JP6427115B2 - 癌などの疾患の処置のためのトリアゾロ[4,5−d]ピリミジン誘導体 - Google Patents
癌などの疾患の処置のためのトリアゾロ[4,5−d]ピリミジン誘導体 Download PDFInfo
- Publication number
- JP6427115B2 JP6427115B2 JP2015560571A JP2015560571A JP6427115B2 JP 6427115 B2 JP6427115 B2 JP 6427115B2 JP 2015560571 A JP2015560571 A JP 2015560571A JP 2015560571 A JP2015560571 A JP 2015560571A JP 6427115 B2 JP6427115 B2 JP 6427115B2
- Authority
- JP
- Japan
- Prior art keywords
- triazolo
- pyrimidin
- phenyl
- hplc
- ylamino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 206010028980 Neoplasm Diseases 0.000 title claims description 136
- 201000011510 cancer Diseases 0.000 title claims description 74
- 238000011282 treatment Methods 0.000 title claims description 73
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 61
- 201000010099 disease Diseases 0.000 title claims description 41
- GIIGHSIIKVOWKZ-UHFFFAOYSA-N 2h-triazolo[4,5-d]pyrimidine Chemical class N1=CN=CC2=NNN=C21 GIIGHSIIKVOWKZ-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 197
- 150000003839 salts Chemical class 0.000 claims description 82
- 239000000203 mixture Substances 0.000 claims description 81
- 239000012453 solvate Substances 0.000 claims description 36
- 239000004480 active ingredient Substances 0.000 claims description 35
- 239000003814 drug Substances 0.000 claims description 26
- 230000002265 prevention Effects 0.000 claims description 21
- 238000011321 prophylaxis Methods 0.000 claims description 18
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 230000004770 neurodegeneration Effects 0.000 claims description 15
- 210000004369 blood Anatomy 0.000 claims description 14
- 239000008280 blood Substances 0.000 claims description 14
- 206010012601 diabetes mellitus Diseases 0.000 claims description 14
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 13
- 201000006417 multiple sclerosis Diseases 0.000 claims description 12
- 201000004681 Psoriasis Diseases 0.000 claims description 10
- 206010006187 Breast cancer Diseases 0.000 claims description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 9
- 208000015181 infectious disease Diseases 0.000 claims description 9
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 230000002503 metabolic effect Effects 0.000 claims description 8
- 210000004556 brain Anatomy 0.000 claims description 7
- 210000002784 stomach Anatomy 0.000 claims description 7
- 210000001519 tissue Anatomy 0.000 claims description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
- 208000010668 atopic eczema Diseases 0.000 claims description 6
- 210000004185 liver Anatomy 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 5
- 241000222722 Leishmania <genus> Species 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 230000001900 immune effect Effects 0.000 claims description 5
- 210000003734 kidney Anatomy 0.000 claims description 5
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 208000036110 Neuroinflammatory disease Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 208000025747 Rheumatic disease Diseases 0.000 claims description 4
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 4
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 4
- 230000001363 autoimmune Effects 0.000 claims description 4
- 210000003679 cervix uteri Anatomy 0.000 claims description 4
- 210000003238 esophagus Anatomy 0.000 claims description 4
- 208000005017 glioblastoma Diseases 0.000 claims description 4
- 210000003128 head Anatomy 0.000 claims description 4
- 210000000987 immune system Anatomy 0.000 claims description 4
- 230000002757 inflammatory effect Effects 0.000 claims description 4
- 210000000936 intestine Anatomy 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 201000005249 lung adenocarcinoma Diseases 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 210000003739 neck Anatomy 0.000 claims description 4
- 210000000056 organ Anatomy 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 210000002307 prostate Anatomy 0.000 claims description 4
- 230000000552 rheumatic effect Effects 0.000 claims description 4
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 4
- 210000001685 thyroid gland Anatomy 0.000 claims description 4
- 210000003932 urinary bladder Anatomy 0.000 claims description 4
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 3
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 3
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 3
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 3
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 206010024305 Leukaemia monocytic Diseases 0.000 claims description 3
- 241000186367 Mycobacterium avium Species 0.000 claims description 3
- 230000000172 allergic effect Effects 0.000 claims description 3
- 210000000988 bone and bone Anatomy 0.000 claims description 3
- 210000000867 larynx Anatomy 0.000 claims description 3
- 210000004324 lymphatic system Anatomy 0.000 claims description 3
- 201000006894 monocytic leukemia Diseases 0.000 claims description 3
- 230000001732 thrombotic effect Effects 0.000 claims description 3
- 201000003076 Angiosarcoma Diseases 0.000 claims description 2
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 2
- 206010008111 Cerebral haemorrhage Diseases 0.000 claims description 2
- 208000005243 Chondrosarcoma Diseases 0.000 claims description 2
- 201000010374 Down Syndrome Diseases 0.000 claims description 2
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 2
- 208000007465 Giant cell arteritis Diseases 0.000 claims description 2
- 208000001258 Hemangiosarcoma Diseases 0.000 claims description 2
- 241000701044 Human gammaherpesvirus 4 Species 0.000 claims description 2
- 241000186362 Mycobacterium leprae Species 0.000 claims description 2
- 201000004404 Neurofibroma Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 241000224016 Plasmodium Species 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 241000700584 Simplexvirus Species 0.000 claims description 2
- 206010044688 Trisomy 21 Diseases 0.000 claims description 2
- 206010002022 amyloidosis Diseases 0.000 claims description 2
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 2
- 210000004602 germ cell Anatomy 0.000 claims description 2
- 208000037906 ischaemic injury Diseases 0.000 claims description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 2
- 206010043207 temporal arteritis Diseases 0.000 claims description 2
- 241000711549 Hepacivirus C Species 0.000 claims 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 claims 1
- 238000004949 mass spectrometry Methods 0.000 description 354
- 238000004128 high performance liquid chromatography Methods 0.000 description 351
- -1 2- (acetyloxy) benzoic acid 3- (nitrooxymethyl) phenyl ester Chemical class 0.000 description 259
- 238000005481 NMR spectroscopy Methods 0.000 description 170
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 112
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
- DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 86
- 239000000243 solution Substances 0.000 description 81
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 74
- 235000002639 sodium chloride Nutrition 0.000 description 67
- 239000011541 reaction mixture Substances 0.000 description 66
- 230000015572 biosynthetic process Effects 0.000 description 55
- 238000003786 synthesis reaction Methods 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 51
- 210000004027 cell Anatomy 0.000 description 42
- 239000007787 solid Substances 0.000 description 41
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 40
- 239000003480 eluent Substances 0.000 description 38
- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 description 38
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 description 38
- 239000000843 powder Substances 0.000 description 38
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
- 230000000694 effects Effects 0.000 description 37
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- 239000000741 silica gel Substances 0.000 description 32
- 229910002027 silica gel Inorganic materials 0.000 description 32
- 239000002253 acid Substances 0.000 description 31
- 238000000034 method Methods 0.000 description 31
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 29
- 230000005764 inhibitory process Effects 0.000 description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- XRLDSWLMHUQECH-UHFFFAOYSA-N cyclopentanecarboxamide Chemical compound NC(=O)C1CCCC1 XRLDSWLMHUQECH-UHFFFAOYSA-N 0.000 description 26
- 239000003112 inhibitor Substances 0.000 description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 26
- 108091000080 Phosphotransferase Proteins 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 25
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- 102000020233 phosphotransferase Human genes 0.000 description 25
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
- 125000004432 carbon atom Chemical group C* 0.000 description 23
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 21
- 108010003374 fms-Like Tyrosine Kinase 3 Proteins 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 208000035475 disorder Diseases 0.000 description 20
- 230000014509 gene expression Effects 0.000 description 19
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 230000035882 stress Effects 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
- 210000001744 T-lymphocyte Anatomy 0.000 description 17
- 230000037361 pathway Effects 0.000 description 16
- 239000002585 base Substances 0.000 description 15
- 239000013078 crystal Substances 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 14
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 14
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 238000001816 cooling Methods 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical group COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 238000013459 approach Methods 0.000 description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- 210000004881 tumor cell Anatomy 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- 125000000217 alkyl group Chemical group 0.000 description 12
- 125000003226 pyrazolyl group Chemical group 0.000 description 12
- 125000002098 pyridazinyl group Chemical group 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 11
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 11
- 208000037581 Persistent Infection Diseases 0.000 description 11
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 11
- 125000002393 azetidinyl group Chemical group 0.000 description 11
- 230000006870 function Effects 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 125000003386 piperidinyl group Chemical group 0.000 description 11
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 239000003826 tablet Substances 0.000 description 11
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 11
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 11
- 125000001425 triazolyl group Chemical group 0.000 description 11
- 108010085376 Activating Transcription Factor 4 Proteins 0.000 description 10
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 10
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 description 10
- 102100022975 Glycogen synthase kinase-3 alpha Human genes 0.000 description 10
- 102100038104 Glycogen synthase kinase-3 beta Human genes 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
- 230000004913 activation Effects 0.000 description 10
- 229940024606 amino acid Drugs 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 108010049611 glycogen synthase kinase 3 alpha Proteins 0.000 description 10
- 125000001715 oxadiazolyl group Chemical group 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- 230000019491 signal transduction Effects 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- IWTUSMBWCYJNMO-UHFFFAOYSA-N 5-chloro-3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(Cl)=NC=C2N=N1 IWTUSMBWCYJNMO-UHFFFAOYSA-N 0.000 description 9
- 102100023580 Cyclic AMP-dependent transcription factor ATF-4 Human genes 0.000 description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 9
- 102000001253 Protein Kinase Human genes 0.000 description 9
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 9
- 239000000427 antigen Substances 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- 230000036039 immunity Effects 0.000 description 9
- 230000036210 malignancy Effects 0.000 description 9
- 108060006633 protein kinase Proteins 0.000 description 9
- 125000004076 pyridyl group Chemical group 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 9
- SOMOINFNYJPSHH-ZIAGYGMSSA-N (1r,3r)-3-[[3-(2-methylquinolin-6-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxylic acid Chemical compound C1=CC2=NC(C)=CC=C2C=C1N(C1=N2)N=NC1=CN=C2N[C@@H]1CC[C@@H](C(O)=O)C1 SOMOINFNYJPSHH-ZIAGYGMSSA-N 0.000 description 8
- INUSQTPGSHFGHM-UHFFFAOYSA-N 2,4-dichloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1Cl INUSQTPGSHFGHM-UHFFFAOYSA-N 0.000 description 8
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 8
- 102000001267 GSK3 Human genes 0.000 description 8
- 108060006662 GSK3 Proteins 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 239000002246 antineoplastic agent Substances 0.000 description 8
- 230000015556 catabolic process Effects 0.000 description 8
- 230000000875 corresponding effect Effects 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 206010025135 lupus erythematosus Diseases 0.000 description 8
- 230000007246 mechanism Effects 0.000 description 8
- NFVJNJQRWPQVOA-UHFFFAOYSA-N n-[2-chloro-5-(trifluoromethyl)phenyl]-2-[3-(4-ethyl-5-ethylsulfanyl-1,2,4-triazol-3-yl)piperidin-1-yl]acetamide Chemical compound CCN1C(SCC)=NN=C1C1CN(CC(=O)NC=2C(=CC=C(C=2)C(F)(F)F)Cl)CCC1 NFVJNJQRWPQVOA-UHFFFAOYSA-N 0.000 description 8
- 125000003566 oxetanyl group Chemical group 0.000 description 8
- 229940002612 prodrug Drugs 0.000 description 8
- 239000000651 prodrug Substances 0.000 description 8
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- 235000019253 formic acid Nutrition 0.000 description 7
- 150000004675 formic acid derivatives Chemical class 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 125000000842 isoxazolyl group Chemical group 0.000 description 7
- 230000004060 metabolic process Effects 0.000 description 7
- 125000002757 morpholinyl group Chemical group 0.000 description 7
- 125000002971 oxazolyl group Chemical group 0.000 description 7
- 125000004193 piperazinyl group Chemical group 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- ZADWXFSZEAPBJS-JTQLQIEISA-N 1-methyl-L-tryptophan Chemical compound C1=CC=C2N(C)C=C(C[C@H](N)C(O)=O)C2=C1 ZADWXFSZEAPBJS-JTQLQIEISA-N 0.000 description 6
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
- 239000004475 Arginine Substances 0.000 description 6
- 208000023275 Autoimmune disease Diseases 0.000 description 6
- 208000011231 Crohn disease Diseases 0.000 description 6
- 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 6
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 6
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 6
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 6
- 206010027476 Metastases Diseases 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 6
- 235000009697 arginine Nutrition 0.000 description 6
- 229960003121 arginine Drugs 0.000 description 6
- 206010003246 arthritis Diseases 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
- 230000002519 immonomodulatory effect Effects 0.000 description 6
- 230000004968 inflammatory condition Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000009401 metastasis Effects 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 230000004783 oxidative metabolism Effects 0.000 description 6
- 244000045947 parasite Species 0.000 description 6
- ZADWXFSZEAPBJS-UHFFFAOYSA-N racemic N-methyl tryptophan Natural products C1=CC=C2N(C)C=C(CC(N)C(O)=O)C2=C1 ZADWXFSZEAPBJS-UHFFFAOYSA-N 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 5
- 102000004452 Arginase Human genes 0.000 description 5
- 108700024123 Arginases Proteins 0.000 description 5
- JQJPBYFTQAANLE-UHFFFAOYSA-N Butyl nitrite Chemical compound CCCCON=O JQJPBYFTQAANLE-UHFFFAOYSA-N 0.000 description 5
- 201000004624 Dermatitis Diseases 0.000 description 5
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 206010060862 Prostate cancer Diseases 0.000 description 5
- 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- 230000033115 angiogenesis Effects 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 210000004443 dendritic cell Anatomy 0.000 description 5
- 229910052805 deuterium Inorganic materials 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 235000003642 hunger Nutrition 0.000 description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 210000001165 lymph node Anatomy 0.000 description 5
- 230000001926 lymphatic effect Effects 0.000 description 5
- 239000002207 metabolite Substances 0.000 description 5
- 229960005419 nitrogen Drugs 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 230000002285 radioactive effect Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 210000003289 regulatory T cell Anatomy 0.000 description 5
- 230000037351 starvation Effects 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- 230000014616 translation Effects 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 4
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 4
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 4
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 4
- 208000023328 Basedow disease Diseases 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 206010009900 Colitis ulcerative Diseases 0.000 description 4
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 4
- 208000015023 Graves' disease Diseases 0.000 description 4
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 4
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 101710150918 Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 4
- 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 4
- 208000008589 Obesity Diseases 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 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 4
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 4
- 206010052779 Transplant rejections Diseases 0.000 description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 description 4
- 208000024780 Urticaria Diseases 0.000 description 4
- 102000009520 Vascular Endothelial Growth Factor C Human genes 0.000 description 4
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 4
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 4
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 4
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 4
- 125000003828 azulenyl group Chemical group 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- USVZFSNDGFNNJT-UHFFFAOYSA-N cyclopenta-1,4-dien-1-yl(diphenyl)phosphane (2,3-dichlorocyclopenta-1,4-dien-1-yl)-diphenylphosphane iron(2+) Chemical compound [Fe++].c1cc[c-](c1)P(c1ccccc1)c1ccccc1.Clc1c(cc[c-]1Cl)P(c1ccccc1)c1ccccc1 USVZFSNDGFNNJT-UHFFFAOYSA-N 0.000 description 4
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 4
- 229940127089 cytotoxic agent Drugs 0.000 description 4
- BSHICDXRSZQYBP-UHFFFAOYSA-N dichloromethane;palladium(2+) Chemical compound [Pd+2].ClCCl BSHICDXRSZQYBP-UHFFFAOYSA-N 0.000 description 4
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 4
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 230000002489 hematologic effect Effects 0.000 description 4
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 230000004957 immunoregulator effect Effects 0.000 description 4
- 125000001041 indolyl group Chemical group 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 206010028417 myasthenia gravis Diseases 0.000 description 4
- 125000001624 naphthyl group Chemical group 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 235000020824 obesity Nutrition 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 125000003373 pyrazinyl group Chemical group 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 238000009097 single-agent therapy Methods 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 235000011150 stannous chloride Nutrition 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- FFGBVRZFYOUMHL-KGLIPLIRSA-N tert-butyl n-[(1s,3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentyl]carbamate Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3C[C@H](CC3)NC(=O)OC(C)(C)C)=NC=C2N=N1 FFGBVRZFYOUMHL-KGLIPLIRSA-N 0.000 description 4
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 4
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 4
- 230000014621 translational initiation Effects 0.000 description 4
- YJRMNPPUVLZEIJ-TYSVMGFPSA-N (1r,3r)-3-aminocyclopentane-1-carboxylic acid;hydrochloride Chemical compound Cl.N[C@@H]1CC[C@@H](C(O)=O)C1 YJRMNPPUVLZEIJ-TYSVMGFPSA-N 0.000 description 3
- OWXHQRMGSCEOAK-JQWIXIFHSA-N (1s,3s)-3-[[3-(4-iodophenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1[C@@H](O)CC[C@@H]1NC1=NC=C(N=NN2C=3C=CC(I)=CC=3)C2=N1 OWXHQRMGSCEOAK-JQWIXIFHSA-N 0.000 description 3
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 3
- AWBOCGIJEIQNOR-UHFFFAOYSA-N 3-[4-(5-chlorotriazolo[4,5-d]pyrimidin-3-yl)phenoxy]propanoic acid Chemical compound C1=CC(OCCC(=O)O)=CC=C1N1C2=NC(Cl)=NC=C2N=N1 AWBOCGIJEIQNOR-UHFFFAOYSA-N 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- PUSZHIWAFZLOMD-UHFFFAOYSA-N 4-amino-2-methylbutan-2-ol Chemical compound CC(C)(O)CCN PUSZHIWAFZLOMD-UHFFFAOYSA-N 0.000 description 3
- BGGUJNSJDQKNOF-UHFFFAOYSA-N 5-chloro-3-(4-iodophenyl)triazolo[4,5-d]pyrimidine Chemical compound C12=NC(Cl)=NC=C2N=NN1C1=CC=C(I)C=C1 BGGUJNSJDQKNOF-UHFFFAOYSA-N 0.000 description 3
- YVQHHMGGCPJIJY-UHFFFAOYSA-N 6-(5-chlorotriazolo[4,5-d]pyrimidin-3-yl)quinoline;hydrochloride Chemical compound Cl.N1=CC=CC2=CC(N3N=NC4=CN=C(N=C43)Cl)=CC=C21 YVQHHMGGCPJIJY-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 3
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 3
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 3
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 3
- 206010002198 Anaphylactic reaction Diseases 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 208000009137 Behcet syndrome Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- 101100072149 Drosophila melanogaster eIF2alpha gene Proteins 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 3
- 229930064664 L-arginine Natural products 0.000 description 3
- 235000014852 L-arginine Nutrition 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 3
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 3
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 3
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 3
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- 230000005867 T cell response Effects 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 3
- 230000001594 aberrant effect Effects 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 230000036783 anaphylactic response Effects 0.000 description 3
- 208000003455 anaphylaxis Diseases 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 230000004900 autophagic degradation Effects 0.000 description 3
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 3
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000002798 bone marrow cell Anatomy 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 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 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 239000002254 cytotoxic agent Substances 0.000 description 3
- 231100000599 cytotoxic agent Toxicity 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000003210 demyelinating effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 201000010064 diabetes insipidus Diseases 0.000 description 3
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 3
- 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 238000006911 enzymatic reaction Methods 0.000 description 3
- 229960001433 erlotinib Drugs 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 229940050410 gluconate Drugs 0.000 description 3
- 208000024908 graft versus host disease Diseases 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- ALBYIUDWACNRRB-UHFFFAOYSA-N hexanamide Chemical compound CCCCCC(N)=O ALBYIUDWACNRRB-UHFFFAOYSA-N 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 125000005945 imidazopyridyl group Chemical group 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 230000006058 immune tolerance Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 description 3
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 125000005956 isoquinolyl group Chemical group 0.000 description 3
- 229940043355 kinase inhibitor Drugs 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 3
- 229960004961 mechlorethamine Drugs 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 230000001400 myeloablative effect Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000006072 paste Substances 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000010837 poor prognosis Methods 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 238000003825 pressing Methods 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 125000000168 pyrrolyl group Chemical group 0.000 description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 3
- 125000005493 quinolyl group Chemical group 0.000 description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 229960004641 rituximab Drugs 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 235000015424 sodium Nutrition 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000003831 tetrazolyl group Chemical group 0.000 description 3
- 125000000335 thiazolyl group Chemical group 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 230000005748 tumor development Effects 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 210000004981 tumor-associated macrophage Anatomy 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- AGTPSAZJSOQXHJ-UHFFFAOYSA-N (1-methylpiperidin-4-yl)methanamine Chemical compound CN1CCC(CN)CC1 AGTPSAZJSOQXHJ-UHFFFAOYSA-N 0.000 description 2
- VDSOEFDPPHAJCG-MWLCHTKSSA-N (1r,3r)-3-[[3-(4-iodophenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(I)=CC=3)C2=N1 VDSOEFDPPHAJCG-MWLCHTKSSA-N 0.000 description 2
- YQQHQHRVSOLMNA-JQWIXIFHSA-N (1s,3s)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3C[C@@H](O)CC3)=NC=C2N=N1 YQQHQHRVSOLMNA-JQWIXIFHSA-N 0.000 description 2
- 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 2
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- DGHHQBMTXTWTJV-BQAIUKQQSA-N 119413-54-6 Chemical compound Cl.C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 DGHHQBMTXTWTJV-BQAIUKQQSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- IOJUJUOXKXMJNF-UHFFFAOYSA-N 2-acetyloxybenzoic acid [3-(nitrooxymethyl)phenyl] ester Chemical compound CC(=O)OC1=CC=CC=C1C(=O)OC1=CC=CC(CO[N+]([O-])=O)=C1 IOJUJUOXKXMJNF-UHFFFAOYSA-N 0.000 description 2
- YUKAEALOOLAOKA-UHFFFAOYSA-N 2-chloro-4-n-(2-methylquinolin-6-yl)pyrimidine-4,5-diamine Chemical compound C1=CC2=NC(C)=CC=C2C=C1NC1=NC(Cl)=NC=C1N YUKAEALOOLAOKA-UHFFFAOYSA-N 0.000 description 2
- QMIHUFXUPHEODZ-UHFFFAOYSA-N 2-chloro-4-n-(4-chloro-3-fluorophenyl)pyrimidine-4,5-diamine Chemical compound NC1=CN=C(Cl)N=C1NC1=CC=C(Cl)C(F)=C1 QMIHUFXUPHEODZ-UHFFFAOYSA-N 0.000 description 2
- YBLMUHNPFMWVSG-UHFFFAOYSA-N 2-chloro-4-n-(4-iodophenyl)pyrimidine-4,5-diamine Chemical compound NC1=CN=C(Cl)N=C1NC1=CC=C(I)C=C1 YBLMUHNPFMWVSG-UHFFFAOYSA-N 0.000 description 2
- LZGUDJSSUMTRGM-UHFFFAOYSA-N 2-chloro-4-n-(4-methoxyphenyl)pyrimidine-4,5-diamine Chemical compound C1=CC(OC)=CC=C1NC1=NC(Cl)=NC=C1N LZGUDJSSUMTRGM-UHFFFAOYSA-N 0.000 description 2
- SUEWBLOZSKHPES-UHFFFAOYSA-N 2-chloro-4-n-[4-(2-methoxyethoxy)phenyl]pyrimidine-4,5-diamine Chemical compound C1=CC(OCCOC)=CC=C1NC1=NC(Cl)=NC=C1N SUEWBLOZSKHPES-UHFFFAOYSA-N 0.000 description 2
- HXZIQEKSQZOCTO-UHFFFAOYSA-N 2-chloro-4-n-quinolin-6-ylpyrimidine-4,5-diamine Chemical compound NC1=CN=C(Cl)N=C1NC1=CC=C(N=CC=C2)C2=C1 HXZIQEKSQZOCTO-UHFFFAOYSA-N 0.000 description 2
- VIPUSSNQCKPXFD-UHFFFAOYSA-N 2-chloro-n-(4-chloro-3-fluorophenyl)-5-nitropyrimidin-4-amine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1NC1=CC=C(Cl)C(F)=C1 VIPUSSNQCKPXFD-UHFFFAOYSA-N 0.000 description 2
- JFXYBRAZAORBEH-UHFFFAOYSA-N 2-chloro-n-(4-iodophenyl)-5-nitropyrimidin-4-amine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1NC1=CC=C(I)C=C1 JFXYBRAZAORBEH-UHFFFAOYSA-N 0.000 description 2
- FSGFVKSATRQXSH-UHFFFAOYSA-N 2-chloro-n-(4-methoxyphenyl)-5-nitropyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1NC1=NC(Cl)=NC=C1[N+]([O-])=O FSGFVKSATRQXSH-UHFFFAOYSA-N 0.000 description 2
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 2
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 2
- UYGZSYIJRHILHY-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-methyltriazolo[4,5-d]pyrimidin-5-amine Chemical compound C12=NC(NC)=NC=C2N=NN1C1=CC=C(OC)C=C1 UYGZSYIJRHILHY-UHFFFAOYSA-N 0.000 description 2
- VBLRMUZBFMPPBP-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-piperidin-3-yltriazolo[4,5-d]pyrimidin-5-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1N1C2=NC(NC3CNCCC3)=NC=C2N=N1 VBLRMUZBFMPPBP-UHFFFAOYSA-N 0.000 description 2
- FBWASTPOKLRJDW-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-piperidin-4-yltriazolo[4,5-d]pyrimidin-5-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1N1C2=NC(NC3CCNCC3)=NC=C2N=N1 FBWASTPOKLRJDW-UHFFFAOYSA-N 0.000 description 2
- LDYYYRMQZJXQBN-UHFFFAOYSA-N 3-[4-[5-[3-(4-nitropyrazol-1-yl)propylamino]triazolo[4,5-d]pyrimidin-3-yl]phenoxy]propanoic acid Chemical compound C1=CC(OCCC(=O)O)=CC=C1N1C2=NC(NCCCN3N=CC(=C3)[N+]([O-])=O)=NC=C2N=N1 LDYYYRMQZJXQBN-UHFFFAOYSA-N 0.000 description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
- 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 2
- OYCSZJFCBXZCDD-UHFFFAOYSA-N 4-N-[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]cyclohexane-1,4-diamine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CCC(N)CC3)=NC=C2N=N1 OYCSZJFCBXZCDD-UHFFFAOYSA-N 0.000 description 2
- RLZRNKHHAZTIAI-UHFFFAOYSA-N 4-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]-1-methylpyrrolidin-2-one Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CC(=O)N(C)C3)=NC=C2N=N1 RLZRNKHHAZTIAI-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- PHRXNVPFDPSIHE-UHFFFAOYSA-N 4-n-(4-bromophenyl)-2-chloropyrimidine-4,5-diamine Chemical compound NC1=CN=C(Cl)N=C1NC1=CC=C(Br)C=C1 PHRXNVPFDPSIHE-UHFFFAOYSA-N 0.000 description 2
- AIZSOCIZJARQLW-UHFFFAOYSA-N 4-n-[3-(4-iodophenyl)triazolo[4,5-d]pyrimidin-5-yl]cyclohexane-1,4-diamine Chemical compound C1CC(N)CCC1NC1=NC=C(N=NN2C=3C=CC(I)=CC=3)C2=N1 AIZSOCIZJARQLW-UHFFFAOYSA-N 0.000 description 2
- QRYOGNCVJHIICD-UHFFFAOYSA-N 5-chloro-3-[4-(2-methoxyethoxy)phenyl]triazolo[4,5-d]pyrimidine Chemical compound C1=CC(OCCOC)=CC=C1N1C2=NC(Cl)=NC=C2N=N1 QRYOGNCVJHIICD-UHFFFAOYSA-N 0.000 description 2
- SZJNYDWDZMRJJG-UHFFFAOYSA-N 6-(5-chlorotriazolo[4,5-d]pyrimidin-3-yl)-2-methylquinoline Chemical compound N1=NC2=CN=C(Cl)N=C2N1C1=CC2=CC=C(C)N=C2C=C1 SZJNYDWDZMRJJG-UHFFFAOYSA-N 0.000 description 2
- 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 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 206010027654 Allergic conditions Diseases 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 2
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 2
- 102100030356 Arginase-2, mitochondrial Human genes 0.000 description 2
- 101710186578 Arginase-2, mitochondrial Proteins 0.000 description 2
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 230000007082 Aβ accumulation Effects 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- 208000027496 Behcet disease Diseases 0.000 description 2
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 2
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 2
- 206010048396 Bone marrow transplant rejection Diseases 0.000 description 2
- 108010037003 Buserelin Proteins 0.000 description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 102100029145 DNA damage-inducible transcript 3 protein Human genes 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 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 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 208000024869 Goodpasture syndrome Diseases 0.000 description 2
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 2
- 108010069236 Goserelin Proteins 0.000 description 2
- 201000005569 Gout Diseases 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000926525 Homo sapiens eIF-2-alpha kinase GCN2 Proteins 0.000 description 2
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 2
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 2
- 208000028622 Immune thrombocytopenia Diseases 0.000 description 2
- 206010062016 Immunosuppression Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 206010022489 Insulin Resistance Diseases 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 208000009388 Job Syndrome Diseases 0.000 description 2
- 208000007976 Ketosis Diseases 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 2
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 2
- 108010000817 Leuprolide Proteins 0.000 description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000007993 MOPS buffer Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 2
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 2
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 201000011152 Pemphigus Diseases 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 206010057190 Respiratory tract infections Diseases 0.000 description 2
- 208000007135 Retinal Neovascularization Diseases 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- 206010039710 Scleroderma Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108091008874 T cell receptors Proteins 0.000 description 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
- 239000012317 TBTU Substances 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 108010078233 Thymalfasin Proteins 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 108020004566 Transfer RNA Proteins 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 241001024096 Uleiota Species 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 206010047115 Vasculitis Diseases 0.000 description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 2
- 208000018254 acute transverse myelitis Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 208000002205 allergic conjunctivitis Diseases 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 2
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 2
- 229960001220 amsacrine Drugs 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229960002932 anastrozole Drugs 0.000 description 2
- 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 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000340 anti-metabolite Effects 0.000 description 2
- 230000001446 anti-myeloma Effects 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000005809 anti-tumor immunity Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 238000011394 anticancer treatment Methods 0.000 description 2
- 229940100197 antimetabolite Drugs 0.000 description 2
- 239000002256 antimetabolite Substances 0.000 description 2
- 229940034982 antineoplastic agent Drugs 0.000 description 2
- 239000003435 antirheumatic agent Substances 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003886 aromatase inhibitor Substances 0.000 description 2
- 229940046844 aromatase inhibitors Drugs 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 208000024998 atopic conjunctivitis Diseases 0.000 description 2
- 230000035578 autophosphorylation Effects 0.000 description 2
- 230000003376 axonal effect Effects 0.000 description 2
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 235000012216 bentonite Nutrition 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 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
- 229960000397 bevacizumab Drugs 0.000 description 2
- 229960000997 bicalutamide Drugs 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 229960001561 bleomycin Drugs 0.000 description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 238000010322 bone marrow transplantation Methods 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 206010006451 bronchitis Diseases 0.000 description 2
- CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 description 2
- 229960002719 buserelin Drugs 0.000 description 2
- 229960002092 busulfan Drugs 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229960004562 carboplatin Drugs 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000004709 cell invasion Effects 0.000 description 2
- 230000033077 cellular process Effects 0.000 description 2
- 230000004637 cellular stress Effects 0.000 description 2
- 229960005395 cetuximab Drugs 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229960004630 chlorambucil Drugs 0.000 description 2
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 2
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 2
- 229960002023 chloroprocaine Drugs 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 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 2
- 230000002950 deficient Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 150000004683 dihydrates Chemical class 0.000 description 2
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
- 239000013024 dilution buffer Substances 0.000 description 2
- 239000002988 disease modifying antirheumatic drug Substances 0.000 description 2
- 230000006806 disease prevention Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 2
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 102100034175 eIF-2-alpha kinase GCN2 Human genes 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 229960001904 epirubicin Drugs 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- 229960000255 exemestane Drugs 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 230000003176 fibrotic effect Effects 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000002875 fluorescence polarization Methods 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 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 2
- 229960002074 flutamide Drugs 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 229960002584 gefitinib Drugs 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 229960002913 goserelin Drugs 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 244000000013 helminth Species 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone 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
- 206010051040 hyper-IgE syndrome Diseases 0.000 description 2
- 229960000908 idarubicin Drugs 0.000 description 2
- 230000037451 immune surveillance Effects 0.000 description 2
- 239000000367 immunologic factor Substances 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000002050 international nonproprietary name Substances 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 229960004768 irinotecan Drugs 0.000 description 2
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 230000005445 isotope effect Effects 0.000 description 2
- 229960003648 ixazomib Drugs 0.000 description 2
- MXAYKZJJDUDWDS-LBPRGKRZSA-N ixazomib Chemical compound CC(C)C[C@@H](B(O)O)NC(=O)CNC(=O)C1=CC(Cl)=CC=C1Cl MXAYKZJJDUDWDS-LBPRGKRZSA-N 0.000 description 2
- YGPSJZOEDVAXAB-UHFFFAOYSA-N kynurenine Chemical compound OC(=O)C(N)CC(=O)C1=CC=CC=C1N YGPSJZOEDVAXAB-UHFFFAOYSA-N 0.000 description 2
- 210000002429 large intestine Anatomy 0.000 description 2
- 206010023841 laryngeal neoplasm Diseases 0.000 description 2
- 229960003881 letrozole Drugs 0.000 description 2
- 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 2
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 2
- 229960004338 leuprorelin Drugs 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 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 2
- 229960003194 meglumine Drugs 0.000 description 2
- 229960001924 melphalan Drugs 0.000 description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- YPFTWHSPSSDEFQ-UHFFFAOYSA-N methyl 3-[4-[(2-chloro-5-nitropyrimidin-4-yl)amino]phenoxy]propanoate Chemical compound C1=CC(OCCC(=O)OC)=CC=C1NC1=NC(Cl)=NC=C1[N+]([O-])=O YPFTWHSPSSDEFQ-UHFFFAOYSA-N 0.000 description 2
- USBBLKADPMJJOA-UHFFFAOYSA-N methyl 3-[4-[(5-amino-2-chloropyrimidin-4-yl)amino]phenoxy]propanoate Chemical compound C1=CC(OCCC(=O)OC)=CC=C1NC1=NC(Cl)=NC=C1N USBBLKADPMJJOA-UHFFFAOYSA-N 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 210000000066 myeloid cell Anatomy 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- KULOHCFSHXZRAM-UHFFFAOYSA-N n-(2-chloro-5-nitropyrimidin-4-yl)quinolin-6-amine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1NC1=CC=C(N=CC=C2)C2=C1 KULOHCFSHXZRAM-UHFFFAOYSA-N 0.000 description 2
- 230000001613 neoplastic effect Effects 0.000 description 2
- 230000000626 neurodegenerative effect Effects 0.000 description 2
- 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 2
- 229960002653 nilutamide Drugs 0.000 description 2
- 229950010203 nimotuzumab Drugs 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 229940049964 oleate Drugs 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 2
- 229950009057 oportuzumab monatox Drugs 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 229960005547 pelareorep Drugs 0.000 description 2
- 201000001976 pemphigus vulgaris Diseases 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 210000003800 pharynx Anatomy 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 210000005134 plasmacytoid dendritic cell Anatomy 0.000 description 2
- 229960003171 plicamycin Drugs 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 2
- 229960004919 procaine Drugs 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000006824 pyrimidine synthesis Effects 0.000 description 2
- 229950011613 racotumomab Drugs 0.000 description 2
- 229960004622 raloxifene Drugs 0.000 description 2
- 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 2
- 230000003938 response to stress Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 229950010265 tabalumab Drugs 0.000 description 2
- 229960001603 tamoxifen Drugs 0.000 description 2
- 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 2
- 229960001674 tegafur Drugs 0.000 description 2
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 2
- 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 2
- 229960001278 teniposide Drugs 0.000 description 2
- FFGBVRZFYOUMHL-UONOGXRCSA-N tert-butyl n-[(1r,3s)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentyl]carbamate Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3C[C@@H](CC3)NC(=O)OC(C)(C)C)=NC=C2N=N1 FFGBVRZFYOUMHL-UONOGXRCSA-N 0.000 description 2
- MODVSQKJJIBWPZ-VLLPJHQWSA-N tesetaxel Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3CC[C@@]2(C)[C@H]2[C@@H](C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C(=CC=CN=4)F)C[C@]1(O)C3(C)C)O[C@H](O2)CN(C)C)C(=O)C1=CC=CC=C1 MODVSQKJJIBWPZ-VLLPJHQWSA-N 0.000 description 2
- 229950009016 tesetaxel Drugs 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 2
- 229960004231 thymalfasin Drugs 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 2
- 229960000303 topotecan Drugs 0.000 description 2
- 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 2
- 229960005026 toremifene Drugs 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 208000009174 transverse myelitis Diseases 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- 108010075758 trebananib Proteins 0.000 description 2
- 229950001210 trebananib Drugs 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 229960000281 trometamol Drugs 0.000 description 2
- 230000001173 tumoral effect Effects 0.000 description 2
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 2
- 239000002691 unilamellar liposome Substances 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 229960003048 vinblastine Drugs 0.000 description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 2
- 229960004355 vindesine Drugs 0.000 description 2
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 2
- 229960002066 vinorelbine Drugs 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- IEQKEWXEYZAHQS-ZIAGYGMSSA-N (1R,3R)-3-[[3-(4-ethoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]-N-(2-hydroxyethyl)cyclopentane-1-carboxamide Chemical compound CCOc1ccc(cc1)-n1nnc2cnc(N[C@@H]3CC[C@H](C3)C(=O)NCCO)nc12 IEQKEWXEYZAHQS-ZIAGYGMSSA-N 0.000 description 1
- FZABKZWTTTZQTG-QZTJIDSGSA-N (1R,3R)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]-N-[2-(4-methylpiperazin-1-yl)ethyl]cyclopentane-1-carboxamide Chemical compound CN1CCN(CC1)CCNC(=O)[C@H]1C[C@@H](CC1)NC=1N=CC2=C(N1)N(N=N2)C2=CC=C(C=C2)OC FZABKZWTTTZQTG-QZTJIDSGSA-N 0.000 description 1
- QKUOSQSFLBBELL-TZMCWYRMSA-N (1R,3R)-3-[[3-[3-fluoro-4-[1-(2-hydroxyethyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound FC=1C=C(C=CC=1C=1C=NN(C=1)CCO)N1N=NC2=C1N=C(N=C2)N[C@H]1C[C@@H](CC1)C(=O)N QKUOSQSFLBBELL-TZMCWYRMSA-N 0.000 description 1
- XSUVGHQZKISALO-GXTWGEPZSA-N (1S,3R)-1-N-[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]-3-N,3-N-dimethylcyclopentane-1,3-diamine Chemical compound COC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@@H]1C[C@@H](CC1)N(C)C XSUVGHQZKISALO-GXTWGEPZSA-N 0.000 description 1
- VIVOBBCWKVKQFO-WPRPVWTQSA-N (1S,3S)-3-[[3-(2,1,3-benzothiadiazol-5-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound N1=C2C(=NS1)C=C(C=C2)N1N=NC2=C1N=C(N=C2)N[C@@H]1C[C@H](CC1)O VIVOBBCWKVKQFO-WPRPVWTQSA-N 0.000 description 1
- PZRFCKXEIUNZBY-JSGCOSHPSA-N (1S,3S)-3-[[3-(2-methylquinazolin-6-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound CC1=NC2=CC=C(C=C2C=N1)N1N=NC2=C1N=C(N=C2)N[C@@H]1C[C@H](CC1)O PZRFCKXEIUNZBY-JSGCOSHPSA-N 0.000 description 1
- LWDBMUAJGMXQAY-GSEQGPDBSA-L (1r,2r)-cyclohexane-1,2-diamine;platinum(2+);tetradecanoate;hydrate Chemical compound O.[Pt+2].N[C@@H]1CCCC[C@H]1N.CCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCC([O-])=O LWDBMUAJGMXQAY-GSEQGPDBSA-L 0.000 description 1
- CCYRXXWXGHGVFC-TZMCWYRMSA-N (1r,3r)-3-[(3-quinolin-6-yltriazolo[4,5-d]pyrimidin-5-yl)amino]cyclopentan-1-ol Chemical compound C1[C@H](O)CC[C@H]1NC1=NC=C(N=NN2C=3C=C4C=CC=NC4=CC=3)C2=N1 CCYRXXWXGHGVFC-TZMCWYRMSA-N 0.000 description 1
- ZSQVFOYWSGAYCC-CHWSQXEVSA-N (1r,3r)-3-[(3-quinolin-6-yltriazolo[4,5-d]pyrimidin-5-yl)amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=C4C=CC=NC4=CC=3)C2=N1 ZSQVFOYWSGAYCC-CHWSQXEVSA-N 0.000 description 1
- VRYMMJHVOVQTMW-VXGBXAGGSA-N (1r,3r)-3-[[3-(1,2-dimethylbenzimidazol-5-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C=1C=C2N(C)C(C)=NC2=CC=1N(C1=N2)N=NC1=CN=C2N[C@@H]1CC[C@@H](C(N)=O)C1 VRYMMJHVOVQTMW-VXGBXAGGSA-N 0.000 description 1
- BOFQVGMQYCUCCJ-GHMZBOCLSA-N (1r,3r)-3-[[3-(1,5-naphthyridin-2-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3N=C4C=CC=NC4=CC=3)C2=N1 BOFQVGMQYCUCCJ-GHMZBOCLSA-N 0.000 description 1
- AIIQNDFHRIUZRE-ZYHUDNBSSA-N (1r,3r)-3-[[3-(1-methylindazol-5-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C=1C=C2N(C)N=CC2=CC=1N(C1=N2)N=NC1=CN=C2N[C@@H]1CC[C@@H](C(N)=O)C1 AIIQNDFHRIUZRE-ZYHUDNBSSA-N 0.000 description 1
- PKGUWQBVAJEISG-RKDXNWHRSA-N (1r,3r)-3-[[3-(2,1,3-benzothiadiazol-5-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C3=CC4=NSN=C4C=C3)C2=N1 PKGUWQBVAJEISG-RKDXNWHRSA-N 0.000 description 1
- KQJINQDUFVERBQ-GHMZBOCLSA-N (1r,3r)-3-[[3-(2-methyl-1,3-benzothiazol-6-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=C2SC(C)=NC2=CC=C1N(C1=N2)N=NC1=CN=C2N[C@@H]1CC[C@@H](C(N)=O)C1 KQJINQDUFVERBQ-GHMZBOCLSA-N 0.000 description 1
- APLGILKUHFDNNZ-ZYHUDNBSSA-N (1r,3r)-3-[[3-(2-methylindazol-5-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC2=NN(C)C=C2C=C1N(C1=N2)N=NC1=CN=C2N[C@@H]1CC[C@@H](C(N)=O)C1 APLGILKUHFDNNZ-ZYHUDNBSSA-N 0.000 description 1
- SCYVFSQFVUWTQQ-ZYHUDNBSSA-N (1r,3r)-3-[[3-(2-methylindazol-6-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C=1C2=NN(C)C=C2C=CC=1N(C1=N2)N=NC1=CN=C2N[C@@H]1CC[C@@H](C(N)=O)C1 SCYVFSQFVUWTQQ-ZYHUDNBSSA-N 0.000 description 1
- TWZJHITZUXGVHU-UKRRQHHQSA-N (1r,3r)-3-[[3-(2-methylquinolin-6-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=CC2=NC(C)=CC=C2C=C1N(C1=N2)N=NC1=CN=C2N[C@@H]1CC[C@@H](O)C1 TWZJHITZUXGVHU-UKRRQHHQSA-N 0.000 description 1
- GJSXPCWXRIJCQD-ZIAGYGMSSA-N (1r,3r)-3-[[3-(2-methylquinolin-6-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC2=NC(C)=CC=C2C=C1N(C1=N2)N=NC1=CN=C2N[C@@H]1CC[C@@H](C(N)=O)C1 GJSXPCWXRIJCQD-ZIAGYGMSSA-N 0.000 description 1
- FLJISZPKRPZTDB-RKDXNWHRSA-N (1r,3r)-3-[[3-(3,5-difluoro-4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=C(F)C(OC)=C(F)C=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(N)=O)=NC=C2N=N1 FLJISZPKRPZTDB-RKDXNWHRSA-N 0.000 description 1
- YUYZDFGBECVFFJ-CHWSQXEVSA-N (1r,3r)-3-[[3-(3-fluoro-4-morpholin-4-ylphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=C(F)C(N4CCOCC4)=CC=3)C2=N1 YUYZDFGBECVFFJ-CHWSQXEVSA-N 0.000 description 1
- HHNGVLXSCQXAAA-MWLCHTKSSA-N (1r,3r)-3-[[3-(3-iodophenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=C(I)C=CC=3)C2=N1 HHNGVLXSCQXAAA-MWLCHTKSSA-N 0.000 description 1
- FBUMNNJVFNLFCQ-HZPDHXFCSA-N (1r,3r)-3-[[3-(4-ethoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]-n-(2-hydroxy-2-methylpropyl)-n-methylcyclopentane-1-carboxamide Chemical compound C1=CC(OCC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(=O)N(C)CC(C)(C)O)=NC=C2N=N1 FBUMNNJVFNLFCQ-HZPDHXFCSA-N 0.000 description 1
- NBMPSIDBGGMQJT-HUUCEWRRSA-N (1r,3r)-3-[[3-(4-ethoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]-n-(2-methoxyethyl)cyclopentane-1-carboxamide Chemical compound C1=CC(OCC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(=O)NCCOC)=NC=C2N=N1 NBMPSIDBGGMQJT-HUUCEWRRSA-N 0.000 description 1
- RRWCKNKKIYGDJL-RTBURBONSA-N (1r,3r)-3-[[3-(4-ethoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]-n-[(1-methylpiperidin-4-yl)methyl]cyclopentane-1-carboxamide Chemical compound C1=CC(OCC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(=O)NCC3CCN(C)CC3)=NC=C2N=N1 RRWCKNKKIYGDJL-RTBURBONSA-N 0.000 description 1
- UYBSHANAGLSBFG-VXGBXAGGSA-N (1r,3r)-3-[[3-(4-ethoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carbohydrazide Chemical compound C1=CC(OCC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(=O)NN)=NC=C2N=N1 UYBSHANAGLSBFG-VXGBXAGGSA-N 0.000 description 1
- QYDZNYFGFJVHQW-VXGBXAGGSA-N (1r,3r)-3-[[3-(4-ethoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC(OCC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(N)=O)=NC=C2N=N1 QYDZNYFGFJVHQW-VXGBXAGGSA-N 0.000 description 1
- IPKVBVIURNWSCI-VXGBXAGGSA-N (1r,3r)-3-[[3-(4-ethoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxylic acid Chemical compound C1=CC(OCC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(O)=O)=NC=C2N=N1 IPKVBVIURNWSCI-VXGBXAGGSA-N 0.000 description 1
- GTWXWSVGCLCNNZ-NXEZZACHSA-N (1r,3r)-3-[[3-(4-hydroxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(O)=CC=3)C2=N1 GTWXWSVGCLCNNZ-NXEZZACHSA-N 0.000 description 1
- OWXHQRMGSCEOAK-ZYHUDNBSSA-N (1r,3r)-3-[[3-(4-iodophenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1[C@H](O)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(I)=CC=3)C2=N1 OWXHQRMGSCEOAK-ZYHUDNBSSA-N 0.000 description 1
- UZEJMPNHSQUKGT-CHWSQXEVSA-N (1r,3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]-n,n-dimethylcyclopentane-1-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(=O)N(C)C)=NC=C2N=N1 UZEJMPNHSQUKGT-CHWSQXEVSA-N 0.000 description 1
- BRGXTOUXZSUTRO-DGCLKSJQSA-N (1r,3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclohexan-1-ol Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3C[C@H](O)CCC3)=NC=C2N=N1 BRGXTOUXZSUTRO-DGCLKSJQSA-N 0.000 description 1
- LUQKQDNVJZFMFR-GHMZBOCLSA-N (1r,3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(N)=O)=NC=C2N=N1 LUQKQDNVJZFMFR-GHMZBOCLSA-N 0.000 description 1
- WONHEPJXOZITSV-GHMZBOCLSA-N (1r,3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxylic acid Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(O)=O)=NC=C2N=N1 WONHEPJXOZITSV-GHMZBOCLSA-N 0.000 description 1
- GABMIDSNANRLGV-GHMZBOCLSA-N (1r,3r)-3-[[3-(4-methylsulfonylphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(N)=O)=NC=C2N=N1 GABMIDSNANRLGV-GHMZBOCLSA-N 0.000 description 1
- DISRXXHLPGWGRL-CHWSQXEVSA-N (1r,3r)-3-[[3-(4-propan-2-yloxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC(OC(C)C)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(N)=O)=NC=C2N=N1 DISRXXHLPGWGRL-CHWSQXEVSA-N 0.000 description 1
- NKQLNYWAEMSQOL-VXGBXAGGSA-N (1r,3r)-3-[[3-[3-fluoro-4-(3-oxomorpholin-4-yl)phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=C(F)C(N4C(COCC4)=O)=CC=3)C2=N1 NKQLNYWAEMSQOL-VXGBXAGGSA-N 0.000 description 1
- VYWQBPZHCIWLFV-GDBMZVCRSA-N (1r,3r)-3-[[3-[3-fluoro-4-[1-(2-methoxyethyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=NN(CCOC)C=C1C1=CC=C(N2C3=NC(N[C@H]4C[C@H](O)CC4)=NC=C3N=N2)C=C1F VYWQBPZHCIWLFV-GDBMZVCRSA-N 0.000 description 1
- HNMWYXZFSXSZCR-UKRRQHHQSA-N (1r,3r)-3-[[3-[3-fluoro-4-[1-(2-methoxyethyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=NN(CCOC)C=C1C1=CC=C(N2C3=NC(N[C@H]4C[C@@H](CC4)C(N)=O)=NC=C3N=N2)C=C1F HNMWYXZFSXSZCR-UKRRQHHQSA-N 0.000 description 1
- YFIFIYWQWQEHOR-ZIAGYGMSSA-N (1r,3r)-3-[[3-[4-(1,3-dimethoxypropan-2-yloxy)phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC(OC(COC)COC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(N)=O)=NC=C2N=N1 YFIFIYWQWQEHOR-ZIAGYGMSSA-N 0.000 description 1
- ISGKBZMTKIREIH-ZIAGYGMSSA-N (1r,3r)-3-[[3-[4-(2-ethoxyethoxy)phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC(OCCOCC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(N)=O)=NC=C2N=N1 ISGKBZMTKIREIH-ZIAGYGMSSA-N 0.000 description 1
- ORKJUCNFVQXKNL-CHWSQXEVSA-N (1r,3r)-3-[[3-[4-(2-hydroxy-2-methylpropoxy)phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC(OCC(C)(O)C)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(N)=O)=NC=C2N=N1 ORKJUCNFVQXKNL-CHWSQXEVSA-N 0.000 description 1
- CEVUMEAPESDIDZ-DGCLKSJQSA-N (1r,3r)-3-[[3-[4-(2-hydroxyethoxy)phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=CC(OCCO)=CC=C1N1C2=NC(N[C@H]3C[C@H](O)CC3)=NC=C2N=N1 CEVUMEAPESDIDZ-DGCLKSJQSA-N 0.000 description 1
- PLJZQYQEBYPMID-VXGBXAGGSA-N (1r,3r)-3-[[3-[4-(2-hydroxyethoxy)phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(OCCO)=CC=3)C2=N1 PLJZQYQEBYPMID-VXGBXAGGSA-N 0.000 description 1
- ZOWOMAOCWFSQLO-CHWSQXEVSA-N (1r,3r)-3-[[3-[4-(2-methoxyethoxy)phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC(OCCOC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(N)=O)=NC=C2N=N1 ZOWOMAOCWFSQLO-CHWSQXEVSA-N 0.000 description 1
- IYTOTZJWSGPUCY-HZPDHXFCSA-N (1r,3r)-3-[[3-[4-(2-morpholin-4-ylethoxy)phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(OCCN4CCOCC4)=CC=3)C2=N1 IYTOTZJWSGPUCY-HZPDHXFCSA-N 0.000 description 1
- PNKKDXFVEPNMBM-ZIAGYGMSSA-N (1r,3r)-3-[[3-[4-(4-hydroxy-2-methylbutan-2-yl)oxyphenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC(OC(C)(CCO)C)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(N)=O)=NC=C2N=N1 PNKKDXFVEPNMBM-ZIAGYGMSSA-N 0.000 description 1
- WRYLPEGCXQSVOS-ZIAGYGMSSA-N (1r,3r)-3-[[3-[4-(oxan-4-yloxy)phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(OC4CCOCC4)=CC=3)C2=N1 WRYLPEGCXQSVOS-ZIAGYGMSSA-N 0.000 description 1
- WBICBOALRUKNMA-NVXWUHKLSA-N (1r,3r)-3-[[3-[4-[1-(2-cyanoethyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(=CC=3)C3=CN(CCC#N)N=C3)C2=N1 WBICBOALRUKNMA-NVXWUHKLSA-N 0.000 description 1
- BJKNKZXOWIUXPU-GDBMZVCRSA-N (1r,3r)-3-[[3-[4-[1-(2-ethoxyethyl)pyrazol-4-yl]-3-fluorophenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=NN(CCOCC)C=C1C1=CC=C(N2C3=NC(N[C@H]4C[C@@H](CC4)C(N)=O)=NC=C3N=N2)C=C1F BJKNKZXOWIUXPU-GDBMZVCRSA-N 0.000 description 1
- MYTALLJNAHFZKC-SJLPKXTDSA-N (1r,3r)-3-[[3-[4-[1-(2-ethoxyethyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=NN(CCOCC)C=C1C1=CC=C(N2C3=NC(N[C@H]4C[C@@H](CC4)C(N)=O)=NC=C3N=N2)C=C1 MYTALLJNAHFZKC-SJLPKXTDSA-N 0.000 description 1
- VEIBUJVHNKDFGM-SJLPKXTDSA-N (1r,3r)-3-[[3-[4-[1-(2-hydroxy-2-methylpropyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=NN(CC(C)(O)C)C=C1C1=CC=C(N2C3=NC(N[C@H]4C[C@H](O)CC4)=NC=C3N=N2)C=C1 VEIBUJVHNKDFGM-SJLPKXTDSA-N 0.000 description 1
- IPDPLFBNSFRVNP-NVXWUHKLSA-N (1r,3r)-3-[[3-[4-[1-(2-hydroxy-2-methylpropyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=NN(CC(C)(O)C)C=C1C1=CC=C(N2C3=NC(N[C@H]4C[C@@H](CC4)C(N)=O)=NC=C3N=N2)C=C1 IPDPLFBNSFRVNP-NVXWUHKLSA-N 0.000 description 1
- SKEGVAQSSKAXHS-NVXWUHKLSA-N (1r,3r)-3-[[3-[4-[1-(2-hydroxyethyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=NN(CCO)C=C1C1=CC=C(N2C3=NC(N[C@H]4C[C@H](O)CC4)=NC=C3N=N2)C=C1 SKEGVAQSSKAXHS-NVXWUHKLSA-N 0.000 description 1
- WQZPBIAEOTXSBY-GDBMZVCRSA-N (1r,3r)-3-[[3-[4-[1-(2-hydroxyethyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(=CC=3)C3=CN(CCO)N=C3)C2=N1 WQZPBIAEOTXSBY-GDBMZVCRSA-N 0.000 description 1
- HIWIDKBMFQBGER-NVXWUHKLSA-N (1r,3r)-3-[[3-[4-[1-(2-methoxyethyl)pyrazol-4-yl]-3-methylphenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=NN(CCOC)C=C1C1=CC=C(N2C3=NC(N[C@H]4C[C@@H](CC4)C(N)=O)=NC=C3N=N2)C=C1C HIWIDKBMFQBGER-NVXWUHKLSA-N 0.000 description 1
- MAIMLFIFUIMCEE-TZIWHRDSSA-N (1r,3r)-3-[[3-[4-[1-(2-pyrrolidin-1-ylethyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1[C@H](O)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(=CC=3)C3=CN(CCN4CCCC4)N=C3)C2=N1 MAIMLFIFUIMCEE-TZIWHRDSSA-N 0.000 description 1
- GTBRLSHAONXJBJ-TZIWHRDSSA-N (1r,3r)-3-[[3-[4-[1-(pyridin-3-ylmethyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1[C@H](O)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(=CC=3)C3=CN(CC=4C=NC=CC=4)N=C3)C2=N1 GTBRLSHAONXJBJ-TZIWHRDSSA-N 0.000 description 1
- FBBNLKBRAWKQRQ-SJLPKXTDSA-N (1r,3r)-3-[[3-[4-[1-[2-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl]pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound O1C(C)=NC(CCN2N=CC(=C2)C=2C=CC(=CC=2)N2C3=NC(N[C@H]4C[C@@H](CC4)C(N)=O)=NC=C3N=N2)=N1 FBBNLKBRAWKQRQ-SJLPKXTDSA-N 0.000 description 1
- OVUPBCCWNNTNEE-IEBWSBKVSA-N (1r,3r)-3-[[3-[4-[1-[2-(6-oxopyridazin-1-yl)ethyl]pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(=CC=3)C3=CN(CCN4C(C=CC=N4)=O)N=C3)C2=N1 OVUPBCCWNNTNEE-IEBWSBKVSA-N 0.000 description 1
- MKACSSNRGRDLEN-GHMZBOCLSA-N (1r,3r)-3-[[3-[4-[3,3,3-trifluoro-2-hydroxy-2-(trifluoromethyl)propoxy]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(OCC(O)(C(F)(F)F)C(F)(F)F)=CC=3)C2=N1 MKACSSNRGRDLEN-GHMZBOCLSA-N 0.000 description 1
- BWPBGAJJMHZMMG-CZUORRHYSA-N (1r,3r)-3-[[3-[5-[1-(2-cyanoethyl)pyrazol-4-yl]pyridin-2-yl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3N=CC(=CC=3)C3=CN(CCC#N)N=C3)C2=N1 BWPBGAJJMHZMMG-CZUORRHYSA-N 0.000 description 1
- OWOAIFASEGFKRP-RHSMWYFYSA-N (1r,3r)-3-[[3-[5-[1-(2-ethoxyethyl)pyrazol-4-yl]pyridin-2-yl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=NN(CCOCC)C=C1C1=CC=C(N2C3=NC(N[C@H]4C[C@@H](CC4)C(N)=O)=NC=C3N=N2)N=C1 OWOAIFASEGFKRP-RHSMWYFYSA-N 0.000 description 1
- OPSLRHLTGWFLSI-IUODEOHRSA-N (1r,3r)-3-[[3-[5-[1-(2-hydroxyethyl)pyrazol-4-yl]pyridin-2-yl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3N=CC(=CC=3)C3=CN(CCO)N=C3)C2=N1 OPSLRHLTGWFLSI-IUODEOHRSA-N 0.000 description 1
- QXERAONEEXHENO-CZUORRHYSA-N (1r,3r)-3-[[3-[5-[1-(2-methoxyethyl)pyrazol-4-yl]pyridin-2-yl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=NN(CCOC)C=C1C1=CC=C(N2C3=NC(N[C@H]4C[C@@H](CC4)C(N)=O)=NC=C3N=N2)N=C1 QXERAONEEXHENO-CZUORRHYSA-N 0.000 description 1
- RSQNEGMNSMOGTN-GDBMZVCRSA-N (1r,3r)-3-[[3-[6-[1-(2-ethoxyethyl)pyrazol-4-yl]pyridin-3-yl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=NN(CCOCC)C=C1C1=CC=C(N2C3=NC(N[C@H]4C[C@@H](CC4)C(N)=O)=NC=C3N=N2)C=N1 RSQNEGMNSMOGTN-GDBMZVCRSA-N 0.000 description 1
- AAFYTTMIPNUSDS-UKRRQHHQSA-N (1r,3r)-3-[[3-[6-[1-(2-methoxyethyl)pyrazol-4-yl]pyridin-3-yl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=NN(CCOC)C=C1C1=CC=C(N2C3=NC(N[C@H]4C[C@@H](CC4)C(N)=O)=NC=C3N=N2)C=N1 AAFYTTMIPNUSDS-UKRRQHHQSA-N 0.000 description 1
- KBVPLFXBRCUGOZ-ZIAGYGMSSA-N (1r,3r)-3-n-[3-(2-methylquinolin-6-yl)triazolo[4,5-d]pyrimidin-5-yl]cyclopentane-1,3-diamine Chemical compound C1=CC2=NC(C)=CC=C2C=C1N(C1=N2)N=NC1=CN=C2N[C@@H]1CC[C@@H](N)C1 KBVPLFXBRCUGOZ-ZIAGYGMSSA-N 0.000 description 1
- OSHLPUOBFBCDRP-GHMZBOCLSA-N (1r,3r)-3-n-[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]cyclopentane-1,3-diamine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3C[C@H](N)CC3)=NC=C2N=N1 OSHLPUOBFBCDRP-GHMZBOCLSA-N 0.000 description 1
- ICMSTQJSDUUQNM-ZIAGYGMSSA-N (1r,3r)-n'-acetyl-3-[[3-(4-ethoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carbohydrazide Chemical compound C1=CC(OCC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(=O)NNC(C)=O)=NC=C2N=N1 ICMSTQJSDUUQNM-ZIAGYGMSSA-N 0.000 description 1
- WONHEPJXOZITSV-MNOVXSKESA-N (1r,3s)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxylic acid Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3C[C@@H](CC3)C(O)=O)=NC=C2N=N1 WONHEPJXOZITSV-MNOVXSKESA-N 0.000 description 1
- OSHLPUOBFBCDRP-MNOVXSKESA-N (1r,3s)-3-n-[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]cyclopentane-1,3-diamine Chemical class C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3C[C@H](N)CC3)=NC=C2N=N1 OSHLPUOBFBCDRP-MNOVXSKESA-N 0.000 description 1
- LKDAZUGBNJDGMN-DHXVBOOMSA-N (1r,3s)-3-n-[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]cyclopentane-1,3-diamine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3C[C@H](N)CC3)=NC=C2N=N1 LKDAZUGBNJDGMN-DHXVBOOMSA-N 0.000 description 1
- NMUHPZACIDPMCM-NWDGAFQWSA-N (1r,4s)-4-[[3-(4-ethoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopent-2-ene-1-carboxamide Chemical class C1=CC(OCC)=CC=C1N1C2=NC(N[C@@H]3C=C[C@@H](C3)C(N)=O)=NC=C2N=N1 NMUHPZACIDPMCM-NWDGAFQWSA-N 0.000 description 1
- AAFJXZWCNVJTMK-GUCUJZIJSA-N (1s,2r)-1-[(2s)-oxiran-2-yl]-2-[(2r)-oxiran-2-yl]ethane-1,2-diol Chemical compound C([C@@H]1[C@H](O)[C@H](O)[C@H]2OC2)O1 AAFJXZWCNVJTMK-GUCUJZIJSA-N 0.000 description 1
- ZSQVFOYWSGAYCC-QWHCGFSZSA-N (1s,3r)-3-[(3-quinolin-6-yltriazolo[4,5-d]pyrimidin-5-yl)amino]cyclopentane-1-carboxamide Chemical compound C1[C@@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=C4C=CC=NC4=CC=3)C2=N1 ZSQVFOYWSGAYCC-QWHCGFSZSA-N 0.000 description 1
- MFJBMLJBZFGGPN-QWHCGFSZSA-N (1s,3r)-3-[(3-quinolin-6-yltriazolo[4,5-d]pyrimidin-5-yl)amino]cyclopentane-1-carboxylic acid Chemical compound C1[C@@H](C(=O)O)CC[C@H]1NC1=NC=C(N=NN2C=3C=C4C=CC=NC4=CC=3)C2=N1 MFJBMLJBZFGGPN-QWHCGFSZSA-N 0.000 description 1
- PKGUWQBVAJEISG-DTWKUNHWSA-N (1s,3r)-3-[[3-(2,1,3-benzothiadiazol-5-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C3=CC4=NSN=C4C=C3)C2=N1 PKGUWQBVAJEISG-DTWKUNHWSA-N 0.000 description 1
- RRENWXNOYKWRMA-WDEREUQCSA-N (1s,3r)-3-[[3-(2-methyl-1,3-benzoxazol-6-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=C2OC(C)=NC2=CC=C1N(C1=N2)N=NC1=CN=C2N[C@@H]1CC[C@H](C(N)=O)C1 RRENWXNOYKWRMA-WDEREUQCSA-N 0.000 description 1
- QYDZNYFGFJVHQW-NWDGAFQWSA-N (1s,3r)-3-[[3-(4-ethoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC(OCC)=CC=C1N1C2=NC(N[C@H]3C[C@H](CC3)C(N)=O)=NC=C2N=N1 QYDZNYFGFJVHQW-NWDGAFQWSA-N 0.000 description 1
- VDSOEFDPPHAJCG-GXSJLCMTSA-N (1s,3r)-3-[[3-(4-iodophenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(I)=CC=3)C2=N1 VDSOEFDPPHAJCG-GXSJLCMTSA-N 0.000 description 1
- ZMYKSTDYLXSONW-GXSJLCMTSA-N (1s,3r)-3-[[3-(4-iodophenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxylic acid Chemical compound C1[C@@H](C(=O)O)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(I)=CC=3)C2=N1 ZMYKSTDYLXSONW-GXSJLCMTSA-N 0.000 description 1
- LUQKQDNVJZFMFR-WDEREUQCSA-N (1s,3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3C[C@H](CC3)C(N)=O)=NC=C2N=N1 LUQKQDNVJZFMFR-WDEREUQCSA-N 0.000 description 1
- WONHEPJXOZITSV-WDEREUQCSA-N (1s,3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxylic acid Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3C[C@H](CC3)C(O)=O)=NC=C2N=N1 WONHEPJXOZITSV-WDEREUQCSA-N 0.000 description 1
- ZOWOMAOCWFSQLO-QWHCGFSZSA-N (1s,3r)-3-[[3-[4-(2-methoxyethoxy)phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC(OCCOC)=CC=C1N1C2=NC(N[C@H]3C[C@H](CC3)C(N)=O)=NC=C2N=N1 ZOWOMAOCWFSQLO-QWHCGFSZSA-N 0.000 description 1
- JJZDBVXJDWFQAY-AZUAARDMSA-N (1s,3r)-3-[[3-[4-[1-(2-pyrrolidin-1-ylethyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1[C@@H](C(=O)N)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(=CC=3)C3=CN(CCN4CCCC4)N=C3)C2=N1 JJZDBVXJDWFQAY-AZUAARDMSA-N 0.000 description 1
- YNMCKTYWLZCBHU-QWHCGFSZSA-N (1s,3r)-3-n-(3-quinolin-6-yltriazolo[4,5-d]pyrimidin-5-yl)cyclopentane-1,3-diamine Chemical compound C1[C@@H](N)CC[C@H]1NC1=NC=C(N=NN2C=3C=C4C=CC=NC4=CC=3)C2=N1 YNMCKTYWLZCBHU-QWHCGFSZSA-N 0.000 description 1
- LKDAZUGBNJDGMN-VZXYPILPSA-N (1s,3r)-3-n-[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]cyclopentane-1,3-diamine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](N)CC3)=NC=C2N=N1 LKDAZUGBNJDGMN-VZXYPILPSA-N 0.000 description 1
- CCYRXXWXGHGVFC-JSGCOSHPSA-N (1s,3s)-3-[(3-quinolin-6-yltriazolo[4,5-d]pyrimidin-5-yl)amino]cyclopentan-1-ol Chemical compound C1[C@@H](O)CC[C@@H]1NC1=NC=C(N=NN2C=3C=C4C=CC=NC4=CC=3)C2=N1 CCYRXXWXGHGVFC-JSGCOSHPSA-N 0.000 description 1
- ZYYCDZNULJXWHK-JQWIXIFHSA-N (1s,3s)-3-[[3-(2-methyl-1,3-benzoxazol-6-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=C2OC(C)=NC2=CC=C1N(C1=N2)N=NC1=CN=C2N[C@H]1CC[C@H](O)C1 ZYYCDZNULJXWHK-JQWIXIFHSA-N 0.000 description 1
- ONZRTNQCSLZWOU-GJZGRUSLSA-N (1s,3s)-3-[[3-(2-methylquinolin-6-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclohexane-1-carboxamide Chemical compound C1=CC2=NC(C)=CC=C2C=C1N(C1=N2)N=NC1=CN=C2N[C@H]1CCC[C@H](C(N)=O)C1 ONZRTNQCSLZWOU-GJZGRUSLSA-N 0.000 description 1
- TWZJHITZUXGVHU-ZFWWWQNUSA-N (1s,3s)-3-[[3-(2-methylquinolin-6-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=CC2=NC(C)=CC=C2C=C1N(C1=N2)N=NC1=CN=C2N[C@H]1CC[C@H](O)C1 TWZJHITZUXGVHU-ZFWWWQNUSA-N 0.000 description 1
- KBDZERDEGZYXSP-JQWIXIFHSA-N (1s,3s)-3-[[3-(4-bromophenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1[C@@H](O)CC[C@@H]1NC1=NC=C(N=NN2C=3C=CC(Br)=CC=3)C2=N1 KBDZERDEGZYXSP-JQWIXIFHSA-N 0.000 description 1
- AXUTYHBUQMIGKE-AAEUAGOBSA-N (1s,3s)-3-[[3-(4-ethoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=CC(OCC)=CC=C1N1C2=NC(N[C@@H]3C[C@@H](O)CC3)=NC=C2N=N1 AXUTYHBUQMIGKE-AAEUAGOBSA-N 0.000 description 1
- PRPHHKUFBZSADY-RYUDHWBXSA-N (1s,3s)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclohexane-1-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3C[C@H](CCC3)C(N)=O)=NC=C2N=N1 PRPHHKUFBZSADY-RYUDHWBXSA-N 0.000 description 1
- LUQKQDNVJZFMFR-QWRGUYRKSA-N (1s,3s)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3C[C@H](CC3)C(N)=O)=NC=C2N=N1 LUQKQDNVJZFMFR-QWRGUYRKSA-N 0.000 description 1
- PCLVEEYLLDXNTJ-GWCFXTLKSA-N (1s,3s)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-sulfonamide Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3C[C@H](CC3)S(N)(=O)=O)=NC=C2N=N1 PCLVEEYLLDXNTJ-GWCFXTLKSA-N 0.000 description 1
- KHMQFTSPQSOVKF-JSGCOSHPSA-N (1s,3s)-3-[[3-(4-propan-2-yloxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=CC(OC(C)C)=CC=C1N1C2=NC(N[C@@H]3C[C@@H](O)CC3)=NC=C2N=N1 KHMQFTSPQSOVKF-JSGCOSHPSA-N 0.000 description 1
- AOODTDKNJQOTHW-BBRMVZONSA-N (1s,3s)-3-[[3-(4-pyrrolidin-1-ylphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1[C@@H](O)CC[C@@H]1NC1=NC=C(N=NN2C=3C=CC(=CC=3)N3CCCC3)C2=N1 AOODTDKNJQOTHW-BBRMVZONSA-N 0.000 description 1
- LEEXEUHIWCHJEN-UWVGGRQHSA-N (1s,3s)-3-[[3-(5-methoxypyridin-2-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound N1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3C[C@@H](O)CC3)=NC=C2N=N1 LEEXEUHIWCHJEN-UWVGGRQHSA-N 0.000 description 1
- SFJZNHAKYPNBSW-JQWIXIFHSA-N (1s,3s)-3-[[3-(6-ethoxypyridin-3-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=NC(OCC)=CC=C1N1C2=NC(N[C@@H]3C[C@@H](O)CC3)=NC=C2N=N1 SFJZNHAKYPNBSW-JQWIXIFHSA-N 0.000 description 1
- GGLNTTWBMIHSSP-HOCLYGCPSA-N (1s,3s)-3-[[3-[4-(1-methylpyrazol-4-yl)phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=NN(C)C=C1C1=CC=C(N2C3=NC(N[C@@H]4C[C@@H](O)CC4)=NC=C3N=N2)C=C1 GGLNTTWBMIHSSP-HOCLYGCPSA-N 0.000 description 1
- GGPWMHCVDCYCCF-JSGCOSHPSA-N (1s,3s)-3-[[3-[4-(2-hydroxypropan-2-yl)phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=CC(C(C)(O)C)=CC=C1N1C2=NC(N[C@@H]3C[C@@H](O)CC3)=NC=C2N=N1 GGPWMHCVDCYCCF-JSGCOSHPSA-N 0.000 description 1
- QNYMZIUEOJSPJA-NBLXOJGSSA-N (1s,3s)-3-[[3-[4-[1-(2-hydroxyethyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol;hydrochloride Chemical compound Cl.C1=NN(CCO)C=C1C1=CC=C(N2C3=NC(N[C@@H]4C[C@@H](O)CC4)=NC=C3N=N2)C=C1 QNYMZIUEOJSPJA-NBLXOJGSSA-N 0.000 description 1
- YGHVVMUZOXRVCJ-RDJZCZTQSA-N (1s,3s)-3-[[3-[4-[1-[2-(2h-tetrazol-5-yl)ethyl]pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1[C@@H](O)CC[C@@H]1NC1=NC=C(N=NN2C=3C=CC(=CC=3)C3=CN(CCC4=NNN=N4)N=C3)C2=N1 YGHVVMUZOXRVCJ-RDJZCZTQSA-N 0.000 description 1
- DXRNIPFLMVCLEF-HOCLYGCPSA-N (1s,3s)-3-[[3-[6-[1-(2-methoxyethyl)pyrazol-4-yl]pyridin-3-yl]triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentan-1-ol Chemical compound C1=NN(CCOC)C=C1C1=CC=C(N2C3=NC(N[C@@H]4C[C@@H](O)CC4)=NC=C3N=N2)C=N1 DXRNIPFLMVCLEF-HOCLYGCPSA-N 0.000 description 1
- SGKRJNWIEGYWGE-FHAQVOQBSA-N (1s,3s)-3-aminocyclopentan-1-ol;hydrochloride Chemical compound Cl.N[C@H]1CC[C@H](O)C1 SGKRJNWIEGYWGE-FHAQVOQBSA-N 0.000 description 1
- LKDAZUGBNJDGMN-ACMTZBLWSA-N (1s,3s)-3-n-[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]cyclopentane-1,3-diamine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3C[C@@H](N)CC3)=NC=C2N=N1 LKDAZUGBNJDGMN-ACMTZBLWSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical class O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- UUBHZHZSIKRVIV-KCXSXWJSSA-N (2e,6e,10e)-3,7,11,15-tetramethylhexadeca-2,4,6,10,14-pentaenoic acid Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\C=C\C(\C)=C\C(O)=O UUBHZHZSIKRVIV-KCXSXWJSSA-N 0.000 description 1
- RGHNJXZEOKUKBD-NRXMZTRTSA-N (2r,3r,4r,5s)-2,3,4,5,6-pentahydroxyhexanoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-NRXMZTRTSA-N 0.000 description 1
- UDQCRUSSQAXPJY-VIFPVBQESA-N (2s)-2-amino-3-(1h-indol-3-yl)propan-1-ol Chemical compound C1=CC=C2C(C[C@@H](CO)N)=CNC2=C1 UDQCRUSSQAXPJY-VIFPVBQESA-N 0.000 description 1
- CRYXXTXWUCPIMU-WNQIDUERSA-N (2s)-2-aminobutanediamide;phenol Chemical compound OC1=CC=CC=C1.NC(=O)[C@@H](N)CC(N)=O CRYXXTXWUCPIMU-WNQIDUERSA-N 0.000 description 1
- PSVUJBVBCOISSP-SPFKKGSWSA-N (2s,3r,4s,5s,6r)-2-bis(2-chloroethylamino)phosphoryloxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OC[C@H]1O[C@@H](OP(=O)(NCCCl)NCCCl)[C@H](O)[C@@H](O)[C@@H]1O PSVUJBVBCOISSP-SPFKKGSWSA-N 0.000 description 1
- HRCXZUUGWKFJDX-LLVKDONJSA-N (3r)-1-[4-(5-chlorotriazolo[4,5-d]pyrimidin-3-yl)phenyl]pyrrolidin-3-ol Chemical compound C1[C@H](O)CCN1C1=CC=C(N2C3=NC(Cl)=NC=C3N=N2)C=C1 HRCXZUUGWKFJDX-LLVKDONJSA-N 0.000 description 1
- ZINPRYHKXVEOOU-SNVBAGLBSA-N (3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]pyrrolidine-1-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3CN(CC3)C(N)=O)=NC=C2N=N1 ZINPRYHKXVEOOU-SNVBAGLBSA-N 0.000 description 1
- OLPTZDHSJZJABS-SNVBAGLBSA-N (3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]pyrrolidine-1-sulfonamide Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3CN(CC3)S(N)(=O)=O)=NC=C2N=N1 OLPTZDHSJZJABS-SNVBAGLBSA-N 0.000 description 1
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 1
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 1
- NZMICYAXDXTDJV-UHFFFAOYSA-N 1-(2-methoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound C1=NN(CCOC)C=C1B1OC(C)(C)C(C)(C)O1 NZMICYAXDXTDJV-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- JCGLATYXMMEIEE-VFRRUGBOSA-N 1-[(1R,3R)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentyl]ethanol Chemical compound COC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@H]2C[C@@H](CC2)C(C)O JCGLATYXMMEIEE-VFRRUGBOSA-N 0.000 description 1
- JCGLATYXMMEIEE-LWNNLKQOSA-N 1-[(1S,3R)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentyl]ethanol Chemical compound COC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@H]2C[C@H](CC2)C(C)O JCGLATYXMMEIEE-LWNNLKQOSA-N 0.000 description 1
- JCGLATYXMMEIEE-SPOOISQMSA-N 1-[(1S,3S)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentyl]ethanol Chemical compound COC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@@H]2C[C@H](CC2)C(C)O JCGLATYXMMEIEE-SPOOISQMSA-N 0.000 description 1
- VQKHGWQLZGCVCA-CQSZACIVSA-N 1-[(3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]pyrrolidin-1-yl]-2-pyrazol-1-ylethanone Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3CN(CC3)C(=O)CN3N=CC=C3)=NC=C2N=N1 VQKHGWQLZGCVCA-CQSZACIVSA-N 0.000 description 1
- JAYSHSSLPROHDG-QGZVFWFLSA-N 1-[(3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]pyrrolidin-1-yl]-3-(4-methylpiperazin-1-yl)propan-1-one Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3CN(CC3)C(=O)CCN3CCN(C)CC3)=NC=C2N=N1 JAYSHSSLPROHDG-QGZVFWFLSA-N 0.000 description 1
- VQKHGWQLZGCVCA-AWEZNQCLSA-N 1-[(3s)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]pyrrolidin-1-yl]-2-pyrazol-1-ylethanone Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3CN(CC3)C(=O)CN3N=CC=C3)=NC=C2N=N1 VQKHGWQLZGCVCA-AWEZNQCLSA-N 0.000 description 1
- PVCULFYROUOVGJ-UHFFFAOYSA-N 1-[2-chloroethyl(methylsulfonyl)amino]-3-methyl-1-methylsulfonylurea Chemical compound CNC(=O)N(S(C)(=O)=O)N(S(C)(=O)=O)CCCl PVCULFYROUOVGJ-UHFFFAOYSA-N 0.000 description 1
- ARPAAPWDHKOMEZ-UHFFFAOYSA-N 1-[3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]piperidin-1-yl]ethanone Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CN(CCC3)C(C)=O)=NC=C2N=N1 ARPAAPWDHKOMEZ-UHFFFAOYSA-N 0.000 description 1
- RGXRDCBVVYZSJU-UHFFFAOYSA-N 1-[4-(5-chlorotriazolo[4,5-d]pyrimidin-3-yl)phenyl]pyrrolidin-2-one Chemical compound C12=NC(Cl)=NC=C2N=NN1C(C=C1)=CC=C1N1CCCC1=O RGXRDCBVVYZSJU-UHFFFAOYSA-N 0.000 description 1
- DNDXERLSWJXEHG-UHFFFAOYSA-N 1-[4-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclohexyl]ethanol Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CCC(CC3)C(C)O)=NC=C2N=N1 DNDXERLSWJXEHG-UHFFFAOYSA-N 0.000 description 1
- ZTEHOZMYMCEYRM-UHFFFAOYSA-N 1-chlorodecane Chemical compound CCCCCCCCCCCl ZTEHOZMYMCEYRM-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- UGCRHVPUHAXAAE-UHFFFAOYSA-N 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound C1=NN(CC)C=C1B1OC(C)(C)C(C)(C)O1 UGCRHVPUHAXAAE-UHFFFAOYSA-N 0.000 description 1
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-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
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- 125000005808 2,4,6-trimethoxyphenyl group Chemical group [H][#6]-1=[#6](-[#8]C([H])([H])[H])-[#6](-*)=[#6](-[#8]C([H])([H])[H])-[#6]([H])=[#6]-1-[#8]C([H])([H])[H] 0.000 description 1
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
- FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 description 1
- YJGBYESQJRDQJA-UHFFFAOYSA-N 2-(3,4-difluorophenyl)-2-[[3-(6-methoxypyridin-3-yl)triazolo[4,5-d]pyrimidin-5-yl]amino]ethanol Chemical compound C1=NC(OC)=CC=C1N1C2=NC(NC(CO)C=3C=C(F)C(F)=CC=3)=NC=C2N=N1 YJGBYESQJRDQJA-UHFFFAOYSA-N 0.000 description 1
- GOWUDHPKGOIDIX-UHFFFAOYSA-N 2-(4-methyl-1-piperazinyl)ethanamine Chemical compound CN1CCN(CCN)CC1 GOWUDHPKGOIDIX-UHFFFAOYSA-N 0.000 description 1
- NSONNEOVVBVJBJ-BTQNPOSSSA-N 2-(dimethylamino)-1-[(3R)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]pyrrolidin-1-yl]ethanone formic acid Chemical compound C(=O)O.CN(CC(=O)N1C[C@@H](CC1)NC=1N=CC2=C(N1)N(N=N2)C2=CC=C(C=C2)OC)C NSONNEOVVBVJBJ-BTQNPOSSSA-N 0.000 description 1
- NSONNEOVVBVJBJ-ZOWNYOTGSA-N 2-(dimethylamino)-1-[(3S)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]pyrrolidin-1-yl]ethanone formic acid Chemical compound C(=O)O.CN(CC(=O)N1C[C@H](CC1)NC=1N=CC2=C(N1)N(N=N2)C2=CC=C(C=C2)OC)C NSONNEOVVBVJBJ-ZOWNYOTGSA-N 0.000 description 1
- NKDSJBAJCYHUEM-UHFFFAOYSA-N 2-(dimethylamino)-1-[3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]azetidin-1-yl]ethanone Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CN(C3)C(=O)CN(C)C)=NC=C2N=N1 NKDSJBAJCYHUEM-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- PIMQWRZWLQKKBJ-SFHVURJKSA-N 2-[(2S)-1-[3-ethyl-7-[(1-oxido-3-pyridin-1-iumyl)methylamino]-5-pyrazolo[1,5-a]pyrimidinyl]-2-piperidinyl]ethanol Chemical compound C=1C(N2[C@@H](CCCC2)CCO)=NC2=C(CC)C=NN2C=1NCC1=CC=C[N+]([O-])=C1 PIMQWRZWLQKKBJ-SFHVURJKSA-N 0.000 description 1
- VVGIMRQUUKNNNM-UYAOXDASSA-N 2-[2-[4-[4-[5-[[(1r,3r)-3-hydroxycyclopentyl]amino]triazolo[4,5-d]pyrimidin-3-yl]phenyl]pyrazol-1-yl]ethyl]pyridazin-3-one Chemical compound C1[C@H](O)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(=CC=3)C3=CN(CCN4C(C=CC=N4)=O)N=C3)C2=N1 VVGIMRQUUKNNNM-UYAOXDASSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- RZHKDBRREKOZEW-AAXZNHDCSA-N 2-[4-[2-[[(2r)-1-[[(4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-4-[[(2r,3r)-1,3-dihydroxybutan-2-yl]carbamoyl]-7-[(1r)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl] Chemical compound C([C@H](C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)NC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1)C1=CC=CC=C1 RZHKDBRREKOZEW-AAXZNHDCSA-N 0.000 description 1
- BLRBFUBMKTZJBO-JKSUJKDBSA-N 2-[4-[4-[5-[[(1r,3s)-3-aminocyclopentyl]amino]triazolo[4,5-d]pyrimidin-3-yl]phenyl]pyrazol-1-yl]ethanol Chemical compound C1[C@@H](N)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(=CC=3)C3=CN(CCO)N=C3)C2=N1 BLRBFUBMKTZJBO-JKSUJKDBSA-N 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- ICDNTZMMFNEWLH-UHFFFAOYSA-N 2-chloro-n-[4-(2-methoxyethoxy)phenyl]-5-nitropyrimidin-4-amine Chemical compound C1=CC(OCCOC)=CC=C1NC1=NC(Cl)=NC=C1[N+]([O-])=O ICDNTZMMFNEWLH-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- NJRXVEJTAYWCQJ-UHFFFAOYSA-L 2-mercaptosuccinate Chemical compound OC(=O)CC([S-])C([O-])=O NJRXVEJTAYWCQJ-UHFFFAOYSA-L 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- OPJKGTJXHVPYIM-UHFFFAOYSA-N 2-methylprop-2-enamide;phenol Chemical compound CC(=C)C(N)=O.OC1=CC=CC=C1 OPJKGTJXHVPYIM-UHFFFAOYSA-N 0.000 description 1
- TYJFYUVDUUACKX-UHFFFAOYSA-N 2-methylquinolin-6-amine Chemical compound C1=C(N)C=CC2=NC(C)=CC=C21 TYJFYUVDUUACKX-UHFFFAOYSA-N 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
- VJCQEPWQSBKWTE-UHFFFAOYSA-N 2h-triazolo[4,5-d]pyrimidin-5-amine Chemical compound N1=C(N)N=CC2=NNN=C21 VJCQEPWQSBKWTE-UHFFFAOYSA-N 0.000 description 1
- YGIDFSRTHSYXJC-UHFFFAOYSA-N 3,3-dimethyl-6-[5-[(5-methylpyrazin-2-yl)methylamino]triazolo[4,5-d]pyrimidin-3-yl]-1h-indol-2-one Chemical compound C1=NC(C)=CN=C1CNC1=NC=C(N=NN2C=3C=C4C(C(C(=O)N4)(C)C)=CC=3)C2=N1 YGIDFSRTHSYXJC-UHFFFAOYSA-N 0.000 description 1
- 125000004362 3,4,5-trichlorophenyl group Chemical group [H]C1=C(Cl)C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 1
- XFYGMOICKGCNFA-CYBMUJFWSA-N 3-(2-methylquinolin-6-yl)-n-[(3r)-pyrrolidin-3-yl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC2=NC(C)=CC=C2C=C1N(C1=N2)N=NC1=CN=C2N[C@@H]1CCNC1 XFYGMOICKGCNFA-CYBMUJFWSA-N 0.000 description 1
- JZZNGNCYHILCCO-UHFFFAOYSA-N 3-(4-bromophenyl)-5-chlorotriazolo[4,5-d]pyrimidine Chemical compound C12=NC(Cl)=NC=C2N=NN1C1=CC=C(Br)C=C1 JZZNGNCYHILCCO-UHFFFAOYSA-N 0.000 description 1
- HXIZYAUSZRLGSW-UHFFFAOYSA-N 3-(4-ethoxyphenyl)-n-[2-(1h-pyrazol-4-yl)ethyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OCC)=CC=C1N1C2=NC(NCCC3=CNN=C3)=NC=C2N=N1 HXIZYAUSZRLGSW-UHFFFAOYSA-N 0.000 description 1
- PUBJONQMYZVHCU-UHFFFAOYSA-N 3-(4-ethoxyphenyl)-n-prop-2-ynyltriazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OCC)=CC=C1N1C2=NC(NCC#C)=NC=C2N=N1 PUBJONQMYZVHCU-UHFFFAOYSA-N 0.000 description 1
- ZZUBHVMHNVYXRR-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-2h-chromen-7-ol Chemical compound C1=CC(O)=CC=C1C1=CC2=CC=C(O)C=C2OC1 ZZUBHVMHNVYXRR-UHFFFAOYSA-N 0.000 description 1
- XZTHEJJAJVNHMX-UHFFFAOYSA-N 3-(4-methoxyphenyl)-N-(2-phenylethyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound COc1ccc(cc1)-n1nnc2cnc(NCCc3ccccc3)nc12 XZTHEJJAJVNHMX-UHFFFAOYSA-N 0.000 description 1
- VMKMYWAETCOKSI-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CC(C)(C)N(C)C(C)(C)C3)=NC=C2N=N1 VMKMYWAETCOKSI-UHFFFAOYSA-N 0.000 description 1
- VMAUOMLINRWGKC-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-(1-methylpiperidin-4-yl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CCN(C)CC3)=NC=C2N=N1 VMAUOMLINRWGKC-UHFFFAOYSA-N 0.000 description 1
- MZNVYVPMOSVCJU-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-(1-propylcyclopropyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound N=1C=C2N=NN(C=3C=CC(OC)=CC=3)C2=NC=1NC1(CCC)CC1 MZNVYVPMOSVCJU-UHFFFAOYSA-N 0.000 description 1
- XECKOTPPPGFCIS-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-(2,2,6,6-tetramethylpiperidin-4-yl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CC(C)(C)NC(C)(C)C3)=NC=C2N=N1 XECKOTPPPGFCIS-UHFFFAOYSA-N 0.000 description 1
- BNAWCACJJOIYGZ-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-(3-methyl-3-azabicyclo[3.1.0]hexan-6-yl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3C4CN(C)CC43)=NC=C2N=N1 BNAWCACJJOIYGZ-UHFFFAOYSA-N 0.000 description 1
- QJSQXIAHAJGIPS-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-(3-pyrrolidin-1-ylpropyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NCCCN3CCCC3)=NC=C2N=N1 QJSQXIAHAJGIPS-UHFFFAOYSA-N 0.000 description 1
- AAOOIQFRMFZBNI-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-(4,5,6,7-tetrahydro-1h-indazol-5-yl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CC=4C=NNC=4CC3)=NC=C2N=N1 AAOOIQFRMFZBNI-UHFFFAOYSA-N 0.000 description 1
- NEJMTHLAUUJREI-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-(oxan-4-yl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CCOCC3)=NC=C2N=N1 NEJMTHLAUUJREI-UHFFFAOYSA-N 0.000 description 1
- WFURDRSNUCDJDU-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-(oxetan-3-yl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3COC3)=NC=C2N=N1 WFURDRSNUCDJDU-UHFFFAOYSA-N 0.000 description 1
- QTXQBRLCTGPBSQ-FZMZJTMJSA-N 3-(4-methoxyphenyl)-n-[(1s,3s)-3-methylsulfanylcyclopentyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3C[C@H](CC3)SC)=NC=C2N=N1 QTXQBRLCTGPBSQ-FZMZJTMJSA-N 0.000 description 1
- GDSSVNNRCKMPPZ-CQSZACIVSA-N 3-(4-methoxyphenyl)-n-[(3r)-1-pyridin-4-ylpyrrolidin-3-yl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3CN(CC3)C=3C=CN=CC=3)=NC=C2N=N1 GDSSVNNRCKMPPZ-CQSZACIVSA-N 0.000 description 1
- AXCPKGPXISAMHI-SNVBAGLBSA-N 3-(4-methoxyphenyl)-n-[(3r)-oxolan-3-yl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3COCC3)=NC=C2N=N1 AXCPKGPXISAMHI-SNVBAGLBSA-N 0.000 description 1
- VJCWAPMVJMBBAC-HNCPQSOCSA-N 3-(4-methoxyphenyl)-n-[(3r)-pyrrolidin-3-yl]triazolo[4,5-d]pyrimidin-5-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3CNCC3)=NC=C2N=N1 VJCWAPMVJMBBAC-HNCPQSOCSA-N 0.000 description 1
- GDSSVNNRCKMPPZ-AWEZNQCLSA-N 3-(4-methoxyphenyl)-n-[(3s)-1-pyridin-4-ylpyrrolidin-3-yl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3CN(CC3)C=3C=CN=CC=3)=NC=C2N=N1 GDSSVNNRCKMPPZ-AWEZNQCLSA-N 0.000 description 1
- AXCPKGPXISAMHI-JTQLQIEISA-N 3-(4-methoxyphenyl)-n-[(3s)-oxolan-3-yl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3COCC3)=NC=C2N=N1 AXCPKGPXISAMHI-JTQLQIEISA-N 0.000 description 1
- VJCWAPMVJMBBAC-PPHPATTJSA-N 3-(4-methoxyphenyl)-n-[(3s)-pyrrolidin-3-yl]triazolo[4,5-d]pyrimidin-5-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3CNCC3)=NC=C2N=N1 VJCWAPMVJMBBAC-PPHPATTJSA-N 0.000 description 1
- CEKGIDDRNXOVTG-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-[1-(2-morpholin-4-ylethyl)piperidin-4-yl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CCN(CCN4CCOCC4)CC3)=NC=C2N=N1 CEKGIDDRNXOVTG-UHFFFAOYSA-N 0.000 description 1
- KMXJYKMHXASJGQ-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-[1-(2-pyrrolidin-1-ylethyl)piperidin-4-yl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CCN(CCN4CCCC4)CC3)=NC=C2N=N1 KMXJYKMHXASJGQ-UHFFFAOYSA-N 0.000 description 1
- BFZTZRBYPKWJHB-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-[3-(4-methylpiperazin-1-yl)propyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NCCCN3CCN(C)CC3)=NC=C2N=N1 BFZTZRBYPKWJHB-UHFFFAOYSA-N 0.000 description 1
- DMIUUIPJBKZJKU-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-propan-2-yltriazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC(C)C)=NC=C2N=N1 DMIUUIPJBKZJKU-UHFFFAOYSA-N 0.000 description 1
- BYVXDLVDVAHPOO-LJQANCHMSA-N 3-(4-methylpiperazin-1-yl)-1-[(3r)-3-[(3-quinolin-6-yltriazolo[4,5-d]pyrimidin-5-yl)amino]pyrrolidin-1-yl]propan-1-one Chemical compound C1CN(C)CCN1CCC(=O)N1C[C@H](NC=2N=C3N(C=4C=C5C=CC=NC5=CC=4)N=NC3=CN=2)CC1 BYVXDLVDVAHPOO-LJQANCHMSA-N 0.000 description 1
- UQXSOBJDIHLPQV-UHFFFAOYSA-N 3-(4-nitropyrazol-1-yl)propan-1-amine;dihydrochloride Chemical compound Cl.Cl.NCCCN1C=C([N+]([O-])=O)C=N1 UQXSOBJDIHLPQV-UHFFFAOYSA-N 0.000 description 1
- PLXXXZBHSBQGSW-UQKRIMTDSA-N 3-(dimethylamino)-1-[(3S)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]pyrrolidin-1-yl]propan-1-one formic acid Chemical compound C(=O)O.CN(CCC(=O)N1C[C@H](CC1)NC=1N=CC2=C(N1)N(N=N2)C2=CC=C(C=C2)OC)C PLXXXZBHSBQGSW-UQKRIMTDSA-N 0.000 description 1
- PLXXXZBHSBQGSW-PFEQFJNWSA-N 3-(dimethylamino)-1-[(3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]pyrrolidin-1-yl]propan-1-one;formic acid Chemical compound OC=O.C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3CN(CC3)C(=O)CCN(C)C)=NC=C2N=N1 PLXXXZBHSBQGSW-PFEQFJNWSA-N 0.000 description 1
- QSFQNANTKCQQBS-UHFFFAOYSA-N 3-(dimethylamino)-1-[3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]azetidin-1-yl]propan-1-one Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CN(C3)C(=O)CCN(C)C)=NC=C2N=N1 QSFQNANTKCQQBS-UHFFFAOYSA-N 0.000 description 1
- VSEVMCJYIOAQAI-UHFFFAOYSA-N 3-(dimethylamino)-1-[4-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]piperidin-1-yl]propan-1-one Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CCN(CC3)C(=O)CCN(C)C)=NC=C2N=N1 VSEVMCJYIOAQAI-UHFFFAOYSA-N 0.000 description 1
- XPAKVERFSWPGKO-UHFFFAOYSA-N 3-(ethyliminomethylideneamino)-1-n',1-n'-dimethylpropane-1,1-diamine Chemical compound CCN=C=NCCC(N)N(C)C XPAKVERFSWPGKO-UHFFFAOYSA-N 0.000 description 1
- DDZYWFHVXMCJJQ-WDEREUQCSA-N 3-[(1s,3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentyl]-2h-1,2,4-oxadiazol-5-one Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3C[C@H](CC3)C=3NOC(=O)N=3)=NC=C2N=N1 DDZYWFHVXMCJJQ-WDEREUQCSA-N 0.000 description 1
- UZFPOOOQHWICKY-UHFFFAOYSA-N 3-[13-[1-[1-[8,12-bis(2-carboxyethyl)-17-(1-hydroxyethyl)-3,7,13,18-tetramethyl-21,24-dihydroporphyrin-2-yl]ethoxy]ethyl]-18-(2-carboxyethyl)-8-(1-hydroxyethyl)-3,7,12,17-tetramethyl-22,23-dihydroporphyrin-2-yl]propanoic acid Chemical compound N1C(C=C2C(=C(CCC(O)=O)C(C=C3C(=C(C)C(C=C4N5)=N3)CCC(O)=O)=N2)C)=C(C)C(C(C)O)=C1C=C5C(C)=C4C(C)OC(C)C1=C(N2)C=C(N3)C(C)=C(C(O)C)C3=CC(C(C)=C3CCC(O)=O)=NC3=CC(C(CCC(O)=O)=C3C)=NC3=CC2=C1C UZFPOOOQHWICKY-UHFFFAOYSA-N 0.000 description 1
- INPKEPKXESXZDD-CQSZACIVSA-N 3-[4-(1-methylpyrazol-4-yl)phenyl]-n-[(3r)-pyrrolidin-3-yl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=NN(C)C=C1C1=CC=C(N2C3=NC(N[C@H]4CNCC4)=NC=C3N=N2)C=C1 INPKEPKXESXZDD-CQSZACIVSA-N 0.000 description 1
- BGKPYKHVUKPFGO-UHFFFAOYSA-N 3-[4-(2-methoxyethoxy)phenyl]-n-(3-pyridin-2-ylpropyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OCCOC)=CC=C1N1C2=NC(NCCCC=3N=CC=CC=3)=NC=C2N=N1 BGKPYKHVUKPFGO-UHFFFAOYSA-N 0.000 description 1
- YHJJRTONRITFJY-UHFFFAOYSA-N 3-[4-(2-methoxyethoxy)phenyl]-n-[(1-methylpyrazol-4-yl)methyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OCCOC)=CC=C1N1C2=NC(NCC3=CN(C)N=C3)=NC=C2N=N1 YHJJRTONRITFJY-UHFFFAOYSA-N 0.000 description 1
- HHJNLYRGKVQGOQ-RDJZCZTQSA-N 3-[4-[4-[5-[[(1s,3s)-3-hydroxycyclopentyl]amino]triazolo[4,5-d]pyrimidin-3-yl]phenyl]pyrazol-1-yl]propanamide Chemical compound C1=NN(CCC(=O)N)C=C1C1=CC=C(N2C3=NC(N[C@@H]4C[C@@H](O)CC4)=NC=C3N=N2)C=C1 HHJNLYRGKVQGOQ-RDJZCZTQSA-N 0.000 description 1
- PUVARLLUFGSYJQ-WMZOPIPTSA-N 3-[4-[4-[5-[[(1s,3s)-3-hydroxycyclopentyl]amino]triazolo[4,5-d]pyrimidin-3-yl]phenyl]pyrazol-1-yl]propanenitrile Chemical compound C1[C@@H](O)CC[C@@H]1NC1=NC=C(N=NN2C=3C=CC(=CC=3)C3=CN(CCC#N)N=C3)C2=N1 PUVARLLUFGSYJQ-WMZOPIPTSA-N 0.000 description 1
- XKRYXQMIGSXJAV-UHFFFAOYSA-N 3-[4-[5-[3-(4-aminopyrazol-1-yl)propylamino]triazolo[4,5-d]pyrimidin-3-yl]phenoxy]propanoic acid Chemical compound C1=C(N)C=NN1CCCNC1=NC=C(N=NN2C=3C=CC(OCCC(O)=O)=CC=3)C2=N1 XKRYXQMIGSXJAV-UHFFFAOYSA-N 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
- DIOBEQCFVVJJBU-UHFFFAOYSA-N 4-(2-methoxyethoxy)aniline Chemical compound COCCOC1=CC=C(N)C=C1 DIOBEQCFVVJJBU-UHFFFAOYSA-N 0.000 description 1
- CLPFFLWZZBQMAO-UHFFFAOYSA-N 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1N2C=NC=C2CCC1 CLPFFLWZZBQMAO-UHFFFAOYSA-N 0.000 description 1
- AKJHMTWEGVYYSE-AIRMAKDCSA-N 4-HPR Chemical compound C=1C=C(O)C=CC=1NC(=O)/C=C(\C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C AKJHMTWEGVYYSE-AIRMAKDCSA-N 0.000 description 1
- XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 description 1
- RAJDJIBBSFYUPZ-UHFFFAOYSA-N 4-[4-(5-chlorotriazolo[4,5-d]pyrimidin-3-yl)phenyl]morpholine Chemical compound C12=NC(Cl)=NC=C2N=NN1C(C=C1)=CC=C1N1CCOCC1 RAJDJIBBSFYUPZ-UHFFFAOYSA-N 0.000 description 1
- JDUQEHFYOAZGKI-UHFFFAOYSA-N 4-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclohexane-1-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CCC(CC3)C(N)=O)=NC=C2N=N1 JDUQEHFYOAZGKI-UHFFFAOYSA-N 0.000 description 1
- QSNWUPMBIWMAKZ-UHFFFAOYSA-N 4-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]piperidin-2-one Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CC(=O)NCC3)=NC=C2N=N1 QSNWUPMBIWMAKZ-UHFFFAOYSA-N 0.000 description 1
- ZLHFILGSQDJULK-UHFFFAOYSA-N 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(NC=2N=C3C4=CC=C(Cl)C=C4C(=NCC3=CN=2)C=2C(=CC=CC=2F)OC)=C1 ZLHFILGSQDJULK-UHFFFAOYSA-N 0.000 description 1
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 1
- ACMJJQYSPUPMPN-UHFFFAOYSA-N 4-chloro-3-fluoroaniline Chemical compound NC1=CC=C(Cl)C(F)=C1 ACMJJQYSPUPMPN-UHFFFAOYSA-N 0.000 description 1
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-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
- MDOJTZQKHMAPBK-UHFFFAOYSA-N 4-iodo-3-nitrobenzamide Chemical compound NC(=O)C1=CC=C(I)C([N+]([O-])=O)=C1 MDOJTZQKHMAPBK-UHFFFAOYSA-N 0.000 description 1
- VLVCDUSVTXIWGW-UHFFFAOYSA-N 4-iodoaniline Chemical compound NC1=CC=C(I)C=C1 VLVCDUSVTXIWGW-UHFFFAOYSA-N 0.000 description 1
- WEDLCLBIHFWCMA-UHFFFAOYSA-N 4-n-(3-quinolin-6-yltriazolo[4,5-d]pyrimidin-5-yl)cyclohexane-1,4-diamine Chemical compound C1CC(N)CCC1NC1=NC=C(N=NN2C=3C=C4C=CC=NC4=CC=3)C2=N1 WEDLCLBIHFWCMA-UHFFFAOYSA-N 0.000 description 1
- HYCBFVMSUQZGDG-UHFFFAOYSA-N 4-n-[3-(4-morpholin-4-ylphenyl)triazolo[4,5-d]pyrimidin-5-yl]cyclohexane-1,4-diamine Chemical compound C1CC(N)CCC1NC1=NC=C(N=NN2C=3C=CC(=CC=3)N3CCOCC3)C2=N1 HYCBFVMSUQZGDG-UHFFFAOYSA-N 0.000 description 1
- UYAKJECHZRZIRE-UHFFFAOYSA-N 4-n-[3-[4-[1-(2-methoxyethyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]cyclohexane-1,4-diamine Chemical compound C1=NN(CCOC)C=C1C1=CC=C(N2C3=NC(NC4CCC(N)CC4)=NC=C3N=N2)C=C1 UYAKJECHZRZIRE-UHFFFAOYSA-N 0.000 description 1
- DGBYXYBJVXLJKE-UHFFFAOYSA-N 4-n-[3-[4-[1-(2-pyrazol-1-ylethyl)pyrazol-4-yl]phenyl]triazolo[4,5-d]pyrimidin-5-yl]cyclohexane-1,4-diamine Chemical compound C1CC(N)CCC1NC1=NC=C(N=NN2C=3C=CC(=CC=3)C3=CN(CCN4N=CC=C4)N=C3)C2=N1 DGBYXYBJVXLJKE-UHFFFAOYSA-N 0.000 description 1
- IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 description 1
- UPALIKSFLSVKIS-UHFFFAOYSA-N 5-amino-2-[2-(dimethylamino)ethyl]benzo[de]isoquinoline-1,3-dione Chemical compound NC1=CC(C(N(CCN(C)C)C2=O)=O)=C3C2=CC=CC3=C1 UPALIKSFLSVKIS-UHFFFAOYSA-N 0.000 description 1
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 description 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
- XEFCOQITPUOVCQ-UHFFFAOYSA-N 5-chloro-3-(4-chloro-3-fluorophenyl)triazolo[4,5-d]pyrimidine Chemical compound C1=C(Cl)C(F)=CC(N2C3=NC(Cl)=NC=C3N=N2)=C1 XEFCOQITPUOVCQ-UHFFFAOYSA-N 0.000 description 1
- PEXXCTFDZVJAAY-UHFFFAOYSA-N 5-chloro-3-(4-ethoxyphenyl)triazolo[4,5-d]pyrimidine Chemical compound C1=CC(OCC)=CC=C1N1C2=NC(Cl)=NC=C2N=N1 PEXXCTFDZVJAAY-UHFFFAOYSA-N 0.000 description 1
- XCPGTPLBKRRPQQ-UHFFFAOYSA-N 5-chloro-3-(4-fluorophenyl)triazolo[4,5-d]pyrimidine Chemical compound C1=CC(F)=CC=C1N1C2=NC(Cl)=NC=C2N=N1 XCPGTPLBKRRPQQ-UHFFFAOYSA-N 0.000 description 1
- CESZSGJIQUVZQH-UHFFFAOYSA-N 5-chloro-3-(6-methoxypyridin-3-yl)triazolo[4,5-d]pyrimidine Chemical compound C1=NC(OC)=CC=C1N1C2=NC(Cl)=NC=C2N=N1 CESZSGJIQUVZQH-UHFFFAOYSA-N 0.000 description 1
- ZYMHCFYHVYGFMS-UHFFFAOYSA-N 5-methyl-1,3-oxazole Chemical compound CC1=CN=CO1 ZYMHCFYHVYGFMS-UHFFFAOYSA-N 0.000 description 1
- BWXSAMJJVYPXLL-UHFFFAOYSA-N 6-(5-chlorotriazolo[4,5-d]pyrimidin-3-yl)-3,3-dimethyl-1h-indol-2-one Chemical compound N1=NC2=CN=C(Cl)N=C2N1C1=CC=C2C(C)(C)C(=O)NC2=C1 BWXSAMJJVYPXLL-UHFFFAOYSA-N 0.000 description 1
- VCPUKFAXIGEIRK-UHFFFAOYSA-N 6-(5-chlorotriazolo[4,5-d]pyrimidin-3-yl)quinoxaline Chemical compound N1=CC=NC2=CC(N3N=NC4=CN=C(N=C43)Cl)=CC=C21 VCPUKFAXIGEIRK-UHFFFAOYSA-N 0.000 description 1
- OZPFIJIOIVJZMN-SFHVURJKSA-N 6-[(7s)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-n-methylnaphthalene-2-carboxamide Chemical compound C1=CC2=CC(C(=O)NC)=CC=C2C=C1[C@]1(O)C2=CN=CN2CC1 OZPFIJIOIVJZMN-SFHVURJKSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- SHGAZHPCJJPHSC-ZVCIMWCZSA-N 9-cis-retinoic acid Chemical compound OC(=O)/C=C(\C)/C=C/C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-ZVCIMWCZSA-N 0.000 description 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 102100039160 Amiloride-sensitive amine oxidase [copper-containing] Human genes 0.000 description 1
- 108010028700 Amine Oxidase (Copper-Containing) Proteins 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 102000012936 Angiostatins Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- MXPOCMVWFLDDLZ-NSCUHMNNSA-N Apaziquone Chemical compound CN1C(\C=C\CO)=C(CO)C(C2=O)=C1C(=O)C=C2N1CC1 MXPOCMVWFLDDLZ-NSCUHMNNSA-N 0.000 description 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- 229940080328 Arginase inhibitor Drugs 0.000 description 1
- 102100021723 Arginase-1 Human genes 0.000 description 1
- 101710129000 Arginase-1 Proteins 0.000 description 1
- 102000015790 Asparaginase Human genes 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 1
- 208000032800 BCR-ABL1 positive blast phase chronic myelogenous leukemia Diseases 0.000 description 1
- 108700020463 BRCA1 Proteins 0.000 description 1
- 102000036365 BRCA1 Human genes 0.000 description 1
- 101150072950 BRCA1 gene Proteins 0.000 description 1
- 102000052609 BRCA2 Human genes 0.000 description 1
- 108700020462 BRCA2 Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose 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-DCSYEGIMSA-N 0.000 description 1
- 101150040844 Bin1 gene Proteins 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 208000004860 Blast Crisis Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 101150008921 Brca2 gene Proteins 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- KDTJIFODBYYBBO-RDJZCZTQSA-N C(C)OC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@@H]2C[C@H](CC2)N2NC=CC=C2 Chemical compound C(C)OC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@@H]2C[C@H](CC2)N2NC=CC=C2 KDTJIFODBYYBBO-RDJZCZTQSA-N 0.000 description 1
- VSEIDZLLWQQJGK-CHOZPQDDSA-N CCC1=C(C)C2=N\C\1=C/C1=C(C)C(C(O)=O)=C(N1)\C(CC(=O)N[C@@H](CC(O)=O)C(O)=O)=C1/N=C(/C=C3\N/C(=C\2)C(C=C)=C3C)[C@@H](C)[C@@H]1CCC(O)=O Chemical compound CCC1=C(C)C2=N\C\1=C/C1=C(C)C(C(O)=O)=C(N1)\C(CC(=O)N[C@@H](CC(O)=O)C(O)=O)=C1/N=C(/C=C3\N/C(=C\2)C(C=C)=C3C)[C@@H](C)[C@@H]1CCC(O)=O VSEIDZLLWQQJGK-CHOZPQDDSA-N 0.000 description 1
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 1
- DAMKSOLJJREOII-WKILWMFISA-N CN1N=CC(=C1)C1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@@H]1CC[C@H](CC1)N Chemical compound CN1N=CC(=C1)C1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@@H]1CC[C@H](CC1)N DAMKSOLJJREOII-WKILWMFISA-N 0.000 description 1
- ABNMOKVCHRWXEK-AULYBMBSSA-N COC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@@H]2CC[C@H](CC2)O Chemical compound COC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@@H]2CC[C@H](CC2)O ABNMOKVCHRWXEK-AULYBMBSSA-N 0.000 description 1
- HYYDRUGPMQWENV-GDBMZVCRSA-N COC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@H]2C[C@@H](CC2)N2CCCC2 Chemical compound COC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@H]2C[C@@H](CC2)N2CCCC2 HYYDRUGPMQWENV-GDBMZVCRSA-N 0.000 description 1
- IBWMNDWZQPZGLH-BETUJISGSA-N COc1ccc(cc1)-n1nnc2cnc(N[C@@H]3C[C@@H](C3)NC(=O)OC(C)(C)C)nc12 Chemical compound COc1ccc(cc1)-n1nnc2cnc(N[C@@H]3C[C@@H](C3)NC(=O)OC(C)(C)C)nc12 IBWMNDWZQPZGLH-BETUJISGSA-N 0.000 description 1
- XBCRQNICKNYEBX-HDJSIYSDSA-N COc1ccc(cc1)-n1nnc2cnc(N[C@H]3CC[C@H](CCO)CC3)nc12 Chemical compound COc1ccc(cc1)-n1nnc2cnc(N[C@H]3CC[C@H](CCO)CC3)nc12 XBCRQNICKNYEBX-HDJSIYSDSA-N 0.000 description 1
- UATMZGGZBAWTDU-MGCOHNPYSA-N COc1ccc(cc1)-n1nnc2cnc(N[C@H]3C[C@@H](C3)C(N)=O)nc12 Chemical compound COc1ccc(cc1)-n1nnc2cnc(N[C@H]3C[C@@H](C3)C(N)=O)nc12 UATMZGGZBAWTDU-MGCOHNPYSA-N 0.000 description 1
- IBWMNDWZQPZGLH-JOCQHMNTSA-N COc1ccc(cc1)-n1nnc2cnc(N[C@H]3C[C@@H](C3)NC(=O)OC(C)(C)C)nc12 Chemical compound COc1ccc(cc1)-n1nnc2cnc(N[C@H]3C[C@@H](C3)NC(=O)OC(C)(C)C)nc12 IBWMNDWZQPZGLH-JOCQHMNTSA-N 0.000 description 1
- QMGGJBPSDVTOOP-HOMQSWHASA-N COc1ccc(cc1)-n1nnc2cnc(N[C@H]3C[C@H](O)C3)nc12 Chemical compound COc1ccc(cc1)-n1nnc2cnc(N[C@H]3C[C@H](O)C3)nc12 QMGGJBPSDVTOOP-HOMQSWHASA-N 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- AOCCBINRVIKJHY-UHFFFAOYSA-N Carmofur Chemical compound CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O AOCCBINRVIKJHY-UHFFFAOYSA-N 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 description 1
- KEZJNXXEEDCYEY-AWLKUTLJSA-N Cl.COC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@@H]2C[C@H](C2)N Chemical compound Cl.COC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@@H]2C[C@H](C2)N KEZJNXXEEDCYEY-AWLKUTLJSA-N 0.000 description 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- HVXBOLULGPECHP-WAYWQWQTSA-N Combretastatin A4 Chemical compound C1=C(O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-WAYWQWQTSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 208000019707 Cryoglobulinemic vasculitis Diseases 0.000 description 1
- 206010068271 Cystic fibrosis related diabetes Diseases 0.000 description 1
- 102000000311 Cytosine Deaminase Human genes 0.000 description 1
- 108010080611 Cytosine Deaminase Proteins 0.000 description 1
- 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 1
- 108020004414 DNA Proteins 0.000 description 1
- 101710156077 DNA damage-inducible transcript 3 protein Proteins 0.000 description 1
- 239000012623 DNA damaging agent Substances 0.000 description 1
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-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
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- GJKXGJCSJWBJEZ-XRSSZCMZSA-N Deslorelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CNC2=CC=CC=C12 GJKXGJCSJWBJEZ-XRSSZCMZSA-N 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 108700038672 Edotreotide Proteins 0.000 description 1
- FLFGNMFWNBOBGE-FNNZEKJRSA-N Elacytarabine Chemical compound O[C@H]1[C@H](O)[C@@H](COC(=O)CCCCCCC/C=C/CCCCCCCC)O[C@H]1N1C(=O)N=C(N)C=C1 FLFGNMFWNBOBGE-FNNZEKJRSA-N 0.000 description 1
- 102400001047 Endostatin Human genes 0.000 description 1
- 108010079505 Endostatins Proteins 0.000 description 1
- 108010041308 Endothelial Growth Factors Proteins 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- SAMRUMKYXPVKPA-VFKOLLTISA-N Enocitabine Chemical compound O=C1N=C(NC(=O)CCCCCCCCCCCCCCCCCCCCC)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 SAMRUMKYXPVKPA-VFKOLLTISA-N 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- OBMLHUPNRURLOK-XGRAFVIBSA-N Epitiostanol Chemical compound C1[C@@H]2S[C@@H]2C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 OBMLHUPNRURLOK-XGRAFVIBSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229940123414 Folate antagonist Drugs 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 206010017943 Gastrointestinal conditions Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 241000006869 Halone Species 0.000 description 1
- 208000018565 Hemochromatosis Diseases 0.000 description 1
- 206010019668 Hepatic fibrosis Diseases 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 108010023610 IL13-PE38 Proteins 0.000 description 1
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- JJKOTMDDZAJTGQ-DQSJHHFOSA-N Idoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN2CCCC2)=CC=1)/C1=CC=C(I)C=C1 JJKOTMDDZAJTGQ-DQSJHHFOSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108010047852 Integrin alphaVbeta3 Proteins 0.000 description 1
- 102000005755 Intercellular Signaling Peptides and Proteins Human genes 0.000 description 1
- 108010070716 Intercellular Signaling Peptides and Proteins Proteins 0.000 description 1
- 102100040018 Interferon alpha-2 Human genes 0.000 description 1
- 108010005716 Interferon beta-1a Proteins 0.000 description 1
- 108010079944 Interferon-alpha2b Proteins 0.000 description 1
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 241000764238 Isis Species 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- BKCJZNIZRWYHBN-UHFFFAOYSA-N Isophosphamide mustard Chemical compound ClCCNP(=O)(O)NCCCl BKCJZNIZRWYHBN-UHFFFAOYSA-N 0.000 description 1
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-M L-tartrate(1-) Chemical compound OC(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-M 0.000 description 1
- NHTGHBARYWONDQ-JTQLQIEISA-N L-α-methyl-Tyrosine Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C=C1 NHTGHBARYWONDQ-JTQLQIEISA-N 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
- 239000005536 L01XE08 - Nilotinib Substances 0.000 description 1
- 239000003798 L01XE11 - Pazopanib Substances 0.000 description 1
- 239000002118 L01XE12 - Vandetanib Substances 0.000 description 1
- 239000002145 L01XE14 - Bosutinib Substances 0.000 description 1
- 239000002146 L01XE16 - Crizotinib Substances 0.000 description 1
- 239000002138 L01XE21 - Regorafenib Substances 0.000 description 1
- 239000002139 L01XE22 - Masitinib Substances 0.000 description 1
- 239000002137 L01XE24 - Ponatinib Substances 0.000 description 1
- 239000002176 L01XE26 - Cabozantinib Substances 0.000 description 1
- 239000002177 L01XE27 - Ibrutinib Substances 0.000 description 1
- UCEQXRCJXIVODC-PMACEKPBSA-N LSM-1131 Chemical compound C1CCC2=CC=CC3=C2N1C=C3[C@@H]1C(=O)NC(=O)[C@H]1C1=CNC2=CC=CC=C12 UCEQXRCJXIVODC-PMACEKPBSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 240000008415 Lactuca sativa Species 0.000 description 1
- 235000003228 Lactuca sativa Nutrition 0.000 description 1
- XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- 241000222732 Leishmania major Species 0.000 description 1
- 229920001491 Lentinan Polymers 0.000 description 1
- 206010024227 Lepromatous leprosy Diseases 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
- 229940124041 Luteinizing hormone releasing hormone (LHRH) antagonist Drugs 0.000 description 1
- 108700041567 MDR Genes Proteins 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000035268 Mast Cell Activation disease Diseases 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- VFKZTMPDYBFSTM-KVTDHHQDSA-N Mitobronitol Chemical compound BrC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-KVTDHHQDSA-N 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- ONXPDKGXOOORHB-BYPYZUCNSA-N N(5)-methyl-L-glutamine Chemical compound CNC(=O)CC[C@H](N)C(O)=O ONXPDKGXOOORHB-BYPYZUCNSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- VIUAUNHCRHHYNE-JTQLQIEISA-N N-[(2S)-2,3-dihydroxypropyl]-3-(2-fluoro-4-iodoanilino)-4-pyridinecarboxamide Chemical compound OC[C@@H](O)CNC(=O)C1=CC=NC=C1NC1=CC=C(I)C=C1F VIUAUNHCRHHYNE-JTQLQIEISA-N 0.000 description 1
- XLLXGMBCQCSCRN-UHFFFAOYSA-N N-[4-(aminomethyl)cyclohexyl]-3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-amine hydrochloride Chemical compound Cl.COc1ccc(cc1)-n1nnc2cnc(NC3CCC(CN)CC3)nc12 XLLXGMBCQCSCRN-UHFFFAOYSA-N 0.000 description 1
- BKAYIFDRRZZKNF-VIFPVBQESA-N N-acetylcarnosine Chemical compound CC(=O)NCCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BKAYIFDRRZZKNF-VIFPVBQESA-N 0.000 description 1
- 150000007945 N-acyl ureas Chemical class 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- UQFQONCQIQEYPJ-UHFFFAOYSA-N N-methylpyrazole Chemical compound CN1C=CC=N1 UQFQONCQIQEYPJ-UHFFFAOYSA-N 0.000 description 1
- GVMXZVQDUJJMGU-HDJSIYSDSA-N N1(CCOCC1)C=1C=CC(=NC=1)N1N=NC2=C1N=C(N=C2)N[C@@H]1CC[C@H](CC1)N Chemical compound N1(CCOCC1)C=1C=CC(=NC=1)N1N=NC2=C1N=C(N=C2)N[C@@H]1CC[C@H](CC1)N GVMXZVQDUJJMGU-HDJSIYSDSA-N 0.000 description 1
- LYPFDBRUNKHDGX-SOGSVHMOSA-N N1C2=CC=C1\C(=C1\C=CC(=N1)\C(=C1\C=C/C(/N1)=C(/C1=N/C(/CC1)=C2/C1=CC(O)=CC=C1)C1=CC(O)=CC=C1)\C1=CC(O)=CC=C1)C1=CC(O)=CC=C1 Chemical compound N1C2=CC=C1\C(=C1\C=CC(=N1)\C(=C1\C=C/C(/N1)=C(/C1=N/C(/CC1)=C2/C1=CC(O)=CC=C1)C1=CC(O)=CC=C1)\C1=CC(O)=CC=C1)C1=CC(O)=CC=C1 LYPFDBRUNKHDGX-SOGSVHMOSA-N 0.000 description 1
- YHVATTIJSSXIPB-QAQDUYKDSA-N N[C@@H]1CC[C@H](CC1)NC=1N=CC2=C(N1)N(N=N2)C2=CC=C(C=C2)C=2C=NN(C2)CCO Chemical compound N[C@@H]1CC[C@H](CC1)NC=1N=CC2=C(N1)N(N=N2)C2=CC=C(C=C2)C=2C=NN(C2)CCO YHVATTIJSSXIPB-QAQDUYKDSA-N 0.000 description 1
- NMEYZHDOYPSOIJ-CKEIUWERSA-N N[C@@H]1CC[C@H](CC1)NC=1N=CC2=C(N=1)N(N=N2)C1=CC=C(C=C1)N1C[C@@H](CC1)O Chemical compound N[C@@H]1CC[C@H](CC1)NC=1N=CC2=C(N=1)N(N=N2)C1=CC=C(C=C1)N1C[C@@H](CC1)O NMEYZHDOYPSOIJ-CKEIUWERSA-N 0.000 description 1
- CCVRMSPBLAYQEJ-HAQNSBGRSA-N N[C@H]1CC[C@@H](CC1)Nc1ncc2nnn(-c3ccc(F)cc3)c2n1 Chemical compound N[C@H]1CC[C@@H](CC1)Nc1ncc2nnn(-c3ccc(F)cc3)c2n1 CCVRMSPBLAYQEJ-HAQNSBGRSA-N 0.000 description 1
- BEMASTLQEGXAPI-HDJSIYSDSA-N N[C@H]1CC[C@@H](CC1)Nc1ncc2nnn(-c3ccc(cc3)N3CCCC3=O)c2n1 Chemical compound N[C@H]1CC[C@@H](CC1)Nc1ncc2nnn(-c3ccc(cc3)N3CCCC3=O)c2n1 BEMASTLQEGXAPI-HDJSIYSDSA-N 0.000 description 1
- 108010021717 Nafarelin Proteins 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 102000003729 Neprilysin Human genes 0.000 description 1
- 108090000028 Neprilysin Proteins 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000003450 Neurogenic Diabetes Insipidus Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 102000004459 Nitroreductase Human genes 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- FOYPRXDENRJFOZ-SHTZXODSSA-N O1CCC(CC1)OC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@@H]2CC[C@H](CC2)N Chemical compound O1CCC(CC1)OC1=CC=C(C=C1)N1N=NC2=C1N=C(N=C2)N[C@@H]2CC[C@H](CC2)N FOYPRXDENRJFOZ-SHTZXODSSA-N 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 108010016076 Octreotide Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 240000007673 Origanum vulgare Species 0.000 description 1
- 235000010677 Origanum vulgare Nutrition 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 108010001441 Phosphopeptides Proteins 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- KMSKQZKKOZQFFG-HSUXVGOQSA-N Pirarubicin Chemical compound O([C@H]1[C@@H](N)C[C@@H](O[C@H]1C)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]1CCCCO1 KMSKQZKKOZQFFG-HSUXVGOQSA-N 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 208000001280 Prediabetic State Diseases 0.000 description 1
- 102100022033 Presenilin-1 Human genes 0.000 description 1
- 108010036933 Presenilin-1 Proteins 0.000 description 1
- 108010050254 Presenilins Proteins 0.000 description 1
- 102000015499 Presenilins Human genes 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 102100024028 Progonadoliberin-1 Human genes 0.000 description 1
- 108010049395 Prokaryotic Initiation Factor-2 Proteins 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108091005682 Receptor kinases Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- YJDYDFNKCBANTM-QCWCSKBGSA-N SDZ PSC 833 Chemical compound C\C=C\C[C@@H](C)C(=O)[C@@H]1N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@H](C(C)C)NC1=O YJDYDFNKCBANTM-QCWCSKBGSA-N 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- OCOKWVBYZHBHLU-UHFFFAOYSA-N Sobuzoxane Chemical compound C1C(=O)N(COC(=O)OCC(C)C)C(=O)CN1CCN1CC(=O)N(COC(=O)OCC(C)C)C(=O)C1 OCOKWVBYZHBHLU-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 101710127774 Stress response protein Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 241000272534 Struthio camelus Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000017274 T cell anergy Effects 0.000 description 1
- NAVMQTYZDKMPEU-UHFFFAOYSA-N Targretin Chemical compound CC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C(=C)C1=CC=C(C(O)=O)C=C1 NAVMQTYZDKMPEU-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 description 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 1
- 229910052771 Terbium Inorganic materials 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 208000026062 Tissue disease Diseases 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 208000008385 Urogenital Neoplasms Diseases 0.000 description 1
- 102000004504 Urokinase Plasminogen Activator Receptors Human genes 0.000 description 1
- 108010042352 Urokinase Plasminogen Activator Receptors Proteins 0.000 description 1
- 206010052568 Urticaria chronic Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 208000024248 Vascular System injury Diseases 0.000 description 1
- 208000012339 Vascular injury Diseases 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- KGRNGVHWVUXNNW-HZPDHXFCSA-N [(1r,3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(=O)N3CCN(C)CC3)=NC=C2N=N1 KGRNGVHWVUXNNW-HZPDHXFCSA-N 0.000 description 1
- KGRNGVHWVUXNNW-CVEARBPZSA-N [(1r,3s)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3C[C@@H](CC3)C(=O)N3CCN(C)CC3)=NC=C2N=N1 KGRNGVHWVUXNNW-CVEARBPZSA-N 0.000 description 1
- KGRNGVHWVUXNNW-JKSUJKDBSA-N [(1s,3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3C[C@H](CC3)C(=O)N3CCN(C)CC3)=NC=C2N=N1 KGRNGVHWVUXNNW-JKSUJKDBSA-N 0.000 description 1
- XSMVECZRZBFTIZ-UHFFFAOYSA-M [2-(aminomethyl)cyclobutyl]methanamine;2-oxidopropanoate;platinum(4+) Chemical compound [Pt+4].CC([O-])C([O-])=O.NCC1CCC1CN XSMVECZRZBFTIZ-UHFFFAOYSA-M 0.000 description 1
- WXIONIWNXBAHRU-UHFFFAOYSA-N [dimethylamino(triazolo[4,5-b]pyridin-3-yloxy)methylidene]-dimethylazanium Chemical compound C1=CN=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 WXIONIWNXBAHRU-UHFFFAOYSA-N 0.000 description 1
- 229960003697 abatacept Drugs 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- GZOSMCIZMLWJML-VJLLXTKPSA-N abiraterone Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CC[C@H](O)CC3=CC2)C)CC[C@@]11C)C=C1C1=CC=CN=C1 GZOSMCIZMLWJML-VJLLXTKPSA-N 0.000 description 1
- 229960000853 abiraterone Drugs 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- 150000007960 acetonitrile Chemical class 0.000 description 1
- 108010052004 acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide Proteins 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- USZYSDMBJDPRIF-SVEJIMAYSA-N aclacinomycin A Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@H]1C)O[C@H]1[C@H](C[C@@H](O[C@H]1C)O[C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1CCC(=O)[C@H](C)O1 USZYSDMBJDPRIF-SVEJIMAYSA-N 0.000 description 1
- 229960004176 aclarubicin Drugs 0.000 description 1
- DUYNJNWVGIWJRI-LJAQVGFWSA-N acolbifene Chemical compound C1=CC([C@H]2C(=C(C3=CC=C(O)C=C3O2)C)C=2C=CC(O)=CC=2)=CC=C1OCCN1CCCCC1 DUYNJNWVGIWJRI-LJAQVGFWSA-N 0.000 description 1
- 229950002421 acolbifene Drugs 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M acrylate group Chemical group C(C=C)(=O)[O-] NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229960002964 adalimumab Drugs 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 229960001686 afatinib Drugs 0.000 description 1
- ULXXDDBFHOBEHA-CWDCEQMOSA-N afatinib Chemical compound N1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-CWDCEQMOSA-N 0.000 description 1
- 229960002833 aflibercept Drugs 0.000 description 1
- 108010081667 aflibercept Proteins 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 108700025316 aldesleukin Proteins 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229950009447 alisertib Drugs 0.000 description 1
- 229960001445 alitretinoin Drugs 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229960000473 altretamine Drugs 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 230000037354 amino acid metabolism Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 1
- 229960003437 aminoglutethimide Drugs 0.000 description 1
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229960004701 amonafide Drugs 0.000 description 1
- 229920000469 amphiphilic block copolymer Polymers 0.000 description 1
- 229960002550 amrubicin Drugs 0.000 description 1
- VJZITPJGSQKZMX-XDPRQOKASA-N amrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC=C4C(=O)C=3C(O)=C21)(N)C(=O)C)[C@H]1C[C@H](O)[C@H](O)CO1 VJZITPJGSQKZMX-XDPRQOKASA-N 0.000 description 1
- 229960004238 anakinra Drugs 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 230000002137 anti-vascular 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
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 229940045985 antineoplastic platinum compound Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229960003982 apatinib Drugs 0.000 description 1
- 229950002465 apaziquone Drugs 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229960003272 asparaginase Drugs 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
- 229940009098 aspartate Drugs 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
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000002886 autophagic effect Effects 0.000 description 1
- 229960003005 axitinib Drugs 0.000 description 1
- RITAVMQDGBJQJZ-FMIVXFBMSA-N axitinib Chemical compound CNC(=O)C1=CC=CC=C1SC1=CC=C(C(\C=C\C=2N=CC=CC=2)=NN2)C2=C1 RITAVMQDGBJQJZ-FMIVXFBMSA-N 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- KLNFSAOEKUDMFA-UHFFFAOYSA-N azanide;2-hydroxyacetic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OCC(O)=O KLNFSAOEKUDMFA-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- 229960002707 bendamustine Drugs 0.000 description 1
- YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 229960002938 bexarotene Drugs 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
- 229960001467 bortezomib Drugs 0.000 description 1
- UBPYILGKFZZVDX-UHFFFAOYSA-N bosutinib Chemical compound C1=C(Cl)C(OC)=CC(NC=2C3=CC(OC)=C(OCCCN4CCN(C)CC4)C=C3N=CC=2C#N)=C1Cl UBPYILGKFZZVDX-UHFFFAOYSA-N 0.000 description 1
- 229960003736 bosutinib Drugs 0.000 description 1
- 229960000455 brentuximab vedotin Drugs 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- BMQGVNUXMIRLCK-OAGWZNDDSA-N cabazitaxel Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3C[C@@H]([C@]2(C(=O)[C@H](OC)C2=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=3C=CC=CC=3)C[C@]1(O)C2(C)C)C)OC)C(=O)C1=CC=CC=C1 BMQGVNUXMIRLCK-OAGWZNDDSA-N 0.000 description 1
- 229960001292 cabozantinib Drugs 0.000 description 1
- ONIQOQHATWINJY-UHFFFAOYSA-N cabozantinib Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(F)=CC=2)CC1 ONIQOQHATWINJY-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 229950002826 canertinib Drugs 0.000 description 1
- OMZCMEYTWSXEPZ-UHFFFAOYSA-N canertinib Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=C(NC(=O)C=C)C=C12 OMZCMEYTWSXEPZ-UHFFFAOYSA-N 0.000 description 1
- 230000005295 cap-dependent translational initiation Effects 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- BLMPQMFVWMYDKT-NZTKNTHTSA-N carfilzomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)[C@]1(C)OC1)NC(=O)CN1CCOCC1)CC1=CC=CC=C1 BLMPQMFVWMYDKT-NZTKNTHTSA-N 0.000 description 1
- 229960002438 carfilzomib Drugs 0.000 description 1
- 108010021331 carfilzomib Proteins 0.000 description 1
- 229960003261 carmofur Drugs 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229960002412 cediranib Drugs 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000036978 cell physiology Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 208000028235 central diabetes insipidus Diseases 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000024376 chronic urticaria Diseases 0.000 description 1
- 229950009003 cilengitide Drugs 0.000 description 1
- AMLYAMJWYAIXIA-VWNVYAMZSA-N cilengitide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C(C)C)N(C)C(=O)[C@H]1CC1=CC=CC=C1 AMLYAMJWYAIXIA-VWNVYAMZSA-N 0.000 description 1
- 229950010810 cintredekin besudotox Drugs 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 229960000928 clofarabine Drugs 0.000 description 1
- WDDPHFBMKLOVOX-AYQXTPAHSA-N clofarabine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1F WDDPHFBMKLOVOX-AYQXTPAHSA-N 0.000 description 1
- 230000006690 co-activation Effects 0.000 description 1
- 229960002271 cobimetinib Drugs 0.000 description 1
- RESIMIUSNACMNW-BXRWSSRYSA-N cobimetinib fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1C(O)([C@H]2NCCCC2)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F.C1C(O)([C@H]2NCCCC2)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F RESIMIUSNACMNW-BXRWSSRYSA-N 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 229960005537 combretastatin A-4 Drugs 0.000 description 1
- 229960005527 combretastatin A-4 phosphate Drugs 0.000 description 1
- HVXBOLULGPECHP-UHFFFAOYSA-N combretastatin A4 Natural products C1=C(O)C(OC)=CC=C1C=CC1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-UHFFFAOYSA-N 0.000 description 1
- WDOGQTQEKVLZIJ-WAYWQWQTSA-N combretastatin a-4 phosphate Chemical compound C1=C(OP(O)(O)=O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 WDOGQTQEKVLZIJ-WAYWQWQTSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000010485 coping Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 description 1
- 229960005061 crizotinib Drugs 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 201000003278 cryoglobulinemia Diseases 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000001186 cumulative effect Effects 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
- VKIRRGRTJUUZHS-UHFFFAOYSA-N cyclohexane-1,4-diamine Chemical compound NC1CCC(N)CC1 VKIRRGRTJUUZHS-UHFFFAOYSA-N 0.000 description 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
- PGPGBZHKWQKWQO-UHFFFAOYSA-N cyclopent-2-ene-1-carboxamide Chemical compound NC(=O)C1CCC=C1 PGPGBZHKWQKWQO-UHFFFAOYSA-N 0.000 description 1
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 1
- 229960000978 cyproterone acetate Drugs 0.000 description 1
- UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229960002465 dabrafenib Drugs 0.000 description 1
- BFSMGDJOXZAERB-UHFFFAOYSA-N dabrafenib Chemical compound S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 BFSMGDJOXZAERB-UHFFFAOYSA-N 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- LVXJQMNHJWSHET-AATRIKPKSA-N dacomitinib Chemical compound C=12C=C(NC(=O)\C=C\CN3CCCCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 LVXJQMNHJWSHET-AATRIKPKSA-N 0.000 description 1
- 229950002205 dacomitinib Drugs 0.000 description 1
- 229960002482 dalotuzumab Drugs 0.000 description 1
- POZRVZJJTULAOH-LHZXLZLDSA-N danazol Chemical compound C1[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=CC2=C1C=NO2 POZRVZJJTULAOH-LHZXLZLDSA-N 0.000 description 1
- 229960000766 danazol Drugs 0.000 description 1
- 229960002448 dasatinib Drugs 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 229960003603 decitabine Drugs 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 229960002272 degarelix Drugs 0.000 description 1
- MEUCPCLKGZSHTA-XYAYPHGZSA-N degarelix Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CC=1C=CC(NC(=O)[C@H]2NC(=O)NC(=O)C2)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(NC(N)=O)C=C1 MEUCPCLKGZSHTA-XYAYPHGZSA-N 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 229960001251 denosumab Drugs 0.000 description 1
- CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229960005408 deslorelin Drugs 0.000 description 1
- 108700025485 deslorelin Proteins 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- LLTVGKHHDXGLMR-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.OC.ClCCl LLTVGKHHDXGLMR-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 1
- 229960000452 diethylstilbestrol Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 description 1
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- 108700003601 dimethylglycine Proteins 0.000 description 1
- 229950009859 dinaciclib Drugs 0.000 description 1
- GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 230000005059 dormancy Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- ZWAOHEXOSAUJHY-ZIYNGMLESA-N doxifluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZWAOHEXOSAUJHY-ZIYNGMLESA-N 0.000 description 1
- 229950005454 doxifluridine Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229950004203 droloxifene Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 229950006595 edotreotide Drugs 0.000 description 1
- 229950003430 elacytarabine Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 229940073621 enbrel Drugs 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229950011487 enocitabine Drugs 0.000 description 1
- 229950005837 entinostat Drugs 0.000 description 1
- INVTYAOGFAGBOE-UHFFFAOYSA-N entinostat Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC(=O)OCC1=CC=CN=C1 INVTYAOGFAGBOE-UHFFFAOYSA-N 0.000 description 1
- 229960004671 enzalutamide Drugs 0.000 description 1
- WXCXUHSOUPDCQV-UHFFFAOYSA-N enzalutamide Chemical compound C1=C(F)C(C(=O)NC)=CC=C1N1C(C)(C)C(=O)N(C=2C=C(C(C#N)=CC=2)C(F)(F)F)C1=S WXCXUHSOUPDCQV-UHFFFAOYSA-N 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000009088 enzymatic function Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 229950002973 epitiostanol Drugs 0.000 description 1
- 229950009760 epratuzumab Drugs 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 229960003649 eribulin Drugs 0.000 description 1
- UFNVPOGXISZXJD-XJPMSQCNSA-N eribulin Chemical compound C([C@H]1CC[C@@H]2O[C@@H]3[C@H]4O[C@H]5C[C@](O[C@H]4[C@H]2O1)(O[C@@H]53)CC[C@@H]1O[C@H](C(C1)=C)CC1)C(=O)C[C@@H]2[C@@H](OC)[C@@H](C[C@H](O)CN)O[C@H]2C[C@@H]2C(=C)[C@H](C)C[C@H]1O2 UFNVPOGXISZXJD-XJPMSQCNSA-N 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229960001842 estramustine Drugs 0.000 description 1
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 229950006566 etanidazole Drugs 0.000 description 1
- WCDWBPCFGJXFJZ-UHFFFAOYSA-N etanidazole Chemical compound OCCNC(=O)CN1C=CN=C1[N+]([O-])=O WCDWBPCFGJXFJZ-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 229960005167 everolimus Drugs 0.000 description 1
- 229950009988 evofosfamide Drugs 0.000 description 1
- UGJWRPJDTDGERK-UHFFFAOYSA-N evofosfamide Chemical compound CN1C(COP(=O)(NCCBr)NCCBr)=CN=C1[N+]([O-])=O UGJWRPJDTDGERK-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 229950011548 fadrozole Drugs 0.000 description 1
- 229950003662 fenretinide Drugs 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
- 229960004039 finasteride Drugs 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 229960000961 floxuridine Drugs 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 150000005699 fluoropyrimidines Chemical class 0.000 description 1
- YLRFCQOZQXIBAB-RBZZARIASA-N fluoxymesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)C[C@@H]2O YLRFCQOZQXIBAB-RBZZARIASA-N 0.000 description 1
- 229960001751 fluoxymesterone Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- KBNUEPOTZHDDJC-UHFFFAOYSA-N formic acid;3-(4-methoxyphenyl)-n-(1-methylpiperidin-3-yl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound OC=O.C1=CC(OC)=CC=C1N1C2=NC(NC3CN(C)CCC3)=NC=C2N=N1 KBNUEPOTZHDDJC-UHFFFAOYSA-N 0.000 description 1
- 229960004783 fotemustine Drugs 0.000 description 1
- YAKWPXVTIGTRJH-UHFFFAOYSA-N fotemustine Chemical compound CCOP(=O)(OCC)C(C)NC(=O)N(CCCl)N=O YAKWPXVTIGTRJH-UHFFFAOYSA-N 0.000 description 1
- 229960002258 fulvestrant Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 229960000578 gemtuzumab Drugs 0.000 description 1
- 238000010914 gene-directed enzyme pro-drug therapy Methods 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 208000004104 gestational diabetes Diseases 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000007946 glucose deprivation Effects 0.000 description 1
- 230000014101 glucose homeostasis Effects 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 229950011595 glufosfamide Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
- 239000002474 gonadorelin antagonist Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000005283 ground state Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
- AILKHAQXUAOOFU-UHFFFAOYSA-N hexanenitrile Chemical compound CCCCCC#N AILKHAQXUAOOFU-UHFFFAOYSA-N 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 108700020746 histrelin Proteins 0.000 description 1
- HHXHVIJIIXKSOE-QILQGKCVSA-N histrelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC(N=C1)=CN1CC1=CC=CC=C1 HHXHVIJIIXKSOE-QILQGKCVSA-N 0.000 description 1
- 229960002193 histrelin Drugs 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000007236 host immunity Effects 0.000 description 1
- 229940048921 humira Drugs 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000000017 hydrogel Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 229960005236 ibandronic acid Drugs 0.000 description 1
- 229960001507 ibrutinib Drugs 0.000 description 1
- XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-GOSISDBHSA-N 0.000 description 1
- 229950007440 icotinib Drugs 0.000 description 1
- QQLKULDARVNMAL-UHFFFAOYSA-N icotinib Chemical compound C#CC1=CC=CC(NC=2C3=CC=4OCCOCCOCCOC=4C=C3N=CN=2)=C1 QQLKULDARVNMAL-UHFFFAOYSA-N 0.000 description 1
- 229950008268 idronoxil Drugs 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
- 229960002411 imatinib Drugs 0.000 description 1
- 230000008102 immune modulation Effects 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 238000003318 immunodepletion Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 229950002133 iniparib Drugs 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229950004101 inotuzumab ozogamicin Drugs 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000012739 integrated shape imaging system Methods 0.000 description 1
- 229960004461 interferon beta-1a Drugs 0.000 description 1
- 229940028885 interleukin-4 Drugs 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229960005386 ipilimumab Drugs 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 229960005280 isotretinoin Drugs 0.000 description 1
- FABUFPQFXZVHFB-CFWQTKTJSA-N ixabepilone Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@H](C)C(=O)C(C)(C)[C@H](O)CC(=O)N1)O)C)=C\C1=CSC(C)=N1 FABUFPQFXZVHFB-CFWQTKTJSA-N 0.000 description 1
- 229960002014 ixabepilone Drugs 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000004140 ketosis Effects 0.000 description 1
- 229940054136 kineret Drugs 0.000 description 1
- 229940124280 l-arginine Drugs 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960004891 lapatinib Drugs 0.000 description 1
- 201000004959 laryngeal benign neoplasm Diseases 0.000 description 1
- 229960004942 lenalidomide Drugs 0.000 description 1
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 1
- 229940115286 lentinan Drugs 0.000 description 1
- 229960003784 lenvatinib Drugs 0.000 description 1
- WOSKHXYHFSIKNG-UHFFFAOYSA-N lenvatinib Chemical compound C=12C=C(C(N)=O)C(OC)=CC2=NC=CC=1OC(C=C1Cl)=CC=C1NC(=O)NC1CC1 WOSKHXYHFSIKNG-UHFFFAOYSA-N 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229950001762 linsitinib Drugs 0.000 description 1
- PKCDDUHJAFVJJB-VLZXCDOPSA-N linsitinib Chemical compound C1[C@](C)(O)C[C@@H]1C1=NC(C=2C=C3N=C(C=CC3=CC=2)C=2C=CC=CC=2)=C2N1C=CN=C2N PKCDDUHJAFVJJB-VLZXCDOPSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229950008991 lobaplatin Drugs 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 229960003538 lonidamine Drugs 0.000 description 1
- WDRYRZXSPDWGEB-UHFFFAOYSA-N lonidamine Chemical compound C12=CC=CC=C2C(C(=O)O)=NN1CC1=CC=C(Cl)C=C1Cl WDRYRZXSPDWGEB-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 230000035168 lymphangiogenesis Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 201000000564 macroglobulinemia Diseases 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- MMIPFLVOWGHZQD-UHFFFAOYSA-N manganese(3+) Chemical compound [Mn+3] MMIPFLVOWGHZQD-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229950008959 marimastat Drugs 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
- 229960004655 masitinib Drugs 0.000 description 1
- WJEOLQLKVOPQFV-UHFFFAOYSA-N masitinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3SC=C(N=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 WJEOLQLKVOPQFV-UHFFFAOYSA-N 0.000 description 1
- 208000008585 mastocytosis Diseases 0.000 description 1
- 229950008001 matuzumab Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229960001786 megestrol Drugs 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- ONPXOECXIYHYMS-VXGBXAGGSA-N methyl (1r,3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxylate Chemical compound C1[C@H](C(=O)OC)CC[C@H]1NC1=NC=C(N=NN2C=3C=CC(OC)=CC=3)C2=N1 ONPXOECXIYHYMS-VXGBXAGGSA-N 0.000 description 1
- ONPXOECXIYHYMS-RYUDHWBXSA-N methyl (1s,3s)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentane-1-carboxylate Chemical compound C1[C@@H](C(=O)OC)CC[C@@H]1NC1=NC=C(N=NN2C=3C=CC(OC)=CC=3)C2=N1 ONPXOECXIYHYMS-RYUDHWBXSA-N 0.000 description 1
- OKUWGQMDTBNVNS-VXGBXAGGSA-N methyl 2-[4-[5-[[(1r,3r)-3-carbamoylcyclopentyl]amino]triazolo[4,5-d]pyrimidin-3-yl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(N)=O)=NC=C2N=N1 OKUWGQMDTBNVNS-VXGBXAGGSA-N 0.000 description 1
- BUXRTYMRNUWARN-UHFFFAOYSA-N methyl 3-(4-aminophenoxy)propanoate Chemical compound COC(=O)CCOC1=CC=C(N)C=C1 BUXRTYMRNUWARN-UHFFFAOYSA-N 0.000 description 1
- USPSHEFNFUBYIL-CHWSQXEVSA-N methyl 3-[4-[5-[[(1r,3r)-3-carbamoylcyclopentyl]amino]triazolo[4,5-d]pyrimidin-3-yl]phenoxy]propanoate Chemical compound C1=CC(OCCC(=O)OC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CC3)C(N)=O)=NC=C2N=N1 USPSHEFNFUBYIL-CHWSQXEVSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960001980 metirosine Drugs 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 206010063344 microscopic polyangiitis Diseases 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- PQLXHQMOHUQAKB-UHFFFAOYSA-N miltefosine Chemical compound CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C PQLXHQMOHUQAKB-UHFFFAOYSA-N 0.000 description 1
- 229960003775 miltefosine Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 229960005485 mitobronitol Drugs 0.000 description 1
- 229960000350 mitotane Drugs 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229950007699 mogamulizumab Drugs 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 229950003968 motesanib Drugs 0.000 description 1
- RAHBGWKEPAQNFF-UHFFFAOYSA-N motesanib Chemical compound C=1C=C2C(C)(C)CNC2=CC=1NC(=O)C1=CC=CN=C1NCC1=CC=NC=C1 RAHBGWKEPAQNFF-UHFFFAOYSA-N 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 206010028537 myelofibrosis Diseases 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940078490 n,n-dimethylglycine Drugs 0.000 description 1
- SLHKYYYCLJBKMZ-UHFFFAOYSA-N n-(1,1-dioxothiolan-3-yl)-3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CS(=O)(=O)CC3)=NC=C2N=N1 SLHKYYYCLJBKMZ-UHFFFAOYSA-N 0.000 description 1
- AVALRMIVTPNQJH-UHFFFAOYSA-N n-(2-chloro-5-nitropyrimidin-4-yl)-2-methylquinolin-6-amine Chemical compound C1=CC2=NC(C)=CC=C2C=C1NC1=NC(Cl)=NC=C1[N+]([O-])=O AVALRMIVTPNQJH-UHFFFAOYSA-N 0.000 description 1
- KRDAVVSRZRLDOF-UHFFFAOYSA-N n-(2-chloro-5-nitropyrimidin-4-yl)-2-methylquinolin-6-amine;hydrochloride Chemical compound Cl.C1=CC2=NC(C)=CC=C2C=C1NC1=NC(Cl)=NC=C1[N+]([O-])=O KRDAVVSRZRLDOF-UHFFFAOYSA-N 0.000 description 1
- YBIJUIQRZPDSJG-UHFFFAOYSA-N n-(4-bromophenyl)-2-chloro-5-nitropyrimidin-4-amine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1NC1=CC=C(Br)C=C1 YBIJUIQRZPDSJG-UHFFFAOYSA-N 0.000 description 1
- AATXKUYWPBAQMK-UHFFFAOYSA-N n-[(1-methylpyrazol-4-yl)methyl]-3-quinolin-6-yltriazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=NN(C)C=C1CNC1=NC=C(N=NN2C=3C=C4C=CC=NC4=CC=3)C2=N1 AATXKUYWPBAQMK-UHFFFAOYSA-N 0.000 description 1
- WPECAIOQBHWOQC-UHFFFAOYSA-N n-[(5-methylpyrazin-2-yl)methyl]-3-quinoxalin-6-yltriazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=NC(C)=CN=C1CNC1=NC=C(N=NN2C=3C=C4N=CC=NC4=CC=3)C2=N1 WPECAIOQBHWOQC-UHFFFAOYSA-N 0.000 description 1
- QGQSTCCADFEIAK-UHFFFAOYSA-N n-[2-(2-aminoethoxy)ethyl]-3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NCCOCCN)=NC=C2N=N1 QGQSTCCADFEIAK-UHFFFAOYSA-N 0.000 description 1
- BYVCJBHSPXPRPO-UHFFFAOYSA-N n-[2-(4-chlorophenyl)cyclopropyl]-3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3C(C3)C=3C=CC(Cl)=CC=3)=NC=C2N=N1 BYVCJBHSPXPRPO-UHFFFAOYSA-N 0.000 description 1
- YWMXOFRBAOENFT-UHFFFAOYSA-N n-[2-(5-fluoro-1h-indol-3-yl)ethyl]-3-[4-(2-methoxyethoxy)phenyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OCCOC)=CC=C1N1C2=NC(NCCC=3C4=CC(F)=CC=C4NC=3)=NC=C2N=N1 YWMXOFRBAOENFT-UHFFFAOYSA-N 0.000 description 1
- QFARGYAOVUBUKA-UHFFFAOYSA-N n-[3-(3-aminopropoxy)propyl]-3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NCCCOCCCN)=NC=C2N=N1 QFARGYAOVUBUKA-UHFFFAOYSA-N 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- WPEWQEMJFLWMLV-UHFFFAOYSA-N n-[4-(1-cyanocyclopentyl)phenyl]-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide Chemical compound C=1C=CN=C(NCC=2C=CN=CC=2)C=1C(=O)NC(C=C1)=CC=C1C1(C#N)CCCC1 WPEWQEMJFLWMLV-UHFFFAOYSA-N 0.000 description 1
- YMFJSWNLGKNJSK-UHFFFAOYSA-N n-benzyl-3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NCC=3C=CC=CC=3)=NC=C2N=N1 YMFJSWNLGKNJSK-UHFFFAOYSA-N 0.000 description 1
- AMWHKADDWYODSP-UHFFFAOYSA-N n-cyclobutyl-3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CCC3)=NC=C2N=N1 AMWHKADDWYODSP-UHFFFAOYSA-N 0.000 description 1
- YCGYPEOSCBELAQ-UHFFFAOYSA-N n-cyclopentyl-3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CCCC3)=NC=C2N=N1 YCGYPEOSCBELAQ-UHFFFAOYSA-N 0.000 description 1
- TYYFTLGTEZPTAG-UHFFFAOYSA-N n-cyclopropyl-3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CC3)=NC=C2N=N1 TYYFTLGTEZPTAG-UHFFFAOYSA-N 0.000 description 1
- XROXHMXWLHQUOR-UHFFFAOYSA-N n-ethyl-3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C12=NC(NCC)=NC=C2N=NN1C1=CC=C(OC)C=C1 XROXHMXWLHQUOR-UHFFFAOYSA-N 0.000 description 1
- LANUNDHWRJFXCM-UHFFFAOYSA-N n-tert-butyl-3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC(C)(C)C)=NC=C2N=N1 LANUNDHWRJFXCM-UHFFFAOYSA-N 0.000 description 1
- RWHUEXWOYVBUCI-ITQXDASVSA-N nafarelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 RWHUEXWOYVBUCI-ITQXDASVSA-N 0.000 description 1
- 229960002333 nafarelin Drugs 0.000 description 1
- 229960004719 nandrolone Drugs 0.000 description 1
- REACBNMPQDINOF-YBBIQVIJSA-N nandrolone cyclotate Chemical compound C1CC(C)(C=C2)CCC12C(=O)O[C@H]1CC[C@H]2[C@H](CCC=3[C@@H]4CCC(=O)C=3)[C@@H]4CC[C@@]21C REACBNMPQDINOF-YBBIQVIJSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 239000006225 natural substrate Substances 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 229950007221 nedaplatin Drugs 0.000 description 1
- IXOXBSCIXZEQEQ-UHTZMRCNSA-N nelarabine Chemical compound C1=NC=2C(OC)=NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O IXOXBSCIXZEQEQ-UHTZMRCNSA-N 0.000 description 1
- 229960000801 nelarabine Drugs 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
- 210000005036 nerve Anatomy 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960001346 nilotinib Drugs 0.000 description 1
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 1
- 229960004918 nimorazole Drugs 0.000 description 1
- MDJFHRLTPRPZLY-UHFFFAOYSA-N nimorazole Chemical compound [O-][N+](=O)C1=CN=CN1CCN1CCOCC1 MDJFHRLTPRPZLY-UHFFFAOYSA-N 0.000 description 1
- 229960001420 nimustine Drugs 0.000 description 1
- VFEDRRNHLBGPNN-UHFFFAOYSA-N nimustine Chemical compound CC1=NC=C(CNC(=O)N(CCCl)N=O)C(N)=N1 VFEDRRNHLBGPNN-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 108020001162 nitroreductase Proteins 0.000 description 1
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
- 229960003301 nivolumab Drugs 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 229950009090 ocaratuzumab Drugs 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 229960002700 octreotide Drugs 0.000 description 1
- 229960002450 ofatumumab Drugs 0.000 description 1
- 229950007283 oregovomab Drugs 0.000 description 1
- 229940035567 orencia Drugs 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 229950004023 orteronel Drugs 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 201000004228 ovarian endometrial cancer Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229950007318 ozogamicin Drugs 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 229950000755 palifosfamide Drugs 0.000 description 1
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 1
- 229960003978 pamidronic acid Drugs 0.000 description 1
- 229960001972 panitumumab Drugs 0.000 description 1
- 229960005184 panobinostat Drugs 0.000 description 1
- FPOHNWQLNRZRFC-ZHACJKMWSA-N panobinostat Chemical compound CC=1NC2=CC=CC=C2C=1CCNCC1=CC=C(\C=C\C(=O)NO)C=C1 FPOHNWQLNRZRFC-ZHACJKMWSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 1
- 229960000639 pazopanib Drugs 0.000 description 1
- 229960005079 pemetrexed Drugs 0.000 description 1
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960002340 pentostatin Drugs 0.000 description 1
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 229950010307 peretinoin Drugs 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 229960002087 pertuzumab Drugs 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000009038 pharmacological inhibition Effects 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-M phenylacetate Chemical compound [O-]C(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-M 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 125000005498 phthalate group Chemical class 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- IIMIOEBMYPRQGU-UHFFFAOYSA-L picoplatin Chemical compound N.[Cl-].[Cl-].[Pt+2].CC1=CC=CC=N1 IIMIOEBMYPRQGU-UHFFFAOYSA-L 0.000 description 1
- 229950005566 picoplatin Drugs 0.000 description 1
- 210000004694 pigment cell Anatomy 0.000 description 1
- 229950002592 pimasertib Drugs 0.000 description 1
- 229960001221 pirarubicin Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- 229960004403 pixantrone Drugs 0.000 description 1
- PEZPMAYDXJQYRV-UHFFFAOYSA-N pixantrone Chemical compound O=C1C2=CN=CC=C2C(=O)C2=C1C(NCCN)=CC=C2NCCN PEZPMAYDXJQYRV-UHFFFAOYSA-N 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 150000003058 platinum compounds Chemical class 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229960001131 ponatinib Drugs 0.000 description 1
- PHXJVRSECIGDHY-UHFFFAOYSA-N ponatinib Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2N3N=CC=CC3=NC=2)=C1 PHXJVRSECIGDHY-UHFFFAOYSA-N 0.000 description 1
- 229960004293 porfimer sodium Drugs 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229960000214 pralatrexate Drugs 0.000 description 1
- OGSBUKJUDHAQEA-WMCAAGNKSA-N pralatrexate Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CC(CC#C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OGSBUKJUDHAQEA-WMCAAGNKSA-N 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- XYWJNTOURDMTPI-UHFFFAOYSA-N procodazole Chemical compound C1=CC=C2NC(CCC(=O)O)=NC2=C1 XYWJNTOURDMTPI-UHFFFAOYSA-N 0.000 description 1
- 229950000989 procodazole Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000009696 proliferative response Effects 0.000 description 1
- 210000005267 prostate cell Anatomy 0.000 description 1
- 238000011471 prostatectomy Methods 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- FVLAYJRLBLHIPV-UHFFFAOYSA-N pyrimidin-5-amine Chemical compound NC1=CN=CN=C1 FVLAYJRLBLHIPV-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- RJSRSRITMWVIQT-UHFFFAOYSA-N quinolin-6-amine Chemical compound N1=CC=CC2=CC(N)=CC=C21 RJSRSRITMWVIQT-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 229960002633 ramucirumab Drugs 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 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
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000010335 redox stress Effects 0.000 description 1
- 229960004836 regorafenib Drugs 0.000 description 1
- FNHKPVJBJVTLMP-UHFFFAOYSA-N regorafenib Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(F)C(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 FNHKPVJBJVTLMP-UHFFFAOYSA-N 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 229940116176 remicade Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000029054 response to nutrient Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 229960005560 rindopepimut Drugs 0.000 description 1
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 description 1
- 229960003452 romidepsin Drugs 0.000 description 1
- OHRURASPPZQGQM-UHFFFAOYSA-N romidepsin Natural products O1C(=O)C(C(C)C)NC(=O)C(=CC)NC(=O)C2CSSCCC=CC1CC(=O)NC(C(C)C)C(=O)N2 OHRURASPPZQGQM-UHFFFAOYSA-N 0.000 description 1
- 108010091666 romidepsin Proteins 0.000 description 1
- 229960003522 roquinimex Drugs 0.000 description 1
- HNMATTJJEPZZMM-BPKVFSPJSA-N s-[(2r,3s,4s,6s)-6-[[(2r,3s,4s,5r,6r)-5-[(2s,4s,5s)-5-[acetyl(ethyl)amino]-4-methoxyoxan-2-yl]oxy-6-[[(2s,5z,9r,13e)-13-[2-[[4-[(2e)-2-[1-[4-(4-amino-4-oxobutoxy)phenyl]ethylidene]hydrazinyl]-2-methyl-4-oxobutan-2-yl]disulfanyl]ethylidene]-9-hydroxy-12-(m Chemical compound C1[C@H](OC)[C@@H](N(CC)C(C)=O)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@@](C/3=C/CSSC(C)(C)CC(=O)N\N=C(/C)C=3C=CC(OCCCC(N)=O)=CC=3)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HNMATTJJEPZZMM-BPKVFSPJSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229960005399 satraplatin Drugs 0.000 description 1
- 190014017285 satraplatin Chemical compound 0.000 description 1
- 238000002821 scintillation proximity assay Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 206010040400 serum sickness Diseases 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 229950010372 sobuzoxane Drugs 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- RCOSUMRTSQULBK-UHFFFAOYSA-N sodium;propan-1-olate Chemical compound [Na+].CCC[O-] RCOSUMRTSQULBK-UHFFFAOYSA-N 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 230000006354 stress signaling Effects 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229950010924 talaporfin Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229960003102 tasonermin Drugs 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 229960002197 temoporfin Drugs 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
- 229960000235 temsirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 1
- GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 description 1
- XAONWBNOVRQVOH-CQSZACIVSA-N tert-butyl (3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]piperidine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3CN(CCC3)C(=O)OC(C)(C)C)=NC=C2N=N1 XAONWBNOVRQVOH-CQSZACIVSA-N 0.000 description 1
- ZVTLWKDTHCIFAH-CYBMUJFWSA-N tert-butyl (3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]pyrrolidine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3CN(CC3)C(=O)OC(C)(C)C)=NC=C2N=N1 ZVTLWKDTHCIFAH-CYBMUJFWSA-N 0.000 description 1
- XAONWBNOVRQVOH-AWEZNQCLSA-N tert-butyl (3s)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]piperidine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3CN(CCC3)C(=O)OC(C)(C)C)=NC=C2N=N1 XAONWBNOVRQVOH-AWEZNQCLSA-N 0.000 description 1
- ZVTLWKDTHCIFAH-ZDUSSCGKSA-N tert-butyl (3s)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]pyrrolidine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3CN(CC3)C(=O)OC(C)(C)C)=NC=C2N=N1 ZVTLWKDTHCIFAH-ZDUSSCGKSA-N 0.000 description 1
- GFTVGKSDTZRGGX-UHFFFAOYSA-N tert-butyl 3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]azetidine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CN(C3)C(=O)OC(C)(C)C)=NC=C2N=N1 GFTVGKSDTZRGGX-UHFFFAOYSA-N 0.000 description 1
- MHEOXGAJHAVIDQ-UHFFFAOYSA-N tert-butyl 4-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]piperidine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CCN(CC3)C(=O)OC(C)(C)C)=NC=C2N=N1 MHEOXGAJHAVIDQ-UHFFFAOYSA-N 0.000 description 1
- FFGBVRZFYOUMHL-KBPBESRZSA-N tert-butyl n-[(1s,3s)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentyl]carbamate Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@@H]3C[C@H](CC3)NC(=O)OC(C)(C)C)=NC=C2N=N1 FFGBVRZFYOUMHL-KBPBESRZSA-N 0.000 description 1
- XDDSFXLIYLWJFZ-LSDHHAIUSA-N tert-butyl n-[[(1s,3r)-3-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclopentyl]methyl]carbamate Chemical compound C1=CC(OC)=CC=C1N1C2=NC(N[C@H]3C[C@@H](CNC(=O)OC(C)(C)C)CC3)=NC=C2N=N1 XDDSFXLIYLWJFZ-LSDHHAIUSA-N 0.000 description 1
- ABKNURZPOGUFHI-UHFFFAOYSA-N tert-butyl n-[[4-[[3-(4-methoxyphenyl)triazolo[4,5-d]pyrimidin-5-yl]amino]cyclohexyl]methyl]carbamate Chemical compound C1=CC(OC)=CC=C1N1C2=NC(NC3CCC(CNC(=O)OC(C)(C)C)CC3)=NC=C2N=N1 ABKNURZPOGUFHI-UHFFFAOYSA-N 0.000 description 1
- 229950003046 tesevatinib Drugs 0.000 description 1
- HVXKQKFEHMGHSL-QKDCVEJESA-N tesevatinib Chemical compound N1=CN=C2C=C(OC[C@@H]3C[C@@H]4CN(C)C[C@@H]4C3)C(OC)=CC2=C1NC1=CC=C(Cl)C(Cl)=C1F HVXKQKFEHMGHSL-QKDCVEJESA-N 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
- ZVQXQPNJHRNGID-UHFFFAOYSA-N tetramethylsuccinonitrile Chemical compound N#CC(C)(C)C(C)(C)C#N ZVQXQPNJHRNGID-UHFFFAOYSA-N 0.000 description 1
- 229960003433 thalidomide Drugs 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 230000035922 thirst Effects 0.000 description 1
- 229960000874 thyrotropin Drugs 0.000 description 1
- 230000001748 thyrotropin Effects 0.000 description 1
- 229950002376 tirapazamine Drugs 0.000 description 1
- ORYDPOVDJJZGHQ-UHFFFAOYSA-N tirapazamine Chemical compound C1=CC=CC2=[N+]([O-])C(N)=N[N+]([O-])=C21 ORYDPOVDJJZGHQ-UHFFFAOYSA-N 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- 229950005976 tivantinib Drugs 0.000 description 1
- 229960003989 tocilizumab Drugs 0.000 description 1
- 230000003614 tolerogenic effect Effects 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229960004066 trametinib Drugs 0.000 description 1
- LIRYPHYGHXZJBZ-UHFFFAOYSA-N trametinib Chemical compound CC(=O)NC1=CC=CC(N2C(N(C3CC3)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 LIRYPHYGHXZJBZ-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 229960001612 trastuzumab emtansine Drugs 0.000 description 1
- YWBFPKPWMSWWEA-UHFFFAOYSA-O triazolopyrimidine Chemical class BrC1=CC=CC(C=2N=C3N=CN[N+]3=C(NCC=3C=CN=CC=3)C=2)=C1 YWBFPKPWMSWWEA-UHFFFAOYSA-O 0.000 description 1
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- PXFLCAQHOZXYED-UHFFFAOYSA-N tripyrrolidin-1-ylphosphane Chemical compound C1CCCN1P(N1CCCC1)N1CCCC1 PXFLCAQHOZXYED-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229960000875 trofosfamide Drugs 0.000 description 1
- UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 229950009811 ubenimex Drugs 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 229960001055 uracil mustard Drugs 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 208000037964 urogenital cancer Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 210000003934 vacuole Anatomy 0.000 description 1
- 229950010938 valspodar Drugs 0.000 description 1
- 108010082372 valspodar Proteins 0.000 description 1
- 229960000241 vandetanib Drugs 0.000 description 1
- UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- NMDYYWFGPIMTKO-HBVLKOHWSA-N vinflunine Chemical compound C([C@@](C1=C(C2=CC=CC=C2N1)C1)(C2=C(OC)C=C3N(C)[C@@H]4[C@@]5(C3=C2)CCN2CC=C[C@]([C@@H]52)([C@H]([C@]4(O)C(=O)OC)OC(C)=O)CC)C(=O)OC)[C@H]2C[C@@H](C(C)(F)F)CN1C2 NMDYYWFGPIMTKO-HBVLKOHWSA-N 0.000 description 1
- 229960000922 vinflunine Drugs 0.000 description 1
- 229960000237 vorinostat Drugs 0.000 description 1
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000005303 weighing Methods 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
- 239000008096 xylene Substances 0.000 description 1
- 229950008250 zalutumumab Drugs 0.000 description 1
- 229950009002 zanolimumab Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229960004276 zoledronic acid Drugs 0.000 description 1
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P11/04—Drugs for disorders of the respiratory system for throat disorders
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/08—Antibacterial agents for leprosy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Psychology (AREA)
- Biotechnology (AREA)
- Pain & Pain Management (AREA)
- Physical Education & Sports Medicine (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
Description
本発明は、価値ある特性を有する新規化合物、特に医薬の調製のために用いることができるものを発見する目的を有した。
式Iで表される化合物は、general control nonderepressible 2(GCN2)と称されるストレス応答eIF2キナーゼEIF2AK4を阻害する。
T細胞は、IDO活性化に対して優先的に感受性であると考えられ、したがって、トリプトファンについて飢餓状態になると、T細胞は分裂することができず、結果として、それらに対して提示される抗原により活性化されることができなくなる。MunnおよびMellorおよび彼らの同僚らは、IDOが、T細胞の活性化を抑制することにより、および腫瘍抗原に対する末梢性寛容を生じることにより、免疫を調節することを明らかにした(MellorおよびMunn、2004)。これらの機構は、腫瘍細胞によりその直近の微小環境または腫瘍を排出するリンパ節にリクルートされた免疫細胞の破壊を包含する。ここで、抗原提示細胞により捕捉(scavenge)された腫瘍抗原は、適応免疫系に交差提示される。直接的に寛容誘発性であることに加えて、成熟DCは、調節性T細胞(Tregs)を増殖させる能力を有する[Moser、2003]。
増大したARG活性は、大腸癌、乳癌、肺癌および前立腺癌を有する患者において、しばしば観察され[Cederbaum、2004]、このことは、前立腺癌において見出されるARGおよびNOSの過剰発現と相関する[Keskinegeら、2001、Aaltomaら、2001、Wangら、2003]。浸潤しているマクロファージにおけるARG活性が、抗原特異的なT細胞応答およびCD3受容体の発現を損なうことが示された。さらに、腫瘍関連骨髄細胞におけるARGおよびNOSの累積活性は、抗原特異的Tリンパ球に対して、最終的にアポトーシスをもたらす阻害的シグナルを生じ得る[Bronte、2003a;2003b]。
IDO/GCN2経路の阻害薬は、慢性かつ持続的な感染症に対する宿主の免疫を増強するために用いることができるであろう。
1. Aaltoma, S.H., P.K. Lipponen, and V.M. Kosma. 2001. Inducible nitric oxide synthase (iNOS) expression and its prognostic value in prostate cancer. Anticancer Res. 21:3101-3106.
2. Brandacher, G.; Perathoner, A.; Ladurner, R.; Schneeberger, S.; Obrist, P.; Winkler, C.; Werner, E. R.; Werner-Felmayer, G.; Weiss, H. G.; Gobel, G.; Margreiter, R.; Konigsrainer, A.; Fuchs, D.; Amberger, A. Prognostic value of indoleamine 2,3- dioxygenase expression in colorectal cancer: effect on tumorinfiltrating T cells. Clin. Cancer Res. 2006, 12, 1144-1151.
3. Bronte V, Zanovello P. (2005). Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol 5: 641-654.
4. Bronte, V., P. Serafini, C. De Santo, I. Marigo, V. Tosello, A. Mazzoni, D.M. Segal, C. Staib, M. Lowel, G. Sutter, et al. 2003a. IL-4- induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice. J. Immunol. 170:270-278.
5. Bronte, V., P. Serafini, A. Mazzoni, D.M. Segal, and P. Zanovello. 2003b. L-arginine metabolism in myeloid cells controls T-lymphocyte functions. Trends Immunol. 24:302-306
6. Carmela De Santo, Paolo Serafini, Ilaria Marigo, Luigi Dolcetti, Manlio Bolla,§ Piero Del Soldato, Cecilia Melani, Cristiana Guiducci, Mario P. Colombo, Manuela Iezzi, Piero Musiani, Paola Zanovello, and Vincenzo Bronte. Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination. Proc Natl Acad Sci U S A. 2005 March 15; 102(11): 4185-4190
7. Cederbaum, S.D., H. Yu, W.W. Grody, R.M. Kern, P. Yoo, and R.K. Iyer. 2004. Arginases I and II: do their functions overlap? Mol. Genet. Metab. 81:S38-44.
8. T. O'Connor, K.R. Sadleir, E. Maus, R.A. Velliquette, J. Zhao, S.L. Cole, W.A. Eimer, B. Hitt, L.A. Bembinster, S. Lammich, S.F. Lichtenthaler, S.S. Hebert, S.B. De, C. Haass, D.A. Bennett, R. Vassar, Phosphorylation of the translation initiation factor eIF2alpha increases BACE1 levels and promotes amyloidogenesis. Neuron, 60 (2008), pp. 988-1009
9. Dey, M., Cao, C., Sicheri, F. and T.E. Dever. Conserved Intermolecular Salt Bridge Required for Activation of Protein Kinases PKR, GCN2, and PERK. JBC 282(9): 6653, 2007.
10. Dunn, G. P.; Old, L. J.; Schreiber, R. D. The immunobiology of cancer immunosurveillance and immunoediting. Immunity 2004, 21, 137-148.
11. Fallarino, F. U. Grohmann, S. You, B.C. et al. The combined effects fo tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J. Immunol. 176:6752, 2006.
12. Friberg M, Jennings R, Alsarraj M, Dessureault S, Cantor A, Extermann M et al. (2002). Indoleamine 2,3-dioxygenase contributes to tumor cell evasion of T cell-mediated rejection. Int. J Cancer 101: 151-155
13. Harding HP, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, Ron D. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell. 2000 Nov;6(5):1099-108.
14. Hou DY, Muller AJ, Sharma MD, DuHadaway J, Banerjee T, Johnson M et al. (2007). Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-メチル-tryptophan correlates with antitumor responses. Cancer Res 67: 792-801.
15. Keskinege, A., S. Elgun, and E. Yilmaz. 2001. Possible implications of arginase and diamine oxidase in prostatic carcinoma. Cancer Detect. Prev. 25:76-79.
16. Mellor AL, Munn DH. (2004). IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 4: 762-774.
17. Mitsuda T, Hayakawa Y, Itoh M, Ohta K, Nakagawa T. ATF4 regulates gamma-secretase activity during amino acid imbalance, Biochem Biophys Res Commun. 2007 Jan 19;352(3):722-7.
18. Moser, M. Dendritic cells in immunity and tolerance-do they display opposite functions? Immunity 2003, 19, 5-8.
19. Muller, A.J. and P.A. Scherle. Targeting the mechanisms of tumoral immune tolerance with small-molecule inhibitors. Nat. Rev. Cancer. 6:613, 2006.
20. Muller AJ, Prendergast GC. (2007). Indoleamine 2,3-dioxygenase in immune suppression and cancer. Curr Cancer Drug Targets 7: 31-40.
21. Muller AJ, DuHadaway JB, Sutanto-Ward E, Donover PS, Prendergast GC. (2005a). Inhibition of indoleamine 2,3-dioxygenase, an immunomodulatory target of the tumor suppressor gene Bin1, potentiates cancer chemotherapy. Nature Med 11: 312-319.
22. Muller AJ, Malachowski WP, Prendergast GC. (2005b). Indoleamine 2,3-dioxygenase in cancer: targeting pathological immune tolerance with small-molecule inhibitors. Expert Opin Ther Targets 9: 831-849.
23. Munn, D.H., M.D. Sharma, B. Baban, H.P. Harding, Y. Zhang, D. Ron, A.L. Mellor. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity. 22:633, 2005
24. Ohta K, Mizuno A, Ueda M, Li S, Suzuki Y, Hida Y, Hayakawa-Yano Y, Itoh M, Ohta E, Kobori M, Nakagawa T. Autophagy impairment stimulates PS1 expression and gamma-secretase activity. Autophagy. 2010 ;6(3):345-52
25. Okamoto, A.; Nikaido, T.; Ochiai, K.; Takakura, S.; Saito, M.; Aoki, Y.; Ishii, N.; Yanaihara, N.; Yamada, K.; Takikawa, O.; Kawaguchi, R.; Isonishi, S.; Tanaka, T.; Urashima, M. Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells. Clin. Cancer Res. 2005, 11, 6030-6039.
26. Oyadomari S, Mori M. Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 2004 Apr;11(4):381-9.
27. GC Prendergast, Immune escape as a fundamental trait of cancer: focus on IDO. Oncogene (2008) 27, 3889-3900
28. Popovic PJ, Zeh III HJ, Ochoa JB. (2007). Arginine and immunity. J Nutr 137: 1681S-1686 S.
29. Rodriguez, P.C., D.G. Quiceno, J. Zabaleta, B. Ortiz, A.H. Zea, M.B. Piazuelo,A.Delgado, P.Correa, J.Brayer, E.M. Sotomayor, S.Antonia, J.B. Ochoa, and A.C. Ochoa. Arginase I Production in the Tumor Microenvironment by Mature Myeloid Cells Inhibits T-Cell Receptor Expression and Antigen-Specific T-Cell Responses. Canc. Res. 64:5839, 2004
30. Rodriguez, P.C., D.G. Quiceno, and A.C. Ochoa. L-arginine availability regulates T-lymphocyte cell-cycle progresion. Blood. 109:1568, 2007.
31. Shankaran, V.; Ikeda, H.; Bruce, A. T.; White, J. M.; Swanson, P. E.; Old, L. J.; Schreiber, R. D. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 2001, 410, 1107-1111.
32. Sharma, M.D., B. Baban, P. Chandler, D-Y. Hou, N. Singh, H. Yagita, M. Azuma, B.R. Blazar, A.L. Mellor, and D.H. Munn. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J. Clin. Invest. 117:2570, 2007.
33. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N et al. (2003). Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3- dioxygenase. Nat Med 9: 1269-1274
34. Wang, J., M. Torbenson, Q. Wang, J.Y. Ro, and M. Becich. 2003. Expression of inducible nitric oxide synthase in paired neoplastic and non-neoplastic primary prostate cell cultures and prostatectomy specimen. Urol. Oncol. 21:117-122.
35. Wek RC, Jiang HY, Anthony TG. Coping with stress: eIF2 kinases and translational control. Biochem Soc Trans. 2006 Feb;34 (Pt 1):7-11.
36. Ye J, Kumanova M, Hart LS, Sloane K, Zhang H, De Panis DN, Bobrovnikova-Marjon E, Diehl JA, Ron D, Koumenis C. The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation. EMBO J. 2010 Jun 16;29(12):2082-96.
さらに、本発明の目的は、限定されないが、固形腫瘍癌、リンパまたは血液系の癌を含む悪性腫瘍、神経変性疾患および慢性感染症の予防および処置のための新たな化合物の合成である。
式Iで表される化合物は、さらに、GCN2の活性または発現の単離および研究のために、用いることができる。さらに、それらは、制御されない、または妨害されたGCN2活性に関連する疾患についての診断方法における使用のために、特に好適である。
式Iで表される化合物はまた、好ましくはGCN2に対する阻害活性に加えて、チロシンキナーゼFMS(CSF1R)、GSK3α、GSK3β、FLT3またはFLT4、またはこれらのキナーゼの組み合わせを阻害することができる。
GSK3阻害剤は、乳癌細胞の増殖を阻害し、したがって、ホルモンに基づく治療に対して耐性の乳癌のための革新的なアプローチを提供する(H.M. Kim et al., PLoS One, 2013; 8(4):e60383)。
GSK3阻害剤の抗骨髄腫活性は、C. Fiondaら(J. Immunol. 2013 Jun 15; 190(12):6662-72)により報告される。
GSK3αおよびGSK3β阻害剤の抗骨髄腫活性は、S.V. Madhunapantula et al., Pigment Cell Melanoma Res. 2013 Aug 19doi: 10.1111/pcmr.12156により報告される。
トリアゾロピリミジン誘導体は、アルツハイマーまたは糖尿病のような疾患の処置のためのGSK3阻害剤として、WO 2005/012307 A1において、およびWO 2006/075023 A2において記載される。
本発明は、式I:
R1は、ArまたはHetを表し、
あるいは
3〜7個のC原子を有するシクロアルキルまたはシクロペンテニルを表し、これらの各々は、Aおよび/またはHalにより一、二、三、四または五置換されることができ、および/または、これは、[C(R3)2]pOR3、O[C(R3)2]pOR3、[C(R3)2]pN(R3)2、O[C(R3)2]pN(R3)2、[C(R3)2]pAr、[C(R3)2]pHet1、O[C(R3)2]pHet1、CN、[C(R3)2]pCOOR3、O[C(R3)2]pCOOR3、CONH2、CONHA、CONA2、[C(R3)2]pNR3COA、CONR3SO2A、NR3SO2A、SO2N(R3)2、S(O)nA、COHet1、O[C(R3)2]mN(R3)2、[C(R3)2]pNR3COOA、[C(R3)2]pNR3COOCH2Ph、NR3CON(R3)2、NHCOO[C(R3)2]mN(R3)2、NHCOO[C(R3)2]pHet1、NHCONH[C(R3)2]mN(R3)2、NHCONH[C(R3)2]pHet1、OCONH[C(R3)2]mN(R3)2、OCONH[C(R3)2]pHet1、CONH(CH2)pHet2、CONR3NR3COA、CONR3N(R3)2、CONHCyc、COA、=S、=NR3および/または=Oにより一または二置換されることができ、
あるいは
ピペリジニル、テトラヒドロピラニル、ピロリジニル、アゼチジニル、チオラニル、オキセタニル、3−アザ−ビシクロ[3.1.0]ヘキシル、テトラヒドロチオフェニル、テトラヒドロチオピラニル、4,5,6,7−テトラヒドロ−1H−インダゾール−5−イル、4,5,6,7−テトラヒドロ−1H−インダゾール−6−イル、テトラヒドロピラゾリル、テトラヒドロフラニルまたはヘキサヒドロピリダジニルを表し、これらの各々は、Aおよび/またはHalにより一、二、三、四または五置換されることができ、および/または、これは、[C(R3)2]pOR3、O[C(R3)2]pOR3、[C(R3)2]pN(R3)2、[C(R3)2]pAr、[C(R3)2]pHet1、[C(R3)2]pHet3、CN、[C(R3)2]pCOOR3、CO[C(R3)2]pN(R3)2、CO[C(R3)2]pHet1、CO[C(R3)2]pHet3、NR3COA、NR3SO2A、SO2N(R3)2、S(O)nA、COHet1、O[C(R3)2]mN(R3)2、O[C(R3)2]pHet1、NHCOOA、NHCON(R3)2、NHCOO[C(R3)2]mN(R3)2、NHCOO[C(R3)2]pHet1、NHCONH[C(R3)2]mN(R3)2、NHCONH[C(R3)2]pHet1、OCONH[C(R3)2]mN(R3)2、OCONH[C(R3)2]pHet1、C(O)R3、=S、=NR3および/または=Oにより一または二置換されることができ、
Arは、フェニルまたはナフチルを表し、これらの各々は、未置換であるか、またはHal、A、[C(R3)2]pOR3、O[C(R3)2]pOR3、[C(R3)2]pN(R3)2、O[C(R3)2]pN(R3)2、[C(R3)2]pHet1、[C(R3)2]pHet3、NO2、CN、[C(R3)2]pCOOR3、O[C(R3)2]pCOOR3、CON(R3)2、NR3COA、NR3SO2A、SO2N(R3)2、S(O)nA、COHet1、O[C(R3)2]pHet1、NHCOOA、NHCON(R3)2、NHCOO[C(R3)2]mN(R3)2、NHCOO[C(R3)2]pHet1、NHCONH[C(R3)2]mN(R3)2、NHCONH[C(R3)2]pHet1、OCONH[C(R3)2]mN(R3)2、OCONH[C(R3)2]pHet1、S(O)nHet1、CHOおよび/またはCOAにより、一、二または三置換されており、
あるいはアズレニルを表し、
Cycは、3〜7個のC原子を有するシクロアルキルを表し、これは、OHにより一または二置換されることができ、
Aは、1〜10個のC原子を有する非分枝状または分枝状のアルキルを表し、ここで、1、2または3個の隣接していないCHおよび/またはCH2基は、N、Oおよび/またはS原子により置き換えられていてもよく、およびここで、1〜7個のH原子は、OH、Fおよび/またはClにより置き換えられていてもよく、
Halは、F、Cl、BrまたはIを表し、
nは、0、1または2を表し、
mは、1、2または3を表し、
pは、0、1、2、3または4を表す、
で表される化合物、ならびにその薬学的に使用可能な誘導体、溶媒和物、塩、互変異性体および立体異性体、ならびに全ての比におけるそれらの混合物に関する。
本発明はまた、式Iで表される化合物の塩の溶媒和物、例えば、塩酸塩の一水和物または二水和物に関する。
用語、化合物の溶媒和物とは、不活性な溶媒分子の化合物への付加を意味するものと考えられ、これは、それらの相互誘引力に起因して形成する。溶媒和物は、例えば、一もしくは二水和物またはアルコラートである。
用語、薬学的に受容可能な誘導体とは、例えば、本発明による化合物の塩およびまたいわゆるプロドラッグ化合物を意味するものと考えられる。
さらに、表現「治療有効量」は、この量を投与されていない対応する対照と比較して、以下の結果を有する量を表す:疾患、症候群、状態、愁訴、障害または副作用の処置、治癒、予防または除去の改善、あるいはまた、疾患、愁訴または障害の進行の軽減。
表現「治療有効量」はまた、正常な生理学機能を増大させるために有効である量を包含する。
それらは、特に好ましくは、立体異性体化合物の混合物である。
式II
で表される化合物を、式III:
R2−NH2 III
式中、R2は、請求項1において示される意味を有する
で表される化合物と反応させること、
および/または
式Iの塩基または酸をその塩の1つに変換すること
を特徴とする。
1回より多く現れる全てのラジカルについて、それらの意味は、互いに独立する。
Aは、非常に特に好ましくは、1、2、3、4、5または6個のC原子を有するアルキル、好ましくはメチル、エチル、プロピル、イソプロピル、ブチル、イソブチル、sec−ブチル、tert−ブチル、ペンチル、ヘキシル、トリフルオロメチル、ペンタフルオロエチルまたは1,1,1−トリフルオロ−エチルを表す。
さらに、Aは、例えば、CH2OCH3、CH2CH2OH、OCH2CH2NH2、CH2NHCH2またはNHCH2CH3を表す。
3〜7個のC原子を有するシクロアルキルは、好ましくは、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシルまたはシクロヘプチルを表す。
あるいは、
好ましくは3〜7個のC原子を有するシクロアルキル、またはシクロペンテニルを表し、これらの各々は、Aおよび/またはHalにより一、二、三、四または五置換されることができ、および/または、これは、[C(R3)2]pOR3、[C(R3)2]pN(R3)2、[C(R3)2]pAr、[C(R3)2]pHet1、[C(R3)2]pCOOR3、[C(R3)2]pNR3COOA、S(O)nA、CN、CONR3SO2A、SO2N(R3)2、CONH2、CONHA、CONA2、CONH(CH2)pHet2、[C(R3)2]pHet1、COHet1、CONR3NR3COA、CONR3N(R3)2、CONHCycおよび/または[C(R3)2]pNR3COOCH2Phにより一または二置換されることができ、
あるいは、
好ましくは、ピペリジニル、テトラヒドロピラニル、ピロリジニル、アゼチジニル、チオラニル、オキセタニル、3−アザ−ビシクロ[3.1.0]ヘキシル、テトラヒドロチオフェニル、テトラヒドロチオピラニル、4,5,6,7−テトラヒドロ−1H−インダゾール−5−イル、4,5,6,7−テトラヒドロ−1H−インダゾール−6−イル、テトラヒドロピラゾリル、テトラヒドロフラニルまたはヘキサヒドロピリダジニルを表し、これらの各々は、Aおよび/またはHalにより一、二、三、四または五置換されることができ、および/または、これは、[C(R3)2]pHet1、[C(R3)2]pHet3、SO2N(R3)2、S(O)nA、[C(R3)2]pCOOR3、CO[C(R3)2]pN(R3)2、CO[C(R3)2]pHet1、CO[C(R3)2]pHet3、C(O)R3、および/または=Oにより一または二置換されていてもよい。
R3は、好ましくは、Hまたは1、2、3もしくは4個のC原子を有するアルキル、特に好ましくはHまたはメチルを表す。
さらに、Arは、アズレニルを表す。
Het2は、好ましくは、ピラゾリル、オキサジアゾリル、ピリジニル、テトラゾリル、ピリダジニル、ピロリジニル、アゼチジニル、アゾキセタニル、テトラヒドロイミダゾリル、テトラヒドロピラゾリル、テトラヒドロフラニル、ピペリジニル、モルホリニル、テトラヒドロピラニルまたはピペラジニルを表し、これらの各々は、未置換であるか、またはAおよび/または=Oにより一置換されている。
Halは、好ましくは、F、ClまたはBrを表すが、またIを表し、特に好ましくはFまたはClを表す。
式Iで表される化合物は、1または2以上のキラル中心を有していてもよく。したがって、多様な立体異性体形態において現れ得る。式Iは、全てのこれらの形態を包含する。
あるいは、
3〜7個のC原子を有するシクロアルキル、またはシクロペンテニルを表し、これらの各々は、Aおよび/またはHalにより一、二、三、四または五置換されることができ、および/または、これは、[C(R3)2]pOR3、[C(R3)2]pN(R3)2、[C(R3)2]pAr、[C(R3)2]pHet1、[C(R3)2]pCOOR3、[C(R3)2]pNR3COOA、S(O)nA、[C(R3)2]pHet1、COHet1、CN、CONR3SO2A、SO2N(R3)2、CONH2、CONHA、CONA2、CONH(CH2)pHet2、CONR3NR3COA、CONR3N(R3)2、CONHCycおよび/または[C(R3)2]pNR3COOCH2Phにより一または二置換されることができ、
あるいは、
ピペリジニル、テトラヒドロピラニル、ピロリジニル、アゼチジニル、チオラニル、オキセタニル、3−アザ−ビシクロ[3.1.0]ヘキシル、テトラヒドロチオフェニル、テトラヒドロチオピラニル、4,5,6,7−テトラヒドロ−1H−インダゾール−5−イル、4,5,6,7−テトラヒドロ−1H−インダゾール−6−イル、テトラヒドロピラゾリル、テトラヒドロフラニルまたはヘキサヒドロピリダジニルを表し、これらの各々は、Aおよび/またはHalにより一、二、三、四または五置換されることができ、および/または、これは、[C(R3)2]pHet1、[C(R3)2]pHet3、SO2N(R3)2、S(O)nA、[C(R3)2]pCOOR3、CO[C(R3)2]pN(R3)2、CO[C(R3)2]pHet1、CO[C(R3)2]pHet3、C(O)R3、および/または=Oにより一または二置換されることができ;
あるいは、アズレニルを表し;
R2は、1〜7個のC原子を有する非分枝状または分枝状のアルキルを表し、ここで、2個の隣接する炭素原子は、二重または三重結合を形成してもよく、これは、Halにより、一、二、三、四または五置換されていてもよく、および/または、これは、CN、CONH2、CONHA、CONA2および/またはO[C(R3)2]mN(R3)2により一または二置換されることができ、
あるいは、
3〜7個のC原子を有するシクロアルキル、またはシクロペンテニルを表し、これらの各々は、Aおよび/またはHalにより一、二、三、四または五置換されることができ、および/または、これは、[C(R3)2]pOR3、[C(R3)2]pN(R3)2、[C(R3)2]pAr、[C(R3)2]pHet1、[C(R3)2]pCOOR3、[C(R3)2]pNR3COOA、S(O)nA、CN、CONR3SO2A、SO2N(R3)2、CONH2、CONHA、CONA2、CONH(CH2)pHet2、[C(R3)2]pHet1、COHet1、CONR3NR3COA、CONR3N(R3)2、CONHCycおよび/または[C(R3)2]pNR3COOCH2Phにより一または二置換されることができ、
あるいは、
ピペリジニル、テトラヒドロピラニル、ピロリジニル、アゼチジニル、チオラニル、オキセタニル、3−アザ−ビシクロ[3.1.0]ヘキシル、テトラヒドロチオフェニル、テトラヒドロチオピラニル、4,5,6,7−テトラヒドロ−1H−インダゾール−5−イル、4,5,6,7−テトラヒドロ−1H−インダゾール−6−イル、テトラヒドロピラゾリル、テトラヒドロフラニルまたはヘキサヒドロピリダジニルを表し、これらの各々は、Aおよび/またはHalにより一、二、三、四または五置換されることができ、および/または、これは、[C(R3)2]pHet1、SO2N(R3)2、S(O)nA、[C(R3)2]pHet3、[C(R3)2]pCOOR3、CO[C(R3)2]pN(R3)2、CO[C(R3)2]pHet1、CO[C(R3)2]pHet3、C(O)R3、および/または=Oにより一または二置換されることができ、
Arは、フェニルまたはナフチルを表し、これらの各々は、未置換であるか、またはHal、A、[C(R3)2]pOR3、O[C(R3)2]pCOOR3、S(O)nA、[C(R3)2]pHet1、O[C(R3)2]pHet1および/または[C(R3)2]pHet3により、一、二または三置換されており、
あるいはアズレニルを表し、
Phは、フェニルを表し、
Cycは、3〜7個のC原子を有するシクロアルキルを表し、これは、OHにより一または二置換されることができ、
Halは、F、Cl、BrまたはIを表し、
nは、0、1または2を表し、
mは、1、2または3を表し、
pは、0、1、2、3または4を表す、
ならびにその薬学的に受容可能な塩、溶媒和物、互変異性体および立体異性体、ならびに全ての比におけるそれらの混合物。
式Iで表される化合物は、好ましくは、式IIで表される化合物を式IIIで表される化合物と反応させることにより、得ることができる。
用いられる条件に依存して、反応時間は、数分間〜14日間であり、反応温度は、約0℃〜140℃、通常は20〜120℃、特に約60〜約110℃である。
好適な不活性な溶媒の例は、ヘキサン、石油エーテル、ベンゼン、トルエンもしくはキシレンなどの炭化水素;トリクロロエチレン、1,2−ジクロロエタン、四塩化炭素、クロロホルムもしくはジクロロメタンなどの塩素化炭化水素;メタノール、エタノール、イソプロパノール、n−プロパノール、n−ブタノールもしくはtert−ブタノールなどのアルコール;ジエチルエーテル、ジイソプロピルエーテル、テトラヒドロフラン(THF)もしくはジオキサンなどのエーテル;エチレングリコールモノメチルもしくはモノエチルエーテル、エチレングリコールジメチルエーテル(diglyme)などのグリコールエーテル;アセトンもしくはブタノンなどのケトン;アセタミド、ジメチルアセタミドもしくはジメチルホルムアミド(DMF)などのアミド;アセトニトリルなどのニトリル;ジメチルスルホキシド(DMSO)などのスルホキシド;二硫化炭素;ギ酸もしくは酢酸などのカルボン酸;ニトロメタンもしくはニトロベンゼンなどのニトロ化合物;酢酸エチルなどのエステル、または前記溶媒の混合物である。
特に好ましいのは、2−メトキシエタノールである。
前記の本発明による化合物は、それらの最終的な非塩形態において用いることができる。一方、本発明はまた、薬学的に受容可能な塩の形態におけるこれらの化合物の使用を包含し、これらは、多様な有機および無機の酸および塩基から、当該分野において公知の手順により誘導することができる。式Iで表される化合物の薬学的に受容可能な塩形態は、大部分において、従来の方法により調製される。式Iで表される化合物がカルボキシル基を含む場合、その好適な塩のうちの1つは、化合物を好適な塩基と反応させて対応する塩基付加塩を得ることにより、形成することができる。かかる塩基は、例えば、水酸化カリウム、水酸化ナトリウムおよび水酸化リチウムを含むアルカリ金属水酸化物;水酸化バリウムおよび水酸化カルシウムなどのアルカリ土類金属水酸化物;アルカリ金属アルコキシド、例えばカリウムエトキシドおよびナトリウムプロポキシド;ならびにピペリジン、ジエタノールアミンおよびN−メチルグルタミンなどの多様な有機塩基である。式Iで表される化合物のアルミニウム塩は、同様に含まれる。特定の式Iで表される化合物の場合、酸付加塩は、これらの化合物を、薬学的に受容可能な有機および無機酸、例えば塩化水素、臭化水素またはヨウ化水素などのハロゲン化水素、他の鉱酸および対応するその塩(硫酸、硝酸またはリン酸など)、ならびにアルキル−およびモノアリールスルホン酸(エタンスルホン酸、トルエンスルホン酸、およびベンゼンスルホン酸など)、ならびに他の有機酸およびその対応する塩(酢酸、トリフルオロ酢酸、酒石酸、マレイン酸、コハク酸、クエン酸、安息香酸、サリチル酸、アスコルビン酸など)で処置することにより、形成することができる。したがって、式Iで表される化合物の薬学的に受容可能な酸付加塩は、以下:酢酸塩、アジピン酸塩、アルギン酸塩、アルギニン酸塩、アスパルギン酸塩、安息香酸塩、ベンゼンスルホン酸塩(ベシル酸塩)、重硫酸塩、亜硫酸水素塩、臭化物、酪酸塩、樟脳酸塩、樟脳スルホン酸塩、カプリル酸塩、塩化物、クロロ安息香酸塩、クエン酸塩、シクロペンタンプロピオン酸塩、二グルコン酸塩、リン酸二水素塩、ジニトロ安息香酸塩、ドデシル硫酸塩、エタンスルホン酸塩、フマル酸塩、ガラクタル酸塩(ムチン酸から)、ガラクツロン酸塩、グルコヘプタン酸塩、グルコン酸塩、グルタミン酸塩、グリセロリン酸塩、ヘミコハク酸塩、ヘミ硫酸塩、ヘプタン酸塩、ヘキサン酸塩、馬尿酸塩、塩酸塩、臭化水素酸塩、ヨウ化水素酸塩、2−ヒドロキシ−エタンスルホン酸塩、ヨウ化物、イセチオン酸塩、イソ酪酸塩、乳酸塩、ラクトビオン酸塩、リンゴ酸塩、マレイン酸塩、マロン酸塩、マンデル酸塩、メタ硫酸塩、メタンスルホン酸塩、メチル安息香酸塩、カルシウムリン酸一水素塩、2−ナフタレンスルホン酸塩、ニコチン酸塩、硝酸塩、シュウ酸塩、オレイン酸塩、パルモ酸塩(palmoate)、ペクチン酸塩、過硫酸塩、フェニル酢酸塩、3−フェニルプロピオン酸塩、リン酸塩、ホスホン酸塩、フタル酸塩を含むが、これは、限定を表すものではない。
特に好ましいのは、塩酸塩、二塩酸塩、臭化水素酸塩、マレイン酸塩、メシル酸塩、リン酸塩、硫酸塩およびコハク酸塩である。
従来の様式において塩の形成を引き起こすことにより、調製される。遊離の酸形態は、塩形態を酸と接触させて、従来の様式において遊離の酸を単離することにより、再生することができる。遊離の酸基形態は、特定の観点において、極性溶媒中での溶解度などの特定の物理学的特性に関して、その対応する塩形態と異なる;しかし、本発明の目的のために、塩は、他の点においては、そのそれぞれの遊離の酸形態に対応する。
さらに、式Iで表される化合物は、その同位体標識された形態を含むことが意図される。式Iで表される化合物の同位体標識された形態は、当該化合物の1または2以上の原子が、通常天然に存在する原子の原子質量または質量数とは異なる原子質量または質量数を有する原子により置き換えられているという事実を除いては、この化合物と同一である。容易に市販で入手し得、周知の方法により式Iで表される化合物中に組み込むことができる同位体の例として、水素、炭素、窒素、酸素、リン、フッ素および塩素の同位体、例えばそれぞれ、2H、3H、13C、14C、15N、18O、17O、31P、32P、35S、18Fおよび36CIが挙げられる。式Iで表される化合物、そのプロドラッグまたは薬学的に受容可能な塩であって、上述の同位体の1または2以上および/または他の原子の他の同位体を含むものはいずれも、本発明の一部であるものと意図される。同位体標識された式Iで表される化合物は、多数の有益な方法において用いることができる。例として、例えば3Hまたは14Cなどの放射性同位体が組み込まれている同位体標識された式Iで表される化合物は、医薬および/または基質組織分布アッセイのために好適である。これらの放射性同位体、すなわちトリチウム(3H)および炭素14(14C)は、それらの簡易な調製および優れた検出能のために、特に好ましい。より重い同位体、例えばデューテリウム(2H)の式Iで表される化合物中への組み込みは、この同位体標識された化合物のより高い代謝安定性のために、治療的利点を有する。より高い代謝安定性は、直接的に、より長いin vivoでの半減期またはより低い投与量と言い換えられ、これらは、殆どの状況において、本発明の好ましい態様を表わすであろう。同位体標識された式Iで表される化合物は、通常は、本文における合成スキームおよび関連する記載において、例のパートにおいて、および調製のパートにおいて開示される手順を、同位体標識されていない反応物を容易に利用可能な同位体標識された反応物で置き換えて行うことにより、調製することができる。
眼または他の外組織、例えば口および皮膚の処置のために、処方物は、好ましくは、局所用軟膏またはクリームとして適用される。軟膏を得るための処方の場合、活性成分は、パラフィン性または水混和性のクリーム用基剤のいずれかと共に使用することができる。あるいは、活性成分は、水中油型のクリーム用基剤または油中水型の基剤と共に、クリームを生じるように処方することができる。
口における局所投与のために適応される医薬処方物は、ロゼンジ、トローチおよび洗口剤を包含する。
直腸投与のために適応される医薬処方物は、坐剤または浣腸の形態において投与することができる。
吸入による投与のために適応される医薬処方物は、微細に粒子化されたダストまたはミストを包含し、これらは、多様な型のエアロゾルによる加圧ディスペンサー、ネブライザーまたは吸入器により発生させることができる。
膣投与のために適応される医薬処方物は、ペッサリー、タンポン、クリーム、ゲル、ペースト、泡体またはスプレー処方物として投与することができる。
以下の医薬は、排他的なものではないが、好ましくは式Iで表される化合物と組み合わされる:
2.糖質コルチコイド(経口での低用量)
3.従来の疾患修飾性抗リウマチ薬(DMARD)
− メトトレキサート
− レフルミノ
− スルファサラジン
− ヒドロキシクロロキン
− アザチオプリン
− シクロスポリン
− ミノサイクリン
− 金
− TNF阻害剤
− エタネルセプト(Enbrel)
− インフリキシマブ(Remicade)
− アダリムマブ(Humira)
− B細胞特異的治療
− リツキシマブ(Rituxan)
− T細胞/B細胞同時活性化シグナル阻害剤
− アバタセプト(Orencia)
− IL-1受容体アンタゴニスト
− アナキンラ(Kineret)
本発明はさらに、少なくとも1つの式Iで表される化合物、ならびに/またはその薬学的に受容可能な塩、溶媒和物、互変異性体および立体異性体、ならびに全ての比におけるそれらの混合物、ならびに少なくとも1つのさらなる医薬活性成分を含む医薬に関する。
(a)式Iで表される化合物ならびに/またはその薬学的に受容可能な塩、溶媒和物、互変異性体および立体異性体、ならびに全ての比におけるそれらの混合物の有効量、
ならびに
(b)さらなる医薬活性成分の有効量
の別々のパックからなる、セット(キット)に関する。
本発明の化合物は、哺乳動物のための、特にヒトのための、免疫調節性およびストレス応答性キナーゼにより誘導される疾患の処置における、医薬活性成分として好適である。これらの疾患として、限定されないが、固形腫瘍癌、リンパまたは血液系の癌を含む悪性腫瘍、腫瘍細胞の増殖、固形腫瘍の増殖を促進する病的血管新生(neovascularisation/angiogenesis)、神経変性疾患(アルツハイマー、脱髄性のコアの障害、多発性硬化症など)、関節炎、乾癬、ループス、または他の自己免疫疾患などの免疫関連障害、ならびに慢性感染症が挙げられる。
血管新生が関連付けられているかかる疾患は、網膜血管新生、糖尿病性網膜症、加齢黄斑変性症などの眼疾患である。
表現「免疫調節性またはストレス応答性キナーゼにより誘導される疾患または状態」とは、1または2以上の免疫調節性またはストレス応答性キナーゼの活性に依存する病理学的状態を指す。免疫調節性またはストレス応答性キナーゼは、増殖、接着、ならびに遊走および分化を含む、多様な細胞活動のシグナル伝達経路において、直接的に、または間接的に関与する。免疫調節性またはストレス応答性キナーゼ活性に関連する疾患として、悪性腫瘍(固形腫瘍癌、リンパまたは血液系の癌など)、神経変性疾患、関節炎、乾癬、ループス、多発性硬化症または他の自己免疫疾患などの免疫関連障害、ならびに慢性感染症が挙げられる。
本発明は特に、GCN2の阻害のための使用のための、式Iで表される化合物、ならびにその薬学的に受容可能な塩、溶媒和物、互変異性体および立体異性体、ならびに全ての比におけるそれらの混合物に関する。
特に好ましいのは、疾患が悪性腫瘍である場合の、疾患の処置のための使用である。
悪性腫瘍は、さらに好ましくは、肺腺癌、小細胞肺癌、膵臓癌、神経膠芽腫、大腸癌および乳癌の群から選択される。
式Iで表される化合物が処置または予防のために有用である代表的なリウマチ性状態として、限定されないが、関節リウマチ、痛風、強直性脊椎炎、または変形性関節症が挙げられる。
別の態様において、本明細書において提供されるのは、限定されないが、アテローム動脈硬化症、心筋梗塞および虚血性脳卒中などの、血栓性のイベントに関連する疾患の処置または予防のための方法である。
さらに、本発明は特に、腫瘍が、急性骨髄性白血病、慢性骨髄性白血病、急性リンパ性白血病および/または慢性リンパ性白血病の群に起源を有する、癌の処置および/または予防のための使用のための化合物に関する。
さらに、本発明は特に、GSK3の阻害のための使用のための、式Iで表される化合物、ならびにその薬学的に受容可能な塩、溶媒和物、互変異性体および立体異性体、ならびに全ての比におけるそれらの混合物に関する。
(i)癌医学において用いられるような、抗増殖/抗新形成/DNA傷害剤およびそれらの組み合わせ、例えば、アルキル化剤(例えばシス−プラチン、カルボプラチン、シクロホスファミド、ナイトロジェンマスタード、メルファラン、クロラムブシル、ブスルファンおよびニトロソウレア);抗代謝薬(例えば、5−フルオロウラシルおよびテガフールなどのフルオロピリミジン、ラルチトレキセド、メトトレキサート、シトシンアラビノシド、ヒドロキシウレアおよびゲムシタビンなどの葉酸代謝拮抗薬);抗腫瘍抗生物質(例えば、アドリアマイシン、ブレオマイシン、ドキソルビシン、ダウノマイシン、エピルビシン、イダルビシン、マイトマイシン−C、ダクチノマイシンおよびミスラマイシンなどのアントラサイクリン);有糸分裂阻害剤(例えば、ビンクリスチン、ビンブラスチン、ビンデシンおよびビノレルビンなどのビンカアルカロイド、ならびにタキソールおよびタキソテールなどのタキソイド) ;トポイソメラーゼ阻害剤(例えば、エトポシドおよびテニポシドなどのエピポドフィロトキシン、アムサクリン、トポテカン、イリノテカンおよびカンプトテシン)、ならびに細胞分化剤(例えばオールトランスレチノイン酸、13−シス−レチノイン酸およびフェンレチニド);
(iii)癌細胞の浸潤を阻害する剤(例えばマリマスタットなどのメタロプロテイナーゼ阻害剤、およびウロキナーゼ型プラスミノーゲン活性化因子受容体の機能の阻害剤);
(vii)アンチセンス治療、例えば、上で列記される標的に向けられたもの、例えば抗RasアンチセンスであるISIS 2503;
(viii)例えば、異常なp53または異常なBRCA1もしくはBRCA2などの異常な遺伝子の置き換えのためのアプローチ、シトシンデアミナーゼ、チミジンキナーゼまたは細菌のニトロレダクターゼ酵素を用いるものなどのGDEPT(遺伝子特異的酵素プロドラッグ治療)アプローチ、ならびに、多剤耐性遺伝子治療などの、化学療法または放射線両方に対する患者の耐容性を増大するアプローチを含む、遺伝子治療アプローチ;ならびに
以下の表1からの医薬は、排他的ではないが、好ましくは、式Iで表される化合物と組み合わせられる。
アルトレタミン、ベンダムスチン、ブスルファン、カルムスチン、クロラムブシル、クロルメチン、シクロホスファミド、ダカルバジン、イホスファミド、インプロスルファン、トシル酸、ロムスチン、メルファラン、ミトブロニトール、ミトラクトール、ニムスチン、ラニムスチン、テモゾロミド、チオテパ、トレオスルファン、メクロレタミン、カルボコン;
アパジクオン、フォテムスチン、グルフォスファミド、パリホスファミド(palifosfamide)、ピポブロマン、トロホスファミド、ウラムスチン、TH-3024、VAL-0834など;
カルボプラチン、シスプラチン、エタプラチン、ミリプラチン水和物、オキサリプラチン、ロバプラチン、ネダプラチン、ピコプラチン、サトラプラチンなど;
DNA改変剤
アムルビシン、ビサントレン、デシタビン、ミトキサントロン、プロカルバジン、トラベクテジン、クロファラビン;
アムサクリン、ブロスタリシン、ピクサントロン、ラロムスチン1,3など;
エトポシド、イリノテカン、ラゾキサン、ソブゾキサン、テニポシド、トポテカン;
アモナフィド、ベロテカン、酢酸エリプチニウム、ボレロキシンなど;
微小管修飾剤
カバジタキセル、ドセタキセル、エリブリン、イクサベピロン、パクリタキセル、ビンブラスチン、ビンクリスチン、ビノレルビン、ビンデシン、ビンフルニン;
フォスブレタブリン、テセタキセル(tesetaxel)など;
抗代謝薬
アスパラギナーゼ3、アザシチジン、レボホリナートカルシウム、カペシタビン、クラドリビン、シタラビン、エノシタビン、フロクスウリジン、フルダラビン、フルオロウラシル、ゲムシタビン、メルカプトプリン、メトトレキサート、ネララビン、ペメトレキセド、プララトレキサート、アザチオプリン、チオグアニン、カルモフール;
ドキシフルリジン、エラシタラビン(elacytarabine)、ラルチトレキセド、サパシタビン、テガフール2,3、トリメトレキサートなど;
ブレオマイシン、ダクチノマイシン、ドキソルビシン、エピルビシン、イダルビシン、レバミゾール、ミルテフォシン、マイトマイシンC、ロミデプシン、ストレプトゾシン、バルルビシン、ジノスタチン、ゾルビシン、ダウノルビシン、プリカマイシン;
アクラルビシン、ペプロマイシン、ピラルビシンなど;
ホルモン/アンタゴニスト
アバレリックス、アビラテロン、ビカルタミド、ブセレリン、カルステロン、クロロトリアニセン、デガレリクス、デキサメタゾン、エストラジオール、フルオコルトロン、フルオキシメステロン、フルタミド、フルベストラント、ゴセレリン、ヒストレリン、リュープロレリン、メゲストロール、ミトタン、ナファレリン、ナンドロロン、ニルタミド、オクトレオチド、プレドニゾロン、ラロキシフェン、タモキシフェン、サイロトロピンアルファ、トレミフェン、トリロスタン、トリプトレリン、ジエチルスチルベストロール;
アコルビフェン、ダナゾール、デスロレリン、エピチオスタノール、オルテロネル、エンザルタミド1,3など;
アミノグルテチミド、アナストロゾール、エキセメスタン、ファドロゾール、レトロゾール、テストラクトン;
ホルメスタンなど;
低分子キナーゼ阻害剤
クリゾチニブ、ダサチニブ、エルロチニブ、イマチニブ、ラパチニブ、ニロチニブ、パゾパニブ、レゴラフェニブ、ルキソリチニブ、ソラフェニブ、スニチニブ、バンデタニブ、ベムラフェニブ、ボスチニブ、ゲフィチニブ、アキシチニブ;
アファチニブ、アリセルチブ、ダブラフェニブ、ダコミチニブ、ジナシクリブ(dinaciclib)、ドビチニブ、エンザスタウリン、ニンテダニブ、レンバチニブ、リニファニブ、リンシチニブ、マシチニブ、ミドスタウリン、モテサニブ、ネラチニブ、オランチニブ、ペリフォシン、ポナチニブ、ラドチニブ(radotinib)、リゴサチブ、ティピファニブ、チバンチニブ、チボザニブ、トラメチニブ、ピマセルチブ、ブリバニブアラニネート、セジラニブ、アパチニブ4、S−マレイン酸カボザンチニブ1,3、イブルチニブ1,3、イコチニブ4、ブパルリシブ2、シパチニブ(cipatinib)4、コビメチニブ1,3、イデラリシブ1,3、フェドラチニブ1、XL-6474など;
メトキサレン3;
ポルフィマーナトリウム、タラポルフィン、テモポルフィンなど;
抗体
アレムツズマブ、ベシレソマブ、ブレンツキシマブベドチン、セツキシマブ、デノスマブ、イピリムマブ、オファツムマブ、パニツムマブ、リツキシマブ、トシツモマブ、トラスツズマブ、ベバシズマブ、ペルツズマブ2,3;
カツマキソマブ、エロツズマブ、エプラツズマブ、ファーレツズマブ、モガムリズマブ、ネシツムマブ、ニモツズマブ(nimotuzumab)、オビヌツズマブ、オカラツズマブ(ocaratuzumab)、オレゴボマブ、ラムシルマブ、リロツムマブ、シルツキシマブ、トシリズマブ、ザルツムマブ、ザノリムマブ、マツズマブ、ダロツズマブ(dalotuzumab)1,2,3、オナルツズマブ1,3、ラコツモマブ(racotumomab)1、タバルマブ(tabalumab)1,3、EMD-5257974、ニボルマブ1,3など;
アルデスロイキン、インターフェロンアルファ2、インターフェロンアルファ2a3、インターフェロンアルファ2b2,3;
セルモロイキン、タソネルミン、テセロイキン、オプレルベキン1,3、組み換えインターフェロンベータ−1a4など;
薬物コンジュゲート
デニロイキンジフチトクス、イブリツモマブチウキセタン、イオベングアンI123、プレドニムスチン、トラスツズマブエムタンシン、エストラムスチン、ゲムツズマブ、オゾガマイシン、アフリベルセプト;
シントレデキンデスドトクス(cintredekin besudotox)、エドトレオチド(edotreotide)、イノツズマブオゾガマイシン、ナプツモマブエスタフェナトクス、オポルツズマブモナトクス(oportuzumab monatox)、テクネチウム(99mTc)アルシツモマブ1,3、
ビンタフォリド1,3など;
ワクチン
シプロイセル3;ビテスペン3、エメペピムト−S3、oncoVAX4、リンドペピムト(rindopepimut)3、troVax4、MGN-16014、MGN-17034など;
アリトレチノイン、ベキサロテン、ボルテゾミブ、エベロリムス、イバンドロン酸、イミキモド、レナリドマイド、レンチナン、メチロシン、ミファムルチド、パミドロン酸、ペグアスパルガーゼ、ペントスタチン、シプロイセル3、シゾフィラン、タミバロテン、テムシロリムス、サリドマイド、トレチノイン、ビスモデギブ、ゾレドロン酸、ボリノスタット;
セレコキシブ、シレンギチド、エンチノスタット、エタニダゾール、ガネテスピブ、イドロノキシル(idronoxil)、イニパリブ、イクサゾミブ、ロニダミン、ニモラゾール、パノビノスタット、ペレチノイン、プリチデプシン(plitidepsin)、ポマリドミド、プロコダゾール、リダフォロリムス、タスキニモッド、テロトリスタット(telotristat)、チマルファシン(thymalfasin)、チラパザミン、トセドスタット、トラベデルセン、ウベニメクス、バルスポダール、ゲンジシン(gendicine)4、ピシバニール4、レオリジン(reolysin)4、塩酸レタスピマイシン1,3、トレバナニブ(trebananib)2,3、ビルリジン(virulizin)4、カルフィルゾミブ1,3、エンドスタチン4、イムコゼル(immucothel)4、ベリノスタット3、MGN-17034;
1Prop. INN(Proposed International Nonproprietary Name:提案されている国際非専売薬名)
2Rec. INN(Recommended International Nonproprietary Names:推奨されている国際非専売薬名)
3USAN(United States Adopted Name:米国において採用された名称)
4INNなし
aq(水性)、h(時間)、g(gram)、L(リットル)、mg(ミリグラム)、MHz(メガヘルツ)、min.(分)、mm(ミリメートル)、mmol(ミリモル)、mM(ミリモル濃度)、m.p.(融点)、eq(当量)、ml(ミリリットル)、μl(マイクロリットル)、ACN(アセトニトリル)、AcOH(酢酸)、CDCl3(重水素化クロロホルム)、CD3OD(重水素化メタノール)、CH3CN(アセトニトリル)、c−hex(シクロヘキサン)、DCC(ジシクロヘキシルカルボジイミド)、DCM(ジクロロメタン)、DIC(ジイソプロピルカルボジイミド)、DIEA(ジイソプロピルエチルアミン)、DMF(ジメチルホルムアミド)、DMSO(ジメチルスルホキシド)、DMSO−d6(重水素化ジメチルスルホキシド)、EDC(1−(3−ジメチル−アミノ−プロピル)−3−エチルカルボジイミド)、ESI(エレクトロスプレーイオン化)、EtOAc(酢酸エチル)、Et2O(ジエチルエーテル)、EtOH(エタノール)、HATU(ジメチルアミノ−([1,2,3]トリアゾロ[4,5−b]ピリジン−3−イルオキシ)−メチレン]−ジメチル−アンモニウムヘキサフルオロリン酸)、HPLC(高速液体クロマトグラフィー)、i−PrOH(2−プロパノール)、K2CO3(炭酸カリウム)、LC(液体クロマトグラフィー)、MeOH(メタノール)、MgSO4(硫酸マグネシウム)、MS(質量分析)、MTBE(メチルtert−ブチルエーテル)、NaHCO3(炭酸水素ナトリウム)、NaBH4(水素化ホウ素ナトリウム)、NMM(N−メチルモルホリン)、NMR(核磁気共鳴)、PyBOP(ベンゾトリアゾール−1−イル−オキシ−トリス−ピロリジノ−ホスホニウムヘキサフルオロリン酸)、RT(室温)、Rt(保持時間)、SPE(固相抽出)、TBTU(2−(1−H−ベンゾトリアゾール−1−イル)−1,1,3,3−テトラメチルウロニウムテトラフルオロホウ酸)、TEA(トリエチルアミン)、TFA(トリフルオロ酢酸)、THF(テトラヒドロフラン)、TLC(薄層クロマトグラフィー)、UV(紫外光)。
GCN2:アッセイの原理&条件
このアッセイは、セリンキナーゼGCN2(general control non-derepressible-2)の活性を定量することができる。
このキナーゼは、細胞のストレス代謝に関与する。それは、飢餓(アミノ酸枯渇)により活性化される。その天然の基質は、eIF2a(真核生物翻訳開始因子2アルファサブユニット)という翻訳因子であり、これは、細胞におけるアミノ酸のボトルネックの場合、GCN2により活性化(リン酸化)される。これは、次いで、タンパク質合成の停止をもたらす。GCN2の阻害は、この機構の停止をもたらす:細胞は、「飢餓」ストレスによっては、タンパク質産生を停止することはできない。
EDTAの添加により、酵素反応を停止させる。リン酸化eIF2アルファの量を、TR-FRET(Lanthascreen)により決定する:複合体は、抗体およびGFP標識ホスホeIF2aからなって形成され、これは、340nmにおける励起によるFRETを可能にする。
GCN2活性は、発光波長520nmにおける蛍光単位と、495nm(参照波長=テルビウムキレートの発光)における単位との比に直接的に比例する(ホスホペプチド感受性の波長=GFPの発光)。
Hepes(pH7.0) 50mM
MgCl2 10mM
MnCl2 5mM
BSA 0.1%
DMSO 1%
ATP 10uM
DTT 2mM
GFP-eIF2a 80nM(基質)
GCN2 30nM(酵素)
4uL 酵素溶液(アッセイバッファー中)
1.5uL 化合物(cmpd希釈バッファー/6.3%のDMSO中)
インキュベーション RTにおいて20分
4uL 基質/ATPミックス(アッセイバッファー中)
インキュベーション RTにおいて90分
10u 停止/検出ミックス(抗体希釈バッファー中)
インキュベーション RTにおいて60分
読み出し Lanthascreen 340/495/520
ヒトU2OS細胞(2000細胞/ウェル)を、384ウェルプレート中に播種して、20時間にわたりインキュベートする。
翌日、細胞を、試験化合物で播種して、2時間にわたりインキュベートする。次いで、トリプトファノールを、600μMの最終濃度において、細胞に添加し、それらを30分間にわたりインキュベートする。
免疫組織化学により、細胞のGCN2活性の分析を行う。簡単に述べると、細胞を、ホルムアルデヒドによりウェル表面上において固定し、Triton X-100で透過処理する。一次抗体(抗ホスホ−eIF2アルファ(Ser51、Cell Signalling Technology、#3398)を、処理細胞において20時間にわたりインキュベートし、その後、二次抗体(抗ウサギIgG−Alexa 488;Molecular Probes、#11008)の60分間のインキュベーションを行う。
Acumen Explorerシステム(TTPLabtech)においてプレートをスキャンすることにより、リン酸化GCN2の分析および定量を行う。得られたデータを、未処置の対照ウェル(DMSOのみ)に対して正規化し、効果の値の%として表す。Graph Pad Prismソフトウェアを用いて、IC50値の決定を行う。
GSK3α(h)を、8mMのMOPS(pH7.0)、0.2mMのEDTA、20μMのYRRAAVPPSPSLSRHSSPHQS(p)EDEEE(ホスホルGS2ペプチド)、10mMのMg−酢酸および[ガンマ−33P−ATP](特異的活性約500cpm/Pmol、必要とされる濃度)と共にインキュベートする。MgATPの添加により、反応を開始させる。室温における40分間にわたるインキュベーションの後で、3%のリン酸溶液の添加により反応を停止させる。10μLの反応物を、次いで、P30フィルターマット上にスポットして、5分間にわたり、50mMのリン酸中で3回、およびエタノール中で1回、洗浄し、その後、乾燥して、シンチレーションカウントする。10μMのATPまたはKm ATPにおいて、アッセイを行う。Km ATPプロトコルのために用いられるATP濃度は、10μMのATPであり、一方、GSK3a(h)のための実際のKM ATPは、10μMである。
GSK3β(h)を、8mMのMOPS(pH7.0)、0.2mMのEDTA、20μMのYRRAAVPPSPSLSRHSSPHQS(p)EDEEE(ホスホルGS2ペプチド)、10mMのMg−酢酸および[ガンマ−33P−ATP](特異的活性約500cpm/Pmol、必要とされる濃度)と共にインキュベートする。MgATPの添加により、反応を開始させる。室温における40分間にわたるインキュベーションの後で、3%のリン酸溶液の添加により反応を停止させる。10μLの反応物を、次いで、P30フィルターマット上にスポットして、5分間にわたり、50mMのリン酸中で3回、およびエタノール中で1回、洗浄し、その後、乾燥して、シンチレーションカウントする。10μMのATPまたはKm ATPにおいて、アッセイを行う。Km ATPプロトコルのために用いられるATP濃度は、10μMのATPであり、一方、GSK3a(h)のための実際のKM ATPは、10μMである。
Bruker 400または500MHz
HPLC/MS条件A
カラム:Chromolith Performance ROD RP-18e、50×4.6mm2
勾配:2.8分において、A:B=96:4〜0:100
流速:2.40ml/分
溶離液A:水+0.05%ギ酸
溶離液B:アセトニトリル+0.04%ギ酸
波長:220nm
質量分析:ポジティブモード
HPLC/MS条件B
カラム:Chromolith Performance ROD RP-18e、100×3mm2
勾配:1.8分において、A:B=99:1〜0:100
流速:2.0ml/分
溶離液A:水+0.05%ギ酸
溶離液B:アセトニトリル+0.04%ギ酸
波長:220nm
質量分析:ポジティブモード
HPLC/MS条件C
カラム:Chromolith Performance ROD RP-18e、100×3mm2
勾配:3.5分において、A:B=99:1〜0:100
流速:2.0ml/分
溶離液A:水+0.05%ギ酸
溶離液B:アセトニトリル+0.04%ギ酸
波長:220nm
質量分析:ポジティブモード
中間体の調製
5−クロロ−3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジンの合成
HPLC/MS 1.87分(B)、[M+H] 317;1H NMR (400 MHz, DMSO-d6) δ [ppm] 9.80 (s, 1H), 7.88 - 7.80 (m, 2H), 7.26 - 7.19 (m, 2H), 3.82 - 3.75 (m, 4H), 3.29 - 3.22 (m, 4H);
HPLC/MS 3.10分(C)、[M+H] 358.
(1−メチル−1H−ピラゾール−4−イルメチル)−(3−キノリン−6−イル−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル)−アミン(「B1」)の合成
[3−(4−エトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−プロパ−2−イニル−アミン(「A1」)
トランス−2−{4−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロヘキシル}−エタノール(「A72」)
[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−メチル−アミン(「A14」)の合成
エチル−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−アミン(「A16」)
HPLC/MS 2.64分(C)、[M+H] 271;1H NMR (400 MHz, DMSO-d6) δ [ppm] 9.36 (s, 1H), 8.08 (d, J = 9.0 Hz, 2H), 7.23 - 7.14 (m, 2H), 4.32 (p, J = 6.5 Hz, 1H), 3.88 (s, 3H), 2.05 (m, 2H), 1.76 (m, 2H), 1.72 - 1.59 (m, 2H).
[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−(1,2,2,6,6−ペンタメチル−ピペリジン−4−イル)−アミン(「A15」)の合成
[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−(2,2,6,6−テトラメチル−ピペリジン−4−イル)−アミン(「A17」)
4−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−1−メチル−ピロリジン−2−オン(「A20」)の合成
シクロブチル−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−アミン(「A21」)
{シス−3−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロブチル}−カルバミン酸tert−ブチルエステル(「A30」)およびシス−N−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−シクロブタン−1,3−ジアミン塩酸塩(「A31」)の合成
{トランス−3−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロブチル}−カルバミン酸tert−ブチルエステル(「A32」)
ジオキサン(1ml)とエタノール(1ml)との混合物中の{シス−3−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロブチル}−カルバミン酸tert−ブチルエステル(49.4mg、0.12mmol)の溶液に、ジオキサン(2ml)中の4NのHClを添加する。反応混合物を、2時間にわたり室温において混合する。形成された沈殿をろ過除去し、ジオキサンで洗浄し、真空下において乾燥させて、シス−N−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−シクロブタン−1,3−ジアミン塩酸塩(「A31」)をクリーム色の粉末として得る;HPLC/MS 1.41分(B)、[M+H] 312;1H NMR (400 MHz, DMSO-d6) δ [ppm] 9.29 (s, 1H), 8.53 (s, 1H), 8.27 (s, 3H), 8.04 (d, J = 8.4 Hz, 2H), 7.25 - 7.16 (m, 3H), 4.09 (m, 1H), 3.87 (s, 3H), 3.50 (m, 1H), 2.70 (m, 2H), 2.19 (m, 2H).
(3−アザ−ビシクロ[3.1.0]ヘキサ−6−イル)−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−アミン塩酸塩(「A37」)
1−{3−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−ピペリジン−1−イル}−エタノン(「A42」)および[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−ピペリジン−3−イル−アミン塩酸塩(「A43」)の合成
トランス−N−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−シクロヘキサン−1,4−ジアミン(「A44」)の合成
シス−N−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−シクロヘキサン−1,4−ジアミン(「A45」)
HPLC/MS 1.43分(B)、[M+H] 340;1H NMR (400 MHz, DMSO-d6) δ [ppm] 9.29 (s, 1H), 8.02 (m, 2H), 7.88 (m, 3H), 7.20 (d, J = 9.1 Hz, 2H), 3.93 (m, 1H), 3.86 (s, 3H), 3.13 (m, 1H), 1.99 (m, 2H), 1.74 (m, 6H);
3−(4−{5−[3−(4−ニトロ−ピラゾール−1−イル)−プロピルアミノ]−[1,2,3]トリアゾロ[4,5−d]ピリミジン−3−イル}−フェノキシ)−プロピオン酸(「A46」)および3−(4−{5−[3−(4−アミノ−ピラゾール−1−イル)−プロピルアミノ]−[1,2,3]トリアゾロ[4,5−d]ピリミジン−3−イル}−フェノキシ)−プロピオン酸(「A47」)の合成
2−ジメチルアミノ−1−{4−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−ピペリジン−1−イル}−エタノン(「A48」)の合成
3−ジメチルアミノ−1−{4−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−ピペリジン−1−イル}−プロパン−1−オン(「A49」)
[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−[2−(4−メチル−ピペラジン−1−イル)−エチル]−アミン(「A50」)の合成
[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−(3−ピロリジン−1−イル−プロピル)−アミン(「A61」)
トランス−3−{3−[4−(1−メチル−1H−ピラゾール−4−イル)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタノール(「A51」)の合成
N−(3−{4−[1−(2−メトキシ−エチル)−1H−ピラゾール−4−イル]−フェニル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル)−シクロヘキサン−1,4−ジアミン(「A52」)
HPLC/MS 1.89分(C)、[M+H] 434;1H NMR (400 MHz, DMSO-d6 /TFA-d1) δ [ppm] 9.29 (s, 1H), 8.24 (s, 1H), 8.18 (d, J = 8.4 Hz, 2H), 8.02 (s, 1H), 7.88 - 7.80 (m, 2H), 4.37 (t, J = 5.2 Hz, 2H), 3.87 (m, 1H), 3.79 (t, J = 5.2 Hz, 2H), 3.31 (s, 3H), 3.10 (m, 1H), 2.12 (m, 4H), 1.52 (m, 4H);
HPLC/MS 1.95分(C)、[M+H] 404;1H NMR (400 MHz, DMSO-d6 /TFA-d1) δ [ppm] 9.28 (s, 1H), 8.27 (d, J = 0.8 Hz, 1H), 8.17 (d, J = 8.3 Hz, 2H), 8.01 (s, 1H), 7.92 - 7.70 (m, 2H), 4.24 (q, J = 7.3 Hz, 2H), 3.84 (m, 1H), 3.09 (m, 1H), 2.28 - 1.99 (m, 4H), 1.68 - 1.27 (m, 7H).
「A10」の、「A55」および「A56」へのキラル分離
第1に溶離した鏡像異性体:「A55」、明黄色粉末;HPLC/MS 1.69分(B)、[M+H] 327(絶対的な立体配置は、任意に割り当てられた)
第2に溶離した鏡像異性体:「A56」、明黄色粉末;HPLC/MS 1.72分(B)、[M+H] 327(絶対的な立体配置は、任意に割り当てられた).
トランス−3−(3−{4−[1−(2−ヒドロキシ−エチル)−1H−ピラゾール−4−イル]−フェニル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタノール(「A57」)の合成
(1S,3R)−N−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−シクロペンタン−1,3−ジアミン(「A58」)[第1の鏡像異性体]および(1R,3S)−N−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−シクロペンタン−1,3−ジアミン(「A59」)[第2の鏡像異性体]の合成
第1に溶離した鏡像異性体:tert−ブチルN−[(1S,3R)−3−[[3−(4−メトキシフェニル)トリアゾロ[4,5−d]ピリミジン−5−イル]アミノ]シクロペンチル]カルバメート、白色の固体。
第2に溶離した鏡像異性体:tert−ブチルN−[(1R,3S)−3−[[3−(4−メトキシフェニル)トリアゾロ[4,5−d]ピリミジン−5−イル]アミノ]シクロペンチル]カルバメート;明るいベージュ色の固体。
tert−ブチルN−[(1R,3S)−3−[[3−(4−メトキシフェニル)トリアゾロ[4,5−d]ピリミジン−5−イル]アミノ]シクロペンチル]カルバメートを同様に処理して、(1R,3S)−N3−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−シクロペンタン−1,3−ジアミン塩酸塩を白色の固体として得る;HPLC/MS 1.44分(B)、[M+H] 326.
{(1R,3S)−3−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンチル}−(4−メチル−ピペラジン−1−イル)−メタノン(「A60」)の合成
{(1S,3R)−3−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンチル}−(4−メチル−ピペラジン−1−イル)−メタノン(「A97」)
トランス−3−{3−[5−(1−メチル−1H−ピラゾール−4−イル)−ピリジン−2−イル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタノール(「A94」)の合成
トランス−N−{3−[4−(2−モルホリン−4−イル−エトキシ)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル}−シクロヘキサン−1,4−ジアミン(「A95」)の合成
(1R,3R)−3−{3−[4−(2−メトキシ−エトキシ)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタンカルボン酸アミド(「A135」)の合成
1H NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H), 9.12 (s, 1H), 7.41 (d, J = 9.0 Hz, 2H), 7.01 (d, J = 9.0 Hz, 1H), 4.38 - 3.96 (m, 2H), 3.87 - 3.56 (m, 2H), 3.32 (s, 3H).
1H NMR (400 MHz, DMSO-d6) δ 8.48 (s, 1H), 7.59 (s, 1H), 7.53 (d, J = 9.0 Hz, 1H), 6.94 (d, J = 9.0 Hz, 1H), 5.17 (s, 2H), 4.20 - 3.97 (m, 2H), 3.80 - 3.50 (m, 2H), 3.31 (s, 3H).
1H NMR (400 MHz, DMSO-d6) δ 9.83 (s, 1H), 7.94 (d, J = 9.1 Hz, 2H), 7.28 (d, J = 9.0 Hz, 2H), 4.42 - 4.06 (m, 3H), 3.90 - 3.66 (m, 2H), 3.35 (s, 3H).
1H NMR (500 MHz, DMSO-d6, TFA-d1) δ 9.23 (s, 1H), 8.05 (bs, 2H), 7.17 (d, J = 8.8 Hz, 2H), 4.31 (bs, 1H), 4.24 - 4.06 (m, 2H), 3.79 - 3.62 (m, 2H), 3.32 (s, 3H), 3.00 - 2.81 (m, 1H), 2.21 (bs, 1H), 2.10 - 1.94 (m, 2H), 1.84 (ddd, J = 13.2, 8.9, 5.8 Hz, 1H), 1.76 (m, 1H), 1.68 (m, 1H).
1H NMR (500 MHz, DMSO-d6, TFA-d1) δ 9.28 (s, 1H), 8.09 (bs, 2H), 7.32 - 6.93 (m, 2H), 4.37 (bs, 1H), 4.32 - 4.08 (m, 2H), 3.79 - 3.68 (m, 2H), 3.36 (s, 3H), 2.87 (p, J = 8.0 Hz, 1H), 2.23 - 2.05 (m, 2H), 2.06 - 1.96 (m, 1H), 1.87 (m, 1H), 1.74 (m, 2H).
(1S,3R)−3−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸アミド(「A136」)
1H NMR (400 MHz, DMSO-d6) δ [ppm] = 9.22 (s, 1H), 8.19 - 7.89 (m, 3H), 7.29 - 7.14 (m, 3H), 6.72 (s, 1H), 3.85 (s, 3H), 3.44 - 3.27 (m, 2H), 2.19 - 2.09 (m, 2H), 1.88 - 1.73 (m, 2H);
1H NMR (400 MHz, DMSO-d6) δ [ppm] = 9.24 (s, 1H), 8.45 (d, J=6.5, 1H), 8.00 (d, J=8.6, 2H), 7.28 - 7.13 (m, 3H), 6.75 (s, 1H), 4.46 - 4.35 (m, 1H), 3.86 (s, 3H), 3.02 - 2.89 (m, 1H), 2.53 - 2.37 (m, 2H), 2.34 - 2.14 (m, 2H);
1H NMR (400 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.24 (s, 1H), 7.98 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 9.1 Hz, 2H), 4.40 - 4.25 (m, 1H), 4.08 (q, J = 6.9 Hz, 2H), 2.77 (p, J = 7.8 Hz, 1H), 2.17 (ddd, J = 12.9, 8.5, 6.7 Hz, 1H), 1.98 - 1.67 (m, 5H), 1.34 (t, J = 7.0 Hz, 3H);
1H NMR (500 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.34 (s, 1H), 8.08 (d, J = 8.5 Hz, 1H), 7.36 - 7.03 (m, 2H), 4.59 - 4.37 (m, 1H), 4.15 (q, J = 7.0 Hz, 2H), 2.98 (p, J = 8.0 Hz, 1H), 2.25 (dt, J = 13.7, 7.4 Hz, 1H), 2.22 - 2.14 (m, 1H), 2.09 (dtd, J = 11.7, 7.7, 4.3 Hz, 1H), 1.95 (ddd, J = 13.5, 8.7, 5.2 Hz, 1H), 1.87 - 1.68 (m, 2H), 1.42 (t, J = 7.0 Hz, 3H);
1H NMR (500 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.28 (s, 1H), 8.05 (d, J = 8.5 Hz, 2H), 7.22 (d, J = 9.0 Hz, 2H), 4.33 (bs, 1H), 4.26 - 4.17 (m, 2H), 3.86 - 3.68 (m, 2H), 3.36 (s, 3H), 2.78 (p, J = 8.1 Hz, 1H), 2.26 - 2.15 (m, 1H), 1.96 (ddt, J = 15.5, 8.1, 4.4 Hz, 1H), 1.91 - 1.83 (m, 2H), 1.78 (td, J = 14.4, 7.3 Hz, 2H);
1H NMR (400 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.25 (s, 1H), 7.97 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.9 Hz, 2H), 4.61 (p, J = 5.1 Hz, 1H), 4.35 (p, J = 6.2 Hz, 1H), 3.52 (d, J = 5.0 Hz, 4H), 3.24 (s, 6H), 2.89 (p, J = 8.0 Hz, 1H), 2.22 - 2.02 (m, 2H), 1.98 (td, J = 8.5, 4.3 Hz, 1H), 1.85 (ddd, J = 13.3, 8.6, 5.1 Hz, 1H), 1.78 - 1.59 (m, 2H);
1H NMR (500 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.28 (s, 1H), 8.08 (bs, 2H), 7.25 (d, J = 8.8 Hz, 2H), 4.70 (tt, J = 8.5, 4.0 Hz, 1H), 4.37 (bs, 1H), 3.91 (dt, J = 11.6, 4.4 Hz, 2H), 3.54 (ddd, J = 11.9, 9.4, 2.8 Hz, 2H), 2.87 (p, J = 8.0 Hz, 1H), 2.25 - 1.95 (m, 5H), 1.88 (m, 1H), 1.81 - 1.59 (m, 4H);
(1R,3R)−3−[3−(4−ヨード−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸アミド(「A170」)の合成
1H NMR (300 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.27 (s, 1H), 8.12 (d, J = 8.4 Hz, 2H), 8.01 (d, J = 8.8 Hz, 2H), 4.41 (bs, 1H), 2.91 (p, J = 7.9 Hz, 1H), 2.43 - 1.97 (m, 3H), 1.96 - 1.59 (m, 3H).
(1S,3R)−3−[3−(4−ヨード−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸アミド(「A171」)
1H NMR (400 MHz, DMSO-d6) δ [ppm] 9.25 (s, 1H), 8.92 (s, 1H), 8.44 - 8.36 (m, 1H), 8.31 - 8.23 (m, 1H), 7.23 (s, 1H), 7.11 (d, J=9.0, 1H), 6.70 (s, 1H), 4.34 - 4.22 (m, 1H), 3.95 (s, 3H), 2.78 (p, J=7.9, 1H), 2.12 - 2.00 (m, 2H), 1.98 - 1.77 (m, 2H), 1.73 - 1.56 (m, 2H);
(1R,3R)−3−[3−(5−エトキシ−ピリジン−2−イル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸アミド(「A178」)
(1R,3R)−3−[3−(2−メチル−ベンゾフラン−5−イル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸アミド(「A180」)
(1R,3R)−3−{3−[2−(2−エトキシ−エトキシ)−キノリン−6−イル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタンカルボン酸アミド(「A182」)
(1R,3R)−3−[3−(2−メチル−キナゾリン−6−イル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸アミド(「A184」)
(1R,3R)−3−[3−(2−メチル−キノリン−6−イル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸アミド(「A187」)の合成
1H NMR (400 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.93 (s, 1H), 9.34 (d, J = 8.6 Hz, 1H), 9.12 (d, J = 2.3 Hz, 1H), 8.90 (dd, J = 9.2, 2.3 Hz, 1H), 8.59 (d, J = 9.2 Hz, 1H), 8.14 (d, J = 8.6 Hz, 1H), 3.04 (s, 3H).
1H NMR (400 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.34 (m, 3H), 9.19 - 9.04 (m, 1H), 8.51 (d, J = 9.3 Hz, 1H), 8.11 (d, J = 8.7 Hz, 1H), 4.56 (m, 1H), 2.95 (p, J = 8.0 Hz, 1H), 2.40 (m, 1H), 2.13 (m, 2H), 1.91 - 1.67 (m, 3H).
(1S,3R)−3−(3−キノリン−6−イル−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタンカルボン酸(「A188」)
1H NMR (400 MHz, DMSO-d6) δ [ppm] = 9.29 (s, 1H), 9.00 (dd, J=4.2, 1.7, 1H), 8.86 (d, J=2.4, 1H), 8.67 - 8.60 (m, 1H), 8.58 - 8.52 (m, 1H), 8.38 (d, J=6.9, 1H), 8.29 (d, J=9.1, 1H), 7.71 - 7.63 (m, 1H), 7.39 - 7.30 (m, 1H), 6.87 - 6.76 (m, 1H), 4.39 - 4.28 (m, 1H), 2.79 - 2.71 (m, 1H), 2.29 - 2.19 (m, 1H), 2.06 - 1.96 (m, 1H), 1.90 - 1.73 (m, 4H);
1H NMR (400 MHz, DMSO-d6) δ [ppm] = 9.30 (s, 1H), 9.03 - 8.93 (m, 2H), 8.68 (dd, J=9.2, 2.5, 1H), 8.60 (d, J=8.3, 1H), 8.36 (d, J=6.5, 1H), 8.28 (d, J=9.3, 1H), 7.70 - 7.62 (m, 1H), 7.34 - 7.21 (m, 1H), 6.80 - 6.66 (m, 1H), 4.47 - 4.33 (m, 1H), 2.89 - 2.77 (m, 1H), 2.32 - 1.53 (m, 6H);
1H NMR (400 MHz, DMSO-d6, TFA-d1) δ [ppm] = 9.32 (s, 1H), 9.26 (m, 2H), 9.08 (d, J = 9.4 Hz, 1H), 8.51 (d, J = 9.3 Hz, 1H), 8.11 (d, J = 8.7 Hz, 1H), 4.48 (bs, 1H), 3.04 (s, 3H), 2.87 (p, J = 7.5 Hz, 1H), 2.28 (dt, J = 13.3, 6.4 Hz, 1H), 1.91 (m, 5H);
(1S,3S)−3−[3−(2−メチル−キノリン−6−イル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸アミド(「A193」)
(1R,3R)−3−(3−[1,5]ナフチリジン−2−イル−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタンカルボン酸アミド(「A194」)
(1R,3R)−3−[[3−(7−メチル−3−キノリル)トリアゾロ[4,5−d]ピリミジン−5−イル]アミノ]シクロペンタンカルボキサミド(「A195a」)
(1R,3R)−3−[3−(4−ヨード−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタノール(「A196」)および(1S,3S)−3−[3−(4−ヨード−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタノール(「A197」)の合成
1H NMR (400 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.26 (s, 1H), 8.16 - 8.05 (m, 2H), 8.06 - 7.96 (m, 2H), 4.51 (bs, 1H), 4.32 (tt, J = 6.0, 3.2 Hz, 1H), 2.24 (dt, J = 12.6, 7.6 Hz, 1H), 2.11 - 1.93 (m, 2H), 1.81 (dt, J = 13.3, 6.6 Hz, 1H), 1.61 (ddt, J = 12.2, 8.1, 5.0 Hz, 2H).
(トランス)−3−[3−(4−ピロリジン−1−イル−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタノール(「A198」)
(トランス)−3−[3−(2−メチル−ベンゾオキサゾール−6−イル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタノール(「A199」)
(トランス)−3−(3−ベンゾ[1,2,5]チアジアゾール−5−イル−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタノール(「A200」)
(トランス)−3−[3−(2−メチル−キノリン−6−イル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタノール(「A202」)
(1R,3R)−3−{3−[4−(2−ヒドロキシ−エトキシ)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタノール(「A203」)
(トランス)−3−{3−[4−((S)−3,3,3−トリフルオロ−2−ヒドロキシ−プロポキシ)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタノール(「A205」)
(トランス)−3−[3−(6−エトキシ−ピリジン−3−イル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタノール(「A206」)
(トランス)−3−[3−(2−メチル−キナゾリン−6−イル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタノール(「A209」)
(1R,3R)−3−(3−{4−[1−(2−エトキシ−エチル)−1H−ピラゾール−4−イル]−フェニル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタンカルボン酸アミド(「A211」)の合成
(1R,3R)−3−(3−{4−[1−(2−メトキシ−エチル)−1H−ピラゾール−4−イル]−フェニル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタノール(「A212」)
(1R,3R)−3−(3−{4−[1−(2−ピロリジン−1−イル−エチル)−1H−ピラゾール−4−イル]−フェニル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタノール(「A213」)
N−(3−{4−[1−(2−ピラゾール−1−イル−エチル)−1H−ピラゾール−4−イル]−フェニル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル)−シクロヘキサン−1,4−ジアミン(「A215」)
(1R,3R)−3−(3−{4−[1−(2−シアノ−エチル)−1H−ピラゾール−4−イル]−フェニル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタンカルボン酸アミド(「A217」)
(1R,3R)−3−(3−{5−[1−(2−メトキシ−エチル)−1H−ピラゾール−4−イル]−ピリジン−2−イル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタンカルボン酸アミド(「A219」)
(1R,3R)−3−(3−{3−フルオロ−4−[1−(2−メトキシ−エチル)−1H−ピラゾール−4−イル]−フェニル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタンカルボン酸アミド(「A221」)
(1R,3R)−3−(3−{4−[1−(2−エトキシ−エチル)−1H−ピラゾール−4−イル]−3−フルオロ−フェニル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタンカルボン酸アミド(「A223」)
(1R,3R)−3−(3−{4−[1−(2−エトキシ−エチル)−1H−ピラゾール−4−イル]−フェニル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタンカルボン酸(2−メトキシ−エチル)−アミド(「A225」)
(1R,3R)−3−(3−{4−[1−(2−エトキシ−エチル)−1H−ピラゾール−4−イル]−フェニル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタノール(「A227」)
(1R,3R)−3−(3−{6−[1−(2−エトキシ−エチル)−1H−ピラゾール−4−イル]−ピリジン−3−イル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタンカルボン酸アミド(「A229」)
(1R,3R)−3−{3−[4−(1−ピリジン−3−イルメチル−1H−ピラゾール−4−イル)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタノール(「A231」)
(トランス)−3−(3−{6−[1−(2−メトキシ−エチル)−1H−ピラゾール−4−イル]−ピリジン−3−イル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタノール(「A234」)
(1R,3R)−3−[3−(4−{1−[2−(6−オキソ−6H−ピリダジン−1−イル)−エチル]−1H−ピラゾール−4−イル}−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸アミド(「A237」)
(1R,3R)−3−(3−{5−[1−(2−シアノ−エチル)−1H−ピラゾール−4−イル]−ピリジン−2−イル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタンカルボン酸アミド(「A239」)
(1R,3R)−3−[3−(4−エトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸(3−ヒドロキシ−3−メチル−ブチル)−アミド(「A240」)の合成
1H NMR (500 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.27 (s, 1H), 8.08 (bs, 2H), 7.28 - 7.03 (m, 2H), 4.37 (bs, 1H), 4.14 (q, J = 7.0 Hz, 2H), 3.24 - 3.08 (m, 2H), 2.82 (p, J = 8.0 Hz, 1H), 2.10 (m, 2H), 2.03 - 1.91 (m, 1H), 1.91 - 1.80 (m, 1H), 1.78 - 1.62 (m, 2H), 1.60 - 1.52 (m, 2H), 1.40 (t, J = 7.0 Hz, 3H), 1.12 (s, 6H).
{(1R,3R)−3−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンチル}−(4−メチル−ピペラジン−1−イル)−メタノン(「A241」)
(1S,3R)−3−(3−キノリン−6−イル−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタンカルボン酸[2−(4−メチル−ピペラジン−1−イル)−エチル]−アミド(「A242」)
(1R,3R)−3−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸[2−(4−メチル−ピペラジン−1−イル)−エチル]−アミド(「A244」)
(1R,3R)−3−[3−(4−エトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸(2−ヒドロキシ−エチル)−アミド(「A247」)
(1R,3R)−3−[3−(4−エトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸(1−メチル−ピペリジン−4−イルメチル)−アミド(「A249」)
HPLC/MS 2.02分(C)、[M+H] 479;1H NMR (500 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.29 (s, 1H), 8.12 (s, 1H), 8.08 (bs, 2H), 7.18 (d, J = 9.0 Hz, 2H), 4.42 (bs, 1H), 4.15 (q, J = 7.0 Hz, 2H), 3.52 - 3.41 (m, 2H), 3.21 (m, 1H), 3.10 - 2.99 (m, 2H), 2.91 (m, 3H), 2.77 (s, 3H), 2.15 (m, 2H), 2.03 (m, 1H), 1.96 - 1.81 (m, 3H), 1.81 - 1.62 (m, 4H), 1.41 (t, J = 7.0 Hz, 3H);
(1R,3R)−3−[3−(4−エトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸(2−ヒドロキシ−2−メチル−プロピル)−メチル−アミド(「A251」)
(1R,3R)−3−[3−(2−メチル−キノリン−6−イル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸(3−ヒドロキシ−3−メチル−ブチル)−アミド(「A253」)
(1R,3R)−3−[[3−(2−メチル−6−キノリル)トリアゾロ[4,5−d]ピリミジン−5−イル]アミノ]−N−(2−モルホリノエチル)シクロペンタンカルボキサミド(「A254a」)
(1R,3R)−3−(3−{4−[1−(2−ヒドロキシ−エチル)−1H−ピラゾール−4−イル]−フェニル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタンカルボン酸アミド(「A255」)の合成
1H NMR (400 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.29 (s, 1H), 8.32 (s, 1H), 8.25 (d, J = 8.3 Hz, 2H), 8.08 (s, 1H), 7.88 (d, J = 8.6 Hz, 2H), 4.42 (bs, 1H), 4.26 (t, J = 5.5 Hz, 2H), 3.85 (t, J = 5.5 Hz, 2H), 2.90 (p, J = 7.9 Hz, 1H), 2.18 (m, 2H), 2.09 - 1.98 (m, 1H), 1.92 (m, 1H), 1.86 - 1.64 (m, 2H).
2−(4−{4−[5−(トランス−4−アミノ−シクロヘキシルアミノ)−[1,2,3]トリアゾロ[4,5−d]ピリミジン−3−イル]−フェニル}−ピラゾール−1−イル)−エタノール(「A256」)
2−(4−{4−[5−((1R,3S)−3−アミノ−シクロペンチルアミノ)−[1,2,3]トリアゾロ[4,5−d]ピリミジン−3−イル]−フェニル}−ピラゾール−1−イル)−エタノール(「A257」)
(1R,3R)−3−(3−{4−[1−(2−ヒドロキシ−エチル)−1H−ピラゾール−4−イル]−フェニル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタノール(「A259」)
(1R,3R)−3−(3−{5−[1−(2−ヒドロキシ−エチル)−1H−ピラゾール−4−イル]−ピリジン−2−イル}−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ)−シクロペンタンカルボン酸アミド(「A261」)
[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−((トランス)−3−メチルスルファニル−シクロペンチル)−アミン(「A262」)、((トランス)−3−メタンスルホニル−シクロペンチル)−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−アミン(「A263」)および((シス)−3−メタンスルホニル−シクロペンチル)−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−アミン(「A264」)の合成
「A263」(トランス異性体):HPLC/MS 1.77分(B)、[M+H] 389;1H NMR (500 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.26 (s, 1H), 8.05 (bs, 2H), 7.20 (d, J = 8.7 Hz, 2H), 4.33 (bs, 1H), 3.87 (s, 3H), 3.81 - 3.59 (m, 1H), 2.95 (s, 3H), 2.47 (m, 1H), 2.06 (m, 4H), 1.79 (m, 1H);
「A264」(シス異性体):HPLC/MS 1.79分(B)、[M+H] 389 ;1H NMR (500 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.22 (s, 1H), 8.30 - 7.78 (m, 2H), 7.14 (d, J = 8.9 Hz, 2H), 4.38 (bs, 1H), 3.82 (s, 3H), 3.77 (td, J = 9.1, 4.6 Hz, 1H), 2.91 (s, 3H), 2.47 - 2.32 (m, 1H), 2.24 - 2.12 (m, 1H), 2.11 - 2.04 (m, 1H), 2.04 - 1.91 (m, 2H), 1.79 (m, 1H).
(1R,3R)−3−[3−(4−{1−[2−(1H−テトラゾール−5−イル)−エチル]−1H−ピラゾール−4−イル}−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸アミド(「A265」)の合成
「A265」:暗紫色の固体;HPLC/MS 1.77分(C)、[M+H] 486;1H NMR (400 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.30 (s, 1H), 8.31 - 8.17 (m, 3H), 8.00 (s, 1H), 7.82 (d, J = 8.4 Hz, 2H), 4.67 (t, J = 6.8 Hz, 2H), 4.46 (bs, 1H), 3.56 (t, J = 6.8 Hz, 2H), 2.95 (p, J = 7.9 Hz, 1H), 2.21 (m, 2H), 2.06 (m, 1H), 1.96 (m, 1H), 1.89 - 1.68 (m, 2H).
[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−[(1R,3S)−3−(5−メチル−オキサゾール−2−イル)−シクロペンチル]−アミン(「A267」)の合成
3−(4−{4−[5−(トランス−3−ヒドロキシ−シクロペンチルアミノ)−[1,2,3]トリアゾロ[4,5−d]ピリミジン−3−イル]−フェニル}−ピラゾール−1−イル)−プロピオンアミド(「A268」)の合成
((R)−1−メタンスルホニル−ピロリジン−3−イル)−(3−キノリン−6−イル−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル)−アミン(「A269」)の合成
(R)−3−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−ピロリジン−1−スルホン酸アミド(「A270」)の合成
1−((R)−3−{3−[4−(1−メチル−1H−ピラゾール−4−イル)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−ピロリジン−1−イル)−4−ピペラジン−1−イル−ブタン−1−オン(「A271」)の合成
(1R,4S)−4−[3−(4−エトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタ−2−エンカルボン酸アミド(「A272」)および(1S,4S)−4−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタ−2−エンカルボン酸アミド(「A273」)の合成
「A273」:HPLC/MS 2.24分(C)、[M+H] 352;1H NMR (500 MHz, DMSO-, TFA-d1) δ [ppm] 9.28 (s, 1H), 8.20 - 7.85 (m, 2H), 7.21 (d, J = 9.0 Hz, 2H), 5.94 (m, 2H), 5.16 (bs, 1H), 3.87 (s, 3H), 3.66 (ddd, J = 8.6, 4.3, 2.2 Hz, 1H), 2.58- 2.51 (m, 1H), 1.99 (ddd, J = 13.2, 8.7, 4.6 Hz, 1H).
(1R,3R)−3−{3−[4−(2−メトキシ−エトキシ)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタンカルボニトリル(「A274」)の合成
(1R,3R)−3−[3−(4−ヒドロキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸アミド(「A276」)、(1R,3R)−3−{3−[4−(2−モルホリン−4−イル−エトキシ)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタンカルボン酸アミド(「A277」)、(1R,3R)−3−{3−[4−(3−ヒドロキシ−1,1−ジメチル−プロポキシ)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタンカルボン酸アミド(「A278」)および(1R,3R)−3−{3−[4−(ピペリジン−4−イルメトキシ)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタンカルボン酸アミド(「A279」)の合成
「A277」:HPLC/MS 1.66分(C)、[M+H] 453;1H NMR (500 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.29 (s, 1H), 8.16 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 9.0 Hz, 2H), 4.55 - 4.51 (m, 2H), 4.39 (bs, 1H), 4.12 - 3.98 (m, 2H), 3.87 - 3.75 (m, 2H), 3.70 (t, J = 4.9 Hz, 2H), 3.63 (d, J = 12.6 Hz, 2H), 3.31 (td, J = 12.3, 3.7 Hz, 2H), 2.92 (p, J = 8.0 Hz, 1H), 2.26 - 2.09 (m, 2H), 2.09 - 1.99 (m, 1H), 1.92 (m, 1H), 1.84 - 1.66 (m, 2H);
「A278」:HPLC/MS 2.20分(C)、[M+H] 426;1H NMR (500 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.30 (s, 1H), 8.21 - 8.05 (m, 2H), 7.25 (d, J = 8.9 Hz, 2H), 4.44 (bs, 1H), 3.73 (t, J = 7.3 Hz, 2H), 2.93 (p, J = 8.0 Hz, 1H), 2.33 - 2.11 (m, 2H), 2.06 (qd, J = 8.1, 4.5 Hz, 1H), 1.95 (t, J = 7.3 Hz, 2H), 1.94 - 1.89 (m, 1H), 1.77 (m, 2H), 1.36 (s, 6H);
「A279」:HPLC/MS 1.78分(C)、[M+H] 437;1H NMR (500 MHz, DMSO-d6) δ [ppm] 9.30 (s, 1H), 8.11 (d, J = 9.5 Hz, 2H), 7.21 (d, J = 8.8 Hz, 2H), 4.41 (bs, 1H), 4.01 (d, J = 6.2 Hz, 2H), 3.40 (d, J = 12.7 Hz, 2H), 3.04 - 2.89 (m, 3H), 2.18 (m, 3H), 2.11 - 1.97 (m, 3H), 1.92 (ddd, J = 13.4, 9.3, 5.6 Hz, 1H), 1.76 (m, 2H), 1.68 - 1.50 (m, 2H).
(1R,3R)−3−[3−(4−エトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸N’−アセチル−ヒドラジド(「A280」)および[3−(4−エトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−[(1R,3R)−3−(5−メチル−[1,3,4]オキサジアゾール−2−イル)−シクロペンチル]−アミン(「A281」)の合成
「A281」:HPLC/MS 2.73分(C)、[M+H] 407;1H NMR (400 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.21 (s, 1H), 8.01 (d, J = 8.4 Hz, 2H), 7.10 (d, J = 9.0 Hz, 2H), 4.45 (bs, 1H), 4.07 (q, J = 6.9 Hz, 2H), 3.53 (p, J = 7.8 Hz, 1H), 2.39 (s, 3H), 2.38 - 2.26 (m, 1H), 2.27 - 2.01 (m, 3H), 1.98 - 1.71 (m, 2H), 1.34 (t, J = 7.0 Hz, 3H).
(1R,3R)−3−[3−(4−エトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸ヒドラジド(「A282」)および[(1R,3R)−3−(5−アミノ−[1,3,4]オキサジアゾール−2−イル)−シクロペンチル]−[3−(4−エトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イル]−アミン(「A283」)の合成
「A283」:HPLC/MS 1.75分(B)、[M+H] 408;1H NMR (500 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.29 (s, 1H), 8.07 (bs, 2H), 7.17 (d, J = 9.1 Hz, 2H), 4.50 (bs, 1H), 4.14 (q, J = 7.0 Hz, 2H), 3.57 (p, J = 8.0 Hz, 1H), 2.36 (dt, J = 14.3, 7.4 Hz, 1H), 2.32 - 2.25 (m, 1H), 2.23 (m, 2H), 1.97 (dq, J = 12.0, 7.5 Hz, 1H), 1.89 (m, 1H), 1.41 (t, J = 7.0 Hz, 3H).
(R)−3−[3−(2−メチル−キノリン−6−イル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−ピロリジン−1−カルボン酸アミド(「A284」)の合成
N−{(1R,3R)−3−[3−(4−エトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボニル}−メタンスルホンアミド(「A286」)の合成
2−{(トランス)−3−[3−(4−エトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンチル}−2H−ピリダジン−3−オン(「A287」)の合成
(トランス)−3−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンスルホン酸アミド(「A288」)の合成
(1R,3R)−3−{3−[4−(1−ヒドロキシ−1−メチル−エチル)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタンカルボン酸アミド(「A289」)の合成
1−{(1R,3R)−3−[3−(4−メトキシ−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンチル}−ピロリジン−2−オン(「A291」)の合成
3−{4−[5−((1R,3R)−3−カルバモイル−シクロペンチルアミノ)−[1,2,3]トリアゾロ[4,5−d]ピリミジン−3−イル]−フェノキシ}−プロピオン酸メチルエステル(「A292」)および(1R,3R)−3−{3−[4−(3−ヒドロキシ−3−メチル−ブトキシ)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタンカルボン酸アミド(「A293」)の合成
「A293」:HPLC/MS 1.62分(B)、[M+H] 426;1H NMR (500 MHz, DMSO-d6, TFA-d1) δ [ppm] 9.30 (s, 1H), 8.09 (bs, 2H), 7.20 (d, J = 9.0 Hz, 2H), 4.41 (bs, 1H), 4.23 (t, J = 7.1 Hz, 2H), 2.91 (p, J = 8.0 Hz, 1H), 2.16 (m, 1H), 2.09 - 1.99 (m, 2H), 1.95 (t, J = 7.1 Hz, 2H), 1.92 - 1.86 (m, 1H), 1.78 (m, 2H), 1.24 (s, 6H).
{4−[5−((1R,3R)−3−カルバモイル−シクロペンチルアミノ)−[1,2,3]トリアゾロ[4,5−d]ピリミジン−3−イル]−フェノキシ}−酢酸メチルエステル(「A294」)
(1R,3R)−3−{3−[4−(2−ヒドロキシ−2−メチル−プロポキシ)−フェニル]−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ}−シクロペンタンカルボン酸アミド(「A295」)
(1R,3R)−3−[3−(4−メタンスルホニル−フェニル)−3H−[1,2,3]トリアゾロ[4,5−d]ピリミジン−5−イルアミノ]−シクロペンタンカルボン酸アミド(「A296」)の合成
3−[(1S,3R)−3−[[3−(4−メトキシフェニル)トリアゾロ[4,5−d]ピリミジン−5−イル]アミノ]シクロペンチル]−4H−1,2,4−オキサジアゾール−5−オン(「A297」)および3−(4−メトキシフェニル)−N−[(1R,3S)−3−(5−メチル−1,2,4−オキサジアゾール−3−イル)シクロペンチル]トリアゾロ[4,5−d]ピリミジン−5−アミン(「A298」)の合成
(1R,3R)−3−[[3−[4−(4−ピペリジルオキシ)フェニル]トリアゾロ[4,5−d]ピリミジン−5−イル]アミノ]シクロペンタンカルボキサミド(「A299」)および(1R,3R)−3−[[3−[4−[(1−メチル−4−ピペリジル)オキシ]フェニル]トリアゾロ[4,5−d]ピリミジン−5−イル]アミノ]シクロペンタンカルボキサミド(「A300」)の合成
表2 幾つかの代表的な式Iで表される化合物のGCN2阻害
例A:注射バイアル
3リットルの再蒸留水中の100gの式Iの活性成分および5gのリン酸水素二ナトリウムの溶液を、2Nの塩酸を用いてpH6.5に調整し、無菌ろ過し、注射バイアル中に移し、無菌条件下において凍結乾燥し、無菌条件下において密封する。各注射バイアルは、5mgの活性成分を含有する。
例B:坐剤
20gの式Iの活性成分と100gの大豆レシチンおよび1400gのカカオバターとの混合物を融解させ、鋳型中に注入し、冷却する。各坐剤は、20mgの活性成分を含有する。
940mlの再蒸留水中で、1gの式Iの活性成分、9.38gのNaH2PO4・2H2O、28.48gのNa2HPO4・12H2Oおよび0.1gの塩化ベンジルから溶液を調製する。pHを6.8に調整し、溶液を1リットルにし、照射により滅菌する。この溶液を、点眼剤の形態において用いることができる。
例D:軟膏
500mgの式Iの活性成分を99.5gのワセリンと無菌条件下において混合する。
1kgの式Iの活性成分、4kgの乳糖、1.2kgの馬鈴薯デンプン、0.2kgのタルクおよび0.1kgのステアリン酸マグネシウムの混合物を、従来の様式において、各錠剤が10mgの活性成分を含有するように圧縮する。
例F:糖衣錠
例Eと同様に錠剤を圧縮し、その後、従来の様式において、ショ糖、馬鈴薯デンプン、タルク、トラガカントおよび色素のコーティングで被覆する。
2kgの式Iの活性成分を、硬質ゼラチンカプセル中に、従来の様式において、各カプセルが20mgの活性成分を含有するように導入する。
例H:アンプル
60リットルの再蒸留水中の1kgの式Iの活性成分の溶液を、無菌ろ過し、アンプル中に移し、無菌条件下において凍結乾燥し、無菌条件下において密封する。各アンプルは、10mgの活性成分を含有する。
Claims (11)
- 以下の群:
- 少なくとも1つの請求項1に記載の化合物、ならびに/またはその薬学的に受容可能な塩、溶媒和物、互変異性体もしくは立体異性体、または全ての比におけるそれらの混合物、ならびに任意に、薬学的に受容可能なキャリア、賦形剤またはビヒクルを含む、医薬。
- 炎症性状態、免疫学的状態、自己免疫性状態、アレルギー性状態、リウマチ性状態、血栓性状態、癌、感染症、神経変性疾患、神経炎症性疾患、心血管疾患、および代謝性状態の処置および/または予防のための使用のための、請求項1に記載の化合物、またはその薬学的に受容可能な塩、溶媒和物、互変異性体もしくは立体異性体、または全ての比におけるそれらの混合物。
- 癌の処置および/または予防のための使用のための、請求項3に記載の化合物であって、ここで、処置されるべき癌が、固形腫瘍または血液および免疫系の腫瘍である、前記化合物。
- 固形腫瘍が、上皮、膀胱、胃、腎臓、頭部頸部、食道、子宮頸部、甲状腺、腸、肝臓、脳、前立腺、泌尿生殖管、リンパ系、胃、喉頭、骨(軟骨肉腫およびユーイング肉腫を含む)、生殖細胞(胚性組織腫瘍を含む)、ならびに/または肺の腫瘍の群、単球性白血病、肺腺癌、小細胞肺癌、膵臓癌、神経膠芽腫、神経線維腫、血管肉腫、乳癌および/または悪性黒色腫の群に起源を有する、請求項4に記載の化合物。
- 関節リウマチ、全身性エリテマトーデス、喘息、多発性硬化症、変形性関節症、虚血傷害、巨細胞性動脈炎、炎症性腸疾患、糖尿病、嚢胞性線維症、乾癬、シェーグレン症候群および移植臓器拒絶の群から選択される疾患の処置および/または予防のための使用のための、請求項5に記載の化合物。
- アルツハイマー病、ダウン症候群、オランダ型アミロイドーシスを伴う遺伝性脳出血、脳アミロイド血管症、クロイツフェルト・ヤコブ病、前頭側頭型認知症、ハンチントン病、パーキンソン病の群から選択される疾患の処置および/または予防のための使用のための、請求項5に記載の化合物。
- リーシュマニア、らい菌、結核菌および/またはマイコバクテリア・アビウムを含むマイコバクテリア、リーシュマニア、マラリア原虫、ヒト免疫不全ウイルス、エプスタイン・バーウイルス、単純ヘルペスウイルス、C型肝炎ウイルスに起因する感染症の群から選択される疾患の処置および/または予防のための使用のための、請求項5に記載の化合物。
- 少なくとも1つの請求項1に記載の化合物、ならびに/またはその薬学的に受容可能な塩、溶媒和物もしくは立体異性体、または全ての比におけるそれらの混合物、ならびに少なくとも1つのさらなる医薬活性成分を含む、医薬。
- 以下の別々のパックからなる、セット(キット):
(a)請求項1に記載の化合物、ならびに/またはその薬学的に受容可能な塩、溶媒和物、塩もしくは立体異性体、または全ての比におけるそれらの混合物の有効量、
ならびに
(b)さらなる医薬活性成分の有効量。 - 以下の群:
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP13001110.9 | 2013-03-05 | ||
EP13001110 | 2013-03-05 | ||
PCT/EP2014/000361 WO2014135244A1 (en) | 2013-03-05 | 2014-02-10 | Triazolo[4,5-d]pyrimidine derivatives for the treatment of diseases such as cancer |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016510044A JP2016510044A (ja) | 2016-04-04 |
JP6427115B2 true JP6427115B2 (ja) | 2018-11-21 |
Family
ID=47843001
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015560571A Expired - Fee Related JP6427115B2 (ja) | 2013-03-05 | 2014-02-10 | 癌などの疾患の処置のためのトリアゾロ[4,5−d]ピリミジン誘導体 |
Country Status (10)
Country | Link |
---|---|
US (1) | US9855268B2 (ja) |
EP (1) | EP2964649B1 (ja) |
JP (1) | JP6427115B2 (ja) |
CN (1) | CN105026398B (ja) |
AR (1) | AR094982A1 (ja) |
AU (1) | AU2014224975B2 (ja) |
CA (1) | CA2903903C (ja) |
ES (1) | ES2636936T3 (ja) |
IL (1) | IL240877A0 (ja) |
WO (1) | WO2014135244A1 (ja) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6888006B2 (ja) * | 2015-10-29 | 2021-06-16 | イーフェクター セラピューティクス, インコーポレイテッド | Mnk1およびmnk2を阻害するピロロ−、ピラゾロ−、イミダゾ−ピリミジンおよびピリジン化合物 |
KR102488323B1 (ko) | 2015-12-10 | 2023-01-12 | 피티씨 테라퓨틱스, 인크. | 헌팅턴병 치료 또는 개선을 위한 조성물 |
TWI794171B (zh) | 2016-05-11 | 2023-03-01 | 美商滬亞生物國際有限公司 | Hdac抑制劑與pd-l1抑制劑之組合治療 |
TWI808055B (zh) | 2016-05-11 | 2023-07-11 | 美商滬亞生物國際有限公司 | Hdac 抑制劑與 pd-1 抑制劑之組合治療 |
MA45940A (fr) | 2016-08-10 | 2019-06-19 | Takeda Pharmaceuticals Co | Composé hétérocyclique |
EP3842442B1 (en) | 2016-12-22 | 2023-11-01 | Precision Pharmaceuticals, Inc. | Compositions and methods for inhibiting arginase activity |
WO2022011171A1 (en) * | 2020-07-08 | 2022-01-13 | Klotho Therapeutics, Inc. | Novel compounds and methods for increasing klotho gene expression |
SG11201911615WA (en) | 2017-06-05 | 2020-01-30 | Ptc Therapeutics Inc | Compounds for treating huntington's disease |
CA3067592A1 (en) | 2017-06-28 | 2019-01-03 | Ptc Therapeutics, Inc. | Methods for treating huntington's disease |
CA3067591A1 (en) | 2017-06-28 | 2019-01-03 | Ptc Therapeutics, Inc. | Methods for treating huntington's disease |
JP7352294B2 (ja) * | 2018-02-02 | 2023-09-28 | ヴァンダービルト ユニバーシティー | ムスカリン性アセチルコリン受容体m4のアンタゴニスト |
WO2019191092A1 (en) | 2018-03-27 | 2019-10-03 | Ptc Therapeutics, Inc. | Compounds for treating huntington's disease |
US11046699B2 (en) | 2018-06-05 | 2021-06-29 | Rapt Therapeutics, Inc. | Pyrazolo-pyrimidin-amino-cycloalkyl compounds and their therapeutic uses |
EP3814360A1 (en) | 2018-06-27 | 2021-05-05 | PTC Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
MX2020014098A (es) | 2018-06-27 | 2021-05-27 | Ptc Therapeutics Inc | Compuestos heterocíclicos y de heteroarilo para tratar la enfermedad de huntington. |
US20210299233A1 (en) * | 2018-07-12 | 2021-09-30 | The Children's Medical Center Corporation | Method for treating cancer |
KR102328423B1 (ko) * | 2018-09-11 | 2021-11-18 | 재단법인 대구경북첨단의료산업진흥재단 | 신규 트리아졸로-피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 단백질 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물 |
GB202008749D0 (en) | 2020-06-09 | 2020-07-22 | Ip2Ipo Innovations Ltd | Novel compounds |
WO2023107705A1 (en) | 2021-12-10 | 2023-06-15 | Incyte Corporation | Bicyclic amines as cdk12 inhibitors |
CN114487157A (zh) * | 2021-12-23 | 2022-05-13 | 苏州华测生物技术有限公司 | 一种分离生物基质中游离态和脂质体态艾立布林的方法 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5962594A (ja) * | 1982-09-30 | 1984-04-10 | Ss Pharmaceut Co Ltd | 3,5―ジ置換―トリアゾロピリミジン誘導体 |
ES2290754T3 (es) * | 2003-07-16 | 2008-02-16 | Janssen Pharmaceutica N.V. | Derivados de triazolopirimidina como inhibidores de la glucogeno sintasa cinasa 3. |
PL1853588T3 (pl) | 2005-02-16 | 2008-11-28 | Astrazeneca Ab | Związki chemiczne |
CN101119988B (zh) * | 2005-02-16 | 2013-03-06 | 阿斯利康(瑞典)有限公司 | 化学化合物 |
WO2006091737A1 (en) | 2005-02-24 | 2006-08-31 | Kemia, Inc. | Modulators of gsk-3 activity |
EA201300282A1 (ru) | 2010-08-27 | 2013-08-30 | Мерк Патент Гмбх | Производные триазолопиразина |
-
2014
- 2014-02-10 EP EP14704286.5A patent/EP2964649B1/en not_active Not-in-force
- 2014-02-10 JP JP2015560571A patent/JP6427115B2/ja not_active Expired - Fee Related
- 2014-02-10 AU AU2014224975A patent/AU2014224975B2/en not_active Ceased
- 2014-02-10 WO PCT/EP2014/000361 patent/WO2014135244A1/en active Application Filing
- 2014-02-10 ES ES14704286T patent/ES2636936T3/es active Active
- 2014-02-10 CA CA2903903A patent/CA2903903C/en active Active
- 2014-02-10 CN CN201480012252.4A patent/CN105026398B/zh not_active Expired - Fee Related
- 2014-02-10 US US14/772,865 patent/US9855268B2/en active Active
- 2014-03-05 AR ARP140100697A patent/AR094982A1/es unknown
-
2015
- 2015-08-27 IL IL240877A patent/IL240877A0/en active IP Right Grant
Also Published As
Publication number | Publication date |
---|---|
IL240877A0 (en) | 2015-10-29 |
US9855268B2 (en) | 2018-01-02 |
WO2014135244A1 (en) | 2014-09-12 |
AR094982A1 (es) | 2015-09-09 |
JP2016510044A (ja) | 2016-04-04 |
CA2903903A1 (en) | 2014-09-12 |
ES2636936T3 (es) | 2017-10-10 |
CN105026398B (zh) | 2018-05-18 |
EP2964649B1 (en) | 2017-05-10 |
US20160015712A1 (en) | 2016-01-21 |
AU2014224975B2 (en) | 2017-09-14 |
CN105026398A (zh) | 2015-11-04 |
CA2903903C (en) | 2021-05-04 |
AU2014224975A1 (en) | 2015-10-22 |
EP2964649A1 (en) | 2016-01-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6427115B2 (ja) | 癌などの疾患の処置のためのトリアゾロ[4,5−d]ピリミジン誘導体 | |
AU2014224976B2 (en) | 9-(aryl or heteroaryl)-2-(pyrazolyl, pyrrolidinyl or cyclopentyl)aminopurine derivatives as anticancer agents | |
AU2013230286B2 (en) | Triazolopyrazine derivatives | |
JP6097770B2 (ja) | フロピリジン誘導体 | |
US11174241B2 (en) | Quinolin-2-one derivatives | |
AU2011295440B2 (en) | Triazolopyrazine derivatives | |
AU2012367141B2 (en) | Triazolo[4,5-d]pyrimidine derivatives | |
JP6059260B2 (ja) | 環状ジアミノピリジン誘導体 | |
KR20210129674A (ko) | 암과 같은 질환의 치료를 위한 인다졸릴-이속사졸 유도체 | |
BR112016001928B1 (pt) | Derivados de piperidina ureia, seu uso, medicamentos, e kit |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20170209 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20171228 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180130 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180427 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180831 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180912 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20180926 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20181026 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6427115 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |