCHJYFZSA-N 0.000 description 1
- BMGNAZWATBEVKF-HKUYNNGSSA-N (2r)-2-amino-n-[(2s)-1-[(6-amino-2-methylpyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-3,3-dimethylbutanamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)[C@H](N)C(C)(C)C)CC1=CC=C(Cl)C(Cl)=C1 BMGNAZWATBEVKF-HKUYNNGSSA-N 0.000 description 1
- YZAXFIAWWZASPC-YADHBBJMSA-N (2r)-2-amino-n-[(2s)-1-[(6-amino-2-methylpyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-3-(4-chlorophenyl)propanamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)[C@H](N)CC=1C=CC(Cl)=CC=1)CC1=CC=C(Cl)C(Cl)=C1 YZAXFIAWWZASPC-YADHBBJMSA-N 0.000 description 1
- DFHFGQZBUVBMGZ-YADHBBJMSA-N (2r)-2-amino-n-[(2s)-1-[(6-amino-2-methylpyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-3-(4-fluorophenyl)propanamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)[C@H](N)CC=1C=CC(F)=CC=1)CC1=CC=C(Cl)C(Cl)=C1 DFHFGQZBUVBMGZ-YADHBBJMSA-N 0.000 description 1
- LDLJJVYPOBZSLW-YADHBBJMSA-N (2r)-2-amino-n-[(2s)-1-[(6-amino-2-methylpyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-3-cyclohexylpropanamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)[C@H](N)CC1CCCCC1)CC1=CC=C(Cl)C(Cl)=C1 LDLJJVYPOBZSLW-YADHBBJMSA-N 0.000 description 1
- UELUZRZCNOTLEG-ZJLLDPBHSA-N (2r)-2-amino-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-1-oxo-3-[2-(trifluoromethyl)phenyl]propan-2-yl]-3-methylpentanamide Chemical compound C([C@H](NC(=O)[C@H](N)C(C)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1C(F)(F)F UELUZRZCNOTLEG-ZJLLDPBHSA-N 0.000 description 1
- WNVPVXNNAVIPKA-RTWAWAEBSA-N (2r)-2-amino-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-3-(4-chlorophenyl)propanamide Chemical compound C([C@@H](N)C(=O)N[C@@H](CC=1C=C(Cl)C(Cl)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C=C1 WNVPVXNNAVIPKA-RTWAWAEBSA-N 0.000 description 1
- MSLHPVVEGHVDSL-SCTOPSOGSA-N (2r)-2-amino-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-3-methylpentanamide Chemical compound C([C@H](NC(=O)[C@H](N)C(C)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C(Cl)=C1 MSLHPVVEGHVDSL-SCTOPSOGSA-N 0.000 description 1
- BPCYCJXQQUBNFF-RTWAWAEBSA-N (2r)-2-amino-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-3-phenylpropanamide Chemical compound C([C@@H](N)C(=O)N[C@@H](CC=1C=C(Cl)C(Cl)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1 BPCYCJXQQUBNFF-RTWAWAEBSA-N 0.000 description 1
- OXZXDFWXSYSSJY-YADHBBJMSA-N (2r)-2-amino-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-4-phenylbutanamide Chemical compound C([C@@H](N)C(=O)N[C@@H](CC=1C=C(Cl)C(Cl)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)CC1=CC=CC=C1 OXZXDFWXSYSSJY-YADHBBJMSA-N 0.000 description 1
- RFKWEXSFHNISAR-SCTOPSOGSA-N (2r)-2-amino-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-difluorophenyl)-1-oxopropan-2-yl]-3-methylpentanamide Chemical compound C([C@H](NC(=O)[C@H](N)C(C)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 RFKWEXSFHNISAR-SCTOPSOGSA-N 0.000 description 1
- VBWXGCHBOATSOT-RTWAWAEBSA-N (2r)-2-amino-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-difluorophenyl)-1-oxopropan-2-yl]-3-phenylpropanamide Chemical compound C([C@@H](N)C(=O)N[C@@H](CC=1C=C(F)C(F)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1 VBWXGCHBOATSOT-RTWAWAEBSA-N 0.000 description 1
- OQIBQMWDGGMPSK-SCTOPSOGSA-N (2r)-2-amino-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,5-difluorophenyl)-1-oxopropan-2-yl]-3-methylpentanamide Chemical compound C([C@H](NC(=O)[C@H](N)C(C)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC(F)=CC(F)=C1 OQIBQMWDGGMPSK-SCTOPSOGSA-N 0.000 description 1
- SYQVQHLUOZPFSX-GUOVVMSNSA-N (2r)-2-amino-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3-cyanophenyl)-1-oxopropan-2-yl]-3-methylpentanamide Chemical compound C([C@H](NC(=O)[C@H](N)C(C)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC(C#N)=C1 SYQVQHLUOZPFSX-GUOVVMSNSA-N 0.000 description 1
- XTNDRMWHBCAUPQ-ZJLLDPBHSA-N (2r)-2-amino-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3-fluorophenyl)-1-oxopropan-2-yl]-3-methylpentanamide Chemical compound C([C@H](NC(=O)[C@H](N)C(C)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC(F)=C1 XTNDRMWHBCAUPQ-ZJLLDPBHSA-N 0.000 description 1
- ACUROTZKSJCGCE-QGZVFWFLSA-N (2r)-3,3-dicyclohexyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound C1CCCCC1C([C@@H](NC(=O)OC(C)(C)C)C(O)=O)C1CCCCC1 ACUROTZKSJCGCE-QGZVFWFLSA-N 0.000 description 1
- RORVXFIZWWTPSL-COBSHVIPSA-N (2r)-3-methyl-2-[methyl(methylsulfonyl)amino]pentanoic acid Chemical compound CCC(C)[C@H](C(O)=O)N(C)S(C)(=O)=O RORVXFIZWWTPSL-COBSHVIPSA-N 0.000 description 1
- MAAWTSLAJSPNJX-MOPGFXCFSA-N (2r)-n-[(2s)-1-[(6-amino-2-methylpyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]piperidine-2-carboxamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)[C@@H]1NCCCC1)CC1=CC=C(Cl)C(Cl)=C1 MAAWTSLAJSPNJX-MOPGFXCFSA-N 0.000 description 1
- GNAPFRRSVAADBO-RBUKOAKNSA-N (2r)-n-[(2s)-1-[(6-amino-2-methylpyridin-3-yl)methylamino]-3-(3,4-difluorophenyl)-1-oxopropan-2-yl]-1-methylpyrrolidine-2-carboxamide Chemical compound CN1CCC[C@@H]1C(=O)N[C@H](C(=O)NCC=1C(=NC(N)=CC=1)C)CC1=CC=C(F)C(F)=C1 GNAPFRRSVAADBO-RBUKOAKNSA-N 0.000 description 1
- FEDNTVKDCDHUOU-ZWKOTPCHSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-1-oxo-3-[2-(trifluoromethyl)phenyl]propan-2-yl]-1-methylpyrrolidine-2-carboxamide Chemical compound CN1CCC[C@@H]1C(=O)N[C@H](C(=O)NCC=1C=NC(N)=CC=1)CC1=CC=CC=C1C(F)(F)F FEDNTVKDCDHUOU-ZWKOTPCHSA-N 0.000 description 1
- XXWGVXQPYSGANF-SJORKVTESA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-2,5-dihydro-1h-pyrrole-2-carboxamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)[C@H]1C=CCN1)CC1=CC=C(Cl)C(Cl)=C1 XXWGVXQPYSGANF-SJORKVTESA-N 0.000 description 1
- KHVNFOSDUNNKFX-XZOQPEGZSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-2-(dimethylamino)-3-phenylpropanamide Chemical compound C([C@@H](N(C)C)C(=O)N[C@@H](CC=1C=C(Cl)C(Cl)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1 KHVNFOSDUNNKFX-XZOQPEGZSA-N 0.000 description 1
- QKNNIJRLOPPXJA-MSOLQXFVSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]piperidine-2-carboxamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)[C@@H]1NCCCC1)CC1=CC=C(Cl)C(Cl)=C1 QKNNIJRLOPPXJA-MSOLQXFVSA-N 0.000 description 1
- CNDIOJJXFAOASE-SJORKVTESA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]pyrrolidine-2-carboxamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)[C@@H]1NCCC1)CC1=CC=C(Cl)C(Cl)=C1 CNDIOJJXFAOASE-SJORKVTESA-N 0.000 description 1
- OUWWYEULZVXMML-AZUAARDMSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-difluorophenyl)-1-oxopropan-2-yl]-2-(dimethylamino)-3-methylbutanamide Chemical compound C([C@H](NC(=O)[C@H](N(C)C)C(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 OUWWYEULZVXMML-AZUAARDMSA-N 0.000 description 1
- WFTBHUZBHNLJQN-XZOQPEGZSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-difluorophenyl)-1-oxopropan-2-yl]-2-(dimethylamino)-3-phenylpropanamide Chemical compound C([C@@H](N(C)C)C(=O)N[C@@H](CC=1C=C(F)C(F)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1 WFTBHUZBHNLJQN-XZOQPEGZSA-N 0.000 description 1
- JDBPYPOYBJLRRK-BJKOFHAPSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-difluorophenyl)-1-oxopropan-2-yl]-3-phenyl-2-(propan-2-ylamino)propanamide Chemical compound C([C@@H](NC(C)C)C(=O)N[C@@H](CC=1C=C(F)C(F)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1 JDBPYPOYBJLRRK-BJKOFHAPSA-N 0.000 description 1
- IYCSTXIRZYFAHU-MSOLQXFVSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-difluorophenyl)-1-oxopropan-2-yl]piperidine-2-carboxamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)[C@@H]1NCCCC1)CC1=CC=C(F)C(F)=C1 IYCSTXIRZYFAHU-MSOLQXFVSA-N 0.000 description 1
- CUSUYMRCPNARON-UNGYYTSISA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,5-difluorophenyl)-1-oxopropan-2-yl]-3-methyl-2-(methylamino)pentanamide Chemical compound C([C@H](NC(=O)[C@H](NC)C(C)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC(F)=CC(F)=C1 CUSUYMRCPNARON-UNGYYTSISA-N 0.000 description 1
- RFTKBZZFPHRRRR-XZOQPEGZSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3-chlorophenyl)-1-oxopropan-2-yl]-2-(dimethylamino)-3-phenylpropanamide Chemical compound C([C@@H](N(C)C)C(=O)N[C@@H](CC=1C=C(Cl)C=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1 RFTKBZZFPHRRRR-XZOQPEGZSA-N 0.000 description 1
- BJRBVAHMZLWYSQ-YADHBBJMSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3-chlorophenyl)-1-oxopropan-2-yl]-2-(methylamino)-3-phenylpropanamide Chemical compound C([C@@H](NC)C(=O)N[C@@H](CC=1C=C(Cl)C=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1 BJRBVAHMZLWYSQ-YADHBBJMSA-N 0.000 description 1
- XHDYXKGJRHLDBB-ICSRJNTNSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(4-fluorophenyl)-1-oxopropan-2-yl]-2-(dimethylamino)-3,3-dimethylbutanamide Chemical compound C([C@H](NC(=O)[C@H](N(C)C)C(C)(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C=C1 XHDYXKGJRHLDBB-ICSRJNTNSA-N 0.000 description 1
- YNUUIUKHHKOPMP-GCXSUNMLSA-N (2r)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(4-tert-butylphenyl)-1-oxopropan-2-yl]-3-methyl-2-(methylamino)pentanamide Chemical compound C([C@H](NC(=O)[C@H](NC)C(C)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(C(C)(C)C)C=C1 YNUUIUKHHKOPMP-GCXSUNMLSA-N 0.000 description 1
- MJOOENWDCIZTRH-RPFBLMCYSA-N (2r)-n-[(2s)-3-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl)-1-[(6-amino-2-methylpyridin-3-yl)methylamino]-1-oxopropan-2-yl]-2-amino-3-methylbutanamide Chemical compound O=C([C@H](CC1C2CCCCC2CCC1)NC(=O)[C@H](N)C(C)C)NCC1=CC=C(N)N=C1C MJOOENWDCIZTRH-RPFBLMCYSA-N 0.000 description 1
- LISXFWPXAVXGQA-XWCYNJGWSA-N (2r)-n-[(2s)-3-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl)-1-[(6-aminopyridin-3-yl)methylamino]-1-oxopropan-2-yl]-2-amino-3-methylbutanamide Chemical compound O=C([C@H](CC1C2CCCCC2CCC1)NC(=O)[C@H](N)C(C)C)NCC1=CC=C(N)N=C1 LISXFWPXAVXGQA-XWCYNJGWSA-N 0.000 description 1
- DCFGRGWCLMEKBN-HBRZWPCVSA-N (2r)-n-[(6-aminopyridin-3-yl)methyl]-3-cyclohexyl-2-[[(2s)-2-[methyl(propan-2-yl)amino]propanoyl]amino]butanamide Chemical compound CC([C@@H](NC(=O)[C@H](C)N(C)C(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1CCCCC1 DCFGRGWCLMEKBN-HBRZWPCVSA-N 0.000 description 1
- FMIPNAUMSPFTHK-RFZPGFLSSA-N (2r,4r)-4-hydroxy-1-methylpyrrolidine-2-carboxylic acid Chemical compound CN1C[C@H](O)C[C@@H]1C(O)=O FMIPNAUMSPFTHK-RFZPGFLSSA-N 0.000 description 1
- IMEFHFJTLYYKNP-PZJWPPBQSA-N (2s)-2-[[(2r)-2-amino-2-phenylacetyl]amino]-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-dichlorophenyl)propanamide Chemical compound C([C@H](NC(=O)[C@H](N)C=1C=CC=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C(Cl)=C1 IMEFHFJTLYYKNP-PZJWPPBQSA-N 0.000 description 1
- IMEFHFJTLYYKNP-FPOVZHCZSA-N (2s)-2-[[(2s)-2-amino-2-phenylacetyl]amino]-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-dichlorophenyl)propanamide Chemical compound C([C@H](NC(=O)[C@@H](N)C=1C=CC=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C(Cl)=C1 IMEFHFJTLYYKNP-FPOVZHCZSA-N 0.000 description 1
- ACFVAACAPHHBKS-BOADVZGGSA-N (2s)-3-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound C1CCCC2C(C[C@H](NC(=O)OC(C)(C)C)C(O)=O)CCCC21 ACFVAACAPHHBKS-BOADVZGGSA-N 0.000 description 1
- XDIIGWBUHUWLGO-PBCBEDCTSA-N (2s)-3-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl)-2-[[(2r)-2-aminopropanoyl]amino]-n-[(6-aminopyridin-3-yl)methyl]propanamide Chemical compound O=C([C@H](CC1C2CCCCC2CCC1)NC(=O)[C@H](N)C)NCC1=CC=C(N)N=C1 XDIIGWBUHUWLGO-PBCBEDCTSA-N 0.000 description 1
- FQYGCARWJHAJDR-KSDVGMQISA-N (2s)-3-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl)-n-[(6-aminopyridin-3-yl)methyl]-2-[[(2r)-2-(dimethylamino)-3-phenylpropanoyl]amino]propanamide Chemical compound C([C@@H](N(C)C)C(=O)N[C@@H](CC1C2CCCCC2CCC1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1 FQYGCARWJHAJDR-KSDVGMQISA-N 0.000 description 1
- RYHSFCRHRLZAFO-GVWQBGCGSA-N (2s)-3-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl)-n-[(6-aminopyridin-3-yl)methyl]-2-[[2-[di(propan-2-yl)amino]acetyl]amino]propanamide Chemical compound O=C([C@H](CC1C2CCCCC2CCC1)NC(=O)CN(C(C)C)C(C)C)NCC1=CC=C(N)N=C1 RYHSFCRHRLZAFO-GVWQBGCGSA-N 0.000 description 1
- UGZIQCCPEDCGGN-NSHDSACASA-N (2s)-3-(3,4-dichlorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(Cl)C(Cl)=C1 UGZIQCCPEDCGGN-NSHDSACASA-N 0.000 description 1
- CYAOPVHXASZUDE-NSHDSACASA-N (2s)-3-(3,4-difluorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(F)C(F)=C1 CYAOPVHXASZUDE-NSHDSACASA-N 0.000 description 1
- KSPIYJQBLVDRRI-GDVGLLTNSA-N (2s)-3-methyl-2-(methylamino)pentanoic acid Chemical compound CCC(C)[C@H](NC)C(O)=O KSPIYJQBLVDRRI-GDVGLLTNSA-N 0.000 description 1
- PJRSUKFWFKUDTH-JWDJOUOUSA-N (2s)-6-amino-2-[[2-[[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]propanoyl]amino]acetyl]amino]propanoyl Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(N)=O PJRSUKFWFKUDTH-JWDJOUOUSA-N 0.000 description 1
- ZOLCKMJZPUXVCG-XZOQPEGZSA-N (2s)-n-[(2r)-1-[(6-amino-2-methylpyridin-3-yl)methylamino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]-2-(methylamino)-3-phenylpropanamide Chemical compound C([C@H](NC)C(=O)N[C@H](CC=1C=C(Cl)C(Cl)=CC=1)C(=O)NCC=1C(=NC(N)=CC=1)C)C1=CC=CC=C1 ZOLCKMJZPUXVCG-XZOQPEGZSA-N 0.000 description 1
- WFTBHUZBHNLJQN-GOTSBHOMSA-N (2s)-n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-difluorophenyl)-1-oxopropan-2-yl]-2-(dimethylamino)-3-phenylpropanamide Chemical compound C([C@H](N(C)C)C(=O)N[C@@H](CC=1C=C(F)C(F)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC=C1 WFTBHUZBHNLJQN-GOTSBHOMSA-N 0.000 description 1
- GAHDUTDKPQGIBK-IBGZPJMESA-N (2s)-n-[(6-amino-2-methylpyridin-3-yl)methyl]-2-[[2-(diethylamino)acetyl]amino]-3-(4-fluorophenyl)propanamide Chemical compound C([C@H](NC(=O)CN(CC)CC)C(=O)NCC=1C(=NC(N)=CC=1)C)C1=CC=C(F)C=C1 GAHDUTDKPQGIBK-IBGZPJMESA-N 0.000 description 1
- JPOVTCKXFLEYNO-FQEVSTJZSA-N (2s)-n-[(6-amino-2-methylpyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[(2-piperidin-1-ylacetyl)amino]propanamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)CN1CCCCC1)CC1=CC=C(F)C(F)=C1 JPOVTCKXFLEYNO-FQEVSTJZSA-N 0.000 description 1
- ILDRNZXYBHLTDY-IERDGZPVSA-N (2s)-n-[(6-amino-2-methylpyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[(2r)-2-piperidin-1-ylpropanoyl]amino]propanamide Chemical compound N1([C@H](C)C(=O)N[C@@H](CC=2C=C(F)C(F)=CC=2)C(=O)NCC=2C(=NC(N)=CC=2)C)CCCCC1 ILDRNZXYBHLTDY-IERDGZPVSA-N 0.000 description 1
- ILDRNZXYBHLTDY-KKSFZXQISA-N (2s)-n-[(6-amino-2-methylpyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[(2s)-2-piperidin-1-ylpropanoyl]amino]propanamide Chemical compound N1([C@@H](C)C(=O)N[C@@H](CC=2C=C(F)C(F)=CC=2)C(=O)NCC=2C(=NC(N)=CC=2)C)CCCCC1 ILDRNZXYBHLTDY-KKSFZXQISA-N 0.000 description 1
- JMKANXYCVIQHAR-FZCLLLDFSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-(2-piperidin-1-ylpropanoylamino)-3-[3-(trifluoromethyl)phenyl]propanamide Chemical compound N([C@@H](CC=1C=C(C=CC=1)C(F)(F)F)C(=O)NCC=1C=NC(N)=CC=1)C(=O)C(C)N1CCCCC1 JMKANXYCVIQHAR-FZCLLLDFSA-N 0.000 description 1
- CRIUUKYMYMLGMB-IBGZPJMESA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[(2-piperidin-1-ylacetyl)amino]-3-[3-(trifluoromethyl)phenyl]propanamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)CN1CCCCC1)CC1=CC=CC(C(F)(F)F)=C1 CRIUUKYMYMLGMB-IBGZPJMESA-N 0.000 description 1
- PALYNQUTHURPKQ-IBGZPJMESA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[(2-piperidin-1-ylacetyl)amino]-3-[4-(trifluoromethyl)phenyl]propanamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)CN1CCCCC1)CC1=CC=C(C(F)(F)F)C=C1 PALYNQUTHURPKQ-IBGZPJMESA-N 0.000 description 1
- ZQAAVOCAZBTKMW-RBUKOAKNSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[(2r)-2-(diethylamino)-3-hydroxypropanoyl]amino]-3-(3,4-difluorophenyl)propanamide Chemical compound C([C@H](NC(=O)[C@@H](CO)N(CC)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 ZQAAVOCAZBTKMW-RBUKOAKNSA-N 0.000 description 1
- XPTWEBWOBQZQHL-UZLBHIALSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[(2r)-2-piperidin-1-ylpropanoyl]amino]-3-[4-(trifluoromethyl)phenyl]propanamide Chemical compound N1([C@H](C)C(=O)N[C@@H](CC=2C=CC(=CC=2)C(F)(F)F)C(=O)NCC=2C=NC(N)=CC=2)CCCCC1 XPTWEBWOBQZQHL-UZLBHIALSA-N 0.000 description 1
- ZQAAVOCAZBTKMW-OALUTQOASA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[(2s)-2-(diethylamino)-3-hydroxypropanoyl]amino]-3-(3,4-difluorophenyl)propanamide Chemical compound C([C@H](NC(=O)[C@H](CO)N(CC)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 ZQAAVOCAZBTKMW-OALUTQOASA-N 0.000 description 1
- ABGWLCRYBPVWAF-KXBFYZLASA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[(2s)-2-(diethylamino)propanoyl]amino]-3-(4-fluorophenyl)propanamide Chemical compound C([C@H](NC(=O)[C@H](C)N(CC)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C=C1 ABGWLCRYBPVWAF-KXBFYZLASA-N 0.000 description 1
- IQBMPAACOFEYQM-UWJYYQICSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[(2s)-2-[di(propan-2-yl)amino]propanoyl]amino]-3-(4-fluorophenyl)propanamide Chemical compound C([C@H](NC(=O)[C@H](C)N(C(C)C)C(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C=C1 IQBMPAACOFEYQM-UWJYYQICSA-N 0.000 description 1
- XPTWEBWOBQZQHL-JXFKEZNVSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[(2s)-2-piperidin-1-ylpropanoyl]amino]-3-[4-(trifluoromethyl)phenyl]propanamide Chemical compound N1([C@@H](C)C(=O)N[C@@H](CC=2C=CC(=CC=2)C(F)(F)F)C(=O)NCC=2C=NC(N)=CC=2)CCCCC1 XPTWEBWOBQZQHL-JXFKEZNVSA-N 0.000 description 1
- BDZZQXDENWKWQV-BPZDKFOGSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[2-(2,6-dimethylpiperidin-1-yl)acetyl]amino]-3-(4-fluorophenyl)propanamide Chemical compound CC1CCCC(C)N1CC(=O)N[C@H](C(=O)NCC=1C=NC(N)=CC=1)CC1=CC=C(F)C=C1 BDZZQXDENWKWQV-BPZDKFOGSA-N 0.000 description 1
- KUSDTWYGPIATAI-NTEVMMBTSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[2-(diethylamino)acetyl]amino]-3-(3,4-difluorophenyl)propanamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C([C@H](NC(=O)CN(CC)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 KUSDTWYGPIATAI-NTEVMMBTSA-N 0.000 description 1
- SCQJBAQKRSLMRA-SFHVURJKSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[2-(diethylamino)acetyl]amino]-3-(4-fluorophenyl)propanamide Chemical compound C([C@H](NC(=O)CN(CC)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C=C1 SCQJBAQKRSLMRA-SFHVURJKSA-N 0.000 description 1
- XKURCVZPQMIWHI-QFIPXVFZSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[2-[benzyl(methyl)amino]acetyl]amino]-3-(3,4-dichlorophenyl)propanamide Chemical compound C([C@H](NC(=O)CN(C)CC=1C=CC=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C(Cl)=C1 XKURCVZPQMIWHI-QFIPXVFZSA-N 0.000 description 1
- MOFFMUFSROYKSP-QFIPXVFZSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[2-[bis(2-methylpropyl)amino]acetyl]amino]-3-(3,4-difluorophenyl)propanamide Chemical compound C([C@H](NC(=O)CN(CC(C)C)CC(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 MOFFMUFSROYKSP-QFIPXVFZSA-N 0.000 description 1
- SWEZFMNJTQEQSI-IBGZPJMESA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[2-[butyl(methyl)amino]acetyl]amino]-3-(3,4-difluorophenyl)propanamide Chemical compound C([C@H](NC(=O)CN(C)CCCC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 SWEZFMNJTQEQSI-IBGZPJMESA-N 0.000 description 1
- IOIFUBXYGIEYJG-QFIPXVFZSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-2-[[2-[cyclohexylmethyl(methyl)amino]acetyl]amino]-3-(3,4-difluorophenyl)propanamide Chemical compound N([C@@H](CC=1C=C(F)C(F)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C(=O)CN(C)CC1CCCCC1 IOIFUBXYGIEYJG-QFIPXVFZSA-N 0.000 description 1
- HPTFZJNGWHYDTG-BZNIZROVSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-dichlorophenyl)-2-[[(2r)-2-(methylamino)propanoyl]amino]propanamide Chemical compound C([C@H](NC(=O)[C@@H](C)NC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C(Cl)=C1 HPTFZJNGWHYDTG-BZNIZROVSA-N 0.000 description 1
- CXLQSEILYMUXNW-INIZCTEOSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-dichlorophenyl)-2-[[2-(dimethylamino)acetyl]amino]propanamide Chemical compound C([C@H](NC(=O)CN(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C(Cl)=C1 CXLQSEILYMUXNW-INIZCTEOSA-N 0.000 description 1
- TVZZNIHTQMVMAC-SFHVURJKSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-dichlorophenyl)-2-[[2-[methyl(propan-2-yl)amino]acetyl]amino]propanamide Chemical compound C([C@H](NC(=O)CN(C)C(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(Cl)C(Cl)=C1 TVZZNIHTQMVMAC-SFHVURJKSA-N 0.000 description 1
- KASBUUOPNLJSGY-MBABXSBOSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-(2-piperidin-1-ylpropanoylamino)propanamide Chemical compound N([C@@H](CC=1C=C(F)C(F)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C(=O)C(C)N1CCCCC1 KASBUUOPNLJSGY-MBABXSBOSA-N 0.000 description 1
- NTLCHXBQKWYUJS-SFHVURJKSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[(2-morpholin-4-ylacetyl)amino]propanamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)CN1CCOCC1)CC1=CC=C(F)C(F)=C1 NTLCHXBQKWYUJS-SFHVURJKSA-N 0.000 description 1
- BNKIBYMZMKRWOC-IBGZPJMESA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[(2-piperidin-1-ylacetyl)amino]propanamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)CN1CCCCC1)CC1=CC=C(F)C(F)=C1 BNKIBYMZMKRWOC-IBGZPJMESA-N 0.000 description 1
- ZZCMIDSHQFHHPQ-SFHVURJKSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[(2-pyrrolidin-1-ylacetyl)amino]propanamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)CN1CCCC1)CC1=CC=C(F)C(F)=C1 ZZCMIDSHQFHHPQ-SFHVURJKSA-N 0.000 description 1
- IUGLKUAATOYDJM-BZNIZROVSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[(2r)-2-(methylamino)propanoyl]amino]propanamide Chemical compound C([C@H](NC(=O)[C@@H](C)NC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 IUGLKUAATOYDJM-BZNIZROVSA-N 0.000 description 1
- XDQVEVYIFGEVAY-SJCJKPOMSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[(2s)-2-(dimethylamino)propanoyl]amino]propanamide Chemical compound C([C@H](NC(=O)[C@@H](N(C)C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 XDQVEVYIFGEVAY-SJCJKPOMSA-N 0.000 description 1
- IUGLKUAATOYDJM-ZBEGNZNMSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[(2s)-2-(methylamino)propanoyl]amino]propanamide Chemical compound C([C@H](NC(=O)[C@H](C)NC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 IUGLKUAATOYDJM-ZBEGNZNMSA-N 0.000 description 1
- YXXDYRDNTOGIKB-OALUTQOASA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[(2s)-3-hydroxy-2-[methyl(propan-2-yl)amino]propanoyl]amino]propanamide Chemical compound C([C@H](NC(=O)[C@H](CO)N(C)C(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 YXXDYRDNTOGIKB-OALUTQOASA-N 0.000 description 1
- UQNBCBPZUBKTLV-BUNACBEFSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[2-(2,6-dimethylpiperidin-1-yl)acetyl]amino]propanamide Chemical compound CC1CCCC(C)N1CC(=O)N[C@H](C(=O)NCC=1C=NC(N)=CC=1)CC1=CC=C(F)C(F)=C1 UQNBCBPZUBKTLV-BUNACBEFSA-N 0.000 description 1
- UKDWHIXSFOXZRW-QHCPKHFHSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[2-(3,4-dihydro-1h-isoquinolin-2-yl)acetyl]amino]propanamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)CN1CC2=CC=CC=C2CC1)CC1=CC=C(F)C(F)=C1 UKDWHIXSFOXZRW-QHCPKHFHSA-N 0.000 description 1
- LVBNCVTWMYQHAB-QFIPXVFZSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[2-(3,4-dihydro-2h-quinolin-1-yl)acetyl]amino]propanamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)CN1C2=CC=CC=C2CCC1)CC1=CC=C(F)C(F)=C1 LVBNCVTWMYQHAB-QFIPXVFZSA-N 0.000 description 1
- BPSNUXSBTKOWFA-FQEVSTJZSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[2-(dipropylamino)acetyl]amino]propanamide Chemical compound C([C@H](NC(=O)CN(CCC)CCC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 BPSNUXSBTKOWFA-FQEVSTJZSA-N 0.000 description 1
- RSRLUWJKPHCUPF-HNNXBMFYSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[2-(methylamino)acetyl]amino]propanamide Chemical compound C([C@H](NC(=O)CNC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 RSRLUWJKPHCUPF-HNNXBMFYSA-N 0.000 description 1
- GTLICTWACZAJKA-NRFANRHFSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[2-(n-methylanilino)acetyl]amino]propanamide Chemical compound C([C@H](NC(=O)CN(C)C=1C=CC=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 GTLICTWACZAJKA-NRFANRHFSA-N 0.000 description 1
- KINDCAPGXOMLKM-IBGZPJMESA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[2-[methyl(2-methylpropyl)amino]acetyl]amino]propanamide Chemical compound C([C@H](NC(=O)CN(C)CC(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 KINDCAPGXOMLKM-IBGZPJMESA-N 0.000 description 1
- CANPUISYQMVQHV-QHCPKHFHSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[2-[methyl(2-phenylethyl)amino]acetyl]amino]propanamide Chemical compound N([C@@H](CC=1C=C(F)C(F)=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C(=O)CN(C)CCC1=CC=CC=C1 CANPUISYQMVQHV-QHCPKHFHSA-N 0.000 description 1
- YPLMOPCUULFCFS-SFHVURJKSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,4-difluorophenyl)-2-[[2-[methyl(propan-2-yl)amino]acetyl]amino]propanamide Chemical compound C([C@H](NC(=O)CN(C)C(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 YPLMOPCUULFCFS-SFHVURJKSA-N 0.000 description 1
- DHBWGMACMTXQJN-MBABXSBOSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3,5-difluorophenyl)-2-(2-piperidin-1-ylpropanoylamino)propanamide Chemical compound N([C@@H](CC=1C=C(F)C=C(F)C=1)C(=O)NCC=1C=NC(N)=CC=1)C(=O)C(C)N1CCCCC1 DHBWGMACMTXQJN-MBABXSBOSA-N 0.000 description 1
- LDNYLNYSPMHNAB-FZCLLLDFSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3-chlorophenyl)-2-(2-piperidin-1-ylpropanoylamino)propanamide Chemical compound N([C@@H](CC=1C=C(Cl)C=CC=1)C(=O)NCC=1C=NC(N)=CC=1)C(=O)C(C)N1CCCCC1 LDNYLNYSPMHNAB-FZCLLLDFSA-N 0.000 description 1
- UAVXPIQMUYHUDZ-IBGZPJMESA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3-chlorophenyl)-2-[(2-piperidin-1-ylacetyl)amino]propanamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)CN1CCCCC1)CC1=CC=CC(Cl)=C1 UAVXPIQMUYHUDZ-IBGZPJMESA-N 0.000 description 1
- QTQULXDFANCWPX-KXBFYZLASA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(3-chlorophenyl)-2-[[(2s)-2-(diethylamino)propanoyl]amino]propanamide Chemical compound C([C@H](NC(=O)[C@H](C)N(CC)CC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=CC(Cl)=C1 QTQULXDFANCWPX-KXBFYZLASA-N 0.000 description 1
- SVGFRRQFJMWKRF-BPZDKFOGSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(4-chlorophenyl)-2-[[2-(2,6-dimethylpiperidin-1-yl)acetyl]amino]propanamide Chemical compound CC1CCCC(C)N1CC(=O)N[C@H](C(=O)NCC=1C=NC(N)=CC=1)CC1=CC=C(Cl)C=C1 SVGFRRQFJMWKRF-BPZDKFOGSA-N 0.000 description 1
- AKHJHMOWDBNFIV-IBGZPJMESA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(4-fluorophenyl)-2-[(2-piperidin-1-ylacetyl)amino]propanamide Chemical compound C1=NC(N)=CC=C1CNC(=O)[C@@H](NC(=O)CN1CCCCC1)CC1=CC=C(F)C=C1 AKHJHMOWDBNFIV-IBGZPJMESA-N 0.000 description 1
- OCXLSTGUNXQIKN-WBMJQRKESA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(4-fluorophenyl)-2-[[(2r)-2-(methylamino)propanoyl]amino]propanamide Chemical compound C([C@H](NC(=O)[C@@H](C)NC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C=C1 OCXLSTGUNXQIKN-WBMJQRKESA-N 0.000 description 1
- HMNUWCAHMNHMFI-UZLBHIALSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(4-fluorophenyl)-2-[[(2r)-2-piperidin-1-ylpropanoyl]amino]propanamide Chemical compound N1([C@H](C)C(=O)N[C@@H](CC=2C=CC(F)=CC=2)C(=O)NCC=2C=NC(N)=CC=2)CCCCC1 HMNUWCAHMNHMFI-UZLBHIALSA-N 0.000 description 1
- OCXLSTGUNXQIKN-LRDDRELGSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(4-fluorophenyl)-2-[[(2s)-2-(methylamino)propanoyl]amino]propanamide Chemical compound C([C@H](NC(=O)[C@H](C)NC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C=C1 OCXLSTGUNXQIKN-LRDDRELGSA-N 0.000 description 1
- NIDOACOBFHTHHY-KXBFYZLASA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(4-fluorophenyl)-2-[[(2s)-2-[methyl(propan-2-yl)amino]propanoyl]amino]propanamide Chemical compound C([C@H](NC(=O)[C@H](C)N(C)C(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C=C1 NIDOACOBFHTHHY-KXBFYZLASA-N 0.000 description 1
- HMNUWCAHMNHMFI-JXFKEZNVSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-(4-fluorophenyl)-2-[[(2s)-2-piperidin-1-ylpropanoyl]amino]propanamide Chemical compound N1([C@@H](C)C(=O)N[C@@H](CC=2C=CC(F)=CC=2)C(=O)NCC=2C=NC(N)=CC=2)CCCCC1 HMNUWCAHMNHMFI-JXFKEZNVSA-N 0.000 description 1
- NVURWFSGDUIWGA-NGICGMGXSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-cyclohexyl-2-[[2-(2,6-dimethylpiperidin-1-yl)acetyl]amino]propanamide Chemical compound CC1CCCC(C)N1CC(=O)N[C@H](C(=O)NCC=1C=NC(N)=CC=1)CC1CCCCC1 NVURWFSGDUIWGA-NGICGMGXSA-N 0.000 description 1
- LQEFFSCKGGUNQN-FQEVSTJZSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-3-cyclohexyl-2-[[2-[di(propan-2-yl)amino]acetyl]amino]propanamide Chemical compound C([C@H](NC(=O)CN(C(C)C)C(C)C)C(=O)NCC=1C=NC(N)=CC=1)C1CCCCC1 LQEFFSCKGGUNQN-FQEVSTJZSA-N 0.000 description 1
- PDKZLJLVQTXFAJ-HOCLYGCPSA-N (2s)-n-[(6-aminopyridin-3-yl)methyl]-4-methyl-2-[[(2s)-2-[methyl(propan-2-yl)amino]propanoyl]amino]pentanamide Chemical compound CC(C)N(C)[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)NCC1=CC=C(N)N=C1 PDKZLJLVQTXFAJ-HOCLYGCPSA-N 0.000 description 1
- QJCNLJWUIOIMMF-YUMQZZPRSA-N (2s,3s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C QJCNLJWUIOIMMF-YUMQZZPRSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
- SIZRIGSBZPWTOL-UHFFFAOYSA-N 1,3-dimethylpyrrole-2-carboxylic acid Chemical compound CC=1C=CN(C)C=1C(O)=O SIZRIGSBZPWTOL-UHFFFAOYSA-N 0.000 description 1
- MAHAMBLNIDMREX-UHFFFAOYSA-N 1-methylindole-2-carboxylic acid Chemical compound C1=CC=C2N(C)C(C(O)=O)=CC2=C1 MAHAMBLNIDMREX-UHFFFAOYSA-N 0.000 description 1
- CWLQUGTUXBXTLF-UHFFFAOYSA-N 1-methylpyrrolidin-1-ium-2-carboxylate Chemical compound CN1CCCC1C(O)=O CWLQUGTUXBXTLF-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 1
- RHXSYTACTOMVLJ-UHFFFAOYSA-N 1H-benzimidazole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=NC2=C1 RHXSYTACTOMVLJ-UHFFFAOYSA-N 0.000 description 1
- GLDQAMYCGOIJDV-UHFFFAOYSA-N 2,3-dihydroxybenzoic acid Chemical class OC(=O)C1=CC=CC(O)=C1O GLDQAMYCGOIJDV-UHFFFAOYSA-N 0.000 description 1
- 125000006069 2,3-dimethyl-2-butenyl group Chemical group 0.000 description 1
- RKOPPJWNONMZGZ-UHFFFAOYSA-N 2,5-dimethylpyrazole-3-carboxamide Chemical compound CC=1C=C(C(N)=O)N(C)N=1 RKOPPJWNONMZGZ-UHFFFAOYSA-N 0.000 description 1
- QRWZFUBHOQWUGH-UHFFFAOYSA-N 2,5-dimethylpyrazole-3-carboxylic acid Chemical compound CC=1C=C(C(O)=O)N(C)N=1 QRWZFUBHOQWUGH-UHFFFAOYSA-N 0.000 description 1
- XVVXKHSKFIGJQV-UHFFFAOYSA-N 2-(diethylamino)acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCN(CC)CC(O)=O XVVXKHSKFIGJQV-UHFFFAOYSA-N 0.000 description 1
- YZZDVCGDIVDQLO-UHFFFAOYSA-N 2-(dimethylamino)-3,3-dimethylbutanamide Chemical compound CN(C)C(C(N)=O)C(C)(C)C YZZDVCGDIVDQLO-UHFFFAOYSA-N 0.000 description 1
- AAAGQVRDZQYDKU-UHFFFAOYSA-N 2-[[2-(2,6-dimethylpiperidin-1-yl)acetyl]amino]propanamide Chemical compound NC(=O)C(C)NC(=O)CN1C(C)CCCC1C AAAGQVRDZQYDKU-UHFFFAOYSA-N 0.000 description 1
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- HVVCAOIEJDVNIH-UHFFFAOYSA-N 2-methyl-2-(methylamino)pentanoic acid Chemical compound CCCC(C)(NC)C(O)=O HVVCAOIEJDVNIH-UHFFFAOYSA-N 0.000 description 1
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
- DOZZSWAOPDYVLH-UHFFFAOYSA-N 2-phenylpropanamide Chemical compound NC(=O)C(C)C1=CC=CC=C1 DOZZSWAOPDYVLH-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- LGCYVLDNGBSOOW-UHFFFAOYSA-N 2H-benzotriazol-4-ol 1-hydroxybenzotriazole Chemical compound OC1=CC=CC2=C1N=NN2.C1=CC=C2N(O)N=NC2=C1 LGCYVLDNGBSOOW-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin 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-VTZDEGQISA-N 0.000 description 1
- ZPBIYZHGBPBZCK-UHFFFAOYSA-N 4,4-difluoropyrrolidin-1-ium-2-carboxylate Chemical compound OC(=O)C1CC(F)(F)CN1 ZPBIYZHGBPBZCK-UHFFFAOYSA-N 0.000 description 1
- QCXJEYYXVJIFCE-UHFFFAOYSA-N 4-acetamidobenzoic acid Chemical class CC(=O)NC1=CC=C(C(O)=O)C=C1 QCXJEYYXVJIFCE-UHFFFAOYSA-N 0.000 description 1
- ACYJFVSEJUENGJ-UHFFFAOYSA-N 4-amino-2-(diethylamino)-4-oxobutanoic acid Chemical compound CCN(CC)C(C(O)=O)CC(N)=O ACYJFVSEJUENGJ-UHFFFAOYSA-N 0.000 description 1
- SGOOQMRIPALTEL-UHFFFAOYSA-N 4-hydroxy-N,1-dimethyl-2-oxo-N-phenyl-3-quinolinecarboxamide Chemical compound OC=1C2=CC=CC=C2N(C)C(=O)C=1C(=O)N(C)C1=CC=CC=C1 SGOOQMRIPALTEL-UHFFFAOYSA-N 0.000 description 1
- XZFYVUSVVAWJGM-UHFFFAOYSA-N 5-(aminomethyl)-6-methylpyridin-2-amine Chemical compound CC1=NC(N)=CC=C1CN XZFYVUSVVAWJGM-UHFFFAOYSA-N 0.000 description 1
- IEXFWMPJBLXWEA-UHFFFAOYSA-N 5-(aminomethyl)pyridin-2-amine 6-aminopyridine-3-carbonitrile dihydrochloride Chemical compound NC1=CC=C(C=N1)C#N.Cl.Cl.NCC=1C=CC(=NC1)N IEXFWMPJBLXWEA-UHFFFAOYSA-N 0.000 description 1
- UNRWJYFQFIQMBC-INIZCTEOSA-N 5-[[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-1-oxo-3-[3-(trifluoromethyl)phenyl]propan-2-yl]carbamoyl]-4-methyl-1h-pyrrole-2-carboxylic acid Chemical compound C1=C(C(O)=O)NC(C(=O)N[C@@H](CC=2C=C(C=CC=2)C(F)(F)F)C(=O)NCC=2C=NC(N)=CC=2)=C1C UNRWJYFQFIQMBC-INIZCTEOSA-N 0.000 description 1
- OZAIJUZOQOBQDW-UHFFFAOYSA-N 6-amino-2-methylpyridine-3-carbonitrile Chemical compound CC1=NC(N)=CC=C1C#N OZAIJUZOQOBQDW-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 208000028185 Angioedema Diseases 0.000 description 1
- 102400000068 Angiostatin Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000022211 Arteriovenous Malformations Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 101710085045 B2 bradykinin receptor Proteins 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 208000003014 Bites and Stings Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 229940122155 Bradykinin receptor antagonist Drugs 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010007270 Carcinoid syndrome Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 201000009047 Chordoma Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 208000000668 Chronic Pancreatitis Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000009798 Craniopharyngioma Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- BWKMGYQJPOAASG-SECBINFHSA-N D-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2CN[C@@H](C(=O)O)CC2=C1 BWKMGYQJPOAASG-SECBINFHSA-N 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 208000008279 Dumping Syndrome Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 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
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 206010015958 Eye pain Diseases 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
- 101710103262 Glandular kallikrein Proteins 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 108010000487 High-Molecular-Weight Kininogen Proteins 0.000 description 1
- 101100453988 Homo sapiens KLK1 gene Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 208000006877 Insect Bites and Stings Diseases 0.000 description 1
- 102000004374 Insulin-like growth factor binding protein 3 Human genes 0.000 description 1
- 108090000965 Insulin-like growth factor binding protein 3 Proteins 0.000 description 1
- 241000764238 Isis Species 0.000 description 1
- 206010023230 Joint stiffness Diseases 0.000 description 1
- FYSKZKQBTVLYEQ-FSLKYBNLSA-N Kallidin Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)CCC1 FYSKZKQBTVLYEQ-FSLKYBNLSA-N 0.000 description 1
- 108010003195 Kallidin Proteins 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- 108010077861 Kininogens Proteins 0.000 description 1
- 102000010631 Kininogens Human genes 0.000 description 1
- 108010093008 Kinins Proteins 0.000 description 1
- 102000002397 Kinins Human genes 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 150000000994 L-ascorbates Chemical class 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
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 229930182821 L-proline Natural products 0.000 description 1
- 201000008197 Laryngitis Diseases 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 108010058188 Low-Molecular-Weight Kininogen Proteins 0.000 description 1
- 208000004852 Lung Injury Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 238000007807 Matrigel invasion assay Methods 0.000 description 1
- 208000007054 Medullary Carcinoma Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 208000019695 Migraine disease 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
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- NZTGCDFLOZSFLV-UHFFFAOYSA-N NC1=NC=C(C=C1)C#N.C(C)(C)(C)OC(NCC=1C=NC(=CC1)N)=O Chemical compound NC1=NC=C(C=C1)C#N.C(C)(C)(C)OC(NCC=1C=NC(=CC1)N)=O NZTGCDFLOZSFLV-UHFFFAOYSA-N 0.000 description 1
- HDQCYGRHPFVRFW-UHFFFAOYSA-N NC=1C=C(C=NC1)CNC(O)=O Chemical compound NC=1C=C(C=NC1)CNC(O)=O HDQCYGRHPFVRFW-UHFFFAOYSA-N 0.000 description 1
- 206010052437 Nasal discomfort Diseases 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000025047 Non-histaminic angioedema Diseases 0.000 description 1
- 239000006057 Non-nutritive feed additive Substances 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- 206010031009 Oral pain Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010033649 Pancreatitis chronic Diseases 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 241000209504 Poaceae Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920000331 Polyhydroxybutyrate Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000032395 Post gastric surgery syndrome Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 1
- 102100038358 Prostate-specific antigen Human genes 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 208000007135 Retinal Neovascularization Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 206010068771 Soft tissue neoplasm Diseases 0.000 description 1
- 239000004147 Sorbitan trioleate Substances 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 208000004732 Systemic Vasculitis Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 108700022175 Tissue Kallikreins Proteins 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 235000008322 Trichosanthes cucumerina Nutrition 0.000 description 1
- 244000078912 Trichosanthes cucumerina Species 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000009443 Vascular Malformations Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 208000014070 Vestibular schwannoma Diseases 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 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 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 208000004064 acoustic neuroma Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 150000003838 adenosines Chemical class 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 210000004712 air sac Anatomy 0.000 description 1
- 230000036428 airway hyperreactivity Effects 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 150000001371 alpha-amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000001740 anti-invasion Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- 230000005744 arteriovenous malformation Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 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 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000003937 benzamidines Chemical class 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- WGNZRLMOMHJUSP-UHFFFAOYSA-N benzotriazol-1-yloxy(tripyrrolidin-1-yl)phosphanium Chemical compound C1CCCN1[P+](N1CCCC1)(N1CCCC1)ON1C2=CC=CC=C2N=N1 WGNZRLMOMHJUSP-UHFFFAOYSA-N 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004155 blood-retinal barrier Anatomy 0.000 description 1
- 230000004378 blood-retinal barrier Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 229960001467 bortezomib Drugs 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 239000003541 chymotrypsin inhibitor Substances 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- GFHNAMRJFCEERV-UHFFFAOYSA-L cobalt chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Co+2] GFHNAMRJFCEERV-UHFFFAOYSA-L 0.000 description 1
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 229940046044 combinations of antineoplastic agent Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- UVJHQYIOXKWHFD-UHFFFAOYSA-N cyclohexa-1,4-diene Chemical compound C1C=CCC=C1 UVJHQYIOXKWHFD-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- AVKNGPAMCBSNSO-UHFFFAOYSA-N cyclohexylmethanamine Chemical class NCC1CCCCC1 AVKNGPAMCBSNSO-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 208000002445 cystadenocarcinoma Diseases 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000004340 degenerative myopia Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- JRBPAEWTRLWTQC-UHFFFAOYSA-N dodecylamine Chemical compound CCCCCCCCCCCCN JRBPAEWTRLWTQC-UHFFFAOYSA-N 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 208000017574 dry cough Diseases 0.000 description 1
- 229940112141 dry powder inhaler Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 208000037828 epithelial carcinoma Diseases 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229960005420 etoposide Drugs 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 150000005699 fluoropyrimidines Chemical class 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- BNRNAKTVFSZAFA-UHFFFAOYSA-N hydrindane Chemical compound C1CCCC2CCCC21 BNRNAKTVFSZAFA-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000004047 hyperresponsiveness Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 201000001371 inclusion conjunctivitis Diseases 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000012739 integrated shape imaging system Methods 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007915 intraurethral administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229960003881 letrozole Drugs 0.000 description 1
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000002583 male contraceptive agent Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 1
- 229950008959 marimastat Drugs 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- RTQIRFLHZVBRJM-SFHVURJKSA-N methyl 5-[[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-1-oxo-3-[3-(trifluoromethyl)phenyl]propan-2-yl]carbamoyl]-1h-pyrrole-2-carboxylate Chemical compound N1C(C(=O)OC)=CC=C1C(=O)N[C@H](C(=O)NCC=1C=NC(N)=CC=1)CC1=CC=CC(C(F)(F)F)=C1 RTQIRFLHZVBRJM-SFHVURJKSA-N 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 230000003232 mucoadhesive effect Effects 0.000 description 1
- 208000001611 myxosarcoma Diseases 0.000 description 1
- KOXMOXKZPBAPJR-INIZCTEOSA-N n-[(2s)-1-[(6-aminopyridin-3-yl)methylamino]-3-(3,4-difluorophenyl)-1-oxopropan-2-yl]-2-methyl-2-(methylamino)propanamide Chemical compound C([C@H](NC(=O)C(C)(C)NC)C(=O)NCC=1C=NC(N)=CC=1)C1=CC=C(F)C(F)=C1 KOXMOXKZPBAPJR-INIZCTEOSA-N 0.000 description 1
- UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical class C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000025189 neoplasm of testis Diseases 0.000 description 1
- 201000003142 neovascular glaucoma Diseases 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- LAIZPRYFQUWUBN-UHFFFAOYSA-L nickel chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ni+2] LAIZPRYFQUWUBN-UHFFFAOYSA-L 0.000 description 1
- 229960002653 nilutamide Drugs 0.000 description 1
- XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 201000010198 papillary carcinoma Diseases 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
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 108010021753 peptide-Gly-Leu-amide Proteins 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- 208000026435 phlegm Diseases 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 208000024724 pineal body neoplasm Diseases 0.000 description 1
- 201000004123 pineal gland cancer Diseases 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- 239000005015 poly(hydroxybutyrate) Substances 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229940124606 potential therapeutic agent Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- BMKDZUISNHGIBY-UHFFFAOYSA-N razoxane Chemical compound C1C(=O)NC(=O)CN1C(C)CN1CC(=O)NC(=O)C1 BMKDZUISNHGIBY-UHFFFAOYSA-N 0.000 description 1
- 229960000460 razoxane Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 229960003522 roquinimex Drugs 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 201000008407 sebaceous adenocarcinoma Diseases 0.000 description 1
- 125000005920 sec-butoxy group Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 206010041232 sneezing Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 208000021792 sore eyes Diseases 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 201000010965 sweat gland carcinoma Diseases 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000012622 synthetic inhibitor Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- RCINICONZNJXQF-XAZOAEDWSA-N taxol® Chemical compound O([C@@H]1[C@@]2(CC(C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3(C21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-XAZOAEDWSA-N 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide 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](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- OJYZHWJCONPUFM-UHFFFAOYSA-N tert-butyl 2-(diethylamino)acetate 2-(diethylamino)acetic acid 2,2,2-trifluoroacetic acid Chemical compound C(C)(C)(C)OC(CN(CC)CC)=O.FC(C(=O)O)(F)F.C(C)N(CC)CC(=O)O OJYZHWJCONPUFM-UHFFFAOYSA-N 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 206010044325 trachoma Diseases 0.000 description 1
- NNBZCPXTIHJBJL-UHFFFAOYSA-N trans-decahydronaphthalene Natural products C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229940099039 velcade Drugs 0.000 description 1
- 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 1
- 229960004528 vincristine Drugs 0.000 description 1
- 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 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- 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
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- 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
- A61P17/04—Antipruritics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7143108P | 2008-04-29 | 2008-04-29 | |
| GBGB0807828.9A GB0807828D0 (en) | 2008-04-29 | 2008-04-29 | Aminopyridine derivatives |
| PCT/GB2009/001062 WO2009133348A1 (en) | 2008-04-29 | 2009-04-28 | Aminopyridine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2010011896A true MX2010011896A (es) | 2010-11-30 |
Family
ID=39522782
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2010011896A MX2010011896A (es) | 2008-04-29 | 2009-04-28 | Derivados de aminopiridina. |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US20100076015A1 (enExample) |
| EP (1) | EP2300428A1 (enExample) |
| JP (1) | JP2011519845A (enExample) |
| KR (1) | KR20110014161A (enExample) |
| CN (1) | CN102076666A (enExample) |
| AR (1) | AR071514A1 (enExample) |
| AU (1) | AU2009241906A1 (enExample) |
| BR (1) | BRPI0911443A2 (enExample) |
| CA (1) | CA2722648A1 (enExample) |
| CO (1) | CO6321287A2 (enExample) |
| EC (1) | ECSP10010648A (enExample) |
| GB (1) | GB0807828D0 (enExample) |
| IL (1) | IL208812A0 (enExample) |
| MX (1) | MX2010011896A (enExample) |
| NZ (1) | NZ588635A (enExample) |
| RU (1) | RU2010148420A (enExample) |
| WO (1) | WO2009133348A1 (enExample) |
| ZA (1) | ZA201007615B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2011006169A (es) * | 2008-12-12 | 2011-06-27 | Univ Vanderbilt | Inhibidores 3.3.0-biciclicos de giyt1 y metodos para hacer y utilizar los mismos. |
| GB0918922D0 (en) * | 2009-10-28 | 2009-12-16 | Vantia Ltd | Aminopyridine derivatives |
| US9290485B2 (en) | 2010-08-04 | 2016-03-22 | Novartis Ag | N-((6-amino-pyridin-3-yl)methyl)-heteroaryl-carboxamides |
| EP3512839A4 (en) | 2016-09-18 | 2020-03-25 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | AGAINST INTERACTION OF YAP1 WITH YCT1 INHIBITORS |
| WO2019178401A1 (en) | 2018-03-14 | 2019-09-19 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Yap1 inhibitors that target the interaction of yap1 with oct4 |
| WO2021032933A1 (en) * | 2019-08-21 | 2021-02-25 | Kalvista Pharmaceuticals Limited | Enzyme inhibitors |
| EP4066896A4 (en) * | 2019-11-27 | 2024-03-27 | Riken | G9A INHIBITOR |
| WO2022255399A1 (ja) * | 2021-06-01 | 2022-12-08 | 国立研究開発法人理化学研究所 | Ｇ９ａ阻害剤 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5187157A (en) * | 1987-06-05 | 1993-02-16 | Du Pont Merck Pharmaceutical Company | Peptide boronic acid inhibitors of trypsin-like proteases |
| SE9301916D0 (sv) * | 1993-06-03 | 1993-06-03 | Ab Astra | New peptides derivatives |
| US5464820A (en) * | 1993-06-22 | 1995-11-07 | The University Hospital | Specific inhibitors of tissue kallikrein |
| NZ547626A (en) * | 2000-08-11 | 2007-10-26 | Wilex Ag | Non-covalent inhibitors of urokinase and blood vessel formation |
| FR2819254B1 (fr) * | 2001-01-08 | 2003-04-18 | Fournier Lab Sa | Nouveaux composes de la n-(phenylsulfonyl) glycine, leur procede de preparation et leur utilisation pour obtenir des compostions pharmaceutiques |
| FR2836143B1 (fr) * | 2002-02-21 | 2004-04-16 | Servier Lab | Nouveaux derives d'acides amines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| CA2557858A1 (en) * | 2004-03-02 | 2005-09-15 | Merck & Co., Inc. | Amino cyclopropane carboxamide derivatives as bradykinin antagonists |
| JP4775259B2 (ja) * | 2004-03-31 | 2011-09-21 | 味の素株式会社 | アニリン誘導体 |
-
2008
- 2008-04-29 GB GBGB0807828.9A patent/GB0807828D0/en not_active Ceased
-
2009
- 2009-04-28 CA CA2722648A patent/CA2722648A1/en not_active Abandoned
- 2009-04-28 AR ARP090101507A patent/AR071514A1/es unknown
- 2009-04-28 NZ NZ588635A patent/NZ588635A/en not_active IP Right Cessation
- 2009-04-28 RU RU2010148420/04A patent/RU2010148420A/ru unknown
- 2009-04-28 AU AU2009241906A patent/AU2009241906A1/en not_active Abandoned
- 2009-04-28 MX MX2010011896A patent/MX2010011896A/es not_active Application Discontinuation
- 2009-04-28 CN CN2009801248942A patent/CN102076666A/zh active Pending
- 2009-04-28 BR BRPI0911443A patent/BRPI0911443A2/pt not_active IP Right Cessation
- 2009-04-28 US US12/431,114 patent/US20100076015A1/en not_active Abandoned
- 2009-04-28 EP EP09738378A patent/EP2300428A1/en not_active Withdrawn
- 2009-04-28 JP JP2011506764A patent/JP2011519845A/ja active Pending
- 2009-04-28 WO PCT/GB2009/001062 patent/WO2009133348A1/en not_active Ceased
- 2009-04-28 KR KR1020107026578A patent/KR20110014161A/ko not_active Withdrawn
-
2010
- 2010-10-19 IL IL208812A patent/IL208812A0/en unknown
- 2010-10-25 CO CO10132210A patent/CO6321287A2/es not_active Application Discontinuation
- 2010-10-25 ZA ZA2010/07615A patent/ZA201007615B/en unknown
- 2010-11-29 EC EC2010010648A patent/ECSP10010648A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| RU2010148420A (ru) | 2012-06-10 |
| GB0807828D0 (en) | 2008-06-04 |
| ZA201007615B (en) | 2011-08-31 |
| CA2722648A1 (en) | 2009-11-05 |
| ECSP10010648A (es) | 2011-01-31 |
| EP2300428A1 (en) | 2011-03-30 |
| JP2011519845A (ja) | 2011-07-14 |
| CN102076666A (zh) | 2011-05-25 |
| BRPI0911443A2 (pt) | 2015-10-06 |
| CO6321287A2 (es) | 2011-09-20 |
| WO2009133348A1 (en) | 2009-11-05 |
| AR071514A1 (es) | 2010-06-23 |
| IL208812A0 (en) | 2011-01-31 |
| AU2009241906A1 (en) | 2009-11-05 |
| US20100076015A1 (en) | 2010-03-25 |
| KR20110014161A (ko) | 2011-02-10 |
| NZ588635A (en) | 2011-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5921679B2 (ja) | 血漿カリクレインの阻害薬としてのベンジルアミン誘導体 | |
| US20100076015A1 (en) | Aminopyridine Derivatives | |
| WO2019106359A1 (en) | Enzyme inhibitors | |
| JP2023518948A (ja) | アンギオテンシンｉｉに関連する疾患、障害又は状態の治療及び／又は予防に有用な新規化合物 | |
| RS66709B1 (sr) | (2s)-n-[(1s)-1-cijano-2-feniletil]-1,4-oksazepan-2-karboksamidi kao inhibitori dipeptidil peptidaze i | |
| JP2004516286A (ja) | ベンジルアミン誘導体およびそれのトロンビン阻害薬としての使用 | |
| CA2925291A1 (en) | Substituted phenylalanine derivatives | |
| EA036456B1 (ru) | Имидазолиновые соединения в качестве ингибиторов эластазы нейтрофилов человека | |
| WO2011051671A1 (en) | Aminopyridine derivatives as kallikrein inhibitors | |
| CN101553219B (zh) | 作为TAFIa抑制剂的脲和磺酰胺衍生物 | |
| CN103491777B (zh) | 组织蛋白酶c抑制剂 | |
| WO2011051673A1 (en) | Aminothiazole derivatives useful as klk1 inhibitors | |
| WO2011051672A1 (en) | Azaindole derivatives | |
| JP2005521641A (ja) | 第ｘａ因子阻害剤としての２−（３−スルホニルアミノ−２−オキソピロリジン−１−イル）プロパンアミド | |
| JPH09118662A (ja) | 尿素誘導体 | |
| JP2013501800A (ja) | カテプシンｃ阻害剤 | |
| JP2006199700A (ja) | 結晶形態 | |
| NZ620271B2 (en) | Benzylamine derivatives as inhibitors of plasma kallikrein | |
| HK1137928B (en) | Urea and sulfamide derivatives as tafia inhibitors | |
| JPWO1992017456A1 (ja) | アミノ酸誘導体およびその塩 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FA | Abandonment or withdrawal |