JP2016539148A - 医薬組成物のためのスルホキシイミン置換キナゾリン - Google Patents
医薬組成物のためのスルホキシイミン置換キナゾリン Download PDFInfo
- Publication number
- JP2016539148A JP2016539148A JP2016536528A JP2016536528A JP2016539148A JP 2016539148 A JP2016539148 A JP 2016539148A JP 2016536528 A JP2016536528 A JP 2016536528A JP 2016536528 A JP2016536528 A JP 2016536528A JP 2016539148 A JP2016539148 A JP 2016539148A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- group
- phenyl
- optionally substituted
- pharmaceutically acceptable
- 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.)
- Granted
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 22
- 150000003246 quinazolines Chemical class 0.000 title description 10
- 238000000034 method Methods 0.000 claims abstract description 46
- 101710138999 MAP kinase-interacting serine/threonine-protein kinase 2 Proteins 0.000 claims abstract description 40
- 102100033610 MAP kinase-interacting serine/threonine-protein kinase 2 Human genes 0.000 claims abstract description 39
- 150000001875 compounds Chemical class 0.000 claims description 125
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 76
- 239000000203 mixture Substances 0.000 claims description 71
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- 150000003839 salts Chemical class 0.000 claims description 49
- 201000010099 disease Diseases 0.000 claims description 48
- 108091000080 Phosphotransferase Proteins 0.000 claims description 47
- 102000020233 phosphotransferase Human genes 0.000 claims description 47
- 238000011282 treatment Methods 0.000 claims description 41
- 206010012601 diabetes mellitus Diseases 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 229910052731 fluorine Inorganic materials 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 28
- 230000000694 effects Effects 0.000 claims description 27
- 229910052799 carbon Inorganic materials 0.000 claims description 25
- 229910052717 sulfur Inorganic materials 0.000 claims description 23
- 208000030159 metabolic disease Diseases 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 230000002265 prevention Effects 0.000 claims description 19
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 125000004434 sulfur atom Chemical group 0.000 claims description 15
- 229940124597 therapeutic agent Drugs 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 208000027866 inflammatory disease Diseases 0.000 claims description 13
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 11
- 229920006395 saturated elastomer Polymers 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 230000004770 neurodegeneration Effects 0.000 claims description 8
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 230000023852 carbohydrate metabolic process Effects 0.000 claims description 7
- 230000006378 damage Effects 0.000 claims description 7
- 230000037356 lipid metabolism Effects 0.000 claims description 7
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 150000001720 carbohydrates Chemical class 0.000 claims description 5
- 208000018706 hematopoietic system disease Diseases 0.000 claims description 5
- 239000002246 antineoplastic agent Substances 0.000 claims description 4
- 210000003734 kidney Anatomy 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 3
- 239000003472 antidiabetic agent Substances 0.000 claims description 3
- 229940034982 antineoplastic agent Drugs 0.000 claims description 3
- 208000016097 disease of metabolism Diseases 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 2
- 239000000883 anti-obesity agent Substances 0.000 claims description 2
- 239000002220 antihypertensive agent Substances 0.000 claims description 2
- 229940125710 antiobesity agent Drugs 0.000 claims description 2
- 229940127218 antiplatelet drug Drugs 0.000 claims description 2
- 239000002934 diuretic Substances 0.000 claims description 2
- 239000000106 platelet aggregation inhibitor Substances 0.000 claims description 2
- 125000005037 alkyl phenyl group Chemical group 0.000 claims 2
- 229940125708 antidiabetic agent Drugs 0.000 claims 1
- 229940030600 antihypertensive agent Drugs 0.000 claims 1
- 239000003524 antilipemic agent Substances 0.000 claims 1
- 239000002327 cardiovascular agent Substances 0.000 claims 1
- 229940125692 cardiovascular agent Drugs 0.000 claims 1
- 229940030606 diuretics Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 claims 1
- 125000005555 sulfoximide group Chemical group 0.000 abstract description 17
- 230000001404 mediated effect Effects 0.000 abstract description 13
- 239000000126 substance Substances 0.000 abstract description 7
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 102100026299 MAP kinase-interacting serine/threonine-protein kinase 1 Human genes 0.000 abstract description 4
- 229940043355 kinase inhibitor Drugs 0.000 abstract description 4
- 239000003757 phosphotransferase inhibitor Substances 0.000 abstract description 4
- 101710139011 MAP kinase-interacting serine/threonine-protein kinase 1 Proteins 0.000 abstract 2
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 184
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 73
- -1 aromatic primary amine Chemical class 0.000 description 71
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 238000004128 high performance liquid chromatography Methods 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- 230000015572 biosynthetic process Effects 0.000 description 27
- 230000005764 inhibitory process Effects 0.000 description 24
- 238000003786 synthesis reaction Methods 0.000 description 24
- 208000035475 disorder Diseases 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 22
- 239000003643 water by type Substances 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- 208000024891 symptom Diseases 0.000 description 20
- 0 *Oc1ncccc1N Chemical compound *Oc1ncccc1N 0.000 description 18
- 125000004432 carbon atom Chemical group C* 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 230000002757 inflammatory effect Effects 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- 239000007858 starting material Substances 0.000 description 17
- 239000003112 inhibitor Substances 0.000 description 16
- 150000003254 radicals Chemical class 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 238000003556 assay Methods 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 14
- 230000026731 phosphorylation Effects 0.000 description 14
- 238000006366 phosphorylation reaction Methods 0.000 description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 239000000460 chlorine Substances 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 239000000758 substrate Substances 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- 206010061218 Inflammation Diseases 0.000 description 11
- 208000008589 Obesity Diseases 0.000 description 11
- 230000004054 inflammatory process Effects 0.000 description 11
- 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 11
- 235000020824 obesity Nutrition 0.000 description 11
- 108090000765 processed proteins & peptides Proteins 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 101001082110 Acanthamoeba polyphaga mimivirus Eukaryotic translation initiation factor 4E homolog Proteins 0.000 description 10
- 101001082109 Danio rerio Eukaryotic translation initiation factor 4E-1B Proteins 0.000 description 10
- 230000001684 chronic effect Effects 0.000 description 10
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 206010039073 rheumatoid arthritis Diseases 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- RJXOVESYJFXCGI-UHFFFAOYSA-N 2,4-difluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1F RJXOVESYJFXCGI-UHFFFAOYSA-N 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 9
- 108090000695 Cytokines Proteins 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 201000004681 Psoriasis Diseases 0.000 description 9
- 208000025747 Rheumatic disease Diseases 0.000 description 9
- 206010003246 arthritis Diseases 0.000 description 9
- 125000004122 cyclic group Chemical group 0.000 description 9
- 238000004007 reversed phase HPLC Methods 0.000 description 9
- 230000000552 rheumatic effect Effects 0.000 description 9
- 208000031226 Hyperlipidaemia Diseases 0.000 description 8
- 206010020772 Hypertension Diseases 0.000 description 8
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 8
- 206010040070 Septic Shock Diseases 0.000 description 8
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 239000012453 solvate Substances 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000003039 volatile agent Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 7
- 208000006673 asthma Diseases 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 230000016396 cytokine production Effects 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 238000000021 kinase assay Methods 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 7
- 201000006417 multiple sclerosis Diseases 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 230000014616 translation Effects 0.000 description 7
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 6
- 206010009900 Colitis ulcerative 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
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 206010018364 Glomerulonephritis Diseases 0.000 description 6
- 239000007995 HEPES buffer Substances 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 201000006704 Ulcerative Colitis Diseases 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 208000038016 acute inflammation Diseases 0.000 description 6
- 230000006022 acute inflammation Effects 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 208000037976 chronic inflammation Diseases 0.000 description 6
- 230000006020 chronic inflammation Effects 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 150000004677 hydrates Chemical class 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000036303 septic shock Effects 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 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 5
- 239000004215 Carbon black (E152) Substances 0.000 description 5
- 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 5
- 201000004624 Dermatitis Diseases 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 102000004877 Insulin Human genes 0.000 description 5
- 108090001061 Insulin Proteins 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 229940100198 alkylating agent Drugs 0.000 description 5
- 239000002168 alkylating agent Substances 0.000 description 5
- 150000001499 aryl bromides Chemical class 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000002131 composite material Substances 0.000 description 5
- 229960000956 coumarin Drugs 0.000 description 5
- 235000001671 coumarin Nutrition 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 229940125396 insulin Drugs 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 201000008482 osteoarthritis Diseases 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- YSNOZTORLKKZMT-RKDXNWHRSA-N (3R,4R)-4-[tert-butyl(dimethyl)silyl]oxyoxolan-3-ol Chemical compound C(C)(C)(C)[Si](O[C@H]1[C@@H](COC1)O)(C)C YSNOZTORLKKZMT-RKDXNWHRSA-N 0.000 description 4
- YSNOZTORLKKZMT-IUCAKERBSA-N (3s,4s)-4-[tert-butyl(dimethyl)silyl]oxyoxolan-3-ol Chemical compound CC(C)(C)[Si](C)(C)O[C@H]1COC[C@@H]1O YSNOZTORLKKZMT-IUCAKERBSA-N 0.000 description 4
- UUOLETYDNTVQDY-UHFFFAOYSA-N 2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1Cl UUOLETYDNTVQDY-UHFFFAOYSA-N 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 4
- 208000004145 Endometritis Diseases 0.000 description 4
- 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 4
- 201000005569 Gout Diseases 0.000 description 4
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 201000002481 Myositis Diseases 0.000 description 4
- 108700020796 Oncogene Proteins 0.000 description 4
- 201000007100 Pharyngitis Diseases 0.000 description 4
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 4
- 208000006374 Uterine Cervicitis Diseases 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
- 230000004913 activation Effects 0.000 description 4
- 150000001413 amino acids Chemical group 0.000 description 4
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 206010008323 cervicitis Diseases 0.000 description 4
- 239000012916 chromogenic reagent Substances 0.000 description 4
- 229960000684 cytarabine Drugs 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- CNXMDTWQWLGCPE-UHFFFAOYSA-N ditert-butyl-(2-phenylphenyl)phosphane Chemical group CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1C1=CC=CC=C1 CNXMDTWQWLGCPE-UHFFFAOYSA-N 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 206010014665 endocarditis Diseases 0.000 description 4
- 238000002875 fluorescence polarization Methods 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 208000006454 hepatitis Diseases 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 210000004153 islets of langerhan Anatomy 0.000 description 4
- 230000036210 malignancy Effects 0.000 description 4
- 230000002632 myometrial effect Effects 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- WVYADZUPLLSGPU-UHFFFAOYSA-N salsalate Chemical compound OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O WVYADZUPLLSGPU-UHFFFAOYSA-N 0.000 description 4
- 201000004595 synovitis Diseases 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 4
- KMVULHBAEVRKCP-UHFFFAOYSA-N 7-bromoquinazoline Chemical class C1=NC=NC2=CC(Br)=CC=C21 KMVULHBAEVRKCP-UHFFFAOYSA-N 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- 206010002383 Angina Pectoris Diseases 0.000 description 3
- VWLOENMPIHFTIE-HZPDHXFCSA-N C(C)(C)(C)OC(=O)N1C[C@H]([C@@H](C1)OC1=NC=CC=C1[N+](=O)[O-])O[Si](C)(C)C(C)(C)C Chemical compound C(C)(C)(C)OC(=O)N1C[C@H]([C@@H](C1)OC1=NC=CC=C1[N+](=O)[O-])O[Si](C)(C)C(C)(C)C VWLOENMPIHFTIE-HZPDHXFCSA-N 0.000 description 3
- HKJMWQGFHROAMY-GJZGRUSLSA-N C(C)(C)(C)[Si](O[C@H]1CNC[C@@H]1OC1=C(C=CC(=C1)F)[N+](=O)[O-])(C)C Chemical compound C(C)(C)(C)[Si](O[C@H]1CNC[C@@H]1OC1=C(C=CC(=C1)F)[N+](=O)[O-])(C)C HKJMWQGFHROAMY-GJZGRUSLSA-N 0.000 description 3
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 3
- 206010006895 Cachexia Diseases 0.000 description 3
- 108010055166 Chemokine CCL5 Proteins 0.000 description 3
- 206010010741 Conjunctivitis Diseases 0.000 description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 208000032928 Dyslipidaemia Diseases 0.000 description 3
- 108010008165 Etanercept Proteins 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 206010022489 Insulin Resistance Diseases 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- 208000017170 Lipid metabolism disease Diseases 0.000 description 3
- 208000019693 Lung disease Diseases 0.000 description 3
- 102000043136 MAP kinase family Human genes 0.000 description 3
- 201000009906 Meningitis Diseases 0.000 description 3
- 208000001145 Metabolic Syndrome Diseases 0.000 description 3
- UQPMANVRZYYQMD-UHFFFAOYSA-N N3-(4-fluorophenyl)-2H-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound C=12C(N)=NC=NC2=NNC=1NC1=CC=C(F)C=C1 UQPMANVRZYYQMD-UHFFFAOYSA-N 0.000 description 3
- 208000001132 Osteoporosis Diseases 0.000 description 3
- 208000018262 Peripheral vascular disease Diseases 0.000 description 3
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 206010006451 bronchitis Diseases 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
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 208000007565 gingivitis Diseases 0.000 description 3
- 231100000283 hepatitis Toxicity 0.000 description 3
- 208000006575 hypertriglyceridemia Diseases 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 150000003462 sulfoxides Chemical class 0.000 description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
- HIXVCAWAPDTYHO-HTQZYQBOSA-N (3R,4R)-4-(3-nitropyridin-2-yl)oxypyrrolidin-3-ol Chemical compound [N+](=O)([O-])C=1C(=NC=CC1)O[C@H]1[C@@H](CNC1)O HIXVCAWAPDTYHO-HTQZYQBOSA-N 0.000 description 2
- INQHWCYKASVEQT-QWWZWVQMSA-N (3R,4R)-4-fluorooxolan-3-ol Chemical compound F[C@H]1[C@@H](COC1)O INQHWCYKASVEQT-QWWZWVQMSA-N 0.000 description 2
- JGRGRNDCSHAJOJ-SFYZADRCSA-N (3R,4S)-4-(3-nitropyridin-2-yl)oxyoxolan-3-ol Chemical compound [N+](=O)([O-])C=1C(=NC=CC1)O[C@@H]1[C@@H](COC1)O JGRGRNDCSHAJOJ-SFYZADRCSA-N 0.000 description 2
- JMKMYDXAEIVARK-BQBZGAKWSA-N (3S,4S)-4-(6-chloro-3-nitropyridin-2-yl)oxyoxolan-3-ol Chemical compound ClC1=CC=C(C(=N1)O[C@@H]1[C@H](COC1)O)[N+](=O)[O-] JMKMYDXAEIVARK-BQBZGAKWSA-N 0.000 description 2
- LVCNGHBRNGEKCO-UHNVWZDZSA-N (3r,4s)-4-methoxyoxolan-3-ol Chemical compound CO[C@H]1COC[C@H]1O LVCNGHBRNGEKCO-UHNVWZDZSA-N 0.000 description 2
- SSYDTHANSGMJTP-ZXZARUISSA-N (3s,4r)-oxolane-3,4-diol Chemical compound O[C@H]1COC[C@H]1O SSYDTHANSGMJTP-ZXZARUISSA-N 0.000 description 2
- WRRSFOZOETZUPG-FFHNEAJVSA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;hydrate Chemical compound O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC WRRSFOZOETZUPG-FFHNEAJVSA-N 0.000 description 2
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- JTLAIKFGRHDNQM-UHFFFAOYSA-N 1-bromo-2-fluoroethane Chemical compound FCCBr JTLAIKFGRHDNQM-UHFFFAOYSA-N 0.000 description 2
- SHCWQWRTKPNTEM-UHFFFAOYSA-N 2,6-dichloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)N=C1Cl SHCWQWRTKPNTEM-UHFFFAOYSA-N 0.000 description 2
- VOXBZHOHGGBLCQ-UHFFFAOYSA-N 2-amino-3,7-dihydropurine-6-thione;hydrate Chemical compound O.N1C(N)=NC(=S)C2=C1N=CN2.N1C(N)=NC(=S)C2=C1N=CN2 VOXBZHOHGGBLCQ-UHFFFAOYSA-N 0.000 description 2
- MIQCEWVIFALFRN-UHFFFAOYSA-N 2-amino-4-bromo-6-fluorobenzonitrile Chemical compound NC1=CC(Br)=CC(F)=C1C#N MIQCEWVIFALFRN-UHFFFAOYSA-N 0.000 description 2
- PTCPUGKKWNMITF-UHFFFAOYSA-N 4-chloro-2-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1F PTCPUGKKWNMITF-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
- KIVCKEDWINMQHU-UHFFFAOYSA-N 7-bromo-n-(4-fluoro-2-phenylmethoxyphenyl)-5-methylquinazolin-4-amine Chemical compound C=12C(C)=CC(Br)=CC2=NC=NC=1NC1=CC=C(F)C=C1OCC1=CC=CC=C1 KIVCKEDWINMQHU-UHFFFAOYSA-N 0.000 description 2
- 206010000890 Acute myelomonocytic leukaemia Diseases 0.000 description 2
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
- 208000027896 Aortic valve disease Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 208000036487 Arthropathies Diseases 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- 206010004637 Bile duct stone Diseases 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 2
- 206010006811 Bursitis Diseases 0.000 description 2
- KGFNHIHDWHHTOP-ROUUACIJSA-N C(C)(C)(C)OC(=O)N1C[C@@H]([C@H](C1)OC1=C(C=CC(=C1)F)[N+](=O)[O-])O[Si](C)(C)C(C)(C)C Chemical compound C(C)(C)(C)OC(=O)N1C[C@@H]([C@H](C1)OC1=C(C=CC(=C1)F)[N+](=O)[O-])O[Si](C)(C)C(C)(C)C KGFNHIHDWHHTOP-ROUUACIJSA-N 0.000 description 2
- AOHCGVZJOFOUSY-HZPDHXFCSA-N C(C)(C)(C)[Si](O[C@@H]1CN(C[C@H]1OC1=C(C=CC(=C1)F)[N+](=O)[O-])S(=O)(=O)C)(C)C Chemical compound C(C)(C)(C)[Si](O[C@@H]1CN(C[C@H]1OC1=C(C=CC(=C1)F)[N+](=O)[O-])S(=O)(=O)C)(C)C AOHCGVZJOFOUSY-HZPDHXFCSA-N 0.000 description 2
- AOHCGVZJOFOUSY-HOTGVXAUSA-N C(C)(C)(C)[Si](O[C@H]1CN(C[C@@H]1OC1=C(C=CC(=C1)F)[N+](=O)[O-])S(=O)(=O)C)(C)C Chemical compound C(C)(C)(C)[Si](O[C@H]1CN(C[C@@H]1OC1=C(C=CC(=C1)F)[N+](=O)[O-])S(=O)(=O)C)(C)C AOHCGVZJOFOUSY-HOTGVXAUSA-N 0.000 description 2
- SPURXXMRDORXBB-ZIAGYGMSSA-N C(C)(C)(C)[Si](O[C@H]1[C@@H](CN(C1)S(=O)(=O)C)OC1=NC=CC=C1[N+](=O)[O-])(C)C Chemical compound C(C)(C)(C)[Si](O[C@H]1[C@@H](CN(C1)S(=O)(=O)C)OC1=NC=CC=C1[N+](=O)[O-])(C)C SPURXXMRDORXBB-ZIAGYGMSSA-N 0.000 description 2
- 239000002080 C09CA02 - Eprosartan Substances 0.000 description 2
- 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 2
- 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 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 206010008690 Chondrocalcinosis pyrophosphate Diseases 0.000 description 2
- 206010010071 Coma Diseases 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 206010057254 Connective tissue inflammation Diseases 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 108010013198 Daptomycin Proteins 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 208000002249 Diabetes Complications Diseases 0.000 description 2
- 208000001380 Diabetic Ketoacidosis Diseases 0.000 description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 2
- 208000032780 Diabetic arthropathy Diseases 0.000 description 2
- 206010012655 Diabetic complications Diseases 0.000 description 2
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 2
- 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 2
- 208000030814 Eating disease Diseases 0.000 description 2
- 208000019454 Feeding and Eating disease Diseases 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 208000007882 Gastritis Diseases 0.000 description 2
- 206010018634 Gouty Arthritis Diseases 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 2
- 101000936277 Homo sapiens Copper-transporting ATPase 1 Proteins 0.000 description 2
- 101000573522 Homo sapiens MAP kinase-interacting serine/threonine-protein kinase 1 Proteins 0.000 description 2
- 101001018978 Homo sapiens MAP kinase-interacting serine/threonine-protein kinase 2 Proteins 0.000 description 2
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 2
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 2
- 241000701041 Human betaherpesvirus 7 Species 0.000 description 2
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
- 241001502974 Human gammaherpesvirus 8 Species 0.000 description 2
- 241000701027 Human herpesvirus 6 Species 0.000 description 2
- 208000000563 Hyperlipoproteinemia Type II Diseases 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
- 206010072877 Intestinal fibrosis Diseases 0.000 description 2
- 206010022941 Iridocyclitis Diseases 0.000 description 2
- 208000012659 Joint disease Diseases 0.000 description 2
- 208000011200 Kawasaki disease Diseases 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 201000008197 Laryngitis Diseases 0.000 description 2
- 108010092217 Long-Acting Insulin Chemical class 0.000 description 2
- 229940100066 Long-acting insulin Drugs 0.000 description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 229930192392 Mitomycin Natural products 0.000 description 2
- 208000011682 Mitral valve disease Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000000112 Myalgia Diseases 0.000 description 2
- 208000003926 Myelitis Diseases 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- 208000033835 Myelomonocytic Acute Leukemia Diseases 0.000 description 2
- 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 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 2
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 2
- 206010030216 Oesophagitis Diseases 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- 206010031252 Osteomyelitis Diseases 0.000 description 2
- 208000005141 Otitis Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 206010033645 Pancreatitis Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 206010035742 Pneumonitis Diseases 0.000 description 2
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 2
- 206010037575 Pustular psoriasis Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 208000012322 Raynaud phenomenon Diseases 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 206010039710 Scleroderma Diseases 0.000 description 2
- 201000010001 Silicosis Diseases 0.000 description 2
- 208000021386 Sjogren Syndrome Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 201000002661 Spondylitis Diseases 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010042496 Sunburn Diseases 0.000 description 2
- 208000000491 Tendinopathy Diseases 0.000 description 2
- 206010043255 Tendonitis Diseases 0.000 description 2
- 206010043780 Thyroiditis acute Diseases 0.000 description 2
- 206010043784 Thyroiditis subacute Diseases 0.000 description 2
- GSNOZLZNQMLSKJ-UHFFFAOYSA-N Trapidil Chemical compound CCN(CC)C1=CC(C)=NC2=NC=NN12 GSNOZLZNQMLSKJ-UHFFFAOYSA-N 0.000 description 2
- 206010046914 Vaginal infection Diseases 0.000 description 2
- 201000008100 Vaginitis Diseases 0.000 description 2
- 206010047115 Vasculitis Diseases 0.000 description 2
- 206010047249 Venous thrombosis Diseases 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 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
- 208000011912 acute myelomonocytic leukemia M4 Diseases 0.000 description 2
- 201000006498 acute thyroiditis Diseases 0.000 description 2
- 229960002964 adalimumab Drugs 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000004450 alkenylene group Chemical group 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 125000004419 alkynylene group Chemical group 0.000 description 2
- 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 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- CHKQALUEEULCPZ-UHFFFAOYSA-N amino 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=CC(C)=C(S(=O)(=O)ON)C(C)=C1 CHKQALUEEULCPZ-UHFFFAOYSA-N 0.000 description 2
- FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical compound NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 description 2
- 201000004612 anterior uveitis Diseases 0.000 description 2
- 229940127003 anti-diabetic drug Drugs 0.000 description 2
- 230000000340 anti-metabolite Effects 0.000 description 2
- 229940100197 antimetabolite Drugs 0.000 description 2
- 239000002256 antimetabolite Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 210000003651 basophil Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- XQLQVROJBPRZPD-VXGBXAGGSA-N benzyl (3r,4r)-3-hydroxy-4-methoxypyrrolidine-1-carboxylate Chemical compound C1[C@@H](O)[C@H](OC)CN1C(=O)OCC1=CC=CC=C1 XQLQVROJBPRZPD-VXGBXAGGSA-N 0.000 description 2
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
- 108091008324 binding proteins Proteins 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
- 230000006583 body weight regulation Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 230000004097 bone metabolism Effects 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 150000001642 boronic acid derivatives Chemical class 0.000 description 2
- 201000009267 bronchiectasis Diseases 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
- 230000000711 cancerogenic effect Effects 0.000 description 2
- 229960004117 capecitabine Drugs 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 201000001352 cholecystitis Diseases 0.000 description 2
- 201000001883 cholelithiasis Diseases 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
- 208000002849 chondrocalcinosis Diseases 0.000 description 2
- 238000011097 chromatography purification Methods 0.000 description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 229960004126 codeine Drugs 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Natural products C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 206010009887 colitis Diseases 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- 201000003146 cystitis Diseases 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- 229960005484 daptomycin Drugs 0.000 description 2
- DOAKLVKFURWEDJ-QCMAZARJSA-N daptomycin Chemical compound C([C@H]1C(=O)O[C@H](C)[C@@H](C(NCC(=O)N[C@@H](CCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@H](CO)C(=O)N[C@H](C(=O)N1)[C@H](C)CC(O)=O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CCCCCCCCC)C(=O)C1=CC=CC=C1N DOAKLVKFURWEDJ-QCMAZARJSA-N 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 2
- 235000014632 disordered eating Nutrition 0.000 description 2
- 208000007784 diverticulitis Diseases 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 208000019258 ear infection Diseases 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 206010014599 encephalitis Diseases 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- OROAFUQRIXKEMV-LDADJPATSA-N eprosartan Chemical compound C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 OROAFUQRIXKEMV-LDADJPATSA-N 0.000 description 2
- 229960004563 eprosartan Drugs 0.000 description 2
- 208000006881 esophagitis Diseases 0.000 description 2
- 229960001842 estramustine Drugs 0.000 description 2
- 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 2
- 229960000403 etanercept Drugs 0.000 description 2
- 229960005420 etoposide Drugs 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
- 230000005284 excitation Effects 0.000 description 2
- 201000001386 familial hypercholesterolemia Diseases 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 2
- 229960000908 idarubicin Drugs 0.000 description 2
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 2
- 229960001101 ifosfamide Drugs 0.000 description 2
- DTGSFFWQUULHIF-UHFFFAOYSA-N imino-dimethyl-oxo-$l^{6}-sulfane Chemical compound CS(C)(=N)=O DTGSFFWQUULHIF-UHFFFAOYSA-N 0.000 description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 229960000598 infliximab Drugs 0.000 description 2
- 210000001503 joint Anatomy 0.000 description 2
- 206010023332 keratitis Diseases 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 201000003265 lymphadenitis Diseases 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 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
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- PYFSLJVSCGXYAJ-UHFFFAOYSA-N methyl 2-hydroxy-4-[[3-(2-hydroxyphenyl)phenyl]sulfonylamino]benzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1NS(=O)(=O)C1=CC=CC(C=2C(=CC=CC=2)O)=C1 PYFSLJVSCGXYAJ-UHFFFAOYSA-N 0.000 description 2
- QSRRZKPKHJHIRB-UHFFFAOYSA-N methyl 4-[(2,5-dichloro-4-methylthiophen-3-yl)sulfonylamino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1NS(=O)(=O)C1=C(Cl)SC(Cl)=C1C QSRRZKPKHJHIRB-UHFFFAOYSA-N 0.000 description 2
- YGDGZDGRCWHDOU-UHFFFAOYSA-N methyl 4-[[5-chloro-4-(2-hydroxyphenyl)thiophen-2-yl]sulfonylamino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1NS(=O)(=O)C1=CC(C=2C(=CC=CC=2)O)=C(Cl)S1 YGDGZDGRCWHDOU-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 229960002009 naproxen Drugs 0.000 description 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 2
- 201000009240 nasopharyngitis Diseases 0.000 description 2
- 201000008383 nephritis Diseases 0.000 description 2
- 150000007523 nucleic acids Chemical group 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 201000001245 periodontitis Diseases 0.000 description 2
- 206010034674 peritonitis Diseases 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 208000001297 phlebitis Diseases 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 206010035653 pneumoconiosis Diseases 0.000 description 2
- 229920001992 poloxamer 407 Polymers 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 201000007094 prostatitis Diseases 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 201000003068 rheumatic fever Diseases 0.000 description 2
- 201000007529 rheumatic myocarditis Diseases 0.000 description 2
- 229960000953 salsalate Drugs 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 201000009890 sinusitis Diseases 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 201000002859 sleep apnea Diseases 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 201000005671 spondyloarthropathy Diseases 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 208000003265 stomatitis Diseases 0.000 description 2
- 201000007497 subacute thyroiditis Diseases 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
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
- 201000004415 tendinitis Diseases 0.000 description 2
- 210000002435 tendon Anatomy 0.000 description 2
- 229960001278 teniposide Drugs 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
- OJFSWLXDIIQXCN-VXGBXAGGSA-N tert-butyl (3r,4r)-3-[tert-butyl(dimethyl)silyl]oxy-4-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@@H](O)[C@H](O[Si](C)(C)C(C)(C)C)C1 OJFSWLXDIIQXCN-VXGBXAGGSA-N 0.000 description 2
- OJFSWLXDIIQXCN-RYUDHWBXSA-N tert-butyl (3s,4s)-3-[tert-butyl(dimethyl)silyl]oxy-4-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@H](O)[C@@H](O[Si](C)(C)C(C)(C)C)C1 OJFSWLXDIIQXCN-RYUDHWBXSA-N 0.000 description 2
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 229940126585 therapeutic drug Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- 206010043778 thyroiditis Diseases 0.000 description 2
- 229960003087 tioguanine Drugs 0.000 description 2
- 206010044008 tonsillitis Diseases 0.000 description 2
- 229960000363 trapidil Drugs 0.000 description 2
- 229960001727 tretinoin Drugs 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- 208000000143 urethritis Diseases 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 208000002003 vulvitis Diseases 0.000 description 2
- CEMAWMOMDPGJMB-UHFFFAOYSA-N (+-)-Oxprenolol Chemical compound CC(C)NCC(O)COC1=CC=CC=C1OCC=C CEMAWMOMDPGJMB-UHFFFAOYSA-N 0.000 description 1
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- NXWGWUVGUSFQJC-GFCCVEGCSA-N (2r)-1-[(2-methyl-1h-indol-4-yl)oxy]-3-(propan-2-ylamino)propan-2-ol Chemical compound CC(C)NC[C@@H](O)COC1=CC=CC2=C1C=C(C)N2 NXWGWUVGUSFQJC-GFCCVEGCSA-N 0.000 description 1
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
- LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 description 1
- BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 description 1
- OVCRIQGJSAKJDR-RKDXNWHRSA-N (3R,4R)-1-methyl-4-(3-nitropyridin-2-yl)oxypyrrolidin-3-ol Chemical compound CN1C[C@H]([C@@H](C1)OC1=NC=CC=C1[N+](=O)[O-])O OVCRIQGJSAKJDR-RKDXNWHRSA-N 0.000 description 1
- WIVOIHJKCLHXSG-RKDXNWHRSA-N (3R,4R)-1-methylsulfonyl-4-(3-nitropyridin-2-yl)oxypyrrolidin-3-ol Chemical compound CS(=O)(=O)N1C[C@H]([C@@H](C1)OC1=NC=CC=C1[N+](=O)[O-])O WIVOIHJKCLHXSG-RKDXNWHRSA-N 0.000 description 1
- SKQDDFMXWWARMQ-GMSGAONNSA-N (3R,4R)-3-fluoro-4-(5-fluoro-2-nitrophenoxy)oxolane Chemical compound F[C@@H]1COC[C@H]1OC1=C(C=CC(=C1)F)[N+](=O)[O-] SKQDDFMXWWARMQ-GMSGAONNSA-N 0.000 description 1
- QMULFBNUFARKLG-PSASIEDQSA-N (3R,4R)-4-(5-chloro-2-nitrophenoxy)oxolan-3-ol Chemical compound ClC=1C=CC(=C(O[C@H]2[C@@H](COC2)O)C=1)[N+](=O)[O-] QMULFBNUFARKLG-PSASIEDQSA-N 0.000 description 1
- WTBVKVCEPTYRRK-MWLCHTKSSA-N (3R,4R)-4-(5-fluoro-2-nitrophenoxy)-1-methylsulfonylpyrrolidin-3-ol Chemical compound FC=1C=CC(=C(O[C@H]2[C@@H](CN(C2)S(=O)(=O)C)O)C1)[N+](=O)[O-] WTBVKVCEPTYRRK-MWLCHTKSSA-N 0.000 description 1
- MBUUOCVLPXCNSF-PSASIEDQSA-N (3R,4R)-4-(5-fluoro-2-nitrophenoxy)oxolan-3-ol Chemical compound FC=1C=CC(=C(O[C@H]2[C@@H](COC2)O)C=1)[N+](=O)[O-] MBUUOCVLPXCNSF-PSASIEDQSA-N 0.000 description 1
- JMKMYDXAEIVARK-RNFRBKRXSA-N (3R,4R)-4-(6-chloro-3-nitropyridin-2-yl)oxyoxolan-3-ol Chemical compound O[C@@H]1COC[C@H]1OC1=NC(Cl)=CC=C1[N+]([O-])=O JMKMYDXAEIVARK-RNFRBKRXSA-N 0.000 description 1
- PPUDUPDASQBRLS-WDEREUQCSA-N (3R,4S)-3-(5-fluoro-2-nitrophenoxy)-4-methoxyoxolane Chemical compound FC=1C=CC(=C(O[C@@H]2COC[C@@H]2OC)C1)[N+](=O)[O-] PPUDUPDASQBRLS-WDEREUQCSA-N 0.000 description 1
- MBUUOCVLPXCNSF-SCZZXKLOSA-N (3R,4S)-4-(5-fluoro-2-nitrophenoxy)oxolan-3-ol Chemical compound FC=1C=CC(=C(O[C@@H]2[C@@H](COC2)O)C1)[N+](=O)[O-] MBUUOCVLPXCNSF-SCZZXKLOSA-N 0.000 description 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- URHPJHFZDZEYTN-WPRPVWTQSA-N (3S,4S)-4-(2-amino-5-fluorophenoxy)oxolan-3-ol Chemical compound NC1=C(O[C@@H]2[C@H](COC2)O)C=C(C=C1)F URHPJHFZDZEYTN-WPRPVWTQSA-N 0.000 description 1
- HSRFNNWYRFKOHY-BQBZGAKWSA-N (3S,4S)-4-(3-amino-6-chloropyridin-2-yl)oxyoxolan-3-ol Chemical compound NC=1C(=NC(=CC1)Cl)O[C@@H]1[C@H](COC1)O HSRFNNWYRFKOHY-BQBZGAKWSA-N 0.000 description 1
- QMULFBNUFARKLG-WPRPVWTQSA-N (3S,4S)-4-(5-chloro-2-nitrophenoxy)oxolan-3-ol Chemical compound ClC=1C=CC(=C(O[C@@H]2[C@H](COC2)O)C=1)[N+](=O)[O-] QMULFBNUFARKLG-WPRPVWTQSA-N 0.000 description 1
- AYHAUEZXMHZXKF-ONGXEEELSA-N (3S,4S)-4-(5-fluoro-2-nitrophenoxy)-1-methylpyrrolidin-3-ol Chemical compound FC=1C=CC(=C(O[C@@H]2[C@H](CN(C2)C)O)C1)[N+](=O)[O-] AYHAUEZXMHZXKF-ONGXEEELSA-N 0.000 description 1
- WTBVKVCEPTYRRK-ONGXEEELSA-N (3S,4S)-4-(5-fluoro-2-nitrophenoxy)-1-methylsulfonylpyrrolidin-3-ol Chemical compound FC=1C=CC(=C(O[C@@H]2[C@H](CN(C2)S(=O)(=O)C)O)C1)[N+](=O)[O-] WTBVKVCEPTYRRK-ONGXEEELSA-N 0.000 description 1
- MBUUOCVLPXCNSF-WPRPVWTQSA-N (3S,4S)-4-(5-fluoro-2-nitrophenoxy)oxolan-3-ol Chemical compound FC=1C=CC(=C(O[C@@H]2[C@H](COC2)O)C1)[N+](=O)[O-] MBUUOCVLPXCNSF-WPRPVWTQSA-N 0.000 description 1
- BOEFFWRCQDASDM-WPRPVWTQSA-N (3S,4S)-4-(5-fluoro-2-nitrophenoxy)pyrrolidin-3-ol Chemical compound FC=1C=CC(=C(O[C@@H]2[C@H](CNC2)O)C1)[N+](=O)[O-] BOEFFWRCQDASDM-WPRPVWTQSA-N 0.000 description 1
- BMUNPNICWOAEEE-WDSKDSINSA-N (3S,6S)-6-methoxy-3,6-dihydro-2H-pyran-3-ol Chemical compound CO[C@@H]1C=C[C@@H](CO1)O BMUNPNICWOAEEE-WDSKDSINSA-N 0.000 description 1
- LVCNGHBRNGEKCO-RFZPGFLSSA-N (3r,4r)-4-methoxyoxolan-3-ol Chemical compound CO[C@@H]1COC[C@H]1O LVCNGHBRNGEKCO-RFZPGFLSSA-N 0.000 description 1
- KZVPMNPHZILVPO-RFZPGFLSSA-N (3r,4s)-4-hydroxyoxolane-3-carbonitrile Chemical compound O[C@@H]1COC[C@H]1C#N KZVPMNPHZILVPO-RFZPGFLSSA-N 0.000 description 1
- NOGVPOUKDSTPPU-HOTGVXAUSA-N (3s,4s)-1-benzyl-4-[tert-butyl(dimethyl)silyl]oxypyrrolidin-3-ol Chemical compound C1[C@H](O)[C@@H](O[Si](C)(C)C(C)(C)C)CN1CC1=CC=CC=C1 NOGVPOUKDSTPPU-HOTGVXAUSA-N 0.000 description 1
- MTDHILKWIRSIHB-UHFFFAOYSA-N (5-azaniumyl-3,4,6-trihydroxyoxan-2-yl)methyl sulfate Chemical compound NC1C(O)OC(COS(O)(=O)=O)C(O)C1O MTDHILKWIRSIHB-UHFFFAOYSA-N 0.000 description 1
- KZSSWXACMCYLBM-RMWNCEGRSA-N (5e)-5-[(3as,4r,5r,6as)-5-hydroxy-4-[(e,3s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-3,3a,4,5,6,6a-hexahydro-1h-pentalen-2-ylidene]pentanoic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound OCC(N)(CO)CO.C1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)C(C)CC#CC)[C@H](O)C[C@@H]21 KZSSWXACMCYLBM-RMWNCEGRSA-N 0.000 description 1
- 125000006717 (C3-C10) cycloalkenyl group Chemical group 0.000 description 1
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl 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
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
- PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-N 0.000 description 1
- KOHIRBRYDXPAMZ-YHBROIRLSA-N (S,R,R,R)-nebivolol Chemical compound C1CC2=CC(F)=CC=C2O[C@H]1[C@H](O)CNC[C@@H](O)[C@H]1OC2=CC=C(F)C=C2CC1 KOHIRBRYDXPAMZ-YHBROIRLSA-N 0.000 description 1
- HJTAZXHBEBIQQX-UHFFFAOYSA-N 1,5-bis(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1CCl HJTAZXHBEBIQQX-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 1
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- ZNWSGPFTULTYSL-VHSXEESVSA-N 2-[(3R,4S)-4-(2-fluoroethoxy)oxolan-3-yl]oxy-3-nitropyridine Chemical compound FCCO[C@@H]1[C@@H](COC1)OC1=NC=CC=C1[N+](=O)[O-] ZNWSGPFTULTYSL-VHSXEESVSA-N 0.000 description 1
- KXXXJJKGWPXLRA-DTWKUNHWSA-N 2-[(3R,4S)-4-methoxyoxolan-3-yl]oxy-3-nitropyridine Chemical compound CO[C@@H]1[C@@H](COC1)OC1=NC=CC=C1[N+](=O)[O-] KXXXJJKGWPXLRA-DTWKUNHWSA-N 0.000 description 1
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
- XILVEPYQJIOVNB-UHFFFAOYSA-N 2-[3-(trifluoromethyl)anilino]benzoic acid 2-(2-hydroxyethoxy)ethyl ester Chemical compound OCCOCCOC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 XILVEPYQJIOVNB-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
- HKKKKTUZACXWLU-UHFFFAOYSA-N 2-amino-6-(trifluoromethyl)benzonitrile Chemical compound NC1=CC=CC(C(F)(F)F)=C1C#N HKKKKTUZACXWLU-UHFFFAOYSA-N 0.000 description 1
- QDKIYDGHCFZBGC-UHFFFAOYSA-N 2-fluoro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1F QDKIYDGHCFZBGC-UHFFFAOYSA-N 0.000 description 1
- CETWDUZRCINIHU-UHFFFAOYSA-N 2-heptanol Chemical compound CCCCCC(C)O CETWDUZRCINIHU-UHFFFAOYSA-N 0.000 description 1
- 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 1
- AIUTZIYTEUMXGG-UHFFFAOYSA-N 3,6-dioxabicyclo[3.1.0]hexane Chemical compound C1OCC2OC12 AIUTZIYTEUMXGG-UHFFFAOYSA-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
- 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 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
- TZHQWUAOIWRFSW-UHFFFAOYSA-N 4-bromo-2,6-difluorobenzonitrile Chemical compound FC1=CC(Br)=CC(F)=C1C#N TZHQWUAOIWRFSW-UHFFFAOYSA-N 0.000 description 1
- TXNLQUKVUJITMX-UHFFFAOYSA-N 4-tert-butyl-2-(4-tert-butylpyridin-2-yl)pyridine Chemical group CC(C)(C)C1=CC=NC(C=2N=CC=C(C=2)C(C)(C)C)=C1 TXNLQUKVUJITMX-UHFFFAOYSA-N 0.000 description 1
- 125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
- 102100036009 5'-AMP-activated protein kinase catalytic subunit alpha-2 Human genes 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
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- GEPMAHVDJHFBJI-UHFFFAOYSA-N 7-[2-hydroxy-3-[2-hydroxyethyl(methyl)amino]propyl]-1,3-dimethylpurine-2,6-dione;pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1.CN1C(=O)N(C)C(=O)C2=C1N=CN2CC(O)CN(CCO)C GEPMAHVDJHFBJI-UHFFFAOYSA-N 0.000 description 1
- ULJIDNMTAINEKN-UHFFFAOYSA-N 7-bromo-5-fluoroquinazoline Chemical compound C1=NC=C2C(F)=CC(Br)=CC2=N1 ULJIDNMTAINEKN-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- PVFOHMXILQEIHX-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-bromophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Br PVFOHMXILQEIHX-UHFFFAOYSA-N 0.000 description 1
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 238000003727 ADP Glo Kinase Assay Methods 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- DJQOOSBJCLSSEY-UHFFFAOYSA-N Acipimox Chemical compound CC1=CN=C(C(O)=O)C=[N+]1[O-] DJQOOSBJCLSSEY-UHFFFAOYSA-N 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 102000015790 Asparaginase Human genes 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 102000014461 Ataxins Human genes 0.000 description 1
- 108010078286 Ataxins Proteins 0.000 description 1
- XHVAWZZCDCWGBK-WYRLRVFGSA-M Aurothioglucose Chemical compound OC[C@H]1O[C@H](S[Au])[C@H](O)[C@@H](O)[C@@H]1O XHVAWZZCDCWGBK-WYRLRVFGSA-M 0.000 description 1
- 206010055128 Autoimmune neutropenia Diseases 0.000 description 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
- 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- MNIPYSSQXLZQLJ-UHFFFAOYSA-N Biofenac Chemical compound OC(=O)COC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl MNIPYSSQXLZQLJ-UHFFFAOYSA-N 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- LDSOBNJIFXTJGB-UHFFFAOYSA-N C(#N)C1=C(C=C(C=C1C)N=S1(CCCC1)=O)N=CN(C)C Chemical compound C(#N)C1=C(C=C(C=C1C)N=S1(CCCC1)=O)N=CN(C)C LDSOBNJIFXTJGB-UHFFFAOYSA-N 0.000 description 1
- XQOSHWPKADMSKX-UHFFFAOYSA-N C(#N)N=[SH2]=O Chemical compound C(#N)N=[SH2]=O XQOSHWPKADMSKX-UHFFFAOYSA-N 0.000 description 1
- VWLOENMPIHFTIE-HOTGVXAUSA-N C(C)(C)(C)OC(=O)N1C[C@@H]([C@H](C1)OC1=NC=CC=C1[N+](=O)[O-])O[Si](C)(C)C(C)(C)C Chemical compound C(C)(C)(C)OC(=O)N1C[C@@H]([C@H](C1)OC1=NC=CC=C1[N+](=O)[O-])O[Si](C)(C)C(C)(C)C VWLOENMPIHFTIE-HOTGVXAUSA-N 0.000 description 1
- KGFNHIHDWHHTOP-QZTJIDSGSA-N C(C)(C)(C)OC(=O)N1C[C@H]([C@@H](C1)OC1=C(C=CC(=C1)F)[N+](=O)[O-])O[Si](C)(C)C(C)(C)C Chemical compound C(C)(C)(C)OC(=O)N1C[C@H]([C@@H](C1)OC1=C(C=CC(=C1)F)[N+](=O)[O-])O[Si](C)(C)C(C)(C)C KGFNHIHDWHHTOP-QZTJIDSGSA-N 0.000 description 1
- LVPDTNPTLOBWMK-IAGOWNOFSA-N C(C)(C)(C)[Si](O[C@@H]1CN(C[C@H]1OC1=C(C=CC(=C1)F)[N+](=O)[O-])C(C)=O)(C)C Chemical compound C(C)(C)(C)[Si](O[C@@H]1CN(C[C@H]1OC1=C(C=CC(=C1)F)[N+](=O)[O-])C(C)=O)(C)C LVPDTNPTLOBWMK-IAGOWNOFSA-N 0.000 description 1
- GIDULMQBUHQMPT-HUUCEWRRSA-N C(C)(C)(C)[Si](O[C@@H]1CN(C[C@H]1OC1=NC=CC=C1[N+](=O)[O-])C(C)=O)(C)C Chemical compound C(C)(C)(C)[Si](O[C@@H]1CN(C[C@H]1OC1=NC=CC=C1[N+](=O)[O-])C(C)=O)(C)C GIDULMQBUHQMPT-HUUCEWRRSA-N 0.000 description 1
- HKJMWQGFHROAMY-HUUCEWRRSA-N C(C)(C)(C)[Si](O[C@@H]1CNC[C@H]1OC1=C(C=CC(=C1)F)[N+](=O)[O-])(C)C Chemical compound C(C)(C)(C)[Si](O[C@@H]1CNC[C@H]1OC1=C(C=CC(=C1)F)[N+](=O)[O-])(C)C HKJMWQGFHROAMY-HUUCEWRRSA-N 0.000 description 1
- LVPDTNPTLOBWMK-IRXDYDNUSA-N C(C)(C)(C)[Si](O[C@H]1CN(C[C@@H]1OC1=C(C=CC(=C1)F)[N+](=O)[O-])C(C)=O)(C)C Chemical compound C(C)(C)(C)[Si](O[C@H]1CN(C[C@@H]1OC1=C(C=CC(=C1)F)[N+](=O)[O-])C(C)=O)(C)C LVPDTNPTLOBWMK-IRXDYDNUSA-N 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
- JHNATZHGTWKSHZ-JQWIXIFHSA-N CC(N(C[C@@H]1O)C[C@@H]1Oc1cc(F)ccc1[N+]([O-])=O)=O Chemical compound CC(N(C[C@@H]1O)C[C@@H]1Oc1cc(F)ccc1[N+]([O-])=O)=O JHNATZHGTWKSHZ-JQWIXIFHSA-N 0.000 description 1
- LDMQKUKYDNRQNR-UHFFFAOYSA-N CCS(C)(=NN)=O Chemical compound CCS(C)(=NN)=O LDMQKUKYDNRQNR-UHFFFAOYSA-N 0.000 description 1
- NFJQHDOIVCXHBB-LICLKQGHSA-N CN(C)/C=N/c1cc(N=S2(CCCC2)=O)cc(Cl)c1C#N Chemical compound CN(C)/C=N/c1cc(N=S2(CCCC2)=O)cc(Cl)c1C#N NFJQHDOIVCXHBB-LICLKQGHSA-N 0.000 description 1
- NLGKCIOQBUJKAZ-UHFFFAOYSA-N CN=S1(CCCC1)=O Chemical compound CN=S1(CCCC1)=O NLGKCIOQBUJKAZ-UHFFFAOYSA-N 0.000 description 1
- WFVQOYLPHHYMBC-CRCLSJGQSA-N CO[C@H](COC1)[C@H]1I Chemical compound CO[C@H](COC1)[C@H]1I WFVQOYLPHHYMBC-CRCLSJGQSA-N 0.000 description 1
- KXXXJJKGWPXLRA-RKDXNWHRSA-N CO[C@H]1[C@@H](COC1)OC1=NC=CC=C1[N+](=O)[O-] Chemical compound CO[C@H]1[C@@H](COC1)OC1=NC=CC=C1[N+](=O)[O-] KXXXJJKGWPXLRA-RKDXNWHRSA-N 0.000 description 1
- IELRVSHSMOMLQC-PHDIDXHHSA-N C[C@H](COC1)[C@@H]1OC Chemical compound C[C@H](COC1)[C@@H]1OC IELRVSHSMOMLQC-PHDIDXHHSA-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
- 206010007749 Cataract diabetic Diseases 0.000 description 1
- 206010008025 Cerebellar ataxia Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 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
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- 102000006311 Cyclin D1 Human genes 0.000 description 1
- 108010058546 Cyclin D1 Proteins 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 206010048843 Cytomegalovirus chorioretinitis Diseases 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
- 206010011878 Deafness Diseases 0.000 description 1
- 101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 description 1
- 101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- 206010048768 Dermatosis Diseases 0.000 description 1
- 208000002230 Diabetic coma Diseases 0.000 description 1
- 208000008960 Diabetic foot Diseases 0.000 description 1
- 206010012665 Diabetic gangrene Diseases 0.000 description 1
- 206010012676 Diabetic mononeuropathy Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 206010056340 Diabetic ulcer Diseases 0.000 description 1
- 208000013600 Diabetic vascular disease Diseases 0.000 description 1
- 102100036869 Diacylglycerol O-acyltransferase 1 Human genes 0.000 description 1
- 108050004099 Diacylglycerol O-acyltransferase 1 Proteins 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
- 229940097420 Diuretic Drugs 0.000 description 1
- 241000255601 Drosophila melanogaster Species 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 206010014824 Endotoxic shock Diseases 0.000 description 1
- 206010014935 Enzyme abnormality Diseases 0.000 description 1
- 108010056764 Eptifibatide Proteins 0.000 description 1
- 206010015278 Erythrodermic psoriasis Diseases 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 108060002636 Eukaryotic Initiation Factor-4E Proteins 0.000 description 1
- 102000005233 Eukaryotic Initiation Factor-4E Human genes 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
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 1
- 108010011459 Exenatide Proteins 0.000 description 1
- BPTLMOPCJZDDAI-UHFFFAOYSA-N FC(C(=O)N=[SH2]=O)(F)F Chemical compound FC(C(=O)N=[SH2]=O)(F)F BPTLMOPCJZDDAI-UHFFFAOYSA-N 0.000 description 1
- KAIBPTCKMSDEFV-RDDDGLTNSA-N FC=1C=CC(=C(O[C@H]2[C@@H](COC2)C#N)C1)[N+](=O)[O-] Chemical compound FC=1C=CC(=C(O[C@H]2[C@@H](COC2)C#N)C1)[N+](=O)[O-] KAIBPTCKMSDEFV-RDDDGLTNSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- 208000022461 Glomerular disease Diseases 0.000 description 1
- 206010051920 Glomerulonephropathy Diseases 0.000 description 1
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 1
- 102000030595 Glucokinase Human genes 0.000 description 1
- 108010021582 Glucokinase Proteins 0.000 description 1
- 208000002705 Glucose Intolerance Diseases 0.000 description 1
- 102000005720 Glutathione transferase Human genes 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 208000024869 Goodpasture syndrome Diseases 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 102100022057 Hepatocyte nuclear factor 1-alpha Human genes 0.000 description 1
- 102000017013 Heterogeneous Nuclear Ribonucleoprotein A1 Human genes 0.000 description 1
- 108010014594 Heterogeneous Nuclear Ribonucleoprotein A1 Proteins 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000783681 Homo sapiens 5'-AMP-activated protein kinase catalytic subunit alpha-2 Proteins 0.000 description 1
- 101001045751 Homo sapiens Hepatocyte nuclear factor 1-alpha Proteins 0.000 description 1
- 101500028620 Homo sapiens Motilin-associated peptide Proteins 0.000 description 1
- 102000005561 Human Isophane Insulin Human genes 0.000 description 1
- 108010084048 Human Isophane Insulin Proteins 0.000 description 1
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010021000 Hypoglycaemic coma Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 108010073961 Insulin Aspart Proteins 0.000 description 1
- 108010089308 Insulin Detemir Proteins 0.000 description 1
- 108010057186 Insulin Glargine Proteins 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- COCFEDIXXNGUNL-RFKWWTKHSA-N Insulin glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 description 1
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 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
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
- 208000003456 Juvenile Arthritis Diseases 0.000 description 1
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
- 206010023379 Ketoacidosis Diseases 0.000 description 1
- 208000007976 Ketosis Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 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
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
- 239000002145 L01XE14 - Bosutinib Substances 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 1
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 1
- 108010019598 Liraglutide Proteins 0.000 description 1
- 108010007859 Lisinopril Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 102000016261 Long-Acting Insulin Human genes 0.000 description 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 101150018665 MAPK3 gene Proteins 0.000 description 1
- 101150024075 Mapk1 gene Proteins 0.000 description 1
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 1
- 208000029725 Metabolic bone disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
- 102000044589 Mitogen-Activated Protein Kinase 1 Human genes 0.000 description 1
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 1
- 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 206010062207 Mycobacterial infection Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 208000014767 Myeloproliferative disease Diseases 0.000 description 1
- 206010064550 Myocarditis post infection Diseases 0.000 description 1
- KOYKFHJFUVFNOD-UHFFFAOYSA-N N'-[2-cyano-3-fluoro-5-[(1-oxothietan-1-ylidene)amino]phenyl]-N,N-dimethylmethanimidamide Chemical compound FC=1C(=C(C=C(C=1)N=S1(CCC1)=O)N=CN(C)C)C#N KOYKFHJFUVFNOD-UHFFFAOYSA-N 0.000 description 1
- FZZDZUOCKDSMSL-UHFFFAOYSA-N N'-[2-cyano-3-fluoro-5-[(1-oxothiolan-1-ylidene)amino]phenyl]-N,N-dimethylmethanimidamide Chemical compound C(#N)C1=C(C=C(C=C1F)N=S1(CCCC1)=O)N=CN(C)C FZZDZUOCKDSMSL-UHFFFAOYSA-N 0.000 description 1
- GBQCNZJDJOHZSL-UHFFFAOYSA-N N'-[2-cyano-3-methyl-5-[(1-oxothietan-1-ylidene)amino]phenyl]-N,N-dimethylmethanimidamide Chemical compound CC=1C(=C(C=C(C=1)N=S1(CCC1)=O)N=CN(C)C)C#N GBQCNZJDJOHZSL-UHFFFAOYSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- COABVVRXKZLELG-UHFFFAOYSA-N NN=S1(CCC1)=O Chemical compound NN=S1(CCC1)=O COABVVRXKZLELG-UHFFFAOYSA-N 0.000 description 1
- HQVKXDYSIGDGSY-IMJSIDKUSA-N N[C@@H](COC1)[C@H]1O Chemical compound N[C@@H](COC1)[C@H]1O HQVKXDYSIGDGSY-IMJSIDKUSA-N 0.000 description 1
- 206010029155 Nephropathy toxic Diseases 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- FAIIFDPAEUKBEP-UHFFFAOYSA-N Nilvadipine Chemical compound COC(=O)C1=C(C#N)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 FAIIFDPAEUKBEP-UHFFFAOYSA-N 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- JVUZFBQCNYTFOS-HNHGDDPOSA-N O[C@H](CNC1)C1Oc(cc(cc1)F)c1N=O Chemical compound O[C@H](CNC1)C1Oc(cc(cc1)F)c1N=O JVUZFBQCNYTFOS-HNHGDDPOSA-N 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 239000005480 Olmesartan Substances 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 206010068319 Oropharyngeal pain Diseases 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 206010049088 Osteopenia Diseases 0.000 description 1
- 201000000023 Osteosclerosis Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 108010015181 PPAR delta Proteins 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- UJEWTUDSLQGTOA-UHFFFAOYSA-N Piretanide Chemical compound C=1C=CC=CC=1OC=1C(S(=O)(=O)N)=CC(C(O)=O)=CC=1N1CCCC1 UJEWTUDSLQGTOA-UHFFFAOYSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 206010036030 Polyarthritis Diseases 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 206010051497 Rhinotracheitis Diseases 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- 206010039984 Senile osteoporosis Diseases 0.000 description 1
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 1
- 108010026951 Short-Acting Insulin Chemical class 0.000 description 1
- 229940123958 Short-acting insulin Drugs 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 1
- 208000006045 Spondylarthropathies Diseases 0.000 description 1
- 208000005279 Status Asthmaticus Diseases 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 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
- 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
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 206010043781 Thyroiditis chronic Diseases 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 206010048873 Traumatic arthritis Diseases 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 206010064390 Tumour invasion Diseases 0.000 description 1
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 1
- ICMGLRUYEQNHPF-UHFFFAOYSA-N Uraprene Chemical compound COC1=CC=CC=C1N1CCN(CCCNC=2N(C(=O)N(C)C(=O)C=2)C)CC1 ICMGLRUYEQNHPF-UHFFFAOYSA-N 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 206010046996 Varicose vein Diseases 0.000 description 1
- 208000024248 Vascular System injury Diseases 0.000 description 1
- 208000012339 Vascular injury Diseases 0.000 description 1
- 206010057469 Vascular stenosis Diseases 0.000 description 1
- 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 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- YWXYYJSYQOXTPL-JGWLITMVSA-N [(3r,3ar,6s,6as)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] nitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-JGWLITMVSA-N 0.000 description 1
- GQENPXQJRUSMDY-UHFFFAOYSA-N [Ir+].ClC1=CCCC=CCC1 Chemical class [Ir+].ClC1=CCCC=CCC1 GQENPXQJRUSMDY-UHFFFAOYSA-N 0.000 description 1
- MFKHROKPYRIBHE-UHFFFAOYSA-O [NH3+]C1C=CC(Cl)=NC1OC1[IH]COC1 Chemical compound [NH3+]C1C=CC(Cl)=NC1OC1[IH]COC1 MFKHROKPYRIBHE-UHFFFAOYSA-O 0.000 description 1
- AKEPZOFDLMZKDT-UHFFFAOYSA-N [SH2]=NC#N Chemical class [SH2]=NC#N AKEPZOFDLMZKDT-UHFFFAOYSA-N 0.000 description 1
- QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 1
- 229960000446 abciximab Drugs 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 229960002122 acebutolol Drugs 0.000 description 1
- GOEMGAFJFRBGGG-UHFFFAOYSA-N acebutolol Chemical compound CCCC(=O)NC1=CC=C(OCC(O)CNC(C)C)C(C(C)=O)=C1 GOEMGAFJFRBGGG-UHFFFAOYSA-N 0.000 description 1
- 229960004420 aceclofenac Drugs 0.000 description 1
- 229960004892 acemetacin Drugs 0.000 description 1
- FSQKKOOTNAMONP-UHFFFAOYSA-N acemetacin Chemical compound CC1=C(CC(=O)OCC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 FSQKKOOTNAMONP-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 229960003526 acipimox Drugs 0.000 description 1
- YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
- 208000017733 acquired polycythemia vera Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000354 acute hepatitis Toxicity 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000002671 adjuvant Substances 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
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 1
- 229960003459 allopurinol Drugs 0.000 description 1
- ZSBOMTDTBDDKMP-OAHLLOKOSA-N alogliptin Chemical compound C=1C=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 ZSBOMTDTBDDKMP-OAHLLOKOSA-N 0.000 description 1
- 229960001667 alogliptin Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229960002749 aminolevulinic acid Drugs 0.000 description 1
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- 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 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 229960001694 anagrelide Drugs 0.000 description 1
- OTBXOEAOVRKTNQ-UHFFFAOYSA-N anagrelide Chemical compound N1=C2NC(=O)CN2CC2=C(Cl)C(Cl)=CC=C21 OTBXOEAOVRKTNQ-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229960002708 antigout preparations Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 229940045696 antineoplastic drug podophyllotoxin derivative Drugs 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 description 1
- 229960002594 arsenic trioxide 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
- GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- AUJRCFUBUPVWSZ-XTZHGVARSA-M auranofin Chemical compound CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O AUJRCFUBUPVWSZ-XTZHGVARSA-M 0.000 description 1
- 229960005207 auranofin Drugs 0.000 description 1
- 230000006470 autoimmune attack Effects 0.000 description 1
- 201000005000 autoimmune gastritis Diseases 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 201000004562 autosomal dominant cerebellar ataxia Diseases 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
- 229960001671 azapropazone Drugs 0.000 description 1
- WOIIIUDZSOLAIW-NSHDSACASA-N azapropazone Chemical compound C1=C(C)C=C2N3C(=O)[C@H](CC=C)C(=O)N3C(N(C)C)=NC2=C1 WOIIIUDZSOLAIW-NSHDSACASA-N 0.000 description 1
- 125000003725 azepanyl group Chemical group 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 125000005604 azodicarboxylate group Chemical group 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 229960004530 benazepril 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
- 229960002707 bendamustine Drugs 0.000 description 1
- RIXDPKUWZMGGJJ-QZTJIDSGSA-N benzyl (3R,4R)-3-(5-fluoro-2-nitrophenoxy)-4-methoxypyrrolidine-1-carboxylate Chemical compound C(C1=CC=CC=C1)OC(=O)N1C[C@H]([C@@H](C1)OC)OC1=C(C=CC(=C1)F)[N+](=O)[O-] RIXDPKUWZMGGJJ-QZTJIDSGSA-N 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent 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
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone 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-DVTGEIKXSA-N 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 229960002938 bexarotene Drugs 0.000 description 1
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
- 229960000516 bezafibrate Drugs 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- 229960002781 bisoprolol Drugs 0.000 description 1
- VHYCDWMUTMEGQY-UHFFFAOYSA-N bisoprolol Chemical compound CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VHYCDWMUTMEGQY-UHFFFAOYSA-N 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
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- UYRCOTSOPWOSJK-JXTBTVDRSA-N bradykinin antagonist Chemical compound C1C2=CC=CC=C2CC1[C@@H](NC(=O)C(CO)NC(=O)C(NC(=O)CNC(=O)[C@H]1N(C[C@H](O)C1)C(=O)C1N(CCC1)C(=O)C(CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=N)CCCCCCC(=N)N[C@H](CCCNC(N)=N)C(=O)NC(CCCNC(N)=N)C(=O)N1C(CCC1)C(=O)N1[C@@H](C[C@@H](O)C1)C(=O)NCC(=O)NC(C1CC2=CC=CC=C2C1)C(=O)NC(CO)C(=O)N[C@H](C1CC2=CC=CC=C2C1)C(=O)N1C2CCCCC2CC1C(=O)NC(CCCNC(N)=N)C(O)=O)C1CC2=CC=CC=C2C1)C(=O)N1C2CCCCC2CC1C(=O)NC(CCCNC(=N)N)C(O)=O UYRCOTSOPWOSJK-JXTBTVDRSA-N 0.000 description 1
- 239000003152 bradykinin antagonist Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 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
- 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
- 230000009400 cancer invasion Effects 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 229960000623 carbamazepine Drugs 0.000 description 1
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
- 125000004452 carbocyclyl group Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229960003362 carbutamide Drugs 0.000 description 1
- VDTNNGKXZGSZIP-UHFFFAOYSA-N carbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 VDTNNGKXZGSZIP-UHFFFAOYSA-N 0.000 description 1
- 229960001222 carteolol Drugs 0.000 description 1
- LWAFSWPYPHEXKX-UHFFFAOYSA-N carteolol Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(O)CNC(C)(C)C LWAFSWPYPHEXKX-UHFFFAOYSA-N 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 description 1
- 229960004195 carvedilol Drugs 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
- 238000004113 cell culture Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 229960001803 cetirizine Drugs 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical class C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
- 229960003677 chloroquine Drugs 0.000 description 1
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 1
- 229960001761 chlorpropamide Drugs 0.000 description 1
- JIVPVXMEBJLZRO-UHFFFAOYSA-N chlorthalidone Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000019069 chronic childhood arthritis Diseases 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 229960005025 cilazapril Drugs 0.000 description 1
- HHHKFGXWKKUNCY-FHWLQOOXSA-N cilazapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N2[C@@H](CCCN2CCC1)C(O)=O)=O)CC1=CC=CC=C1 HHHKFGXWKKUNCY-FHWLQOOXSA-N 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 229960002881 clemastine Drugs 0.000 description 1
- YNNUSGIPVFPVBX-NHCUHLMSSA-N clemastine Chemical compound CN1CCC[C@@H]1CCO[C@@](C)(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 YNNUSGIPVFPVBX-NHCUHLMSSA-N 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- OJBNDADUQQUPLL-UHFFFAOYSA-N colestipol hydrochloride Chemical compound Cl.ClCC1CO1.NCCNCCN OJBNDADUQQUPLL-UHFFFAOYSA-N 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000002188 cycloheptatrienyl group Chemical group C1(=CC=CC=CC1)* 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 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
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 208000001763 cytomegalovirus retinitis Diseases 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229960002448 dasatinib Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 229960002923 denileukin diftitox Drugs 0.000 description 1
- 108010017271 denileukin diftitox Proteins 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 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
- 229960002783 dexketoprofen Drugs 0.000 description 1
- DKYWVDODHFEZIM-NSHDSACASA-N dexketoprofen Chemical compound OC(=O)[C@@H](C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-NSHDSACASA-N 0.000 description 1
- 201000009101 diabetic angiopathy Diseases 0.000 description 1
- 201000007025 diabetic cataract Diseases 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 201000002249 diabetic peripheral angiopathy Diseases 0.000 description 1
- 201000002342 diabetic polyneuropathy Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
- 229960000616 diflunisal Drugs 0.000 description 1
- 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
- 229960004993 dimenhydrinate Drugs 0.000 description 1
- MZDOIJOUFRQXHC-UHFFFAOYSA-N dimenhydrinate Chemical compound O=C1N(C)C(=O)N(C)C2=NC(Cl)=N[C]21.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 MZDOIJOUFRQXHC-UHFFFAOYSA-N 0.000 description 1
- 229940008099 dimethicone Drugs 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229940120889 dipyrone Drugs 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000001882 diuretic effect Effects 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
- FGXWKSZFVQUSTL-UHFFFAOYSA-N domperidone Chemical compound C12=CC=CC=C2NC(=O)N1CCCN(CC1)CCC1N1C2=CC=C(Cl)C=C2NC1=O FGXWKSZFVQUSTL-UHFFFAOYSA-N 0.000 description 1
- 229960001253 domperidone Drugs 0.000 description 1
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 1
- 229960001389 doxazosin Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 229960000284 efalizumab Drugs 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229940073621 enbrel Drugs 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 210000002409 epiglottis Anatomy 0.000 description 1
- 208000001606 epiglottitis Diseases 0.000 description 1
- 229960004468 eptifibatide Drugs 0.000 description 1
- GLGOPUHVAZCPRB-LROMGURASA-N eptifibatide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCCNC(=N)N)NC(=O)CCSSC[C@@H](C(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]1CC1=CN=C2[C]1C=CC=C2 GLGOPUHVAZCPRB-LROMGURASA-N 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 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 1
- 229960001433 erlotinib Drugs 0.000 description 1
- HCZKYJDFEPMADG-UHFFFAOYSA-N erythro-nordihydroguaiaretic acid Natural products C=1C=C(O)C(O)=CC=1CC(C)C(C)CC1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-UHFFFAOYSA-N 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 229960005293 etodolac Drugs 0.000 description 1
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
- 229960001493 etofenamate Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 229960005167 everolimus Drugs 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 229960001519 exenatide Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- 229960001419 fenoprofen Drugs 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 229960000676 flunisolide Drugs 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229960002490 fosinopril Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 208000001130 gallstones Diseases 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 108010036598 gastric inhibitory polypeptide receptor Proteins 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 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 1
- 229960002584 gefitinib Drugs 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- 229960000578 gemtuzumab Drugs 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 229960002849 glucosamine sulfate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229940076085 gold Drugs 0.000 description 1
- 229940015045 gold sodium thiomalate Drugs 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229960002706 gusperimus Drugs 0.000 description 1
- IDINUJSAMVOPCM-UHFFFAOYSA-N gusperimus Chemical compound NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-UHFFFAOYSA-N 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- WNRQPCUGRUFHED-DETKDSODSA-N humalog Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 WNRQPCUGRUFHED-DETKDSODSA-N 0.000 description 1
- 102000056485 human MKNK2 Human genes 0.000 description 1
- 229940048921 humira Drugs 0.000 description 1
- 229960002474 hydralazine Drugs 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- IKGLACJFEHSFNN-UHFFFAOYSA-N hydron;triethylazanium;trifluoride Chemical compound F.F.F.CCN(CC)CC IKGLACJFEHSFNN-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229960004171 hydroxychloroquine Drugs 0.000 description 1
- XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 230000003345 hyperglycaemic effect Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 229960001680 ibuprofen Drugs 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
- 230000001900 immune effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- NDDAHWYSQHTHNT-UHFFFAOYSA-N indapamide Chemical compound CC1CC2=CC=CC=C2N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 NDDAHWYSQHTHNT-UHFFFAOYSA-N 0.000 description 1
- 229960004569 indapamide Drugs 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000006759 inflammatory activation Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229960005436 inositol nicotinate Drugs 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 229960004717 insulin aspart Drugs 0.000 description 1
- 229960003948 insulin detemir Drugs 0.000 description 1
- 229960002869 insulin glargine Drugs 0.000 description 1
- 229960002068 insulin lispro Drugs 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 1
- 229960003827 isosorbide mononitrate Drugs 0.000 description 1
- 229960002014 ixabepilone 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
- 208000018937 joint inflammation Diseases 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 229960004752 ketorolac Drugs 0.000 description 1
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 206010023841 laryngeal neoplasm Diseases 0.000 description 1
- 229960000681 leflunomide Drugs 0.000 description 1
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- UGOZVNFCFYTPAZ-IOXYNQHNSA-N levemir Chemical compound CCCCCCCCCCCCCC(=O)NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=2C=CC=CC=2)C(C)C)CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)CSSC[C@H](NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CSSC1)C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=C(O)C=C1 UGOZVNFCFYTPAZ-IOXYNQHNSA-N 0.000 description 1
- 229960001120 levocabastine Drugs 0.000 description 1
- ZCGOMHNNNFPNMX-KYTRFIICSA-N levocabastine Chemical compound C1([C@@]2(C(O)=O)CCN(C[C@H]2C)[C@@H]2CC[C@@](CC2)(C#N)C=2C=CC(F)=CC=2)=CC=CC=C1 ZCGOMHNNNFPNMX-KYTRFIICSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229960002701 liraglutide Drugs 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- CZRQXSDBMCMPNJ-ZUIPZQNBSA-N lisinopril dihydrate Chemical compound O.O.C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 CZRQXSDBMCMPNJ-ZUIPZQNBSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 229960003768 lonazolac Drugs 0.000 description 1
- XVUQHFRQHBLHQD-UHFFFAOYSA-N lonazolac Chemical compound OC(=O)CC1=CN(C=2C=CC=CC=2)N=C1C1=CC=C(Cl)C=C1 XVUQHFRQHBLHQD-UHFFFAOYSA-N 0.000 description 1
- 238000012153 long-term therapy Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960003088 loratadine Drugs 0.000 description 1
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
- OXROWJKCGCOJDO-JLHYYAGUSA-N lornoxicam Chemical compound O=C1C=2SC(Cl)=CC=2S(=O)(=O)N(C)\C1=C(\O)NC1=CC=CC=N1 OXROWJKCGCOJDO-JLHYYAGUSA-N 0.000 description 1
- 229960002202 lornoxicam Drugs 0.000 description 1
- 229960004773 losartan Drugs 0.000 description 1
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 229940124302 mTOR inhibitor Drugs 0.000 description 1
- 208000038015 macular disease Diseases 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 229960003951 masoprocol Drugs 0.000 description 1
- HCZKYJDFEPMADG-TXEJJXNPSA-N masoprocol Chemical compound C([C@H](C)[C@H](C)CC=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-TXEJJXNPSA-N 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 229960003803 meclofenamic acid Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 229960003134 mepindolol Drugs 0.000 description 1
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 1
- 229960004963 mesalazine Drugs 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- YUUAYBAIHCDHHD-UHFFFAOYSA-N methyl 5-aminolevulinate Chemical compound COC(=O)CCC(=O)CN YUUAYBAIHCDHHD-UHFFFAOYSA-N 0.000 description 1
- OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 1
- 229960005033 methyl aminolevulinate Drugs 0.000 description 1
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 1
- 229960004503 metoclopramide Drugs 0.000 description 1
- 229960002237 metoprolol Drugs 0.000 description 1
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 229960001110 miglitol Drugs 0.000 description 1
- 229960005249 misoprostol Drugs 0.000 description 1
- 229960000350 mitotane 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
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- XLFWDASMENKTKL-UHFFFAOYSA-N molsidomine Chemical compound O1C(N=C([O-])OCC)=C[N+](N2CCOCC2)=N1 XLFWDASMENKTKL-UHFFFAOYSA-N 0.000 description 1
- 229960004027 molsidomine Drugs 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- MYCMTMIGRXJNSO-UHFFFAOYSA-N moxaverine Chemical compound N=1C(CC)=CC2=CC(OC)=C(OC)C=C2C=1CC1=CC=CC=C1 MYCMTMIGRXJNSO-UHFFFAOYSA-N 0.000 description 1
- 229960002902 moxaverine Drugs 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 208000027531 mycobacterial infectious disease Diseases 0.000 description 1
- MFZCIDXOLLEMOO-GYSGTQPESA-N myo-inositol hexanicotinate Chemical compound O([C@H]1[C@@H]([C@H]([C@@H](OC(=O)C=2C=NC=CC=2)[C@@H](OC(=O)C=2C=NC=CC=2)[C@@H]1OC(=O)C=1C=NC=CC=1)OC(=O)C=1C=NC=CC=1)OC(=O)C=1C=NC=CC=1)C(=O)C1=CC=CN=C1 MFZCIDXOLLEMOO-GYSGTQPESA-N 0.000 description 1
- WFSBUKVQYMFJDJ-UHFFFAOYSA-N n'-(5-bromo-2-cyano-3-fluorophenyl)-n,n-dimethylmethanimidamide Chemical compound CN(C)C=NC1=CC(Br)=CC(F)=C1C#N WFSBUKVQYMFJDJ-UHFFFAOYSA-N 0.000 description 1
- HSPYMPUQHMZQLY-UHFFFAOYSA-N n'-[3-chloro-2-cyano-5-[(1-oxothietan-1-ylidene)amino]phenyl]-n,n-dimethylmethanimidamide Chemical compound ClC1=C(C#N)C(N=CN(C)C)=CC(N=S2(=O)CCC2)=C1 HSPYMPUQHMZQLY-UHFFFAOYSA-N 0.000 description 1
- NFJQHDOIVCXHBB-UHFFFAOYSA-N n'-[3-chloro-2-cyano-5-[(1-oxothiolan-1-ylidene)amino]phenyl]-n,n-dimethylmethanimidamide Chemical compound ClC1=C(C#N)C(N=CN(C)C)=CC(N=S2(=O)CCCC2)=C1 NFJQHDOIVCXHBB-UHFFFAOYSA-N 0.000 description 1
- 229960004255 nadolol Drugs 0.000 description 1
- VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 description 1
- 229960005027 natalizumab Drugs 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229960000619 nebivolol Drugs 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 230000007694 nephrotoxicity Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- 229960005366 nilvadipine Drugs 0.000 description 1
- 229960000965 nimesulide Drugs 0.000 description 1
- HYWYRSMBCFDLJT-UHFFFAOYSA-N nimesulide Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1=CC=CC=C1 HYWYRSMBCFDLJT-UHFFFAOYSA-N 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 229960005425 nitrendipine Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 230000002020 noncytotoxic effect Effects 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 125000005482 norpinyl group Chemical group 0.000 description 1
- VOMXSOIBEJBQNF-UTTRGDHVSA-N novorapid Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 VOMXSOIBEJBQNF-UTTRGDHVSA-N 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 125000002347 octyl 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])[H] 0.000 description 1
- VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 description 1
- 229960005117 olmesartan Drugs 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 230000003287 optical effect Effects 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
- 229960002739 oxaprozin Drugs 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 229960004570 oxprenolol Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 150000002927 oxygen compounds Chemical class 0.000 description 1
- 229960000649 oxyphenbutazone Drugs 0.000 description 1
- CNDQSXOVEQXJOE-UHFFFAOYSA-N oxyphenbutazone hydrate Chemical compound O.O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=C(O)C=C1 CNDQSXOVEQXJOE-UHFFFAOYSA-N 0.000 description 1
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 229960004662 parecoxib Drugs 0.000 description 1
- TZRHLKRLEZJVIJ-UHFFFAOYSA-N parecoxib Chemical compound C1=CC(S(=O)(=O)NC(=O)CC)=CC=C1C1=C(C)ON=C1C1=CC=CC=C1 TZRHLKRLEZJVIJ-UHFFFAOYSA-N 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229960002035 penbutolol Drugs 0.000 description 1
- KQXKVJAGOJTNJS-HNNXBMFYSA-N penbutolol Chemical compound CC(C)(C)NC[C@H](O)COC1=CC=CC=C1C1CCCC1 KQXKVJAGOJTNJS-HNNXBMFYSA-N 0.000 description 1
- 229960001639 penicillamine Drugs 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
- 229960002582 perindopril Drugs 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
- 229960003243 phenformin Drugs 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- 150000004633 phorbol derivatives Chemical class 0.000 description 1
- 239000002644 phorbol ester Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960005330 pimecrolimus Drugs 0.000 description 1
- KASDHRXLYQOAKZ-ZPSXYTITSA-N pimecrolimus Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](Cl)[C@H](OC)C1 KASDHRXLYQOAKZ-ZPSXYTITSA-N 0.000 description 1
- 229960002508 pindolol Drugs 0.000 description 1
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229960001085 piretanide Drugs 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical class COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 1
- 239000003600 podophyllotoxin derivative Substances 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 208000037244 polycythemia vera Diseases 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 229960004293 porfimer sodium Drugs 0.000 description 1
- 230000003703 positive regulation of response to drug Effects 0.000 description 1
- 208000001685 postmenopausal osteoporosis Diseases 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960003611 pramlintide Drugs 0.000 description 1
- 108010029667 pramlintide Proteins 0.000 description 1
- NRKVKVQDUCJPIZ-MKAGXXMWSA-N pramlintide acetate Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NRKVKVQDUCJPIZ-MKAGXXMWSA-N 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 229960001289 prazosin Drugs 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
- 230000001686 pro-survival effect Effects 0.000 description 1
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
- 229960003081 probenecid Drugs 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
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 229960003910 promethazine Drugs 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960002189 propyphenazone Drugs 0.000 description 1
- PXWLVJLKJGVOKE-UHFFFAOYSA-N propyphenazone Chemical compound O=C1C(C(C)C)=C(C)N(C)N1C1=CC=CC=C1 PXWLVJLKJGVOKE-UHFFFAOYSA-N 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 208000009305 pseudorabies Diseases 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 150000003216 pyrazines Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 1
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
- 229960001455 quinapril Drugs 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- RWRDJVNMSZYMDV-UHFFFAOYSA-L radium chloride Chemical compound [Cl-].[Cl-].[Ra+2] RWRDJVNMSZYMDV-UHFFFAOYSA-L 0.000 description 1
- 229910001630 radium chloride Inorganic materials 0.000 description 1
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 230000017567 regulation of heat generation Effects 0.000 description 1
- 229940116176 remicade Drugs 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 230000019254 respiratory burst Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 210000001957 retinal vein Anatomy 0.000 description 1
- 208000004644 retinal vein occlusion Diseases 0.000 description 1
- 150000004492 retinoid derivatives Chemical class 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- VHXNKPBCCMUMSW-FQEVSTJZSA-N rubitecan Chemical compound C1=CC([N+]([O-])=O)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VHXNKPBCCMUMSW-FQEVSTJZSA-N 0.000 description 1
- 229950009213 rubitecan Drugs 0.000 description 1
- 229960002052 salbutamol Drugs 0.000 description 1
- 229960004017 salmeterol Drugs 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 229960005399 satraplatin Drugs 0.000 description 1
- 190014017285 satraplatin Chemical compound 0.000 description 1
- 229960004937 saxagliptin Drugs 0.000 description 1
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 1
- 108010033693 saxagliptin Proteins 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229940083037 simethicone Drugs 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[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 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 1
- 229960004034 sitagliptin Drugs 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- AGHLUVOCTHWMJV-UHFFFAOYSA-J sodium;gold(3+);2-sulfanylbutanedioate Chemical compound [Na+].[Au+3].[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O AGHLUVOCTHWMJV-UHFFFAOYSA-J 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 229960002370 sotalol Drugs 0.000 description 1
- ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical class C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 230000006354 stress signaling Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- GLBQVJGBPFPMMV-UHFFFAOYSA-N sulfilimine Chemical compound S=N GLBQVJGBPFPMMV-UHFFFAOYSA-N 0.000 description 1
- 229960003329 sulfinpyrazone Drugs 0.000 description 1
- MBGGBVCUIVRRBF-UHFFFAOYSA-N sulfinpyrazone Chemical compound O=C1N(C=2C=CC=CC=2)N(C=2C=CC=CC=2)C(=O)C1CCS(=O)C1=CC=CC=C1 MBGGBVCUIVRRBF-UHFFFAOYSA-N 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 229960003658 talinolol Drugs 0.000 description 1
- MXFWWQICDIZSOA-UHFFFAOYSA-N talinolol Chemical compound C1=CC(OCC(O)CNC(C)(C)C)=CC=C1NC(=O)NC1CCCCC1 MXFWWQICDIZSOA-UHFFFAOYSA-N 0.000 description 1
- 229960005187 telmisartan 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
- 229960000195 terbutaline Drugs 0.000 description 1
- 229960000351 terfenadine Drugs 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000002673 tetrahydropyranonyl group Chemical group O1C(C(CCC1)*)=O 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- RBNBDIMXFJYDLQ-UHFFFAOYSA-N thieno[3,2-d]pyrimidine Chemical class C1=NC=C2SC=CC2=N1 RBNBDIMXFJYDLQ-UHFFFAOYSA-N 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
- 229960003425 tirofiban Drugs 0.000 description 1
- HWAAPJPFZPHHBC-FGJQBABTSA-N tirofiban hydrochloride Chemical compound O.Cl.C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCCC1CCNCC1 HWAAPJPFZPHHBC-FGJQBABTSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- 229960005267 tositumomab Drugs 0.000 description 1
- 229960002051 trandolapril Drugs 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 229940079023 tysabri Drugs 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 229960001055 uracil mustard Drugs 0.000 description 1
- 229960001130 urapidil Drugs 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 229960003895 verteporfin Drugs 0.000 description 1
- ZQFGRJWRSLZCSQ-ZSFNYQMMSA-N verteporfin Chemical compound C=1C([C@@]2([C@H](C(=O)OC)C(=CC=C22)C(=O)OC)C)=NC2=CC(C(=C2C=C)C)=NC2=CC(C(=C2CCC(O)=O)C)=NC2=CC2=NC=1C(C)=C2CCC(=O)OC ZQFGRJWRSLZCSQ-ZSFNYQMMSA-N 0.000 description 1
- 229960001254 vildagliptin Drugs 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- 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 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- 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 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 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 1
- 229960001729 voglibose Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- 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
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
それらのあらゆる互変異性体および立体異性体、
またはそれらの塩、
またはそれらの溶媒和物もしくは水和物に関する
{式中、
Arは、
XはCHまたはNであり;
R3はH、ハロゲン、CNまたは−C(=O)−NH2であり;
nは0または1であり;
YはOまたはNRN1であり;
RN1は、H、C1〜3−アルキル、−C(O)−C1〜3−アルキル、−C(O)−O−(CH2)1〜3−フェニルおよび−SO2−C1〜3−アルキルからなる群から選択され;
R7は、F、CN、OH、−O−(C1〜3−アルキル)、−O−(CH2)1〜3−(C3〜7−シクロアルキル)、−O−(CH2)1〜3−フェニル、−O−オキセタニルおよび−O−C(O)−C1〜4−アルキルからなる群から選択され;
R9は、R7と一緒に−CH2−または−(CH2)2−を形成するHまたはR9であり;
RNおよびR7の定義で言及されている各アルキル基は、1個またはそれ以上のFもしくは−O−(C1〜3−アルキル)で場合により置換されている)
からなる群R4−G1から選択される]
からなる群Ar−G1から選択され;
R5は、C1〜5−アルキル、C2〜3−アルケニル、C2〜3−アルキニル、C3〜7−シクロアルキル、ヘテロシクリル、ヘテロアリールおよびアリールからなる群から選択
され、
R5の各アルキル基は、1個またはそれ以上のFまたは1個の−O−(C1〜3−アルキル)、−O−C3〜7−シクロアルキル、−O−ヘテロシクリル、C3〜7−シクロアルキル、ヘテロシクリルまたはフェニルで場合により置換されており;
R6は、1個またはそれ以上のFで場合により置換されているC1〜3−アルキルであり、
または、R5およびR6は、それらが結合する硫黄原子と一緒になって、3から7員の飽和もしくは部分不飽和複素環を形成し、複素環はこの硫黄原子に加えて、O、SおよびNRN2(式中、RN2は、H、C1〜3−アルキル、−C(=O)−(C1〜3−アルキル)、−C(=O)−O−(C1〜4−アルキル),−C(=O)−(C1〜3−アルキル)−O−(C1〜4−アルキル)、−C(=O)−NH2、−C(=O)−NH(C1〜3−アルキル)、−C(=O)−N(C1〜3−アルキル)2または−SO2(C1〜4−アルキル)である)からなる群から選択される1個の追加のヘテロ原子を含むこともあり;
R5、R6、ならびにR5およびR6とそれらが結合する硫黄原子と一緒になって形成される複素環は、各々は独立して、ハロゲン、CN、OH、C1〜3−アルキルまたは−O−(C1〜3−アルキル)で置換されていることもある]
からなる群R1−G1から選択され;
R2は、ハロゲン、CN、OH、C1〜3−アルキル、C3〜5−シクロアルキルおよび−O−(C1〜3−アルキル)からなる群R2−G1(ここで、各アルキル基は、1個またはそれ以上のFで場合により置換されている)から選択され;
RxはHまたはハロゲンであり;
特に断りがなければ、上の定義における各アルキル基は、直鎖状または分枝鎖状であり、1から3個のFで置換されていることもある}。
Ar−G1:
一実施形態によれば、基Arは、以上および以下で定義されている群Ar−G1から選択される。
別の実施形態によれば、基Arは、
XはCHまたはNであり;
R3はH、F、Cl、Br、CNまたは−C(=O)−NH2であり;
R4は、以上または以下に定義されている通りである)
からなる群Ar−G2から選択される。
別の実施形態によれば、基Arは、
R3は、H、FまたはClであり;
R4は、以上または以下に定義されている通りである)
からなる群Ar−G3から選択される。
R4−G1:
一実施形態によれば、基R4は、以上および以下に定義されている群R4−G1から選択される。
別の実施形態によれば、基R4は、
nは0または1であり;
YはOまたはNRN1であり;
RN1は、H、C1〜3−アルキル、−C(O)−C1〜3−アルキル、−C(O)−O−(CH2)1〜3−フェニルおよび−SO2−C1〜3−アルキルからなる群から選択され;
R7は、F、CN、OH、−O−(C1〜3−アルキル)、−O−(CH2)1〜3−(C3〜7−シクロアルキル)、−O−(CH2)1〜3−フェニル、−O−オキセタニルおよび−O−C(O)−C1〜4−アルキルからなる群から選択され;
RNおよびR7の定義で言及されている各アルキル基は、1つまたはそれ以上のFまたは−O−(C1〜3−アルキル)で場合により置換されている]
からなる群R4−G2から選択される。
別の実施形態によれば、基R4は、
nは0または1であり;
YはOまたはNRN1であり;
RN1は、H、C1〜3−アルキル、−C(O)−C1〜3−アルキル、−C(O)−O−(CH2)1〜3−フェニルおよび−SO2−C1〜3−アルキルからなる群から選択され;
R7は、F、CN、OH、−O−(C1〜3−アルキル)、−O−(CH2)1〜3−(C3〜7−シクロアルキル)、−O−(CH2)1〜3−フェニル、−O−オキセタニルおよび−O−C(O)−C1〜4−アルキルからなる群から選択され;
RNおよびR7の定義で言及されている各アルキル基は、1つまたはそれ以上のFまたは−O−(C1〜3−アルキル)で場合により置換されている]
からなる群R4−G2aから選択される。
別の実施形態によれば、基R4は、
RN1は、H、C1〜3−アルキル、−C(O)−C1〜3−アルキル、−C(O)−O−(CH2)−フェニルおよび−SO2−C1〜3−アルキルからなる群から選択され;R7は、F、CN、OH、−O−(C1〜3−アルキル)、−O−(CH2)−(C3〜7−シクロアルキル)、−O−(CH2)1〜3−フェニル、−O−オキセタニルおよび−O−C(O)−C1〜4−アルキルからなる群から選択され;
R7aは、OHおよび−O−(C1〜3−アルキル)からなる群から選択され、
RN、R7およびR7aの定義で言及されている各アルキル基は、1個またはそれ以上のFまたは1個の−O−(C1〜3−アルキル)で場合により置換されている]
からなる群R4−G3から選択される。
別の実施形態によれば、基R4は、
RN1は、H、C1〜3−アルキル、−C(O)−C1〜3−アルキル、−C(O)−O−(CH2)−フェニルおよび−SO2−C1〜3−アルキルからなる群から選択され;R7は、F、CN、OH、−O−(C1〜3−アルキル)、−O−(CH2)−(C3〜7−シクロアルキル)、−O−(CH2)1〜3−フェニル、−O−オキセタニルおよび−O−C(O)−C1〜4−アルキルからなる群から選択され;
R7aは、OHおよび−O−(C1〜3−アルキル)からなる群から選択される
RN、R7およびR7aの定義で言及されている各アルキル基は、1個またはそれ以上のFまたは1個の−O−(C1〜3−アルキル)で場合により置換されている]
からなる群R4−G3aから選択される。
別の実施形態によれば、基R4は、
RN1は、H、C1〜3−アルキル、−C(O)−CH3および−SO2−CH3からなる群から選択され;
R7は、F、CN、OH、−O−(C1〜3−アルキル)および−O−(CH2)−シクロプロピルからなる群から選択され;
R7aは、OHおよび−O−CH3からなる群から選択される
RN、R7およびR7aの定義で言及されている各アルキル基は、1個またはそれ以上のFまたは1個の−O−CH3で場合により置換されている]
からなる群R4−G4から選択される。
別の実施形態によれば、基R4は、
R7は、F、CN、OHおよび−O−(C1〜3−アルキル)からなる群から選択され、R7の定義で言及されている各アルキル基は、1から3個のFまたは1個の−O−CH3で場合により置換されている]
からなる群R4−G4aから選択される。
別の実施形態によれば、基R4は、
RN1は、H、C1〜3−アルキル、−C(O)−CH3および−SO2−CH3からなる群から選択され;
R7は、OHおよび−O−CH3からなる群から選択され、
RN1の定義で言及されているアルキル基およびR7の定義で言及されているCH3基は、場合により1から3個のFで置換されている]
からなる群R4−G4bから選択される。
別の実施形態によれば、基R4は、
RN1は、H、CH3および−SO2−CH3からなる群から選択され;
R7およびR7aは、OHおよび−O−(C1〜3−アルキル)からなる群から選択され、
R7の定義で言及されている−O−アルキル基は、1から3個のFで場合により置換されている]
からなる群R4−G5から選択される。
別の実施形態によれば、基R4は、
R7は、OHおよび−O−(C1〜3−アルキル)からなる群から選択され、
(−O−アルキル基は1から3個のFで場合により置換されている]
からなる群R4−G5aから選択される。
R1−G1:
一実施形態によれば、基R1は、以上および以下に定義されている群R1−G1から選択される。
別の実施形態によれば、基R1は、
R5は、C1〜4−アルキル、C3〜7−シクロアルキル、テトラヒドロピラニル、ピリジニルおよびフェニルからなる群から選択され(ここで、各アルキル基は、1個もしくはそれ以上のF、または1個の−O−(C1〜3−アルキル)、−O−C3〜7−シクロアルキル、C3〜7−シクロアルキルもしくはフェニルで場合により置換されている);
R6は、1個またはそれ以上のFで場合により置換されているC1〜3−アルキルであり;
または、R5およびR6は、それらが結合する硫黄原子と一緒になって、3から7員の飽和もしくは部分不飽和複素環を形成し、複素環はこの硫黄原子に加えて、O、SおよびNRN2(式中、RN2はHまたはC1〜3−アルキルである)からなる群から選択される1個の追加のヘテロ原子を含むこともあり;
R5、R6、ならびにR5およびR6とそれらが結合する硫黄原子と一緒になって形成される複素環は、各々は独立して、F、Cl、Br、CN、OH、−O−(C1〜3−アルキル)、C1〜3−アルキルで置換されていることもある]
からなる群R1−G2から選択される。
別の実施形態によれば、基R1は、
R5は、C1〜4−アルキル、シクロプロピル、テトラヒドロピラニル、ピリジニルおよびフェニルからなる群から選択され(ここで、アルキル基は、1から3個のFまたは1個の−O−CH3もしくはフェニルで場合により置換されている);
R6は、1から3個のFで場合により置換されているC1〜3−アルキルであり;
または、R5およびR6は、それらが結合する硫黄原子と一緒になって4、5または6員の飽和複素環を形成し、複素環はOHまたはCH3で場合により置換されている]
からなる群R1−G3から選択される。
別の実施形態によれば、基R1は、
R5は、C1〜4−アルキル、シクロプロピル、テトラヒドロピラニル、ピリジニルまたはフェニルであり;
R6はメチルである)
からなる群R1−G3aから選択される。
別の実施形態によれば、基R1は、
からなる群R1−G3bから選択される。
別の実施形態によれば、基R1は、
R5は、1個またはそれ以上のFで場合により置換されているC1〜4−アルキルであり;
R6は1から3個のFで場合により置換されているCH3であり;
R8はH、OHまたはCH3である)
からなる群R1−G4から選択される。
R2−G1:
一実施形態によれば、基R2は、以上および以下に定義されている群R2−G1から選択される。
別の実施形態によれば、基R2は、F、Cl、Br、CN、C1〜3−アルキル、C3−5−シクロアルキルおよび−O−C1〜3−アルキルからなる群R2−G2から選択され、各アルキル基は、1から3個のFで場合により置換されている。
別の実施形態によれば、基R2は、F、Cl、Br、CH3、CF3、シクロプロピルおよび−O−(C1〜2−アルキル)(ここで、各アルキル基は、1から3個のFで場合により置換されている)からなる群R2−G3から選択される。
別の実施形態によれば、基R2は、F、Cl、Br、CH3、−O−CH3および−O−CH2CH3からなる群R2−G4から選択される。
別の実施形態によれば、基R2は、F、Cl、CH3および−O−CH3からなる群R2−G5から選択される。
別の実施形態によれば、基R2は、CH3からなる群R2−G6から選択される。
RX−G1:
一実施形態によれば、基RXは、以上および以下で定義されている群RX−G1から選択される。
別の実施形態によれば、基RXは、HおよびFからなる群RX−G2から選択される。
別の実施形態によれば、基RXは、Hからなる群X−G3から選択される。
RN1は、H、C1〜3−アルキル、−C(O)−C1〜3−アルキル、−C(O)−O−(CH2)−フェニルおよび−SO2−C1〜3−アルキルからなる群から選択され;R7は、F、CN、OH、−O−(C1〜3−アルキル)、−O−(CH2)−(C3〜7−シクロアルキル)、−O−(CH2)1〜3−フェニル、−O−オキセタニルおよび−O−C(O)−C1〜4−アルキルからなる群から選択され;
R7aはOHおよび−O−(C1〜3−アルキル)からなる群から選択され、
RN、R7およびR7aの定義で言及されている各アルキル基は、1個もしくはそれ以上のFまたは1個の−O−(C1〜3−アルキル)で場合により置換されている)
からなる群R4−G3から選択される]
からなる群Ar−G3から選択され、
R5は、C1〜4−アルキル、シクロプロピル、テトラヒドロピラニル、ピリジニルおよびフェニルからなる群から選択され(ここで、アルキル基は、1から3個のFまたは1個の−O−CH3もしくはフェニルで場合により置換されている);
R6は、1から3個のFで場合により置換されているC1〜3−アルキルであり;
または、R5およびR6は、それらが結合する硫黄原子と一緒になって、4、5または6員の飽和複素環を形成し、複素環は、OHまたはCH3で場合により置換されている];からなる群R1−G3から選択され、
R2は、F、Cl、Br、CH3、CF3、シクロプロピルおよび−O−(C1〜2−アルキル)(ここで、各アルキル基は、1から3個のFで場合により置換されている)からなる群R2−G3から選択され;
RXは、HおよびFからなるRX−G2群から選択される}
のそれらの化合物および医薬として許容されるそれらの塩に関する。
R2は、F、Cl、CH3および−O−CH3からなる群R2−G5から選択され;
RXは、Hからなる群RX−G3から選択される]
のそれらの化合物および医薬として許容されるそれらの塩に関する。
の反応により、一般式7−1(式中、R5およびR6は以前に定義した通りである)の対応するスルホキシドから製造される。ジクロロメタンのような適切な溶媒が使用される。
本明細書において具体的に定義されない用語は、本開示および文脈を踏まえて、当業者により示される意味が示される。しかし、明細書に使用されている場合、異なる規定がなければ、以下の用語は、指示された意味を有し、以下の慣例が順守される。
炭素原子の少なくとも2個が、二重結合によって互いに結合する場合である。例えば、C2〜3−アルケニルという用語は、−CH=CH2、−CH=CH−CH3、−CH2−CH=CH2を含む。
以下の方法により、化合物の生物学的活性を判定した:
MNK2aのin vitroキナーゼアッセイは、具体的にはWO2011/104340に記載されている。
アッセイの設定:予備活性化GST−MNK2aを使用して、MNK2aのキナーゼ活性の阻害を評価した。キナーゼ反応は、24μMの基質ペプチド(NH2−TATKSGSTTKNR−CONH2、C−末端−CONH2基によるWO2011/104340のSeq.ID No.5と異なる)、20μMのATP、14nMのリガンドおよび2nMの予備活性化MNK2aを含む。反応緩衝液の条件は、pH7.4である16mMのHEPES/KOH、8mMのMgCl2、0.4mMのDTT、0.08%(w/v)のウシ血清アルブミン(BSA、Sigma、Germany、cat.no.A3059)、0.008%(w/v)Pluronic F127(Sigma、Germany、cat.no.P2443)、3%(v/v)DMSO(Applichem、Germany、cat.no.A3006)である。キナーゼ反応は、室温で60分間である。pH7.4である20mMのHEPES/KOH、50mMのエチレンジアミン四酢酸、二ナトリウム塩(EDTA、Sigma、Germany、cat.no.E5134)、0.5mMのDTT、0.05%(w/v)ポリオキシエチレン−ソルビタンモノラウレート(Tween20、Sigma、Germany、cat.no.P7949)中の1μMの抗体を0.67反応体積添加することにより、キナーゼ反応を終了させる。室温での平衡時間の1時間後、試料に蛍光偏光測定を施した。蛍光偏光測定値を、FP Dual Emissionフィルタおよびミラーセット(PerkinElmer2100−4260)を備えたEnvisionマルチモードリーダ(PerkinElmer)で生成した。励起フィルタ620nm、SおよびP偏光放射フィルタ688nM。
アッセイ設定:予備活性化GST−MNK2aを使用して、MNK2aのキナーゼ活性の阻害を評価した。白色の384−ウェルOptiPlate FというプレートをPerkinElmerから購入した。ADP−Glo Kinase Assay(超高純度ATPを含む)を、Promega(V9103)から購入した。活性化MNK2aをWO2011/104340に記載されているように得た。非標識elF4Eペプチド(NH2−TATKSGSTTKNR−CONH2)は、C−末端−CONH2基によるWO2011/104340のSeq.ID No.5とは異なり、Thermo Fisher Scientificから購入した。他の材料はすべて、市販の最高グレードのものである。化合物を、連続希釈液中または単回用量濃度で試験した。化合物の保存溶液は100%DMSO中の10mMである。化合物の連続希釈を100%DMSO中で製造し、続いて、アッセイ緩衝液中の中間希釈液を1:27.3とする。アッセイにおけるDMSO最終濃度は<3%になるであろう。384−ウェルプレートにおいて、中間希釈液からの3μlの試験化合物は、4μlの活性化MNK酵素(10nMの最終濃度)および4μlのペプチド(25μMの最終濃度)/超高純度ATP(20μMの最終濃度)と混合され、すべてがアッセイ緩衝液に溶解される。この工程は、90分間のインキュベーション時間の後に続き、次いで10μlのADP Glo 試薬が加えられ、続いて40分間インキュベーションされる。次いで20μlのキナーゼ検出試薬が混和される。プレートを封止し、30分間のインキュベーション後、発光シグナルをEnvisionリーダーで測定して、生成されたADPの量を判定する。すべてのインキュベーション工程を室温で行う。アッセイ緩衝液は、20mMのHEPES、2mMのDTT、0.01%BSA、20mMのMgCl2および0.1%Pluronic F−127からなる。
(RLU(試料)−RLU(低対照))*100/(RLU(高値)−RLU(低対照))
[RLU=相対発光単位]
MNK1のデータは、MNK1Z’−LYTE(登録商標)アッセイから得られる。MNK1Z’−LYTE(登録商標)スクリーニングプロトコールおよびアッセイ条件も、www.invitrogen.comに記載されている。
Z’−LYTE(登録商標)は、蛍光ベースの結合酵素フォーマットを用い、タンパク質分解切断に対するリン酸化および非リン酸化ペプチドの感受性の差に基づいている生化学的アッセイである。2個のフルオロフォアを各末端に1個用いて、FRETのペアを作り、ペプチド基質を標識する。
放出比=クマリン放出(445nm)/フルオレセイン放出(520nm)
試験化合物:
ウェルにおける1%DMSO(最終)中で、試験化合物をスクリーニングする。
ペプチド/キナーゼ混合物:
ペプチド/キナーゼ混合物を、MNK1キナーゼ緩衝液中ですべて2倍の作用濃度に希釈する。
ATP溶液:
ATP溶液をすべて、キナーゼ緩衝液(pH7.5である50mMのHEPES、0.01%BRIJ−35、10mMのMgCl2、1mMのEGTA)中で4倍の作用濃度に希釈する。
発色試薬溶液:
発色試薬を発色緩衝液中で希釈する。
バーコード化したCorning低体積NBS、384−ウェルプレート(Corning Cat.#3676)
1.2.5μL−4倍の試験化合物
2.5μL−2倍のペプチド/キナーゼ混合物
3.2.5μL−4倍のATP溶液
4.30秒間にわたるプレート振とう
5.室温にて60分間にわたるキナーゼ反応インキュベーション
6.5μL−発色試薬溶液
7.30秒間にわたるプレート振とう
8.室温にて60分間にわたる発色反応インキュベーション
9.蛍光プレートリーダーを読み取り、データを分析する
以下の方程式を、データポイントの各セットに使用する:
バックグラウンド蛍光に対する補正:FI試料−FITCFl対照
放出比(バックグラウンド蛍光に対して補正した値を使用):クマリン放出(445nm)/フルオレセイン放出(520nm)
%リン酸化(%Phos):
1−((放出比×F100%)−C100%)/((C0%−C100%)+[放出比×(F100%−F0%)])*100
%阻害:
1−(%Phos試料/%Phos0%阻害 対照)*100
________________________________
FI=蛍光強度
C100%=100%Phos.対照の平均クマリン放出シグナル
C0%=0%Phos.対照の平均クマリン放出シグナル
F100%=100%Phos.対照の平均フルオレセイン放出シグナル
F0%=0%Phos.対照の平均フルオレセイン放出シグナル
SelectScreen(登録商標)Kinase Profiling Serviceは、IDBSからXLfitを使用する。用量反応曲線は、モデルナンバー205(S字用量反応モデル)に当てはまる曲線である。曲線の下が、−20%から20%の阻害の間に当てはまらない場合、0%阻害とされる。曲線の上が70%から130%の阻害の間に当てはまらない場合、100%阻害とされる。
MNK1(MNK1aもしくはMNK1b)および/またはMNK2(MNK2aもしくはMNK2b)キナーゼの活性を阻害する能力を鑑みると、本発明による一般式Iの化合物(その対応する塩を含む)は、理論上は、MNK1(MNK1aもしくはMNK1b)および/またはMNK2(MNK2aもしくはMNK2b)キナーゼの阻害により影響が及ぼされるまたは媒介される疾患または症状すべての処置に適している。
場合により、1種またはそれ以上のさらなる治療薬と組み合わせた、式Iの化合物を投与するために適切な製造は、当業者に明らかであり、例えば錠剤、丸剤、カプセル剤、坐剤、ロゼンジ剤、トローチ剤、液剤、シロップ剤、エリキシル剤、サシェ剤、注射剤、吸入剤および散剤などの経口製剤を含み、特に固形、例えば錠剤またはカプセル剤が好ましい。医薬として活性化合物(複数可)の含有量は、有利なことには、全体として組成物の0.1から90重量%、例えば1から70重量%の範囲である。
本発明の化合物は、1種またはそれ以上の、好ましくは1種の追加の治療薬とさらに組み合わせられる。一実施形態によれば、追加の治療薬は、以上に記載されている疾患または症状、特に代謝性疾患または症状、例えば真性糖尿病、肥満、糖尿病性合併症、高血圧、高脂血症に関連するものの処置に有用な治療薬の群から選択される。そのような組合せに適している追加の治療薬は、具体的には、例えば、言及された徴候の1つに対して、1種またはそれ以上の活性物質の治療効果を増強するもの、および/または1種またはそれ以上の活性物質の投与量を低下させるものを含む。
以下に記載されている化合物は、イオン化後における質量分光計での、それらの特徴的な質量により、薄層クロマトグラフィープレートでのそれらのRf値により、ならびに/または分析HPLCでのそれらの保持時間により特徴づけられる。
ACN アセトニトリル
AcOH 酢酸
aq. 水溶液
BINAP 2,2’−ビス(ジフェニルホスフィノ)−1,1’−ビナフチル
BOC tert−ブトキシ−カルボニル−
℃ 摂氏〜度
CH シクロヘキサン
DA ダイオードアレイ
dba ジベンジリデンアセトン
DCM ジクロロメタン
DMF N,N−ジメチルホルムアミド
Eq. モル当量(複数可)
ESI−MS エレクトロスプレーイオン化質量分析
EtOAc 酢酸エチル
EtOH エタノール
FC フラッシュクロマトグラフィー、SiO2は、さらなる詳細が示されない場合に使用される
h 時間
HPLC 高速液体クロマトグラフィー
RP−HPLC 逆相HPLC
L リットル
LiHMDS リチウムヘキサメチルジシルアジド
m/z 質量対電荷比
MeOH メタノール
min 分
ml ミリリットル
MS 質量スペクトル
μW 電子レンジで反応を行った
n.d. 判定されず
NH4OH 水中のNH3溶液
psi 重量ポンド毎平方インチ
pTsOH p−トルエンスルホン酸
Rac. ラセミ
RT 室温(約20℃)
Rt 保持時間
Sol 溶媒
TF/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
中間体I.1:2−アミノ−4−ブロモ−6−フルオロ−ベンゾニトリル
収率:4.9g(99%)、ESI−MS:m/z=213/215(M−H)−、Rt(HPLC):1.72分(HPLC−S)
収率:20.5g(96%)、ESI−MS:m/z=270/272(M+H)+、Rt(HPLC):0.83分(HPLC−H)
収率:0.4g(83%)、ESI−MS:m/z=279(M+H)+、Rt(HPL
C):0.59分(HPLC−H)
ESI−MS:m/z=305(M+H)+、Rt(HPLC):0.63分(HPLC−B)
ESI−MS:m/z=309(M+H)+、Rt(HPLC):0.64分(HPLC−B)
ESI−MS:m/z=283(M+H)+、Rt(HPLC):0.58分(HPLC−B)
ESI−MS:m/z=295(M+H)+
ESI−MS:m/z=291(M+H)+、Rt(HPLC):0.63分(HPLC−E)
収率:0.1g(58%)、ESI−MS:m/z=299(M+H)+、Rt(HPLC):0.68分(HPLC−M)
ESI−MS:m/z=325/327(M+H)+、Rt(HPLC):0.75分(HPLC−M)
ESI−MS:m/z=311/313(M+H)+、Rt(HPLC):0.55分(HPLC−A)
ESI−MS:m/z=343/345(M+H)+、Rt(HPLC):0.66分(HPLC−E)
ESI−MS:m/z=331(M+H)+、Rt(HPLC):1.01分(HPLC−E)
ESI−MS:m/z=333(M+H)+、Rt(HPLC):0.71分(HPLC−E)
ESI−MS:m/z=359(M+H)+、Rt(HPLC):0.77分(HPLC−E)
ESI−MS:m/z=297(M+H)+、Rt(HPLC):0.77分(HPLC−M)
収率:70mg(79%)、ESI−MS:m/z=305(M+H)+、Rt(HPLC):0.68分(HPLC−A)
収率:6.07g(66%)、ESI−MS:m/z=358(M+H)+
ESI−MS:m/z=258(M+H)+
ESI−MS:m/z=241(M+H)+
ESI−MS:m/z=227(M+H)+
ESI−MS:m/z=244(M+H)+
ESI−MS:m/z=244(M+H)+
ESI−MS:m/z=457(M+H)+
ESI−MS:m/z=457(M+H)+
ESI−MS:m/z=447(M+H)+
ESI−MS:m/z=391(M+H)+
ESI−MS:m/z=374(M+H)+
ESI−MS:m/z=440(M+H)+
ESI−MS:m/z=440(M+H)+
ESI−MS:m/z=276(M+Na)+
ESI−MS:m/z=254(M+H)+
ESI−MS:m/z=245(M*)+
収率:2.95g(95%)、ESI−MS:m/z=244(M+H)+、比旋光度:[α]D 20(MeOH)=+21°
ESI−MS:m/z=244(M+H)+、比旋光度:[α]D 20(MeOH)=−18°
ESI−MS:m/z=260(M+H)+
ESI−MS:m/z=260(M+H)+
ESI−MS:m/z=227(M+H)+、比旋光度:[α]D 20(MeOH)=+53°
ESI−MS:m/z=227(M+H)+、比旋光度:[α]D 20(MeOH)=−52°
ESI−MS:m/z=261(M+H)+
ESI−MS:m/z=261(M+H)+
ESI−MS:m/z=321(M+H)+
ESI−MS:m/z=268(M+H)+
ESI−MS:m/z=304(M+H)+
ESI−MS:m/z=321(M+H)+
収率:1.11g(18%)、ESI−MS:m/z=273(M+H)+
収率:170mg(50%)、ESI−MS:m/z=287(M+NH4)+、Rt(HPLC):0.62分(HPLC−AA)
収率:1.52g(83%)、ESI−MS:m/z=243(M+H)+
収率:300mg(70%)、ESI−MS:m/z=243(M+H)+
収率:1.13g(81%)、ESI−MS:m/z=257(M+H)+
ESI−MS:m/z=257(M+H)+
ESI−MS:m/z=240(M+H)+
収率:1.43g(69%)、ESI−MS:m/z=357(M+H)+
ESI−MS:m/z=357(M+H)+
収率:0.70g(94%)、ESI−MS:m/z=399(M+H)+
ESI−MS:m/z=399(M+H)+
ESI−MS:m/z=382(M+H)+
収率:0.325g(65%)、ESI−MS:m/z=285(M+H)+
ESI−MS:m/z=285(M+H)+
収率:1.08g(82%)、ESI−MS:m/z=435(M+H)+
ESI−MS:m/z=418(M+H)+
ESI−MS:m/z=435(M+H)+
収率:6.15g(62%)、ESI−MS:m/z=435(M+H)+
収率:15%、ESI−MS:m/z=226(M+H)+
収率:0.39g(66%)、ESI−MS:m/z=231(M+H)+、比旋光度:[α]D 20(MeOH)=+43°
収率:2.36g(61%)、ESI−MS:m/z=214(M+H)+、比旋光度:[α]D 20(MeOH)=+18°
収率:419mg(82%)、ESI−MS:m/z=223(M+H)+
鏡像異性体1、中間体IV.4:収率:1.55g(41%)、Rt(HPLC):2.15分
鏡像異性体2、中間体IV.4A:収率:1.46g(39%)、Rt(HPLC):2.54分
収率:7.1g(65%)、ESI−MS:m/z=438(M+H)+、Rt(HPLC):1.12分(HPLC−M)
収率:2.8g(88%)、ESI−MS:m/z=451(M+H)+
収率:2.5g(89%)、ESI−MS:m/z=361(M+H)+、Rt(HPLC):1.12分(HPLC−T)
ESI−MS:m/z=387(M+H)+、Rt(HPLC):0.56分(HPLC−M)
収率:510mg(60%)
例えば表1に示される一般的手順1(P1):
等モル量の中間体IIおよびIVは、それぞれ、AcOHに溶解し、所定の時間にわたって所定の温度に加熱した。水および飽和NaHCO3水溶液を用いて反応混合物を希釈した。代わりの検査は、反応混合物の蒸発ならびにMeOHおよび水を用いた残留物の処理を含む。万が一生成物が沈殿した場合は、沈殿物を濾別した、そうでなければ、EtOAcを用いて混合物を抽出した。有機相をプールし、乾燥させ、蒸発させた。必要とされる場合、粗生成物をFCまたはHPLCによりさらに精製した。
1当量の臭化アリール(II)、1.2当量のスルホキシイミン(V)、25mol%の2−(ジ−t−ブチルホスフィノ)ビフェニル、8mol%のPd2dba3および1.4当量のナトリウムtert−ブトキシドを、ジオキサンと混合し、所定の時間にわたり所定の温度に加熱した。反応混合物を濃縮し、粗生成物をHPLCまたはFCにより精製した。
1当量の臭化アリール、1.25当量のスルホキシイミン、20mol%のrac−BINAP、15mol%のPd(OAc)2および1.4当量のCs2CO3を、トルエン中に懸濁し、所定の時間にわたり所定の温度に加熱した。反応混合物を濃縮し、粗生成物を、HPLCまたはFCにより精製した。
指示された溶媒混合物中に出発原料を溶解し、所定の温度で終夜撹拌した。反応混合物を濃縮し、必要な場合は、粗生成物をHPLCにより精製した。
水素雰囲気下(30psiのH2)で、それぞれの出発原料、炭担持(10%、0.1質量当量)パラジウムおよびEtOHの混合物を、HPLC分析により出発原料の完全な消費が指し示されるまで撹拌した。吸引により、不溶性物質を濾別し、濾液を蒸発させ、残留物を、FC(DCM/MeOH/NH4OH)により精製した。
それぞれの出発原料(1当量)、アルキル化剤(3当量)、トリエチルアミン(5当量)およびACNの混合物を120℃で3時間にわたり撹拌した(密封バイアル、マイクロ波加熱)。揮発性物質を蒸発させ、残留物をDCM中に取り込み、水を用いて抽出した。有機層を分離し、乾燥させ、蒸発させた。残留物をRP−HPLCにより精製した
それぞれの出発原料(1当量)、トリエチルアミン(3当量)および氷浴で冷却したDCMの混合物に、アシル化剤(1当量)を加えた。混合物を、RTで終夜撹拌した。揮発性物質を蒸発させ、残留物をDCM中に取り込み、水を用いて抽出した。有機層を分離し、乾燥させ、蒸発させた。残留物を、RP−HPLCより精製した。
0℃に冷却したDMF中のそれぞれの出発原料の溶液(1当量)に、水素化ナトリウム(鉱油中に55%、1.2当量)を加えた。混合物を30分間にわたり撹拌し、次いでそれぞれのアルキル化剤(1当量)を加えた。さらに冷却せずに、混合物を終夜撹拌した。水を加え、DCMを用いて混合物を抽出した。有機層を分離し、乾燥させ、蒸発させた。残留物を、RP−HPLCまたはFCにより精製した。
それぞれの出発原料(1.0当量)、炭酸セシウム(1.2当量)、メタノール(40質量当量)およびジオキサンの混合物を90℃で2時間にわたり撹拌した。水を加えた。沈殿した生成物を濾過し、乾燥させた。あるいは、DCMを用いて混合物を抽出し、有機層を分離し、乾燥させ、蒸発させた。残留物を、RP−HPLCまたはFCにより精製した。
THF/クエン酸ナトリウム緩衝液pH5(9:1)中のアミン出発原料(1当量)、ホルムアルデヒド(37%水溶液;2当量)、およびナトリウムトリアセトキシボロヒドリド(1,2当量)の混合物をRTで1時間にわたり撹拌した。揮発性物質を蒸発させ、残留物をDCM中に取り込み、水を用いて抽出した。有機層を分離し、乾燥させ、蒸発させた。残留物をFC(DCM/MeOH/NH4OH)により精製した。
フェノール出発原料(1当量)、アルコール出発原料(1.5当量)、トリフェニルホスフィン(3当量)およびTHFの混合物を、RTで10分間にわたり撹拌した。ジ−tert−ブチルアゾジカルボキシレート(3当量)を加え、混合物をRTで終夜撹拌した。揮発性物質を蒸発させ、残留物をHPLCにより精製した。
ラセミ出発原料を、キラルHPLCにより純粋な鏡像異性体に分離した。絶対配置は判定されなかったが、任意に割り付けた。すべてのキラルHPLC−分離は、40℃および150barの背圧で実行した。
Claims (22)
- 式
Arは、
XはCHまたはNであり;
R3はH、ハロゲン、CNまたは−C(=O)−NH2であり;
R4は、
nは0または1であり;
YはOまたはNRN1であり;
RN1は、H、C1〜3−アルキル、−C(O)−C1〜3−アルキル、−C(O)−O−(CH2)1〜3−フェニルおよび−SO2−C1〜3−アルキルからなる群から選択され;
R7は、F、CN、OH、−O−(C1〜3−アルキル)、−O−(CH2)1〜3−(C3〜7−シクロアルキル)、−O−(CH2)1〜3−フェニル、−O−オキセタニルおよび−O−C(O)−C1〜4−アルキルからなる群から選択され;
R9は、R7と一緒に−CH2−または−(CH2)2−を形成するHまたはR9であり;
RNおよびR7の定義で言及されている各アルキル基は、1個またはそれ以上のFもし
くは−O−(C1〜3−アルキル)で場合により置換されている)
である]
であり;
R1は、
R5は、C1〜5−アルキル、C2〜3−アルケニル、C2〜3−アルキニル、C3〜7−シクロアルキル、ヘテロシクリル、ヘテロアリールおよびアリールからなる群から選択され、
R5の各アルキル基は、1個またはそれ以上のFまたは1個の−O−(C1〜3−アルキル)、−O−C3〜7−シクロアルキル、−O−ヘテロシクリル、C3〜7−シクロアルキル、ヘテロシクリルまたはフェニルで場合により置換されており;
R6は、1個またはそれ以上のFで場合により置換されているC1〜3−アルキルであり、
または、R5およびR6は、それらが結合する硫黄原子と一緒になって、3から7員の飽和もしくは部分不飽和複素環を形成し、複素環はこの硫黄原子に加えて、O、SおよびNRN2(式中、RN2は、H、C1〜3−アルキル、−C(=O)−(C1〜3−アルキル)、−C(=O)−O−(C1〜4−アルキル),−C(=O)−(C1〜3−アルキル)−O−(C1〜4−アルキル)、−C(=O)−NH2、−C(=O)−NH(C1〜3−アルキル)、−C(=O)−N(C1〜3−アルキル)2または−SO2(C1〜4−アルキル)である)からなる群から選択される1個の追加のヘテロ原子を含むこともあり;
R5、R6、ならびにR5およびR6とそれらが結合する硫黄原子と一緒になって形成される複素環は、各々は独立して、ハロゲン、CN、OH、C1〜3−アルキルまたは−O−(C1〜3−アルキル)で置換されていることもある]
であり;
R2は、ハロゲン、CN、OH、C1〜3−アルキル、C3〜5−シクロアルキルおよび−O−(C1〜3−アルキル)からなる群(ここで、各アルキル基は、1個またはそれ以上のFで場合により置換されている)から選択され;
RxはHまたはハロゲンであり;
特に断りがなければ、上の定義における各アルキル基が、直鎖状または分枝鎖状であり、1から3個のFで置換されていることもある}
の化合物、あるいはそれらの立体異性体または塩。 - R2は、F、Cl、Br、CH3、CF3、シクロプロピルおよび−O−(C1〜2−アルキル)(ここで、各アルキル基は1から3個のFで場合により置換されている)からなる群から選択され;
RxはHである、
請求項1または2に記載の化合物またはその塩。 - R4は、
nは0または1であり;
YはOまたはNRN1であり;
RN1はH、C1〜3−アルキル、−C(O)−C1〜3−アルキル、−C(O)−O−(CH2)1〜3−フェニルおよび−SO2−C1〜3−アルキルからなる群から選択され;
R7は、F、CN、OH、−O−(C1〜3−アルキル)、−O−(CH2)1〜3−(C3〜7−シクロアルキル)、−O−(CH2)1〜3−フェニル、−O−オキセタニルおよび−O−C(O)−C1〜4−アルキルからなる群から選択され、
RNおよびR7の定義で言及されている各アルキル基は、1個またはそれ以上のFまた
は−O−(C1〜3−アルキル)で場合により置換されている]
からなる群から選択される、請求項1〜4のいずれか一項に記載の化合物またはその塩。 - R4は、
RN1は、H、C1〜3−アルキル、−C(O)−C1〜3−アルキル、−C(O)−O−(CH2)−フェニルおよび−SO2−C1〜3−アルキルからなる群から選択され;
R7は、F、CN、OH、−O−(C1〜3−アルキル)、−O−(CH2)−(C3〜7−シクロアルキル)、−O−(CH2)1〜3−フェニル、−O−オキセタニルおよび−O−C(O)−C1〜4−アルキルからなる群から選択され;
R7aは、OHおよび−O−(C1〜3−アルキル)からなる群から選択され、
RNおよびR7の定義で言及されている各アルキル基は、1個またはそれ以上のFもしくは1個の−O−(C1〜3−アルキル)で場合により置換されている]、
からなる群から選択される、請求項1〜5のいずれか一項に記載の化合物または医薬として許容されるその塩。 - Arは、
XはCHまたはNであり;
R3はH、FまたはClであり;
R4は、
R7は、F、CN、OH、−O−(C1〜3−アルキル)、−O−(CH2)−(C3〜7−シクロアルキル)、−O−(CH2)1〜3−フェニル、−O−オキセタニルおよび−O−C(O)−C1〜4−アルキルからなる群から選択され;
R7aは、OHおよび−O−(C1〜3−アルキル)からなる群から選択され、
RN、R7およびR7aの定義で言及されている各アルキル基は、1個またはそれ以上のFまたは1個の−O−(C1〜3−アルキル)で場合により置換されている)
からなる群から選択される]
から選択され;
R1は、
R5は、C1〜4−アルキル、シクロプロピル、テトラヒドロピラニル、ピリジニルおよびフェニルからなる群から選択され(ここで、アルキル基は、1から3個のFまたは1個の−O−CH3またはフェニルで場合により置換されている);
R6は、1から3個のFで場合により置換されているC1〜3−アルキルであり;
または、R5およびR6は、それらが結合する硫黄原子と一緒になって、4、5または6員飽和複素環を形成し、複素環がOHまたはCH3で場合により置換されている]
であり;
R2は、F、Cl、Br、CH3、CF3、シクロプロピルおよび−O−(C1〜2−アルキル)(ここで、各アルキル基は、1から3個のFで場合により置換されている)からなる群から選択され;
RXはHまたはFである、
請求項1に記載の化合物または医薬として許容されるその塩。 - 請求項1〜10のいずれか1項に記載の化合物の、医薬として許容される塩。
- 請求項1〜10のいずれか1項に記載の化合物または医薬として許容されるその塩、および場合により医薬として許容される担体を含む、医薬組成物。
- 追加の治療薬をさらに含む、請求項12に記載の医薬組成物。
- 追加の治療薬は、抗糖尿病薬、脂質低下薬、心血管作動薬、降圧薬、利尿薬、血小板凝集阻害薬、抗新生物薬または抗肥満薬から選択される、請求項13に記載の医薬組成物。
- 薬剤として使用するための、請求項1〜10のいずれか1項に記載の化合物、または医薬として許容されるその塩。
- MNK1もしくはMNK2(MNK2a、MNK2b)またはその変異体のキナーゼ活性の阻害に使用するための、請求項1〜10のいずれか1項に記載の化合物または医薬として許容されるその塩。
- 代謝性疾患、造血障害、神経変性疾患、腎臓損傷、炎症性障害および癌ならびにそれらの続発性合併症および疾患の予防または治療に使用するための、請求項1〜10のいずれか1項で定義した化合物または医薬として許容されるその塩。
- 炭水化物および/または脂質代謝の代謝性疾患ならびにその続発性合併症および障害の予防または治療に使用するための、請求項1〜10のいずれか1項に記載の化合物または医薬として許容されるその塩。
- 糖尿病の予防または治療に使用するための、請求項1〜10のいずれか1項に記載の化合物または医薬として許容されるその塩。
- 請求項15〜18のいずれか1項に記載の使用のための化合物であって、該使用は、追加の治療薬と組み合わせた、患者への同時または逐次投与を含む、前記化合物。
- 炭水化物および/または脂質代謝の代謝性疾患ならびにその続発性合併症および障害を防止または処置する方法であって、医薬として活性な量の、請求項1〜10のいずれか1項に記載の化合物または医薬として許容されるその塩を、それを必要とする患者に投与する工程を含む、前記方法。
- 炭水化物および/または脂質代謝の代謝性疾患ならびにそれらの続発性合併症および障害の処置に有用な薬剤を製造するための、請求項1〜10のいずれか1項に記載の化合物または医薬として許容されるその塩の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP13195720.1 | 2013-12-04 | ||
EP13195720 | 2013-12-04 | ||
PCT/EP2014/075890 WO2015082324A1 (en) | 2013-12-04 | 2014-11-28 | Sulfoximine substituted quinazolines for pharmaceutical compositions |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2016539148A true JP2016539148A (ja) | 2016-12-15 |
JP2016539148A5 JP2016539148A5 (ja) | 2017-11-30 |
JP6457523B2 JP6457523B2 (ja) | 2019-01-23 |
Family
ID=49726564
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016536528A Active JP6457523B2 (ja) | 2013-12-04 | 2014-11-28 | 医薬組成物のためのスルホキシイミン置換キナゾリン |
Country Status (7)
Country | Link |
---|---|
US (1) | US10093660B2 (ja) |
EP (1) | EP3077383B1 (ja) |
JP (1) | JP6457523B2 (ja) |
AU (1) | AU2014359456B2 (ja) |
CA (1) | CA2929742C (ja) |
ES (1) | ES2693520T3 (ja) |
WO (1) | WO2015082324A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2944103A1 (en) * | 2014-05-07 | 2015-11-12 | Evotec International Gmbh | Sulfoximine substituted quinazolines for pharmaceutical compositions |
UY38540A (es) * | 2019-01-14 | 2020-08-31 | Pi Industries Ltd | Compuestos de fenilamidina 3-sustituida, preparación y uso |
CN112812136B (zh) * | 2019-11-15 | 2022-04-12 | 武汉光谷亚太医药研究院有限公司 | 新型2,3-二氢化茚衍生化合物、制备方法和应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009532407A (ja) * | 2006-04-07 | 2009-09-10 | デヴェロゲン アクチエンゲゼルシャフト | 医薬組成物用のmnk1/mnk2阻害活性を有するチエノピリミジン |
JP2013520472A (ja) * | 2010-02-26 | 2013-06-06 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 医薬組成物のためのヘテロシクロアルキル含有チエノピリミジン |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3987192A (en) | 1974-01-07 | 1976-10-19 | The Upjohn Company | Compositions and process of treatment |
US5602118A (en) | 1993-03-16 | 1997-02-11 | American Cyanamid Company | 2-thiosubstituted carbapenems |
CA2188772A1 (en) | 1994-06-08 | 1995-12-14 | Balreddy Kamireddy | Cyclic sulfonamide herbicides |
SE0102147D0 (sv) | 2001-06-18 | 2001-06-18 | Pharmacia Ab | New methods |
EP1439863B1 (en) | 2001-10-29 | 2011-01-12 | Boehringer Ingelheim International GmbH | Mnk kinase homologous proteins involved in the regulation of energy homeostasis and organelle metabolism |
JP2005527511A (ja) | 2002-03-01 | 2005-09-15 | ファイザー インコーポレイテッド | 抗血管形成剤として有用なチエノピリジンのインドリル−尿素誘導体およびその使用法 |
GB0315587D0 (en) | 2003-07-03 | 2003-08-13 | Univ Dundee | Anti-inflammatory assay and compounds |
ZA200607292B (en) | 2004-04-08 | 2008-05-28 | Dow Agrosciences Llc | Insecticidal N-substituted sulfoximines |
EP1746099A1 (en) | 2004-12-23 | 2007-01-24 | DeveloGen Aktiengesellschaft | Mnk1 or Mnk2 inhibitors |
EP1899353A1 (en) * | 2005-06-22 | 2008-03-19 | DeveloGen Aktiengesellschaft | Thienopyrimidines for pharmaceutical compositions |
EP1991547A2 (en) | 2006-03-09 | 2008-11-19 | Pharmacopeia, Inc. | 8-heteroarylpurine mnk2 inhibitors for treating metabolic disorders |
CN101472912A (zh) | 2006-06-22 | 2009-07-01 | 比奥维特罗姆上市公司 | 作为mnk激酶抑制剂的吡啶和吡嗪衍生物 |
JP2010527951A (ja) * | 2007-05-24 | 2010-08-19 | バイエル・シエーリング・ファーマ アクチエンゲゼルシャフト | キナーゼ阻害剤としての新規なスルホキシイミン置換型キノリン及びキナゾリン誘導体 |
DE102007024470A1 (de) | 2007-05-24 | 2008-11-27 | Bayer Schering Pharma Aktiengesellschaft | Neue Sulfoximin-substituierte Chinolin- bzw. Chinazolinderivate als Kinase-Inhibitoren |
JP2011510033A (ja) | 2008-01-25 | 2011-03-31 | シンジェンタ パーティシペーションズ アクチェンゲゼルシャフト | 化合物 |
WO2011062885A1 (en) | 2009-11-23 | 2011-05-26 | Schering Corporation | Fused bicyclic pyrimidine derivatives and methods of use thereof |
BR112012021453A2 (pt) | 2010-02-26 | 2017-02-21 | Boehringer Ingelheim Int | tienopirimidina, sua composição farmacêutica e seu uso |
AR088082A1 (es) | 2011-10-13 | 2014-05-07 | Lilly Co Eli | Moduladores selectivos del receptor androgeno |
ES2635262T3 (es) * | 2012-11-09 | 2017-10-03 | Evotec International Gmbh | Quinazolinas sustituidas con sulfoximina para composiciones farmacéuticas |
WO2014206922A1 (en) * | 2013-06-28 | 2014-12-31 | Boehringer Ingelheim International Gmbh | Sulfoximine substituted quinazolines and their use as mnk1 and/or mnk2 kinase inhibitors |
-
2014
- 2014-11-28 ES ES14808895.8T patent/ES2693520T3/es active Active
- 2014-11-28 CA CA2929742A patent/CA2929742C/en active Active
- 2014-11-28 EP EP14808895.8A patent/EP3077383B1/en active Active
- 2014-11-28 US US15/101,620 patent/US10093660B2/en active Active
- 2014-11-28 WO PCT/EP2014/075890 patent/WO2015082324A1/en active Application Filing
- 2014-11-28 AU AU2014359456A patent/AU2014359456B2/en active Active
- 2014-11-28 JP JP2016536528A patent/JP6457523B2/ja active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009532407A (ja) * | 2006-04-07 | 2009-09-10 | デヴェロゲン アクチエンゲゼルシャフト | 医薬組成物用のmnk1/mnk2阻害活性を有するチエノピリミジン |
JP2013520472A (ja) * | 2010-02-26 | 2013-06-06 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 医薬組成物のためのヘテロシクロアルキル含有チエノピリミジン |
Non-Patent Citations (1)
Title |
---|
OYARZABAL, JULEN 他: "Discovery of Mitogen-Activated Protein Kinase-Interacting Kinase 1 Inhibitors by a Comprehensive Fra", JOURNAL OF MEDICINAL CHEMISTRY, vol. 53(18), JPN6018046793, 2010, pages 6618 - 6628, ISSN: 0003927404 * |
Also Published As
Publication number | Publication date |
---|---|
ES2693520T3 (es) | 2018-12-12 |
JP6457523B2 (ja) | 2019-01-23 |
EP3077383B1 (en) | 2018-08-22 |
EP3077383A1 (en) | 2016-10-12 |
AU2014359456A1 (en) | 2016-06-09 |
AU2014359456B2 (en) | 2019-01-24 |
CA2929742C (en) | 2022-09-20 |
WO2015082324A1 (en) | 2015-06-11 |
US20170174668A1 (en) | 2017-06-22 |
US10093660B2 (en) | 2018-10-09 |
CA2929742A1 (en) | 2015-06-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6549109B2 (ja) | スルホキシイミン置換キナゾリンならびにmnk1および/またはmnk2キナーゼ阻害薬としてのその使用 | |
JP5639197B2 (ja) | 医薬組成物のためのヘテロシクロアルキル含有チエノピリミジン | |
JP6306035B2 (ja) | 医薬組成物のためのスルホキシミン置換キナゾリン | |
KR20210018204A (ko) | 면역조절제로서 복소환형 화합물 | |
HUE028723T2 (en) | Piperidin-4-yl azetidine derivatives as JAK-1 inhibitors | |
JP2013520474A (ja) | 医薬組成物のための置換アルキル基含有チエノピリミジン | |
JP2013520473A (ja) | 医薬組成物用のMnk1/Mnk2阻害活性を有するハロゲン又はシアノ置換されたチエノ[2,3−d]ピリミジン | |
JP6457523B2 (ja) | 医薬組成物のためのスルホキシイミン置換キナゾリン | |
EP2513108B1 (fr) | NOUVEAUX DERIVES D' (HETEROCYCLE-PIPERIDINE CONDENSEE)-(PIPERAZINYL)-1-ALCANONE OU D' (HETEROCYCLE-PYRROLIDINE CONDENSEE)-(PIPERAZINYL)-1-ALCANONE ET LEUR UTILISATION COMME INHIBITEURS DE p75 | |
RU2367662C2 (ru) | Производные пирролопиримидина, применяемые для лечения пролиферативных заболеваний | |
JP6479854B2 (ja) | 医薬組成物のためのスルホキシイミン置換キナゾリン | |
TW201712011A (zh) | 作為bet家族溴結構域抑制劑之新穎吡啶吡酮 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171017 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20171017 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180703 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20180705 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180928 |
|
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: 20181204 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20181220 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6457523 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 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |