EP3157919A1 - Bet-proteininhibitorische 3,4-dihydropyrido[2,3-b]pyrazinone mit meta-substituierter aromatischer amino- oder ethergruppe - Google Patents
Bet-proteininhibitorische 3,4-dihydropyrido[2,3-b]pyrazinone mit meta-substituierter aromatischer amino- oder ethergruppeInfo
- Publication number
- EP3157919A1 EP3157919A1 EP15729444.8A EP15729444A EP3157919A1 EP 3157919 A1 EP3157919 A1 EP 3157919A1 EP 15729444 A EP15729444 A EP 15729444A EP 3157919 A1 EP3157919 A1 EP 3157919A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- alkyl
- phenyl
- unsubstituted
- dimethyl
- amino
- 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.)
- Withdrawn
Links
- HIGOCZJARKJCGG-UHFFFAOYSA-N 3,4-dihydro-1h-pyrido[2,3-b]pyrazin-2-one Chemical class C1=CC=C2NC(=O)CNC2=N1 HIGOCZJARKJCGG-UHFFFAOYSA-N 0.000 title abstract description 9
- 230000002401 inhibitory effect Effects 0.000 title abstract description 8
- 125000001033 ether group Chemical group 0.000 title abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 325
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 28
- 201000010099 disease Diseases 0.000 claims abstract description 27
- 230000003463 hyperproliferative effect Effects 0.000 claims abstract description 11
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 11
- 208000036142 Viral infection Diseases 0.000 claims abstract description 8
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 8
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 8
- 230000009385 viral infection Effects 0.000 claims abstract description 8
- 230000035558 fertility Effects 0.000 claims abstract description 7
- 230000003143 atherosclerotic effect Effects 0.000 claims abstract description 6
- -1 Ci-C3-alkyl Chemical group 0.000 claims description 265
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 154
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 147
- 125000001424 substituent group Chemical group 0.000 claims description 128
- 229910052739 hydrogen Inorganic materials 0.000 claims description 91
- 239000001257 hydrogen Substances 0.000 claims description 91
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 89
- 229910052731 fluorine Inorganic materials 0.000 claims description 80
- 239000011737 fluorine Substances 0.000 claims description 80
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 77
- 229910052801 chlorine Inorganic materials 0.000 claims description 77
- 239000000460 chlorine Substances 0.000 claims description 77
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 70
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 68
- 150000002431 hydrogen Chemical group 0.000 claims description 47
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 44
- 229910052757 nitrogen Inorganic materials 0.000 claims description 44
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 42
- 150000003839 salts Chemical class 0.000 claims description 41
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 40
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 35
- 238000002360 preparation method Methods 0.000 claims description 34
- HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 claims description 33
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 33
- 238000002560 therapeutic procedure Methods 0.000 claims description 33
- 238000011321 prophylaxis Methods 0.000 claims description 29
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 28
- 150000002367 halogens Chemical class 0.000 claims description 26
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 25
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 25
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 25
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 25
- 229910052794 bromium Inorganic materials 0.000 claims description 25
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 18
- 125000004043 oxo group Chemical group O=* 0.000 claims description 17
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 16
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 16
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 16
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 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 claims description 12
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 12
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 12
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000003386 piperidinyl group Chemical group 0.000 claims description 10
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims description 9
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 9
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 9
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 8
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 4
- AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical compound FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 claims description 4
- GIMWVXKMKDZLFY-QGZVFWFLSA-N (3R)-1,3-dimethyl-4-(1-methylpiperidin-4-yl)-6-(3-propan-2-ylsulfonylanilino)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C(C)(C)S(=O)(=O)C=1C=C(C=CC=1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCN(CC2)C)N=1 GIMWVXKMKDZLFY-QGZVFWFLSA-N 0.000 claims description 3
- TZYQXDHGNRRZOT-MRXNPFEDSA-N (3R)-1,3-dimethyl-4-(1-methylpiperidin-4-yl)-6-[5-propan-2-ylsulfonyl-2-(trifluoromethoxy)anilino]-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C(C)(C)S(=O)(=O)C=1C=CC(=C(C=1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCN(CC2)C)N=1)OC(F)(F)F TZYQXDHGNRRZOT-MRXNPFEDSA-N 0.000 claims description 3
- KNWBQJRDNFRLLC-MRXNPFEDSA-N (3R)-1,3-dimethyl-4-(oxan-4-yl)-6-(3-propan-2-ylsulfonylanilino)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound CC(C)S(=O)(=O)C1=CC=CC(NC2=CC=C3N(C)C(=O)[C@@H](C)N(C4CCOCC4)C3=N2)=C1 KNWBQJRDNFRLLC-MRXNPFEDSA-N 0.000 claims description 3
- KFVQYVOQJOSFCN-QGZVFWFLSA-N (3R)-4-[1-(2,2-difluoroethyl)piperidin-4-yl]-6-(2-methoxy-5-propan-2-ylsulfonylanilino)-1,3-dimethyl-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound COC1=C(NC2=CC=C3N(C)C(=O)[C@@H](C)N(C4CCN(CC(F)F)CC4)C3=N2)C=C(C=C1)S(=O)(=O)C(C)C KFVQYVOQJOSFCN-QGZVFWFLSA-N 0.000 claims description 3
- BVNKMEOGYOFLKB-CQSZACIVSA-N (3R)-6-(2-methoxy-5-methylsulfonylanilino)-1,3-dimethyl-4-(oxan-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound COC1=C(NC2=CC=C3N(C)C(=O)[C@@H](C)N(C4CCOCC4)C3=N2)C=C(C=C1)S(C)(=O)=O BVNKMEOGYOFLKB-CQSZACIVSA-N 0.000 claims description 3
- OVDHMLGXXGXDSD-CQSZACIVSA-N (3R)-6-(2-methoxy-5-methylsulfonylanilino)-1,3-dimethyl-4-piperidin-4-yl-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound COC1=C(NC2=CC=C3N(C)C(=O)[C@@H](C)N(C4CCNCC4)C3=N2)C=C(C=C1)S(C)(=O)=O OVDHMLGXXGXDSD-CQSZACIVSA-N 0.000 claims description 3
- AUAAMLKXISPBIK-MRXNPFEDSA-N (3R)-6-(2-methoxy-5-propan-2-ylsulfonylanilino)-1,3-dimethyl-4-piperidin-4-yl-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound COC1=C(NC2=CC=C3N(C)C(=O)[C@@H](C)N(C4CCNCC4)C3=N2)C=C(C=C1)S(=O)(=O)C(C)C AUAAMLKXISPBIK-MRXNPFEDSA-N 0.000 claims description 3
- XXWDJWZUYWREQD-OAHLLOKOSA-N (3R)-6-(3-cyclopropylsulfonylanilino)-1,3-dimethyl-4-(oxan-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C1(CC1)S(=O)(=O)C=1C=C(C=CC=1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCOCC2)N=1 XXWDJWZUYWREQD-OAHLLOKOSA-N 0.000 claims description 3
- FXPKPXBCAHGADT-MRXNPFEDSA-N (3R)-6-(5-cyclopropylsulfonyl-2-methoxyanilino)-1,3-dimethyl-4-(1-methylpiperidin-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C1(CC1)S(=O)(=O)C=1C=CC(=C(C=1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCN(CC2)C)N=1)OC FXPKPXBCAHGADT-MRXNPFEDSA-N 0.000 claims description 3
- XRRSGHNXHZZEFE-OAHLLOKOSA-N (3R)-6-(5-cyclopropylsulfonyl-2-methoxyanilino)-1,3-dimethyl-4-(oxan-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound COC1=C(NC2=CC=C3N(C)C(=O)[C@@H](C)N(C4CCOCC4)C3=N2)C=C(C=C1)S(=O)(=O)C1CC1 XRRSGHNXHZZEFE-OAHLLOKOSA-N 0.000 claims description 3
- OKEPPRINGSZIRP-HXUWFJFHSA-N (3R)-6-(5-ethylsulfonyl-2-phenoxyanilino)-1,3-dimethyl-4-(1-methylpiperidin-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C(C)S(=O)(=O)C=1C=CC(=C(C=1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCN(CC2)C)N=1)OC1=CC=CC=C1 OKEPPRINGSZIRP-HXUWFJFHSA-N 0.000 claims description 3
- MWUVTRQXQHNZPZ-CQSZACIVSA-N (3R)-6-[(1,1-dioxo-2,3-dihydro-1-benzothiophen-6-yl)amino]-1,3-dimethyl-4-(oxan-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound O=S1(CCC2=C1C=C(C=C2)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCOCC2)N=1)=O MWUVTRQXQHNZPZ-CQSZACIVSA-N 0.000 claims description 3
- NCIQPRXZGWYGSQ-QGZVFWFLSA-N (3R)-6-[2-methoxy-5-(oxan-4-ylsulfonyl)anilino]-1,3-dimethyl-4-(oxan-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound COC1=C(C=C(C=C1)S(=O)(=O)C1CCOCC1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCOCC2)N=1 NCIQPRXZGWYGSQ-QGZVFWFLSA-N 0.000 claims description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 3
- LNYRUUVXYKSERY-OAHLLOKOSA-N (3R)-1,3-dimethyl-4-(1-methylpiperidin-4-yl)-6-(3-methylsulfonylanilino)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C[C@H]1N(C2CCN(C)CC2)C2=NC(NC3=CC(=CC=C3)S(C)(=O)=O)=CC=C2N(C)C1=O LNYRUUVXYKSERY-OAHLLOKOSA-N 0.000 claims description 2
- NWZYECGSOWYJGE-OAHLLOKOSA-N (3R)-1,3-dimethyl-4-(oxan-4-yl)-6-[5-propan-2-ylsulfonyl-2-(trifluoromethoxy)anilino]-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C(C)(C)S(=O)(=O)C=1C=CC(=C(C=1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCOCC2)N=1)OC(F)(F)F NWZYECGSOWYJGE-OAHLLOKOSA-N 0.000 claims description 2
- UEHVDENYFNAOKA-GOSISDBHSA-N (3R)-1,3-dimethyl-6-(3-propan-2-ylsulfonylanilino)-4-[1-(3,3,3-trifluoropropyl)piperidin-4-yl]-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound CC(C)S(=O)(=O)C1=CC=CC(NC2=CC=C3N(C)C(=O)[C@@H](C)N(C4CCN(CCC(F)(F)F)CC4)C3=N2)=C1 UEHVDENYFNAOKA-GOSISDBHSA-N 0.000 claims description 2
- UGXBRLSWMVWJBA-QGZVFWFLSA-N (3R)-6-(2-methoxy-5-propan-2-ylsulfonylanilino)-1,3-dimethyl-4-(1-methylpiperidin-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound COC1=C(NC2=CC=C3N(C)C(=O)[C@@H](C)N(C4CCN(C)CC4)C3=N2)C=C(C=C1)S(=O)(=O)C(C)C UGXBRLSWMVWJBA-QGZVFWFLSA-N 0.000 claims description 2
- JXBWOTGDVFZTAZ-MRXNPFEDSA-N (3R)-6-(2-methoxy-5-propan-2-ylsulfonylanilino)-1,3-dimethyl-4-(oxan-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound COC1=C(NC2=CC=C3N(C)C(=O)[C@@H](C)N(C4CCOCC4)C3=N2)C=C(C=C1)S(=O)(=O)C(C)C JXBWOTGDVFZTAZ-MRXNPFEDSA-N 0.000 claims description 2
- SIWMIJMPKDIOGZ-QGZVFWFLSA-N (3R)-6-(2-methoxy-5-propan-2-ylsulfonylanilino)-1,3-dimethyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C(C)(C)S(=O)(=O)C=1C=CC(=C(C=1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCN(CC2)CC(F)(F)F)N=1)OC SIWMIJMPKDIOGZ-QGZVFWFLSA-N 0.000 claims description 2
- MFQCWWODEYWRJW-GOSISDBHSA-N (3R)-6-(2-methoxy-5-propan-2-ylsulfonylanilino)-1,3-dimethyl-4-[1-(3,3,3-trifluoropropyl)piperidin-4-yl]-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C(C)(C)S(=O)(=O)C=1C=CC(=C(C=1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCN(CC2)CCC(F)(F)F)N=1)OC MFQCWWODEYWRJW-GOSISDBHSA-N 0.000 claims description 2
- ILEHGOFEJWJLJE-OAHLLOKOSA-N (3R)-6-(2-methoxy-5-propan-2-ylsulfonylanilino)-1,3-dimethyl-4-propan-2-yl-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C(C)(C)N1C2=C(N(C([C@H]1C)=O)C)C=CC(=N2)NC1=C(C=CC(=C1)S(=O)(=O)C(C)C)OC ILEHGOFEJWJLJE-OAHLLOKOSA-N 0.000 claims description 2
- NLTAQZBHFCQORB-CQSZACIVSA-N (3R)-6-(3-methoxy-5-methylsulfonylanilino)-1,3-dimethyl-4-(oxan-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound COC1=CC(=CC(NC2=CC=C3N(C)C(=O)[C@@H](C)N(C4CCOCC4)C3=N2)=C1)S(C)(=O)=O NLTAQZBHFCQORB-CQSZACIVSA-N 0.000 claims description 2
- PNGFPYCFFCGRDT-MRXNPFEDSA-N (3R)-6-(5-cyclobutylsulfonyl-2-methoxyanilino)-1,3-dimethyl-4-(oxan-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C1(CCC1)S(=O)(=O)C=1C=CC(=C(C=1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCOCC2)N=1)OC PNGFPYCFFCGRDT-MRXNPFEDSA-N 0.000 claims description 2
- HTCOEVCGYBBSAQ-CQSZACIVSA-N (3R)-6-(5-cyclopropylsulfonyl-2-methoxyanilino)-1,3-dimethyl-4-propan-2-yl-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound COC1=C(NC2=CC=C3N(C)C(=O)[C@@H](C)N(C(C)C)C3=N2)C=C(C=C1)S(=O)(=O)C1CC1 HTCOEVCGYBBSAQ-CQSZACIVSA-N 0.000 claims description 2
- CKNKZFVVXFDPFW-LJQANCHMSA-N (3R)-6-(5-ethylsulfonyl-2-phenoxyanilino)-1,3-dimethyl-4-(oxan-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C(C)S(=O)(=O)C=1C=CC(=C(C=1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCOCC2)N=1)OC1=CC=CC=C1 CKNKZFVVXFDPFW-LJQANCHMSA-N 0.000 claims description 2
- SFNRTJNHNKKTMV-GOSISDBHSA-N (3R)-6-[2-methoxy-5-(oxan-4-ylsulfonyl)anilino]-1,3-dimethyl-4-(1-methylpiperidin-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound COC1=C(C=C(C=C1)S(=O)(=O)C1CCOCC1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCN(CC2)C)N=1 SFNRTJNHNKKTMV-GOSISDBHSA-N 0.000 claims description 2
- HRAHVDSNSXILBR-CQSZACIVSA-N (3R)-6-[2-methoxy-5-(trifluoromethylsulfonyl)anilino]-1,3-dimethyl-4-(1-methylpiperidin-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound COC1=C(NC2=CC=C3N(C)C(=O)[C@@H](C)N(C4CCN(C)CC4)C3=N2)C=C(C=C1)S(=O)(=O)C(F)(F)F HRAHVDSNSXILBR-CQSZACIVSA-N 0.000 claims description 2
- RYMAHVHCPIDRMK-CYBMUJFWSA-N (3R)-6-[2-methoxy-5-(trifluoromethylsulfonyl)anilino]-1,3-dimethyl-4-(oxan-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound COC1=C(NC2=CC=C3N(C)C(=O)[C@@H](C)N(C4CCOCC4)C3=N2)C=C(C=C1)S(=O)(=O)C(F)(F)F RYMAHVHCPIDRMK-CYBMUJFWSA-N 0.000 claims description 2
- TZEGSSVXEKVECD-LJQANCHMSA-N (3R)-6-[5-ethylsulfonyl-2-(4-fluorophenoxy)anilino]-1,3-dimethyl-4-(1-methylpiperidin-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C(C)S(=O)(=O)C=1C=CC(=C(C=1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCN(CC2)C)N=1)OC1=CC=C(C=C1)F TZEGSSVXEKVECD-LJQANCHMSA-N 0.000 claims description 2
- XXUXNYGQEWBEEL-GOSISDBHSA-N (3R)-6-[5-ethylsulfonyl-2-(4-fluorophenoxy)anilino]-1,3-dimethyl-4-(oxan-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C(C)S(=O)(=O)C=1C=CC(=C(C=1)NC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCOCC2)N=1)OC1=CC=C(C=C1)F XXUXNYGQEWBEEL-GOSISDBHSA-N 0.000 claims description 2
- WQQJVNJLVMKTBC-UHFFFAOYSA-N 1,3-dimethyl-6-(3-methylsulfonylanilino)-4-phenyl-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound CN1C2=C(N(C(C1=O)C)C1=CC=CC=C1)N=C(C=C2)NC1=CC(=CC=C1)S(=O)(=O)C WQQJVNJLVMKTBC-UHFFFAOYSA-N 0.000 claims description 2
- CEFMCNXZJUGAEX-UHFFFAOYSA-N 1-(oxan-4-yl)-3,4-dihydropyrido[2,3-b]pyrazin-2-one Chemical compound O=C1CNC2=NC=CC=C2N1C1CCOCC1 CEFMCNXZJUGAEX-UHFFFAOYSA-N 0.000 claims description 2
- BHHMPZQRVWVAAR-UHFFFAOYSA-N 7-bromo-8-methylpyrido[2,3-b]pyrazine Chemical compound C1=CN=C2C(C)=C(Br)C=NC2=N1 BHHMPZQRVWVAAR-UHFFFAOYSA-N 0.000 claims description 2
- DEUARJFJONJXTK-CYBMUJFWSA-N (3R)-1,3-dimethyl-4-(oxan-4-yl)-6-[3-(trifluoromethyl)anilino]-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound CN1C2=C(N([C@@H](C1=O)C)C1CCOCC1)N=C(C=C2)NC1=CC(=CC=C1)C(F)(F)F DEUARJFJONJXTK-CYBMUJFWSA-N 0.000 claims 1
- WKSQSQJMHMBFFI-CQSZACIVSA-N (3R)-1,3-dimethyl-6-(3-methylsulfonylanilino)-4-(oxan-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C[C@H]1N(C2CCOCC2)C2=NC(NC3=CC(=CC=C3)S(C)(=O)=O)=CC=C2N(C)C1=O WKSQSQJMHMBFFI-CQSZACIVSA-N 0.000 claims 1
- MJVPBYMBDFPFGX-GOSISDBHSA-N (3R)-1,3-dimethyl-6-[3-(4-methylpiperazin-1-yl)anilino]-4-(oxan-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C[C@H]1N(C2CCOCC2)C2=NC(NC3=CC(=CC=C3)N3CCN(C)CC3)=CC=C2N(C)C1=O MJVPBYMBDFPFGX-GOSISDBHSA-N 0.000 claims 1
- LUKNGCDGWLGWCV-MRXNPFEDSA-N (3R)-4-cycloheptyl-1,3-dimethyl-6-(3-methylsulfonylanilino)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C[C@H]1N(C2CCCCCC2)C2=NC(NC3=CC(=CC=C3)S(C)(=O)=O)=CC=C2N(C)C1=O LUKNGCDGWLGWCV-MRXNPFEDSA-N 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 102100029895 Bromodomain-containing protein 4 Human genes 0.000 abstract description 58
- 108091005625 BRD4 Proteins 0.000 abstract description 56
- 230000001225 therapeutic effect Effects 0.000 abstract description 8
- 239000008177 pharmaceutical agent Substances 0.000 abstract description 3
- 230000000069 prophylactic effect Effects 0.000 abstract description 3
- 229940121649 protein inhibitor Drugs 0.000 abstract description 3
- 239000012268 protein inhibitor Substances 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 288
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 198
- 239000000543 intermediate Substances 0.000 description 158
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 140
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
- 239000000243 solution Substances 0.000 description 107
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 94
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 90
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 81
- 239000000203 mixture Substances 0.000 description 76
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 69
- 238000006243 chemical reaction Methods 0.000 description 69
- 239000002904 solvent Substances 0.000 description 65
- 239000012074 organic phase Substances 0.000 description 59
- 238000004587 chromatography analysis Methods 0.000 description 58
- 238000005481 NMR spectroscopy Methods 0.000 description 57
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 51
- 229920006395 saturated elastomer Polymers 0.000 description 48
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
- 239000011780 sodium chloride Substances 0.000 description 43
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 41
- 229910052938 sodium sulfate Inorganic materials 0.000 description 41
- 235000011152 sodium sulphate Nutrition 0.000 description 41
- 239000012300 argon atmosphere Substances 0.000 description 39
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 36
- 239000000741 silica gel Substances 0.000 description 36
- 229910002027 silica gel Inorganic materials 0.000 description 36
- 229910000024 caesium carbonate Inorganic materials 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 34
- 238000005160 1H NMR spectroscopy Methods 0.000 description 32
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 31
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 28
- 239000012071 phase Substances 0.000 description 28
- 208000026310 Breast neoplasm Diseases 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000003112 inhibitor Substances 0.000 description 24
- 238000000034 method Methods 0.000 description 24
- 238000004007 reversed phase HPLC Methods 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 206010060862 Prostate cancer Diseases 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 21
- 230000002757 inflammatory effect Effects 0.000 description 21
- 108090000623 proteins and genes Proteins 0.000 description 21
- 238000011282 treatment Methods 0.000 description 21
- 206010006187 Breast cancer Diseases 0.000 description 20
- 239000000126 substance Substances 0.000 description 19
- 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 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 235000019253 formic acid Nutrition 0.000 description 18
- 150000001721 carbon Chemical group 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- 230000008569 process Effects 0.000 description 16
- 230000002062 proliferating effect Effects 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 230000000172 allergic effect Effects 0.000 description 15
- 208000010668 atopic eczema Diseases 0.000 description 15
- 208000032839 leukemia Diseases 0.000 description 15
- 201000001514 prostate carcinoma Diseases 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 14
- 125000001309 chloro group Chemical group Cl* 0.000 description 13
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- MJVZSRZTBDMYLX-UHFFFAOYSA-N 2,6-dichloropyridin-3-amine Chemical compound NC1=CC=C(Cl)N=C1Cl MJVZSRZTBDMYLX-UHFFFAOYSA-N 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- 108010033040 Histones Proteins 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 108091008039 hormone receptors Proteins 0.000 description 12
- 150000003254 radicals Chemical class 0.000 description 12
- 239000012453 solvate Substances 0.000 description 12
- 102100032187 Androgen receptor Human genes 0.000 description 11
- 102000006947 Histones Human genes 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 108010080146 androgen receptors Proteins 0.000 description 11
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 10
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
- 108091052242 Bromo- and Extra-Terminal domain (BET) family Proteins 0.000 description 9
- 102100033641 Bromodomain-containing protein 2 Human genes 0.000 description 9
- 101000871850 Homo sapiens Bromodomain-containing protein 2 Proteins 0.000 description 9
- 208000034578 Multiple myelomas Diseases 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- NIFAOMSJMGEFTQ-UHFFFAOYSA-N 4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C=C1 NIFAOMSJMGEFTQ-UHFFFAOYSA-N 0.000 description 8
- 239000005909 Kieselgur Substances 0.000 description 8
- 239000012425 OXONE® Substances 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 125000004122 cyclic group Chemical group 0.000 description 8
- 230000014509 gene expression Effects 0.000 description 8
- ZMPXGSYLKFAGOV-UHFFFAOYSA-N hydron;3-methylsulfonylaniline;chloride Chemical compound Cl.CS(=O)(=O)C1=CC=CC(N)=C1 ZMPXGSYLKFAGOV-UHFFFAOYSA-N 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 230000003287 optical effect Effects 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 8
- 206010035226 Plasma cell myeloma Diseases 0.000 description 7
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 7
- 208000006265 Renal cell carcinoma Diseases 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- VHPBBGKGMPAVPE-UHFFFAOYSA-N 2-methoxy-5-methylsulfonylaniline Chemical compound COC1=CC=C(S(C)(=O)=O)C=C1N VHPBBGKGMPAVPE-UHFFFAOYSA-N 0.000 description 6
- UNOAJKVKTDUTAI-UHFFFAOYSA-N 3-propan-2-ylsulfonylaniline Chemical compound CC(C)S(=O)(=O)C1=CC=CC(N)=C1 UNOAJKVKTDUTAI-UHFFFAOYSA-N 0.000 description 6
- UGYZVBUANICGLW-UHFFFAOYSA-N 7,8-dihydro-5h-pteridin-6-one Chemical compound C1=NC=C2NC(=O)CNC2=N1 UGYZVBUANICGLW-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 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 206010014759 Endometrial neoplasm Diseases 0.000 description 6
- 102100038595 Estrogen receptor Human genes 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- PYHZXOYNICJOTG-UHFFFAOYSA-N [2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P PYHZXOYNICJOTG-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 201000008275 breast carcinoma Diseases 0.000 description 6
- 208000019065 cervical carcinoma Diseases 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 6
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 6
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
- 201000001441 melanoma Diseases 0.000 description 6
- 229910017604 nitric acid Inorganic materials 0.000 description 6
- 208000008443 pancreatic carcinoma Diseases 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 6
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- 108010007005 Estrogen Receptor alpha Proteins 0.000 description 5
- 206010029098 Neoplasm skin Diseases 0.000 description 5
- 208000000453 Skin Neoplasms Diseases 0.000 description 5
- 239000012131 assay buffer Substances 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000004296 chiral HPLC Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 230000000155 isotopic effect Effects 0.000 description 5
- 201000010893 malignant breast melanoma Diseases 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- ADAQUIXTJJUTCN-SBSPUUFOSA-N (3R)-6-chloro-1,3-dimethyl-4-piperidin-4-yl-3H-pyrido[2,3-b]pyrazin-2-one hydrochloride Chemical compound Cl.C[C@H]1N(C2CCNCC2)c2nc(Cl)ccc2N(C)C1=O ADAQUIXTJJUTCN-SBSPUUFOSA-N 0.000 description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 4
- VETAODCIKKRRTR-UHFFFAOYSA-N 1-chloro-4-ethylsulfonyl-2-nitrobenzene Chemical compound CCS(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 VETAODCIKKRRTR-UHFFFAOYSA-N 0.000 description 4
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 4
- 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 4
- ILLHORFDXDLILE-UHFFFAOYSA-N 2-bromopropanoyl bromide Chemical compound CC(Br)C(Br)=O ILLHORFDXDLILE-UHFFFAOYSA-N 0.000 description 4
- 208000026872 Addison Disease Diseases 0.000 description 4
- 208000023275 Autoimmune disease Diseases 0.000 description 4
- 102100029894 Bromodomain testis-specific protein Human genes 0.000 description 4
- 102100033642 Bromodomain-containing protein 3 Human genes 0.000 description 4
- 102000001805 Bromodomains Human genes 0.000 description 4
- 108050009021 Bromodomains Proteins 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- 108010077544 Chromatin Proteins 0.000 description 4
- 101000794028 Homo sapiens Bromodomain testis-specific protein Proteins 0.000 description 4
- 101000871851 Homo sapiens Bromodomain-containing protein 3 Proteins 0.000 description 4
- 206010025323 Lymphomas Diseases 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 210000003483 chromatin Anatomy 0.000 description 4
- 239000000824 cytostatic agent Substances 0.000 description 4
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 108010056274 polo-like kinase 1 Proteins 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 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 4
- MUALRAIOVNYAIW-UHFFFAOYSA-N (R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl Substances 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 3
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 3
- XUUSYXJGMRQBKQ-UHFFFAOYSA-N 2h-2-benzazepine Chemical compound N1C=CC=C2C=CC=CC2=C1 XUUSYXJGMRQBKQ-UHFFFAOYSA-N 0.000 description 3
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 3
- 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 3
- IVBVKTPDEWDNRW-UHFFFAOYSA-N 4-bromooxane Chemical compound BrC1CCOCC1 IVBVKTPDEWDNRW-UHFFFAOYSA-N 0.000 description 3
- PPJOPHZGZOCQEQ-UHFFFAOYSA-N 6-chloro-3-methyl-4-phenyl-1,3-dihydropyrido[2,3-b]pyrazin-2-one Chemical compound C12=NC(Cl)=CC=C2NC(=O)C(C)N1C1=CC=CC=C1 PPJOPHZGZOCQEQ-UHFFFAOYSA-N 0.000 description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 3
- 206010010356 Congenital anomaly Diseases 0.000 description 3
- 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 3
- 206010014733 Endometrial cancer Diseases 0.000 description 3
- 108010074604 Epoetin Alfa Proteins 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 108010012271 Positive Transcriptional Elongation Factor B Proteins 0.000 description 3
- 102000019014 Positive Transcriptional Elongation Factor B Human genes 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Chemical compound 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 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 125000005605 benzo group Chemical group 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 description 3
- LKXYJYDRLBPHRS-UHFFFAOYSA-N bromocyclopropane Chemical compound BrC1CC1 LKXYJYDRLBPHRS-UHFFFAOYSA-N 0.000 description 3
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 229960002412 cediranib Drugs 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000001085 cytostatic effect Effects 0.000 description 3
- 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 3
- 239000008298 dragée Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 201000003914 endometrial carcinoma Diseases 0.000 description 3
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 150000004677 hydrates Chemical class 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 3
- 229960004338 leuprorelin Drugs 0.000 description 3
- ANMYAHDLKVNJJO-LTCKWSDVSA-M levothyroxine sodium hydrate Chemical compound O.[Na+].IC1=CC(C[C@H](N)C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 ANMYAHDLKVNJJO-LTCKWSDVSA-M 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 125000002757 morpholinyl group Chemical group 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- 125000004193 piperazinyl group Chemical group 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- PAQZWJGSJMLPMG-UHFFFAOYSA-N propylphosphonic anhydride Substances CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 230000001850 reproductive effect Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- BMKDZUISNHGIBY-ZETCQYMHSA-N (+)-dexrazoxane Chemical compound C([C@H](C)N1CC(=O)NC(=O)C1)N1CC(=O)NC(=O)C1 BMKDZUISNHGIBY-ZETCQYMHSA-N 0.000 description 2
- OEERZWJCPPSANF-LLVKDONJSA-N (3R)-6-chloro-4-cycloheptyl-1,3-dimethyl-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound ClC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCCCCC2)N=1 OEERZWJCPPSANF-LLVKDONJSA-N 0.000 description 2
- RUDLGFJSXJWIMX-SSDOTTSWSA-N (3r)-6-chloro-3-methyl-4-propan-2-yl-1,3-dihydropyrido[2,3-b]pyrazin-2-one Chemical compound C1=C(Cl)N=C2N(C(C)C)[C@H](C)C(=O)NC2=C1 RUDLGFJSXJWIMX-SSDOTTSWSA-N 0.000 description 2
- FRJKWCKVARJCGH-SNVBAGLBSA-N (3r)-6-chloro-4-cycloheptyl-3-methyl-1,3-dihydropyrido[2,3-b]pyrazin-2-one Chemical compound N1([C@@H](C(NC2=CC=C(Cl)N=C21)=O)C)C1CCCCCC1 FRJKWCKVARJCGH-SNVBAGLBSA-N 0.000 description 2
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 2
- 125000006568 (C4-C7) heterocycloalkyl group Chemical group 0.000 description 2
- ULIYQAUQKZDZOX-UHFFFAOYSA-N 1,1,1-trifluoro-3-iodopropane Chemical compound FC(F)(F)CCI ULIYQAUQKZDZOX-UHFFFAOYSA-N 0.000 description 2
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 2
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- DGHHQBMTXTWTJV-BQAIUKQQSA-N 119413-54-6 Chemical compound Cl.C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 DGHHQBMTXTWTJV-BQAIUKQQSA-N 0.000 description 2
- RTMMSCJWQYWMNK-UHFFFAOYSA-N 2,2,2-trifluoroethyl trifluoromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(F)(F)F RTMMSCJWQYWMNK-UHFFFAOYSA-N 0.000 description 2
- NKULBUOBGILEAR-UHFFFAOYSA-N 2,2-difluoroethyl trifluoromethanesulfonate Chemical compound FC(F)COS(=O)(=O)C(F)(F)F NKULBUOBGILEAR-UHFFFAOYSA-N 0.000 description 2
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 2
- MWYDSXOGIBMAET-UHFFFAOYSA-N 2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene]pyrimidine-5-carboxamide Chemical compound NC1=NC=C(C=N1)C(=O)N=C1N=C2C(=C(C=CC2=C2N1CCN2)OCCCN1CCOCC1)OC MWYDSXOGIBMAET-UHFFFAOYSA-N 0.000 description 2
- VBJAOHICUVNRCE-UHFFFAOYSA-N 2-cyclobutyl-1-(2-cyclobutyl-4-methoxy-3-nitrophenyl)sulfonyl-4-methoxy-3-nitrobenzene Chemical compound C1(CCC1)C1=C(C=CC(=C1[N+](=O)[O-])OC)S(=O)(=O)C1=C(C(=C(C=C1)OC)[N+](=O)[O-])C1CCC1 VBJAOHICUVNRCE-UHFFFAOYSA-N 0.000 description 2
- LGMHWRWMXFNLFH-UHFFFAOYSA-N 2-cyclobutyl-1-(2-cyclobutyl-4-methoxyphenyl)sulfonyl-4-methoxybenzene Chemical compound C1(CCC1)C1=C(C=CC(=C1)OC)S(=O)(=O)C1=C(C=C(C=C1)OC)C1CCC1 LGMHWRWMXFNLFH-UHFFFAOYSA-N 0.000 description 2
- CKQRVJNDIULNET-UHFFFAOYSA-N 2-cyclopropyl-1-(2-cyclopropyl-3-nitrophenyl)sulfanyl-3-nitrobenzene Chemical compound C1(CC1)C1=C(C=CC=C1[N+](=O)[O-])SC1=C(C(=CC=C1)[N+](=O)[O-])C1CC1 CKQRVJNDIULNET-UHFFFAOYSA-N 0.000 description 2
- NGZZMKBSOSNWAW-UHFFFAOYSA-N 2-cyclopropyl-1-(2-cyclopropyl-3-nitrophenyl)sulfonyl-3-nitrobenzene Chemical compound C1(CC1)C1=C(C=CC=C1[N+](=O)[O-])S(=O)(=O)C1=C(C(=CC=C1)[N+](=O)[O-])C1CC1 NGZZMKBSOSNWAW-UHFFFAOYSA-N 0.000 description 2
- MCEKCLYSHFBQQV-UHFFFAOYSA-N 2-cyclopropyl-1-(2-cyclopropyl-4-methoxy-3-nitrophenyl)sulfonyl-4-methoxy-3-nitrobenzene Chemical compound C1(CC1)C1=C(C=CC(=C1[N+](=O)[O-])OC)S(=O)(=O)C1=C(C(=C(C=C1)OC)[N+](=O)[O-])C1CC1 MCEKCLYSHFBQQV-UHFFFAOYSA-N 0.000 description 2
- PLOFFGFBQWRXIN-UHFFFAOYSA-N 2-cyclopropyl-1-(2-cyclopropyl-4-methoxyphenyl)sulfonyl-4-methoxybenzene Chemical compound C1(CC1)C1=C(C=CC(=C1)OC)S(=O)(=O)C1=C(C=C(C=C1)OC)C1CC1 PLOFFGFBQWRXIN-UHFFFAOYSA-N 0.000 description 2
- PLESGWQBPARRQO-UHFFFAOYSA-N 2-methoxy-5-(trifluoromethylsulfonyl)aniline Chemical compound COC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1N PLESGWQBPARRQO-UHFFFAOYSA-N 0.000 description 2
- KKXVUYXCVDXUDA-UHFFFAOYSA-N 2-methoxy-5-propan-2-ylsulfonylaniline Chemical compound COC1=CC=C(S(=O)(=O)C(C)C)C=C1N KKXVUYXCVDXUDA-UHFFFAOYSA-N 0.000 description 2
- LAQJGAKLLZAETL-UHFFFAOYSA-N 2h-pyrazin-3-one Chemical compound O=C1CN=CC=N1 LAQJGAKLLZAETL-UHFFFAOYSA-N 0.000 description 2
- HYTIPJFUWHYQON-UHFFFAOYSA-N 3,4-dihydro-1h-quinoxalin-2-one Chemical class C1=CC=C2NC(=O)CNC2=C1 HYTIPJFUWHYQON-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 2
- FMVREQADBPVLTH-UHFFFAOYSA-N 4-(3-aminophenyl)benzonitrile Chemical compound NC1=CC=CC(C=2C=CC(=CC=2)C#N)=C1 FMVREQADBPVLTH-UHFFFAOYSA-N 0.000 description 2
- RXESTRAJUGPIOZ-UHFFFAOYSA-N 4-(4-methoxy-3-nitrophenyl)sulfonyloxane Chemical compound COC1=C(C=C(C=C1)S(=O)(=O)C1CCOCC1)[N+](=O)[O-] RXESTRAJUGPIOZ-UHFFFAOYSA-N 0.000 description 2
- NGRZDJOVZLZZDJ-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfanyloxane Chemical compound COC1=CC=C(C=C1)SC1CCOCC1 NGRZDJOVZLZZDJ-UHFFFAOYSA-N 0.000 description 2
- JQXYJCFGDTUNDB-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyloxane Chemical compound COC1=CC=C(C=C1)S(=O)(=O)C1CCOCC1 JQXYJCFGDTUNDB-UHFFFAOYSA-N 0.000 description 2
- JHVNSRJPBXPZJU-UHFFFAOYSA-N 4-(trifluoromethoxy)benzenethiol Chemical compound FC(F)(F)OC1=CC=C(S)C=C1 JHVNSRJPBXPZJU-UHFFFAOYSA-N 0.000 description 2
- MMFLBHOLSSWFQU-UHFFFAOYSA-N 4-ethylsulfonyl-1-(4-fluorophenoxy)-2-nitrobenzene Chemical compound FC1=CC=C(OC2=C(C=C(C=C2)S(=O)(=O)CC)[N+](=O)[O-])C=C1 MMFLBHOLSSWFQU-UHFFFAOYSA-N 0.000 description 2
- HPPHBBLKKAAMPG-UHFFFAOYSA-N 5-cyclobutylsulfonyl-2-methoxyaniline Chemical compound C1(CCC1)S(=O)(=O)C=1C=CC(=C(N)C=1)OC HPPHBBLKKAAMPG-UHFFFAOYSA-N 0.000 description 2
- VTQGKTGYNLQGSQ-UHFFFAOYSA-N 5-cyclopropylsulfonyl-2-methoxyaniline Chemical compound C1(CC1)S(=O)(=O)C=1C=CC(=C(N)C=1)OC VTQGKTGYNLQGSQ-UHFFFAOYSA-N 0.000 description 2
- CFYJYHLQKSHWNI-UHFFFAOYSA-N 5-ethylsulfonyl-2-phenoxyaniline Chemical compound CCS(=O)(=O)C1=CC(N)=C(OC2=CC=CC=C2)C=C1 CFYJYHLQKSHWNI-UHFFFAOYSA-N 0.000 description 2
- JBWWWDFSDXQGLA-UHFFFAOYSA-N 5-propan-2-ylsulfonyl-2-(trifluoromethoxy)aniline Chemical compound C(C)(C)S(=O)(=O)C=1C=CC(=C(N)C=1)OC(F)(F)F JBWWWDFSDXQGLA-UHFFFAOYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-CFWMRBGOSA-N 5j49q6b70f 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=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 OGWKCGZFUXNPDA-CFWMRBGOSA-N 0.000 description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
- MKBLHFILKIKSQM-UHFFFAOYSA-N 9-methyl-3-[(2-methyl-1h-imidazol-3-ium-3-yl)methyl]-2,3-dihydro-1h-carbazol-4-one;chloride Chemical compound Cl.CC1=NC=CN1CC1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 MKBLHFILKIKSQM-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 2
- 206010002199 Anaphylactic shock Diseases 0.000 description 2
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 2
- 108010024976 Asparaginase Proteins 0.000 description 2
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 2
- 206010048962 Brain oedema Diseases 0.000 description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 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
- 201000009030 Carcinoma Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- OHZLWZFUODPQOM-PGMHMLKASA-N Cl.C[C@@H](N)C(=O)Nc1ccc(Cl)nc1Cl Chemical compound Cl.C[C@@H](N)C(=O)Nc1ccc(Cl)nc1Cl OHZLWZFUODPQOM-PGMHMLKASA-N 0.000 description 2
- OUYSBYXPOQCPHX-UHFFFAOYSA-N ClC=1C=CC2=C(N(C(C(N2C)=O)C)C2=CC=CC=C2)N=1 Chemical compound ClC=1C=CC2=C(N(C(C(N2C)=O)C)C2=CC=CC=C2)N=1 OUYSBYXPOQCPHX-UHFFFAOYSA-N 0.000 description 2
- 208000015943 Coeliac disease Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 102000016736 Cyclin Human genes 0.000 description 2
- 108050006400 Cyclin Proteins 0.000 description 2
- 108010058546 Cyclin D1 Proteins 0.000 description 2
- 102100024457 Cyclin-dependent kinase 9 Human genes 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 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 2
- 108010029961 Filgrastim Proteins 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 230000005526 G1 to G0 transition Effects 0.000 description 2
- 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 2
- 239000007821 HATU Substances 0.000 description 2
- 101100326315 Homo sapiens BRD4 gene Proteins 0.000 description 2
- 101000980930 Homo sapiens Cyclin-dependent kinase 9 Proteins 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 108010078049 Interferon alpha-2 Proteins 0.000 description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 2
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 2
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 2
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 2
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 2
- 239000002138 L01XE21 - Regorafenib Substances 0.000 description 2
- 108010000817 Leuprolide Proteins 0.000 description 2
- HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 2
- 101710135898 Myc proto-oncogene protein Proteins 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
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 108010016076 Octreotide Proteins 0.000 description 2
- 241001631646 Papillomaviridae Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 2
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 2
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 206010037423 Pulmonary oedema Diseases 0.000 description 2
- 102000009572 RNA Polymerase II Human genes 0.000 description 2
- 108010009460 RNA Polymerase II Proteins 0.000 description 2
- 208000025747 Rheumatic disease Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 206010039807 Secondary adrenocortical insufficiency Diseases 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- 239000012317 TBTU Substances 0.000 description 2
- 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 2
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 2
- 108091005646 acetylated proteins Proteins 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 229960000473 altretamine Drugs 0.000 description 2
- JKOQGQFVAUAYPM-UHFFFAOYSA-N amifostine Chemical compound NCCCNCCSP(O)(O)=O JKOQGQFVAUAYPM-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 150000001504 aryl thiols Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229960003005 axitinib Drugs 0.000 description 2
- 150000001538 azepines Chemical class 0.000 description 2
- 229960000397 bevacizumab Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 208000006752 brain edema Diseases 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 238000012822 chemical development Methods 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
- 230000001684 chronic effect Effects 0.000 description 2
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 2
- 201000010989 colorectal carcinoma Diseases 0.000 description 2
- 229950002550 copanlisib Drugs 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 229960000605 dexrazoxane Drugs 0.000 description 2
- 150000004908 diazepines Chemical class 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000011067 equilibration Methods 0.000 description 2
- 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 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 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 2
- 229960000578 gemtuzumab Drugs 0.000 description 2
- QBKSWRVVCFFDOT-UHFFFAOYSA-N gossypol Chemical compound CC(C)C1=C(O)C(O)=C(C=O)C2=C(O)C(C=3C(O)=C4C(C=O)=C(O)C(O)=C(C4=CC=3C)C(C)C)=C(C)C=C21 QBKSWRVVCFFDOT-UHFFFAOYSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 201000005787 hematologic cancer Diseases 0.000 description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 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 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 2
- 229960004942 lenalidomide Drugs 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 210000003800 pharynx Anatomy 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- VJZLQIPZNBPASX-OJJGEMKLSA-L prednisolone sodium phosphate Chemical compound [Na+].[Na+].O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COP([O-])([O-])=O)[C@@H]4[C@@H]3CCC2=C1 VJZLQIPZNBPASX-OJJGEMKLSA-L 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 208000005333 pulmonary edema Diseases 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- XYEVREOOMFVLLS-UHFFFAOYSA-N pyrazolo[4,3-c]diazepine Chemical class C1=CC=NN=C2C=NN=C21 XYEVREOOMFVLLS-UHFFFAOYSA-N 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 230000007420 reactivation Effects 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- 229960004836 regorafenib Drugs 0.000 description 2
- FNHKPVJBJVTLMP-UHFFFAOYSA-N regorafenib Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(F)C(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 FNHKPVJBJVTLMP-UHFFFAOYSA-N 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000002165 resonance energy transfer Methods 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- 201000000306 sarcoidosis Diseases 0.000 description 2
- 208000023087 secondary adrenal insufficiency Diseases 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 229960003787 sorafenib Drugs 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 125000005555 sulfoximide group Chemical group 0.000 description 2
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 2
- 229960001796 sunitinib Drugs 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 230000009885 systemic effect Effects 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
- 229960000235 temsirolimus Drugs 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 229960003433 thalidomide Drugs 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000005029 transcription elongation Effects 0.000 description 2
- 125000004306 triazinyl group Chemical group 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 235000012431 wafers Nutrition 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- VOLGAXAGEUPBDM-UHFFFAOYSA-N $l^{1}-oxidanylethane Chemical compound CC[O] VOLGAXAGEUPBDM-UHFFFAOYSA-N 0.000 description 1
- WYRSGXAIHNMKOL-UHFFFAOYSA-N $l^{1}-sulfanylethane Chemical compound CC[S] WYRSGXAIHNMKOL-UHFFFAOYSA-N 0.000 description 1
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 1
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
- RWRDJVNMSZYMDV-SIUYXFDKSA-L (223)RaCl2 Chemical compound Cl[223Ra]Cl RWRDJVNMSZYMDV-SIUYXFDKSA-L 0.000 description 1
- BGCBGPFPXYBBOU-SNVBAGLBSA-N (2R)-2-amino-N-cycloheptyl-N-(2,6-dichloropyridin-3-yl)propanamide Chemical compound C1(CCCCCC1)N(C([C@H](N)C)=O)C=1C(=NC(=CC=1)Cl)Cl BGCBGPFPXYBBOU-SNVBAGLBSA-N 0.000 description 1
- BNJIBAAYHKSDJG-MRVPVSSYSA-N (2R)-N-(2,6-dichloropyridin-3-yl)-2-(oxan-4-ylamino)propanamide Chemical compound ClC1=NC(=CC=C1NC([C@H](NC1CCOCC1)C)=O)Cl BNJIBAAYHKSDJG-MRVPVSSYSA-N 0.000 description 1
- SOCYWMMDFLRNJM-SSDOTTSWSA-N (2R)-N-(2,6-dichloropyridin-3-yl)-2-(propan-2-ylamino)propanamide Chemical compound CC(C)N[C@H](C)C(=O)NC=1C(=NC(=CC=1)Cl)Cl SOCYWMMDFLRNJM-SSDOTTSWSA-N 0.000 description 1
- UPDAKLDSSNQKJG-VIFPVBQESA-N (2S)-2-anilino-N-(2,6-dichloropyridin-3-yl)propanamide Chemical compound ClC1=NC(=CC=C1NC([C@@H](NC1=CC=CC=C1)C)=O)Cl UPDAKLDSSNQKJG-VIFPVBQESA-N 0.000 description 1
- FKHUGQZRBPETJR-RXSRXONKSA-N (2r)-2-[[(4r)-4-[[(2s)-2-[[(2r)-2-[(3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxypropanoyl]amino]propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-6-(octadecanoylamino)hexanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(=O)NCCCC[C@H](C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)OC(O)[C@@H]1NC(C)=O FKHUGQZRBPETJR-RXSRXONKSA-N 0.000 description 1
- WDQLRUYAYXDIFW-RWKIJVEZSA-N (2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-4-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxy-6-(hydroxymethyl)oxane-2,3,5-triol Chemical compound O[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)O1 WDQLRUYAYXDIFW-RWKIJVEZSA-N 0.000 description 1
- OHDRDSMYHJXAIE-QMMMGPOBSA-N (2s)-2-amino-2-(oxan-4-yl)propanamide Chemical compound NC(=O)[C@](N)(C)C1CCOCC1 OHDRDSMYHJXAIE-QMMMGPOBSA-N 0.000 description 1
- VESKBLGTHHPZJF-QNWVGRARSA-N (2s)-2-amino-5-[[(2r)-2-amino-3-[2-[bis[bis(2-chloroethyl)amino]phosphoryloxy]ethylsulfonyl]propanoyl]-[(r)-carboxy(phenyl)methyl]amino]-5-oxopentanoic acid Chemical compound ClCCN(CCCl)P(=O)(N(CCCl)CCCl)OCCS(=O)(=O)C[C@H](N)C(=O)N(C(=O)CC[C@H](N)C(O)=O)[C@@H](C(O)=O)C1=CC=CC=C1 VESKBLGTHHPZJF-QNWVGRARSA-N 0.000 description 1
- ZBVJFYPGLGEMIN-OYLNGHKZSA-N (2s)-n-[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2r)-1-[[(2s)-1-[[(2s)-1-[(2s)-2-[(2-amino-2-oxoethyl)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1h-indol-3-yl)-1-oxopropan-2-yl]amino]-3-( Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1.C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 ZBVJFYPGLGEMIN-OYLNGHKZSA-N 0.000 description 1
- CVCLJVVBHYOXDC-IAZSKANUSA-N (2z)-2-[(5z)-5-[(3,5-dimethyl-1h-pyrrol-2-yl)methylidene]-4-methoxypyrrol-2-ylidene]indole Chemical compound COC1=C\C(=C/2N=C3C=CC=CC3=C\2)N\C1=C/C=1NC(C)=CC=1C CVCLJVVBHYOXDC-IAZSKANUSA-N 0.000 description 1
- WQRZXDCOHSABGM-CQSZACIVSA-N (3R)-4-(1-benzylpiperidin-4-yl)-6-chloro-3-methyl-1,3-dihydropyrido[2,3-b]pyrazin-2-one Chemical compound C(C1=CC=CC=C1)N1CCC(CC1)N1C2=C(NC([C@H]1C)=O)C=CC(=N2)Cl WQRZXDCOHSABGM-CQSZACIVSA-N 0.000 description 1
- SPXSOQNOSALTMS-SNVBAGLBSA-N (3R)-6-chloro-1,3-dimethyl-4-(1-methylpiperidin-4-yl)-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound ClC=1C=CC2=C(N([C@@H](C(N2C)=O)C)C2CCN(CC2)C)N=1 SPXSOQNOSALTMS-SNVBAGLBSA-N 0.000 description 1
- RREPAXNQTDUCBG-LLVKDONJSA-N (3R)-6-chloro-1,3-dimethyl-4-[1-(3,3,3-trifluoropropyl)piperidin-4-yl]-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound C[C@H]1N(C2CCN(CCC(F)(F)F)CC2)C2=NC(Cl)=CC=C2N(C)C1=O RREPAXNQTDUCBG-LLVKDONJSA-N 0.000 description 1
- FLDFORGZDGCJQN-MRVPVSSYSA-N (3R)-6-chloro-1,3-dimethyl-4-propan-2-yl-3H-pyrido[2,3-b]pyrazin-2-one Chemical compound CC(C)N1[C@H](C)C(=O)N(C)c2ccc(Cl)nc12 FLDFORGZDGCJQN-MRVPVSSYSA-N 0.000 description 1
- UYVMKCRNMXGDAY-LLVKDONJSA-N (3R)-6-chloro-4-[1-(2,2-difluoroethyl)piperidin-4-yl]-1,3-dimethyl-2,3-dihydropyrido[2,3-b]pyrazine Chemical compound ClC=1C=CC2=C(N([C@@H](CN2C)C)C2CCN(CC2)CC(F)F)N=1 UYVMKCRNMXGDAY-LLVKDONJSA-N 0.000 description 1
- NASDIRMKFXVBJD-MRVPVSSYSA-N (3r)-6-chloro-3-methyl-4-(oxan-4-yl)-1,3-dihydropyrido[2,3-b]pyrazin-2-one Chemical compound N1([C@@H](C(NC2=CC=C(Cl)N=C21)=O)C)C1CCOCC1 NASDIRMKFXVBJD-MRVPVSSYSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- SWXOGPJRIDTIRL-DOUNNPEJSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-n-[(2s)-1-amino-3-(1h-indol-3-yl)-1-oxopropan-2-yl]-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-7-propan-2-yl-1,2-dithia-5,8,11,14,17-pent Chemical compound C([C@H]1C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](N)CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(N)=O)=O)C(C)C)C1=CC=C(O)C=C1 SWXOGPJRIDTIRL-DOUNNPEJSA-N 0.000 description 1
- PUDHBTGHUJUUFI-SCTWWAJVSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-n-[(2s,3r)-1-amino-3-hydroxy-1-oxobutan-2-yl]-19-[[(2r)-2-amino-3-naphthalen-2-ylpropanoyl]amino]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-7-propan-2-yl-1,2-dithia-5,8,11,14,17-p Chemical compound C([C@H]1C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](N)CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(N)=O)=O)C(C)C)C1=CC=C(O)C=C1 PUDHBTGHUJUUFI-SCTWWAJVSA-N 0.000 description 1
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 1
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 description 1
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- ZGMJYTYLTJFNCS-VQYXCCSOSA-N (e)-but-2-enedioic acid;1-[4-(2-hydroxy-3-quinolin-5-yloxypropyl)piperazin-1-yl]-2,2-diphenylethanone Chemical compound OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.C=1C=CC2=NC=CC=C2C=1OCC(O)CN(CC1)CCN1C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1.C=1C=CC2=NC=CC=C2C=1OCC(O)CN(CC1)CCN1C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 ZGMJYTYLTJFNCS-VQYXCCSOSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-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
- QOOQLKSEGVNYLA-UHFFFAOYSA-N 1-$l^{1}-oxidanylbutane Chemical compound CCCC[O] QOOQLKSEGVNYLA-UHFFFAOYSA-N 0.000 description 1
- VVKMHTWFAUCCOD-UHFFFAOYSA-N 1-(3-aminopropyl)-8-[3-[2-(dimethylamino)-2-oxoethyl]anilino]-n-[(2-methylpyridin-4-yl)methyl]-4,5-dihydropyrazolo[4,3-h]quinazoline-3-carboxamide Chemical group CN(C)C(=O)CC1=CC=CC(NC=2N=C3C=4N(CCCN)N=C(C=4CCC3=CN=2)C(=O)NCC=2C=C(C)N=CC=2)=C1 VVKMHTWFAUCCOD-UHFFFAOYSA-N 0.000 description 1
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
- MLEGMEBCXGDFQT-UHFFFAOYSA-N 1-benzylpiperidin-2-one Chemical compound O=C1CCCCN1CC1=CC=CC=C1 MLEGMEBCXGDFQT-UHFFFAOYSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- UEZLKKCYKRPJJZ-UHFFFAOYSA-N 1-cyclobutylsulfanyl-4-methoxybenzene Chemical compound C1=CC(OC)=CC=C1SC1CCC1 UEZLKKCYKRPJJZ-UHFFFAOYSA-N 0.000 description 1
- JLURWBIBHMXAHE-UHFFFAOYSA-N 1-cyclohexyl-n-(cyclohexylmethyl)methanamine Chemical compound C1CCCCC1CNCC1CCCCC1 JLURWBIBHMXAHE-UHFFFAOYSA-N 0.000 description 1
- UHYWUNFIAXWGDE-UHFFFAOYSA-N 1-cyclopropylsulfanyl-4-methoxybenzene Chemical compound C1=CC(OC)=CC=C1SC1CC1 UHYWUNFIAXWGDE-UHFFFAOYSA-N 0.000 description 1
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- JOBWVXIMTXJWLT-UHFFFAOYSA-N 1-methoxy-4-(4-methoxy-3-nitro-2-propan-2-ylphenyl)sulfonyl-2-nitro-3-propan-2-ylbenzene Chemical compound C(C)(C)C1=C(C=CC(=C1[N+](=O)[O-])OC)S(=O)(=O)C1=C(C(=C(C=C1)OC)[N+](=O)[O-])C(C)C JOBWVXIMTXJWLT-UHFFFAOYSA-N 0.000 description 1
- MJVQNQFTOQCSFX-UHFFFAOYSA-N 1-methoxy-4-propan-2-ylsulfanylbenzene Chemical compound COC1=CC=C(SC(C)C)C=C1 MJVQNQFTOQCSFX-UHFFFAOYSA-N 0.000 description 1
- QDMNBJRPIRLYRL-UHFFFAOYSA-N 1-methoxy-4-propan-2-ylsulfonylbenzene Chemical compound COC1=CC=C(S(=O)(=O)C(C)C)C=C1 QDMNBJRPIRLYRL-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- FHISPMXQZUXQMU-UHFFFAOYSA-N 1-propan-2-ylsulfanyl-4-(trifluoromethoxy)benzene Chemical compound CC(C)SC1=CC=C(OC(F)(F)F)C=C1 FHISPMXQZUXQMU-UHFFFAOYSA-N 0.000 description 1
- QYVQULJBQGYIEF-UHFFFAOYSA-N 1-propan-2-ylsulfonyl-4-(trifluoromethoxy)benzene Chemical compound CC(C)S(=O)(=O)C1=CC=C(OC(F)(F)F)C=C1 QYVQULJBQGYIEF-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 1
- POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical class N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 description 1
- QMVPQBFHUJZJCS-NTKFZFFISA-N 1v8x590xdp Chemical compound O=C1N(NC(CO)CO)C(=O)C(C2=C3[CH]C=C(O)C=C3NC2=C23)=C1C2=C1C=CC(O)=C[C]1N3[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O QMVPQBFHUJZJCS-NTKFZFFISA-N 0.000 description 1
- MJNNGMNZUQSJNV-UHFFFAOYSA-N 2,4-dihydro-1h-pyrido[3,4-b]pyrazin-3-one Chemical class C1=NC=C2NC(=O)CNC2=C1 MJNNGMNZUQSJNV-UHFFFAOYSA-N 0.000 description 1
- QXLQZLBNPTZMRK-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-(2,4-dimethylphenyl)prop-2-en-1-one Chemical compound CN(C)CC(=C)C(=O)C1=CC=C(C)C=C1C QXLQZLBNPTZMRK-UHFFFAOYSA-N 0.000 description 1
- RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 description 1
- HGKUPDZBTAQFGJ-UHFFFAOYSA-N 2-amino-2-phenylpropanamide Chemical compound NC(=O)C(N)(C)C1=CC=CC=C1 HGKUPDZBTAQFGJ-UHFFFAOYSA-N 0.000 description 1
- SCFGITNETSUKBH-UHFFFAOYSA-N 2-ethyl-1-(2-ethyl-3-nitro-4-phenoxyphenyl)sulfonyl-3-nitro-4-phenoxybenzene Chemical compound C(C)C1=C(C=CC(=C1[N+](=O)[O-])OC1=CC=CC=C1)S(=O)(=O)C1=C(C(=C(C=C1)OC1=CC=CC=C1)[N+](=O)[O-])CC SCFGITNETSUKBH-UHFFFAOYSA-N 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 1
- NMRWCWSCPIVWKV-UHFFFAOYSA-N 2-methoxy-5-(oxan-4-ylsulfonyl)aniline Chemical compound COC1=C(N)C=C(C=C1)S(=O)(=O)C1CCOCC1 NMRWCWSCPIVWKV-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- LGEXGKUJMFHVSY-UHFFFAOYSA-N 2-n,4-n,6-n-trimethyl-1,3,5-triazine-2,4,6-triamine Chemical compound CNC1=NC(NC)=NC(NC)=N1 LGEXGKUJMFHVSY-UHFFFAOYSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- PHNQOKOZTVTGPL-UHFFFAOYSA-N 2h-thieno[3,2-b]azepine Chemical group C1=CC=NC2=CCSC2=C1 PHNQOKOZTVTGPL-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
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 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
- WUIABRMSWOKTOF-OYALTWQYSA-N 3-[[2-[2-[2-[[(2s,3r)-2-[[(2s,3s,4r)-4-[[(2s,3r)-2-[[6-amino-2-[(1s)-3-amino-1-[[(2s)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[(2r,3s,4s,5s,6s)-3-[(2r,3s,4s,5r,6r)-4-carbamoyloxy-3,5-dihydroxy-6-(hydroxymethyl)ox Chemical compound OS([O-])(=O)=O.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=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C WUIABRMSWOKTOF-OYALTWQYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- STPYCWFQVXRWEW-UHFFFAOYSA-N 3-cyclopropylsulfonylaniline Chemical compound NC1=CC=CC(S(=O)(=O)C2CC2)=C1 STPYCWFQVXRWEW-UHFFFAOYSA-N 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- MWWNNNAOGWPTQY-UHFFFAOYSA-N 3-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=CC(S(Cl)(=O)=O)=C1 MWWNNNAOGWPTQY-UHFFFAOYSA-N 0.000 description 1
- QNNMMIMBOFCDQK-UHFFFAOYSA-N 4-(4-bromophenyl)-3h-1,3-thiazole-2-thione Chemical compound S1C(S)=NC(C=2C=CC(Br)=CC=2)=C1 QNNMMIMBOFCDQK-UHFFFAOYSA-N 0.000 description 1
- CLPFFLWZZBQMAO-UHFFFAOYSA-N 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1N2C=NC=C2CCC1 CLPFFLWZZBQMAO-UHFFFAOYSA-N 0.000 description 1
- ASNHGEVAWNWCRQ-UHFFFAOYSA-N 4-(hydroxymethyl)oxolane-2,3,4-triol Chemical compound OCC1(O)COC(O)C1O ASNHGEVAWNWCRQ-UHFFFAOYSA-N 0.000 description 1
- AKJHMTWEGVYYSE-AIRMAKDCSA-N 4-HPR Chemical compound C=1C=C(O)C=CC=1NC(=O)/C=C(\C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C AKJHMTWEGVYYSE-AIRMAKDCSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- JDCSJDBVPBMRFB-UHFFFAOYSA-N 4-ethylsulfonyl-2-nitro-1-phenoxybenzene Chemical compound [N+](=O)([O-])C=1C=C(C=CC=1OC1=CC=CC=C1)S(=O)(=O)CC JDCSJDBVPBMRFB-UHFFFAOYSA-N 0.000 description 1
- MDOJTZQKHMAPBK-UHFFFAOYSA-N 4-iodo-3-nitrobenzamide Chemical compound NC(=O)C1=CC=C(I)C([N+]([O-])=O)=C1 MDOJTZQKHMAPBK-UHFFFAOYSA-N 0.000 description 1
- FYIDNNSLEVZDSB-UHFFFAOYSA-N 4-methoxy-1-(4-methoxy-2-propan-2-ylphenyl)sulfonyl-2-propan-2-ylbenzene Chemical compound C(C)(C)C1=C(C=CC(=C1)OC)S(=O)(=O)C1=C(C=C(C=C1)OC)C(C)C FYIDNNSLEVZDSB-UHFFFAOYSA-N 0.000 description 1
- 125000001826 4H-pyranyl group Chemical group O1C(=CCC=C1)* 0.000 description 1
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 description 1
- SRSGVKWWVXWSJT-ATVHPVEESA-N 5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-n-(2-pyrrolidin-1-ylethyl)-1h-pyrrole-3-carboxamide Chemical compound CC=1NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C(C)C=1C(=O)NCCN1CCCC1 SRSGVKWWVXWSJT-ATVHPVEESA-N 0.000 description 1
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 description 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 1
- HTNVKXJIQAZVKE-UHFFFAOYSA-N 5-ethylsulfonyl-2-(4-fluorophenoxy)aniline Chemical compound C(C)S(=O)(=O)C=1C=CC(=C(N)C=1)OC1=CC=C(C=C1)F HTNVKXJIQAZVKE-UHFFFAOYSA-N 0.000 description 1
- HFEKDTCAMMOLQP-RRKCRQDMSA-N 5-fluorodeoxyuridine monophosphate Chemical compound O1[C@H](COP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C(F)=C1 HFEKDTCAMMOLQP-RRKCRQDMSA-N 0.000 description 1
- KYXLYJWGRDSBIK-UHFFFAOYSA-N 5h-pyrido[3,2-b]azepine Chemical compound N1C=CC=CC2=NC=CC=C12 KYXLYJWGRDSBIK-UHFFFAOYSA-N 0.000 description 1
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 1
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- COKSZOPYKLRICP-UHFFFAOYSA-N 9-(6-amino-7h-purin-2-yl)nonan-1-ol Chemical compound NC1=NC(CCCCCCCCCO)=NC2=C1NC=N2 COKSZOPYKLRICP-UHFFFAOYSA-N 0.000 description 1
- SHGAZHPCJJPHSC-ZVCIMWCZSA-N 9-cis-retinoic acid Chemical compound OC(=O)/C=C(\C)/C=C/C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-ZVCIMWCZSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 208000002008 AIDS-Related Lymphoma Diseases 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000005676 Adrenogenital syndrome Diseases 0.000 description 1
- 108010012934 Albumin-Bound Paclitaxel Proteins 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 1
- 206010057380 Allergic keratitis Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010001889 Alveolitis Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000028185 Angioedema Diseases 0.000 description 1
- 206010003267 Arthritis reactive Diseases 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 102000015790 Asparaginase Human genes 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 208000004736 B-Cell Leukemia Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 description 1
- VGGGPCQERPFHOB-UHFFFAOYSA-N Bestatin Natural products CC(C)CC(C(O)=O)NC(=O)C(O)C(N)CC1=CC=CC=C1 VGGGPCQERPFHOB-UHFFFAOYSA-N 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- NPZCIIMYQIUAER-OAHLLOKOSA-N C(C1=CC=CC=C1)N1CCC(CC1)N1C2=C(N(C([C@H]1C)=O)C)C=CC(=N2)Cl Chemical compound C(C1=CC=CC=C1)N1CCC(CC1)N1C2=C(N(C([C@H]1C)=O)C)C=CC(=N2)Cl NPZCIIMYQIUAER-OAHLLOKOSA-N 0.000 description 1
- RPBDCDQMCRHNLM-UHFFFAOYSA-N C1=NNC=C2C=CC=CC2=C1 Chemical class C1=NNC=C2C=CC=CC2=C1 RPBDCDQMCRHNLM-UHFFFAOYSA-N 0.000 description 1
- XCPIUZWJHPEXQY-UHFFFAOYSA-N CC(Br)C(=O)Nc1ccc(Cl)nc1Cl Chemical compound CC(Br)C(=O)Nc1ccc(Cl)nc1Cl XCPIUZWJHPEXQY-UHFFFAOYSA-N 0.000 description 1
- HCIRSUPTOIVBKU-UHFFFAOYSA-N CC1(C(NC2=C(N1C1CCN(CC1)C)N=CC=C2)=O)C Chemical compound CC1(C(NC2=C(N1C1CCN(CC1)C)N=CC=C2)=O)C HCIRSUPTOIVBKU-UHFFFAOYSA-N 0.000 description 1
- JGJSUMYHANRPKT-UHFFFAOYSA-N CC1=CC=NC=C1.O1CCCCC1 Chemical compound CC1=CC=NC=C1.O1CCCCC1 JGJSUMYHANRPKT-UHFFFAOYSA-N 0.000 description 1
- YUMRFJRHSBBFNB-UHFFFAOYSA-N CC1C(N(C2=C(N1)N=CC=C2)C)NC3=C(C=CC(=C3)S(=O)(=O)C(C)C)OC Chemical compound CC1C(N(C2=C(N1)N=CC=C2)C)NC3=C(C=CC(=C3)S(=O)(=O)C(C)C)OC YUMRFJRHSBBFNB-UHFFFAOYSA-N 0.000 description 1
- YERWEBZKQLGPHU-UHFFFAOYSA-N COC1=C(C=C(C=C1)S(=O)(=O)C(C)C)[N+](=O)[O-] Chemical compound COC1=C(C=C(C=C1)S(=O)(=O)C(C)C)[N+](=O)[O-] YERWEBZKQLGPHU-UHFFFAOYSA-N 0.000 description 1
- AWENQFDEZNOXGD-CQSZACIVSA-N C[C@@H]1CN(C2=C(N1C(C)C)N=C(C=C2)NC3=C(C=CC(=C3)S(=O)(=O)C)OC)C Chemical compound C[C@@H]1CN(C2=C(N1C(C)C)N=C(C=C2)NC3=C(C=CC(=C3)S(=O)(=O)C)OC)C AWENQFDEZNOXGD-CQSZACIVSA-N 0.000 description 1
- HNUALPPJLMYHDK-UHFFFAOYSA-N C[CH]C Chemical compound C[CH]C HNUALPPJLMYHDK-UHFFFAOYSA-N 0.000 description 1
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 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
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
- JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000027932 Collagen disease Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000759568 Corixa Species 0.000 description 1
- 108010058544 Cyclin D2 Proteins 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229960005500 DHA-paclitaxel Drugs 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 108010019673 Darbepoetin alfa Proteins 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
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 206010012441 Dermatitis bullous Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- GJKXGJCSJWBJEZ-XRSSZCMZSA-N Deslorelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CNC2=CC=CC=C12 GJKXGJCSJWBJEZ-XRSSZCMZSA-N 0.000 description 1
- 208000035240 Disease Resistance Diseases 0.000 description 1
- CYQFCXCEBYINGO-DLBZAZTESA-N Dronabinol Natural products C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@H]21 CYQFCXCEBYINGO-DLBZAZTESA-N 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 206010014824 Endotoxic shock Diseases 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 206010015226 Erythema nodosum Diseases 0.000 description 1
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 1
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 1
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 1
- 208000028387 Felty syndrome Diseases 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 1
- 102100024185 G1/S-specific cyclin-D2 Human genes 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 208000007465 Giant cell arteritis Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 1
- 108010069236 Goserelin Proteins 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 208000017891 HER2 positive breast carcinoma Diseases 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001122114 Homo sapiens NUT family member 1 Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- DOMWKUIIPQCAJU-LJHIYBGHSA-N Hydroxyprogesterone caproate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)CCCCC)[C@@]1(C)CC2 DOMWKUIIPQCAJU-LJHIYBGHSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021067 Hypopituitarism Diseases 0.000 description 1
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 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 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
- 208000005726 Inflammatory Breast Neoplasms Diseases 0.000 description 1
- 206010021980 Inflammatory carcinoma of the breast Diseases 0.000 description 1
- 208000006877 Insect Bites and Stings Diseases 0.000 description 1
- 101710125507 Integrase/recombinase Proteins 0.000 description 1
- 102100039350 Interferon alpha-7 Human genes 0.000 description 1
- 108010005716 Interferon beta-1a Proteins 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 206010061252 Intraocular melanoma Diseases 0.000 description 1
- 229910021577 Iron(II) chloride Inorganic materials 0.000 description 1
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
- 239000003798 L01XE11 - Pazopanib Substances 0.000 description 1
- 239000002118 L01XE12 - Vandetanib Substances 0.000 description 1
- 239000002145 L01XE14 - Bosutinib Substances 0.000 description 1
- 239000002146 L01XE16 - Crizotinib Substances 0.000 description 1
- 239000002144 L01XE18 - Ruxolitinib Substances 0.000 description 1
- UIARLYUEJFELEN-LROUJFHJSA-N LSM-1231 Chemical compound C12=C3N4C5=CC=CC=C5C3=C3C(=O)NCC3=C2C2=CC=CC=C2N1[C@]1(C)[C@](CO)(O)C[C@H]4O1 UIARLYUEJFELEN-LROUJFHJSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 1
- 229920001491 Lentinan Polymers 0.000 description 1
- 241000408529 Libra Species 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 208000002030 Merkel cell carcinoma Diseases 0.000 description 1
- XOGTZOOQQBDUSI-UHFFFAOYSA-M Mesna Chemical compound [Na+].[O-]S(=O)(=O)CCS XOGTZOOQQBDUSI-UHFFFAOYSA-M 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- GCKMFJBGXUYNAG-HLXURNFRSA-N Methyltestosterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GCKMFJBGXUYNAG-HLXURNFRSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-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
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102100027086 NUT family member 1 Human genes 0.000 description 1
- 201000004253 NUT midline carcinoma Diseases 0.000 description 1
- 108010021717 Nafarelin Proteins 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- CZYWHNTUXNGDGR-UHFFFAOYSA-L Pamidronate disodium Chemical compound O.O.O.O.O.[Na+].[Na+].NCCC(O)(P(O)([O-])=O)P(O)([O-])=O CZYWHNTUXNGDGR-UHFFFAOYSA-L 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 201000011152 Pemphigus Diseases 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- KMSKQZKKOZQFFG-HSUXVGOQSA-N Pirarubicin Chemical compound O([C@H]1[C@@H](N)C[C@@H](O[C@H]1C)O[C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1CCCCO1 KMSKQZKKOZQFFG-HSUXVGOQSA-N 0.000 description 1
- 208000007048 Polymyalgia Rheumatica Diseases 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 206010052381 Primary adrenal insufficiency Diseases 0.000 description 1
- 206010036774 Proctitis Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 102000013009 Pyruvate Kinase Human genes 0.000 description 1
- 108020005115 Pyruvate Kinase Proteins 0.000 description 1
- IKMPWMZBZSAONZ-UHFFFAOYSA-N Quazepam Chemical compound FC1=CC=CC=C1C1=NCC(=S)N(CC(F)(F)F)C2=CC=C(Cl)C=C12 IKMPWMZBZSAONZ-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 208000030934 Restrictive pulmonary disease Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 102100033536 Ribosomal protein S6 kinase alpha-1 Human genes 0.000 description 1
- 101710119197 Ribosomal protein S6 kinase alpha-1 Proteins 0.000 description 1
- 102100033643 Ribosomal protein S6 kinase alpha-3 Human genes 0.000 description 1
- 101710119204 Ribosomal protein S6 kinase alpha-3 Proteins 0.000 description 1
- 241001303601 Rosacea Species 0.000 description 1
- YJDYDFNKCBANTM-QCWCSKBGSA-N SDZ PSC 833 Chemical compound C\C=C\C[C@@H](C)C(=O)[C@@H]1N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@H](C(C)C)NC1=O YJDYDFNKCBANTM-QCWCSKBGSA-N 0.000 description 1
- KQXDHUJYNAXLNZ-XQSDOZFQSA-N Salinomycin Chemical compound O1[C@@H]([C@@H](CC)C(O)=O)CC[C@H](C)[C@@H]1[C@@H](C)[C@H](O)[C@H](C)C(=O)[C@H](CC)[C@@H]1[C@@H](C)C[C@@H](C)[C@@]2(C=C[C@@H](O)[C@@]3(O[C@@](C)(CC3)[C@@H]3O[C@@H](C)[C@@](O)(CC)CC3)O2)O1 KQXDHUJYNAXLNZ-XQSDOZFQSA-N 0.000 description 1
- 239000004189 Salinomycin Substances 0.000 description 1
- 206010061934 Salivary gland cancer Diseases 0.000 description 1
- 238000000297 Sandmeyer reaction Methods 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 229920000519 Sizofiran Polymers 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 206010054184 Small intestine carcinoma Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 208000016247 Soft tissue disease Diseases 0.000 description 1
- 108010087999 Steryl-Sulfatase Proteins 0.000 description 1
- 102100038021 Steryl-sulfatase Human genes 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 1
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 108700011582 TER 286 Proteins 0.000 description 1
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 1
- DRHKJLXJIQTDTD-OAHLLOKOSA-N Tamsulosine Chemical compound CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 DRHKJLXJIQTDTD-OAHLLOKOSA-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
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 1
- QHOPXUFELLHKAS-UHFFFAOYSA-N Thespesin Natural products CC(C)c1c(O)c(O)c2C(O)Oc3c(c(C)cc1c23)-c1c2OC(O)c3c(O)c(O)c(C(C)C)c(cc1C)c23 QHOPXUFELLHKAS-UHFFFAOYSA-N 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 108010078233 Thymalfasin Proteins 0.000 description 1
- 102400000800 Thymosin alpha-1 Human genes 0.000 description 1
- 201000002015 Thyroid Crisis Diseases 0.000 description 1
- 206010043786 Thyrotoxic crisis Diseases 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 239000003819 Toceranib Substances 0.000 description 1
- IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 1
- 206010048873 Traumatic arthritis Diseases 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 108010050144 Triptorelin Pamoate Proteins 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 201000005969 Uveal melanoma Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 201000003761 Vaginal carcinoma Diseases 0.000 description 1
- 206010047112 Vasculitides Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- ZVNYJIZDIRKMBF-UHFFFAOYSA-N Vesnarinone Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)N1CCN(C=2C=C3CCC(=O)NC3=CC=2)CC1 ZVNYJIZDIRKMBF-UHFFFAOYSA-N 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
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L Zinc chloride Inorganic materials [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
- ATGDEBVDBLZOCB-SSDOTTSWSA-N [(2R)-1-[(2,6-dichloropyridin-3-yl)amino]-1-oxopropan-2-yl] N-tert-butylcarbamate Chemical compound C(C)(C)(C)NC(O[C@@H](C(=O)NC=1C(=NC(=CC=1)Cl)Cl)C)=O ATGDEBVDBLZOCB-SSDOTTSWSA-N 0.000 description 1
- XJXKGUZINMNEDK-GPJOBVNKSA-L [(4r,5r)-5-(aminomethyl)-2-propan-2-yl-1,3-dioxolan-4-yl]methanamine;platinum(2+);propanedioate Chemical compound [Pt+2].[O-]C(=O)CC([O-])=O.CC(C)C1O[C@H](CN)[C@@H](CN)O1 XJXKGUZINMNEDK-GPJOBVNKSA-L 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- IBXPAFBDJCXCDW-MHFPCNPESA-A [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].Cc1cn([C@H]2C[C@H](O)[C@@H](COP([S-])(=O)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3CO)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3cnc4c3nc(N)[nH]c4=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].Cc1cn([C@H]2C[C@H](O)[C@@H](COP([S-])(=O)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3CO)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3cnc4c3nc(N)[nH]c4=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O IBXPAFBDJCXCDW-MHFPCNPESA-A 0.000 description 1
- UVIQSJCZCSLXRZ-UBUQANBQSA-N abiraterone acetate Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CC[C@@H](CC4=CC[C@H]31)OC(=O)C)C=C2C1=CC=CN=C1 UVIQSJCZCSLXRZ-UBUQANBQSA-N 0.000 description 1
- 229960004103 abiraterone acetate Drugs 0.000 description 1
- 229940028652 abraxane Drugs 0.000 description 1
- HPPONSCISKROOD-OYLNGHKZSA-N acetic acid;(2s)-n-[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2r)-1-[[(2s)-1-[[(2s)-1-[(2s)-2-[(2-amino-2-oxoethyl)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1h-indol-3-yl)-1-oxopropan-2-y Chemical compound CC(O)=O.C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 HPPONSCISKROOD-OYLNGHKZSA-N 0.000 description 1
- MGVGMXLGOKTYKP-ZFOBEOMCSA-N acetic acid;(6s,8s,9s,10r,11s,13s,14s,17r)-11,17-dihydroxy-17-(2-hydroxyacetyl)-6,10,13-trimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-3-one Chemical compound CC(O)=O.C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)CO)CC[C@H]21 MGVGMXLGOKTYKP-ZFOBEOMCSA-N 0.000 description 1
- 108010052004 acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide Proteins 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 229940099550 actimmune Drugs 0.000 description 1
- 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 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 231100000354 acute hepatitis Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 210000000593 adipose tissue white Anatomy 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229960001686 afatinib Drugs 0.000 description 1
- ULXXDDBFHOBEHA-CWDCEQMOSA-N afatinib Chemical compound N1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-CWDCEQMOSA-N 0.000 description 1
- 229940042992 afinitor Drugs 0.000 description 1
- 229960002833 aflibercept Drugs 0.000 description 1
- 108010081667 aflibercept Proteins 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 108700025316 aldesleukin Proteins 0.000 description 1
- 229960005310 aldesleukin Drugs 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 229960004343 alendronic acid Drugs 0.000 description 1
- 229960001445 alitretinoin Drugs 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229960003459 allopurinol Drugs 0.000 description 1
- 208000004631 alopecia areata Diseases 0.000 description 1
- 229940062334 aloprim Drugs 0.000 description 1
- 229940014175 aloxi Drugs 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229960001097 amifostine Drugs 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 150000003927 aminopyridines Chemical class 0.000 description 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 1
- 229960002550 amrubicin Drugs 0.000 description 1
- VJZITPJGSQKZMX-XDPRQOKASA-N amrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC=C4C(=O)C=3C(O)=C21)(N)C(=O)C)[C@H]1C[C@H](O)[C@H](O)CO1 VJZITPJGSQKZMX-XDPRQOKASA-N 0.000 description 1
- 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
- 201000007538 anal carcinoma Diseases 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 238000011122 anti-angiogenic therapy Methods 0.000 description 1
- 230000003388 anti-hormonal effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229960003982 apatinib Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229940115115 aranesp Drugs 0.000 description 1
- 229940087620 aromasin Drugs 0.000 description 1
- 238000007080 aromatic substitution reaction Methods 0.000 description 1
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- GJMNAFGEUJBOCE-MEQIQULJSA-N asoprisnil Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@]([C@]3(C2)C)(COC)OC)=CC=C(\C=N\O)C=C1 GJMNAFGEUJBOCE-MEQIQULJSA-N 0.000 description 1
- 229950003620 asoprisnil Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 229950010993 atrasentan Drugs 0.000 description 1
- MOTJMGVDPWRKOC-QPVYNBJUSA-N atrasentan Chemical compound C1([C@H]2[C@@H]([C@H](CN2CC(=O)N(CCCC)CCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 MOTJMGVDPWRKOC-QPVYNBJUSA-N 0.000 description 1
- 239000005441 aurora Substances 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 229940120638 avastin Drugs 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- KLNFSAOEKUDMFA-UHFFFAOYSA-N azanide;2-hydroxyacetic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OCC(O)=O KLNFSAOEKUDMFA-UHFFFAOYSA-N 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 125000000656 azaniumyl group Chemical group [H][N+]([H])([H])[*] 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 125000003725 azepanyl group Chemical group 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 208000002479 balanitis Diseases 0.000 description 1
- 229960002707 bendamustine Drugs 0.000 description 1
- YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001559 benzoic acids Chemical class 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 229960004648 betamethasone acetate Drugs 0.000 description 1
- AKUJBENLRBOFTD-QZIXMDIESA-N betamethasone acetate 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)COC(C)=O)(O)[C@@]1(C)C[C@@H]2O AKUJBENLRBOFTD-QZIXMDIESA-N 0.000 description 1
- PLCQGRYPOISRTQ-LWCNAHDDSA-L betamethasone sodium phosphate Chemical compound [Na+].[Na+].C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COP([O-])([O-])=O)(O)[C@@]1(C)C[C@@H]2O PLCQGRYPOISRTQ-LWCNAHDDSA-L 0.000 description 1
- 229960005354 betamethasone sodium phosphate Drugs 0.000 description 1
- 229960002938 bexarotene Drugs 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 229960004395 bleomycin sulfate Drugs 0.000 description 1
- 208000010217 blepharitis Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000003914 blood derivative Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229960001467 bortezomib Drugs 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
- 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
- KXVUSQIDCZRUKF-UHFFFAOYSA-N bromocyclobutane Chemical compound BrC1CCC1 KXVUSQIDCZRUKF-UHFFFAOYSA-N 0.000 description 1
- 229940125763 bromodomain inhibitor Drugs 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 229950004398 broxuridine Drugs 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- BMQGVNUXMIRLCK-OAGWZNDDSA-N cabazitaxel Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3C[C@@H]([C@]2(C(=O)[C@H](OC)C2=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=3C=CC=CC=3)C[C@]1(O)C2(C)C)C)OC)C(=O)C1=CC=CC=C1 BMQGVNUXMIRLCK-OAGWZNDDSA-N 0.000 description 1
- 229960001573 cabazitaxel Drugs 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 1
- KVUAALJSMIVURS-ZEDZUCNESA-L calcium folinate Chemical compound [Ca+2].C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)C=C1 KVUAALJSMIVURS-ZEDZUCNESA-L 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 229940112129 campath Drugs 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
- 230000005907 cancer growth Effects 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- BLMPQMFVWMYDKT-NZTKNTHTSA-N carfilzomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)[C@]1(C)OC1)NC(=O)CN1CCOCC1)CC1=CC=CC=C1 BLMPQMFVWMYDKT-NZTKNTHTSA-N 0.000 description 1
- 229960002438 carfilzomib Drugs 0.000 description 1
- 108010021331 carfilzomib Proteins 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229940097647 casodex Drugs 0.000 description 1
- 229960000419 catumaxomab Drugs 0.000 description 1
- 229940047495 celebrex 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
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 229950001357 celmoleukin Drugs 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 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
- 229960004630 chlorambucil Drugs 0.000 description 1
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960002286 clodronic acid Drugs 0.000 description 1
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 1
- 229960000928 clofarabine Drugs 0.000 description 1
- WDDPHFBMKLOVOX-AYQXTPAHSA-N clofarabine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1F WDDPHFBMKLOVOX-AYQXTPAHSA-N 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- SBRXTSOCZITGQG-UHFFFAOYSA-N crisnatol Chemical compound C1=CC=C2C(CNC(CO)(CO)C)=CC3=C(C=CC=C4)C4=CC=C3C2=C1 SBRXTSOCZITGQG-UHFFFAOYSA-N 0.000 description 1
- 229950007258 crisnatol Drugs 0.000 description 1
- 229960005061 crizotinib Drugs 0.000 description 1
- KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 description 1
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
- 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 description 1
- 125000004144 cyclobuten-1-yl group Chemical group [H]C1=C(*)C([H])([H])C1([H])[H] 0.000 description 1
- CGZZMOTZOONQIA-UHFFFAOYSA-N cycloheptanone Chemical compound O=C1CCCCCC1 CGZZMOTZOONQIA-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 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
- 125000004145 cyclopenten-1-yl group Chemical group [H]C1=C(*)C([H])([H])C([H])([H])C1([H])[H] 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
- 229960000978 cyproterone acetate Drugs 0.000 description 1
- UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 229960002448 dasatinib Drugs 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 229940107841 daunoxome Drugs 0.000 description 1
- 229940026692 decadron Drugs 0.000 description 1
- 229960003603 decitabine Drugs 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 229960002272 degarelix Drugs 0.000 description 1
- MEUCPCLKGZSHTA-XYAYPHGZSA-N degarelix Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CC=1C=CC(NC(=O)[C@H]2NC(=O)NC(=O)C2)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(NC(N)=O)C=C1 MEUCPCLKGZSHTA-XYAYPHGZSA-N 0.000 description 1
- 229940005558 delestrogen Drugs 0.000 description 1
- 108010017271 denileukin diftitox Proteins 0.000 description 1
- 229960002923 denileukin diftitox Drugs 0.000 description 1
- 229960001251 denosumab Drugs 0.000 description 1
- 229940003382 depo-medrol Drugs 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 229960005408 deslorelin Drugs 0.000 description 1
- 108700025485 deslorelin Proteins 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- PLCQGRYPOISRTQ-FCJDYXGNSA-L dexamethasone sodium phosphate Chemical compound [Na+].[Na+].C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COP([O-])([O-])=O)(O)[C@@]1(C)C[C@@H]2O PLCQGRYPOISRTQ-FCJDYXGNSA-L 0.000 description 1
- LRCZQSDQZJBHAF-PUBGEWHCSA-N dha-paclitaxel Chemical compound N([C@H]([C@@H](OC(=O)CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC)C(=O)O[C@@H]1C(=C2[C@@H](OC(C)=O)C(=O)[C@]3(C)[C@@H](O)C[C@H]4OC[C@]4([C@H]3[C@H](OC(=O)C=3C=CC=CC=3)[C@](C2(C)C)(O)C1)OC(C)=O)C)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1 LRCZQSDQZJBHAF-PUBGEWHCSA-N 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
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 1
- 229960000452 diethylstilbestrol Drugs 0.000 description 1
- 229940063123 diflucan Drugs 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- ZWAOHEXOSAUJHY-ZIYNGMLESA-N doxifluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZWAOHEXOSAUJHY-ZIYNGMLESA-N 0.000 description 1
- 229950005454 doxifluridine Drugs 0.000 description 1
- 229960004242 dronabinol Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- JWJOTENAMICLJG-QWBYCMEYSA-N dutasteride Chemical compound O=C([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)N[C@@H]4CC3)C)CC[C@@]21C)NC1=CC(C(F)(F)F)=CC=C1C(F)(F)F JWJOTENAMICLJG-QWBYCMEYSA-N 0.000 description 1
- 229960004199 dutasteride Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 229950001287 edotecarin Drugs 0.000 description 1
- 229960001776 edrecolomab Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 229960002759 eflornithine Drugs 0.000 description 1
- VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 description 1
- 229940053603 elitek Drugs 0.000 description 1
- 229940087477 ellence Drugs 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 229940108890 emend Drugs 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 229960004671 enzalutamide Drugs 0.000 description 1
- WXCXUHSOUPDCQV-UHFFFAOYSA-N enzalutamide Chemical compound C1=C(F)C(C(=O)NC)=CC=C1N1C(C)(C)C(=O)N(C=2C=C(C(C#N)=CC=2)C(F)(F)F)C1=S WXCXUHSOUPDCQV-UHFFFAOYSA-N 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 201000009458 epididymis cancer Diseases 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 229960003388 epoetin alfa Drugs 0.000 description 1
- 229940089118 epogen Drugs 0.000 description 1
- 229930013356 epothilone Natural products 0.000 description 1
- 150000003883 epothilone derivatives Chemical class 0.000 description 1
- 229950006835 eptaplatin Drugs 0.000 description 1
- 229960001433 erlotinib Drugs 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 229940064258 estrace Drugs 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- IIUMCNJTGSMNRO-VVSKJQCTSA-L estramustine sodium phosphate Chemical compound [Na+].[Na+].ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)OP([O-])([O-])=O)[C@@H]4[C@@H]3CCC2=C1 IIUMCNJTGSMNRO-VVSKJQCTSA-L 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- VUCAHVBMSFIGAI-ZFINNJDLSA-M estrone sodium sulfate Chemical compound [Na+].[O-]S(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 VUCAHVBMSFIGAI-ZFINNJDLSA-M 0.000 description 1
- 229960002568 ethinylestradiol Drugs 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- 229940098617 ethyol Drugs 0.000 description 1
- 229940009626 etidronate Drugs 0.000 description 1
- 229960004585 etidronic acid Drugs 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 229960000752 etoposide phosphate Drugs 0.000 description 1
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=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 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 1
- 229960005167 everolimus Drugs 0.000 description 1
- 229950009429 exatecan Drugs 0.000 description 1
- ZVYVPGLRVWUPMP-FYSMJZIKSA-N exatecan Chemical compound C1C[C@H](N)C2=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC3=CC(F)=C(C)C1=C32 ZVYVPGLRVWUPMP-FYSMJZIKSA-N 0.000 description 1
- 229960000255 exemestane Drugs 0.000 description 1
- 201000008815 extraosseous osteosarcoma Diseases 0.000 description 1
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 229950011548 fadrozole Drugs 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229950003662 fenretinide Drugs 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 229960004177 filgrastim Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
- 229960004039 finasteride Drugs 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229960000961 floxuridine Drugs 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 229960004884 fluconazole Drugs 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000008191 folinic acid Nutrition 0.000 description 1
- 239000011672 folinic acid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229960002258 fulvestrant Drugs 0.000 description 1
- 150000002238 fumaric acids Chemical class 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 201000010175 gallbladder cancer Diseases 0.000 description 1
- 201000007487 gallbladder carcinoma Diseases 0.000 description 1
- 229940009600 gammagard Drugs 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
- 229960002584 gefitinib Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 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 1
- 229940080856 gleevec Drugs 0.000 description 1
- 229940084910 gliadel Drugs 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229960002913 goserelin Drugs 0.000 description 1
- 229950005277 gossypol Drugs 0.000 description 1
- 229930000755 gossypol Natural products 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 229960003607 granisetron hydrochloride Drugs 0.000 description 1
- 230000009643 growth defect Effects 0.000 description 1
- 210000002768 hair cell Anatomy 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960004931 histamine dihydrochloride Drugs 0.000 description 1
- PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 description 1
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 1
- 229960002193 histrelin Drugs 0.000 description 1
- HHXHVIJIIXKSOE-QILQGKCVSA-N histrelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC(N=C1)=CN1CC1=CC=CC=C1 HHXHVIJIIXKSOE-QILQGKCVSA-N 0.000 description 1
- 108700020746 histrelin Proteins 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229940088013 hycamtin Drugs 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QYZRTBKYBJRGJB-UHFFFAOYSA-N hydron;1-methyl-n-(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)indazole-3-carboxamide;chloride Chemical compound Cl.C1=CC=C2C(C(=O)NC3CC4CCCC(C3)N4C)=NN(C)C2=C1 QYZRTBKYBJRGJB-UHFFFAOYSA-N 0.000 description 1
- 229950000801 hydroxyprogesterone caproate Drugs 0.000 description 1
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 229960005236 ibandronic acid Drugs 0.000 description 1
- 229960001001 ibritumomab tiuxetan Drugs 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229960002411 imatinib Drugs 0.000 description 1
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 201000004653 inflammatory breast carcinoma Diseases 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 229950002133 iniparib Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000001023 inorganic pigment Substances 0.000 description 1
- 108010042414 interferon gamma-1b Proteins 0.000 description 1
- 229960001388 interferon-beta Drugs 0.000 description 1
- 229940065638 intron a Drugs 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229960005386 ipilimumab Drugs 0.000 description 1
- 229940084651 iressa Drugs 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 1
- 201000004614 iritis Diseases 0.000 description 1
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 1
- 235000013980 iron oxide Nutrition 0.000 description 1
- VBMVTYDPPZVILR-UHFFFAOYSA-N iron(2+);oxygen(2-) Chemical class [O-2].[Fe+2] VBMVTYDPPZVILR-UHFFFAOYSA-N 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 229960005280 isotretinoin 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
- 210000001117 keloid Anatomy 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 210000000244 kidney pelvis Anatomy 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960002437 lanreotide Drugs 0.000 description 1
- 108010021336 lanreotide Proteins 0.000 description 1
- 229960004891 lapatinib Drugs 0.000 description 1
- 201000005264 laryngeal carcinoma Diseases 0.000 description 1
- 229960002367 lasofoxifene Drugs 0.000 description 1
- GXESHMAMLJKROZ-IAPPQJPRSA-N lasofoxifene Chemical compound C1([C@@H]2[C@@H](C3=CC=C(C=C3CC2)O)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 GXESHMAMLJKROZ-IAPPQJPRSA-N 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 229940115286 lentinan Drugs 0.000 description 1
- 229950001845 lestaurtinib Drugs 0.000 description 1
- 229960003881 letrozole Drugs 0.000 description 1
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
- 229960001691 leucovorin Drugs 0.000 description 1
- 229960001614 levamisole Drugs 0.000 description 1
- 229940080161 levothroid Drugs 0.000 description 1
- 229940080162 levoxyl Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- DHMTURDWPRKSOA-RUZDIDTESA-N lonafarnib Chemical compound C1CN(C(=O)N)CCC1CC(=O)N1CCC([C@@H]2C3=C(Br)C=C(Cl)C=C3CCC3=CC(Br)=CN=C32)CC1 DHMTURDWPRKSOA-RUZDIDTESA-N 0.000 description 1
- 229950001750 lonafarnib Drugs 0.000 description 1
- WDRYRZXSPDWGEB-UHFFFAOYSA-N lonidamine Chemical compound C12=CC=CC=C2C(C(=O)O)=NN1CC1=CC=C(Cl)C=C1Cl WDRYRZXSPDWGEB-UHFFFAOYSA-N 0.000 description 1
- 229960003538 lonidamine Drugs 0.000 description 1
- 239000006210 lotion Substances 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
- 108010078259 luprolide acetate gel depot Proteins 0.000 description 1
- 208000025036 lymphosarcoma Diseases 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 150000002689 maleic acids Chemical class 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229940099262 marinol Drugs 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 229960005321 mecobalamin Drugs 0.000 description 1
- 229960002985 medroxyprogesterone acetate Drugs 0.000 description 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 230000021121 meiosis Effects 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- 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 1
- 229940101513 menest Drugs 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 229960004635 mesna Drugs 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 238000006263 metalation reaction Methods 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- YUUAYBAIHCDHHD-UHFFFAOYSA-N methyl 5-aminolevulinate Chemical compound COC(=O)CCC(=O)CN YUUAYBAIHCDHHD-UHFFFAOYSA-N 0.000 description 1
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 description 1
- 235000007672 methylcobalamin Nutrition 0.000 description 1
- 239000011585 methylcobalamin Substances 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229960005225 mifamurtide Drugs 0.000 description 1
- JMUHBNWAORSSBD-WKYWBUFDSA-N mifamurtide Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCC)COP(O)(=O)OCCNC(=O)[C@H](C)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)OC(O)[C@@H]1NC(C)=O JMUHBNWAORSSBD-WKYWBUFDSA-N 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 229960003775 miltefosine Drugs 0.000 description 1
- PQLXHQMOHUQAKB-UHFFFAOYSA-N miltefosine Chemical compound CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C PQLXHQMOHUQAKB-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229960004023 minocycline Drugs 0.000 description 1
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 description 1
- VMMKGHQPQIEGSQ-UHFFFAOYSA-N minodronic acid Chemical compound C1=CC=CN2C(CC(O)(P(O)(O)=O)P(O)(O)=O)=CN=C21 VMMKGHQPQIEGSQ-UHFFFAOYSA-N 0.000 description 1
- 229950011129 minodronic acid Drugs 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 229960000350 mitotane Drugs 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- RDSACQWTXKSHJT-NSHDSACASA-N n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-[(2s)-2,3-dihydroxypropyl]cyclopropane-1-sulfonamide Chemical compound C1CC1(C[C@H](O)CO)S(=O)(=O)NC=1C(OC)=CC(F)=C(F)C=1NC1=CC=C(I)C=C1F RDSACQWTXKSHJT-NSHDSACASA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- WPEWQEMJFLWMLV-UHFFFAOYSA-N n-[4-(1-cyanocyclopentyl)phenyl]-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide Chemical compound C=1C=CN=C(NCC=2C=CN=CC=2)C=1C(=O)NC(C=C1)=CC=C1C1(C#N)CCCC1 WPEWQEMJFLWMLV-UHFFFAOYSA-N 0.000 description 1
- 229960002333 nafarelin Drugs 0.000 description 1
- RWHUEXWOYVBUCI-ITQXDASVSA-N nafarelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 RWHUEXWOYVBUCI-ITQXDASVSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 229950007221 nedaplatin Drugs 0.000 description 1
- 229960000801 nelarabine Drugs 0.000 description 1
- IXOXBSCIXZEQEQ-UHTZMRCNSA-N nelarabine Chemical compound C1=NC=2C(OC)=NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O IXOXBSCIXZEQEQ-UHTZMRCNSA-N 0.000 description 1
- CTMCWCONSULRHO-UHQPFXKFSA-N nemorubicin Chemical compound C1CO[C@H](OC)CN1[C@@H]1[C@H](O)[C@H](C)O[C@@H](O[C@@H]2C3=C(O)C=4C(=O)C5=C(OC)C=CC=C5C(=O)C=4C(O)=C3C[C@](O)(C2)C(=O)CO)C1 CTMCWCONSULRHO-UHQPFXKFSA-N 0.000 description 1
- 229950010159 nemorubicin Drugs 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 229950008835 neratinib Drugs 0.000 description 1
- JWNPDZNEKVCWMY-VQHVLOKHSA-N neratinib Chemical compound C=12C=C(NC(=O)\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 JWNPDZNEKVCWMY-VQHVLOKHSA-N 0.000 description 1
- 229940071846 neulasta Drugs 0.000 description 1
- 229940082926 neumega Drugs 0.000 description 1
- 229940029345 neupogen Drugs 0.000 description 1
- 201000011519 neuroendocrine tumor Diseases 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- 229960002653 nilutamide Drugs 0.000 description 1
- XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
- VFEDRRNHLBGPNN-UHFFFAOYSA-N nimustine Chemical compound CC1=NC=C(CNC(=O)N(CCCl)N=O)C(N)=N1 VFEDRRNHLBGPNN-UHFFFAOYSA-N 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- XHWRWCSCBDLOLM-UHFFFAOYSA-N nolatrexed Chemical compound CC1=CC=C2NC(N)=NC(=O)C2=C1SC1=CC=NC=C1 XHWRWCSCBDLOLM-UHFFFAOYSA-N 0.000 description 1
- 229950000891 nolatrexed Drugs 0.000 description 1
- 229940085033 nolvadex Drugs 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 229950006584 obatoclax Drugs 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 229960000435 oblimersen Drugs 0.000 description 1
- 229960002700 octreotide Drugs 0.000 description 1
- 201000002575 ocular melanoma Diseases 0.000 description 1
- 229960002450 ofatumumab Drugs 0.000 description 1
- FAQDUNYVKQKNLD-UHFFFAOYSA-N olaparib Chemical compound FC1=CC=C(CC2=C3[CH]C=CC=C3C(=O)N=N2)C=C1C(=O)N(CC1)CCN1C(=O)C1CC1 FAQDUNYVKQKNLD-UHFFFAOYSA-N 0.000 description 1
- 229960000572 olaparib Drugs 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 229960000770 ondansetron hydrochloride Drugs 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 108010046821 oprelvekin Proteins 0.000 description 1
- 229940003515 orapred Drugs 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 206010033072 otitis externa Diseases 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
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000000369 oxido group Chemical group [*]=O 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- OLDRWYVIKMSFFB-SSPJITILSA-N palonosetron hydrochloride Chemical compound Cl.C1N(CC2)CCC2[C@@H]1N1C(=O)C(C=CC=C2CCC3)=C2[C@H]3C1 OLDRWYVIKMSFFB-SSPJITILSA-N 0.000 description 1
- 229960003978 pamidronic acid Drugs 0.000 description 1
- 229960001972 panitumumab Drugs 0.000 description 1
- 210000002990 parathyroid gland Anatomy 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229960000639 pazopanib Drugs 0.000 description 1
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 1
- 229940097097 pediapred Drugs 0.000 description 1
- 229960001744 pegaspargase Drugs 0.000 description 1
- 108010001564 pegaspargase Proteins 0.000 description 1
- 229940002988 pegasys Drugs 0.000 description 1
- 108010044644 pegfilgrastim Proteins 0.000 description 1
- 108010092853 peginterferon alfa-2a Proteins 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 description 1
- 229960005079 pemetrexed Drugs 0.000 description 1
- 201000001976 pemphigus vulgaris Diseases 0.000 description 1
- 208000030940 penile carcinoma Diseases 0.000 description 1
- 201000008174 penis carcinoma Diseases 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960002340 pentostatin Drugs 0.000 description 1
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 229960002087 pertuzumab Drugs 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- RNAICSBVACLLGM-GNAZCLTHSA-N pilocarpine hydrochloride Chemical compound Cl.C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C RNAICSBVACLLGM-GNAZCLTHSA-N 0.000 description 1
- 229960002139 pilocarpine hydrochloride Drugs 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 229960001221 pirarubicin Drugs 0.000 description 1
- 206010035116 pityriasis rubra pilaris Diseases 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229960002169 plerixafor Drugs 0.000 description 1
- YIQPUIGJQJDJOS-UHFFFAOYSA-N plerixafor Chemical compound C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 YIQPUIGJQJDJOS-UHFFFAOYSA-N 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229960004293 porfimer sodium Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- HDMGAZBPFLDBCX-UHFFFAOYSA-N potassium;sulfooxy hydrogen sulfate Chemical compound [K+].OS(=O)(=O)OOS(O)(=O)=O HDMGAZBPFLDBCX-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 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
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 229940063238 premarin Drugs 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 229960000624 procarbazine 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
- 229940029359 procrit Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 229960001964 quazepam Drugs 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- FFRYUAVNPBUEIC-UHFFFAOYSA-N quinoxalin-2-ol Chemical class C1=CC=CC2=NC(O)=CN=C21 FFRYUAVNPBUEIC-UHFFFAOYSA-N 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 229940092814 radium (223ra) dichloride Drugs 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 229960004432 raltitrexed Drugs 0.000 description 1
- 108010084837 rasburicase Proteins 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 229940038850 rebif Drugs 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 description 1
- 108010091666 romidepsin Proteins 0.000 description 1
- 229960003452 romidepsin Drugs 0.000 description 1
- OHRURASPPZQGQM-UHFFFAOYSA-N romidepsin Natural products O1C(=O)C(C(C)C)NC(=O)C(=CC)NC(=O)C2CSSCCC=CC1CC(=O)NC(C(C)C)C(=O)N2 OHRURASPPZQGQM-UHFFFAOYSA-N 0.000 description 1
- 229950003733 romurtide Drugs 0.000 description 1
- 108700033545 romurtide Proteins 0.000 description 1
- 201000004700 rosacea Diseases 0.000 description 1
- 229960000215 ruxolitinib Drugs 0.000 description 1
- HFNKQEVNSGCOJV-OAHLLOKOSA-N ruxolitinib Chemical compound C1([C@@H](CC#N)N2N=CC(=C2)C=2C=3C=CNC=3N=CN=2)CCCC1 HFNKQEVNSGCOJV-OAHLLOKOSA-N 0.000 description 1
- 229940063635 salagen Drugs 0.000 description 1
- 229960001548 salinomycin Drugs 0.000 description 1
- 235000019378 salinomycin Nutrition 0.000 description 1
- 201000003804 salivary gland carcinoma Diseases 0.000 description 1
- 229940072272 sandostatin Drugs 0.000 description 1
- 108010038379 sargramostim Proteins 0.000 description 1
- 229960002530 sargramostim Drugs 0.000 description 1
- 229960005399 satraplatin Drugs 0.000 description 1
- 190014017285 satraplatin Chemical compound 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 208000008742 seborrheic dermatitis Diseases 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229950009921 seocalcitol Drugs 0.000 description 1
- LVLLALCJVJNGQQ-ZCPUWASBSA-N seocalcitol Chemical compound C1(/[C@H]2CC[C@@H]([C@@]2(CCC1)C)[C@H](C)/C=C/C=C/C(O)(CC)CC)=C/C=C1/C[C@H](O)C[C@@H](O)C1=C LVLLALCJVJNGQQ-ZCPUWASBSA-N 0.000 description 1
- 108700022137 serine(71)- interleukin-1 beta Proteins 0.000 description 1
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 229960000714 sipuleucel-t Drugs 0.000 description 1
- 229950001403 sizofiran Drugs 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229940083575 sodium dodecyl sulfate Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- UWPXRVDIKGZQQW-UHFFFAOYSA-N sodium;(3-fluoro-4-methoxyphenyl)-(2,3,4,5,6-pentafluorophenyl)sulfonylazanide Chemical compound [Na+].C1=C(F)C(OC)=CC=C1[N-]S(=O)(=O)C1=C(F)C(F)=C(F)C(F)=C1F UWPXRVDIKGZQQW-UHFFFAOYSA-N 0.000 description 1
- 229940087854 solu-medrol Drugs 0.000 description 1
- 230000021595 spermatogenesis Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 229940084642 strontium-89 chloride Drugs 0.000 description 1
- AHBGXTDRMVNFER-FCHARDOESA-L strontium-89(2+);dichloride Chemical compound [Cl-].[Cl-].[89Sr+2] AHBGXTDRMVNFER-FCHARDOESA-L 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 229940099268 synthroid Drugs 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229960002613 tamsulosin Drugs 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
- 229960003102 tasonermin Drugs 0.000 description 1
- 229950001699 teceleukin Drugs 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
- 206010043207 temporal arteritis Diseases 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
- 229960001278 teniposide Drugs 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229960001712 testosterone propionate Drugs 0.000 description 1
- 229940085503 testred Drugs 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 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
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 1
- 229960004231 thymalfasin Drugs 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 229960000874 thyrotropin Drugs 0.000 description 1
- 230000001748 thyrotropin Effects 0.000 description 1
- 229940111100 tice bcg Drugs 0.000 description 1
- 229960005324 tiludronic acid Drugs 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 1
- PLHJCIYEEKOWNM-HHHXNRCGSA-N tipifarnib Chemical compound CN1C=NC=C1[C@](N)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)N(C)C2=CC=1)C1=CC=C(Cl)C=C1 PLHJCIYEEKOWNM-HHHXNRCGSA-N 0.000 description 1
- 229950009158 tipifarnib Drugs 0.000 description 1
- 229950002376 tirapazamine Drugs 0.000 description 1
- QVMPZNRFXAKISM-UHFFFAOYSA-N tirapazamine Chemical compound C1=CC=C2[N+]([O-])=NC(=N)N(O)C2=C1 QVMPZNRFXAKISM-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229960005048 toceranib Drugs 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
- 229960005267 tositumomab Drugs 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 229940111528 trexall Drugs 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 229960004319 trichloroacetic acid Drugs 0.000 description 1
- GQHWSLKNULCZGI-UHFFFAOYSA-N trifluoromethoxybenzene Chemical compound FC(F)(F)OC1=CC=CC=C1 GQHWSLKNULCZGI-UHFFFAOYSA-N 0.000 description 1
- KVJXBPDAXMEYOA-CXANFOAXSA-N trilostane Chemical compound OC1=C(C#N)C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@@]32O[C@@H]31 KVJXBPDAXMEYOA-CXANFOAXSA-N 0.000 description 1
- 229960001670 trilostane Drugs 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- 229960000434 triptorelin acetate Drugs 0.000 description 1
- 229960000294 triptorelin pamoate Drugs 0.000 description 1
- 150000004043 trisaccharides Chemical class 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229960000875 trofosfamide Drugs 0.000 description 1
- UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 229950009811 ubenimex Drugs 0.000 description 1
- KIGCDEJCMKDBHU-NIQQUOCOSA-K ukrain Chemical compound [OH-].[OH-].[OH-].C([C@H](O)[C@@H]1C2=CC=C3OCOC3=C2C2)C3=CC=4OCOC=4C=C3[C@H]1[N+]2(C)CCNP(=S)(NCC[N+]1(C)[C@@H]2C3=CC=4OCOC=4C=C3C[C@H](O)[C@@H]2C2=CC=C3OCOC3=C2C1)NCC[N+]1(C)[C@@H]2C3=CC(OCO4)=C4C=C3C[C@H](O)[C@@H]2C2=CC=C3OCOC3=C2C1 KIGCDEJCMKDBHU-NIQQUOCOSA-K 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- AUFUWRKPQLGTGF-FMKGYKFTSA-N uridine triacetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1N1C(=O)NC(=O)C=C1 AUFUWRKPQLGTGF-FMKGYKFTSA-N 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 229960000653 valrubicin Drugs 0.000 description 1
- ZOCKGBMQLCSHFP-KQRAQHLDSA-N valrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)CCCC)[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1 ZOCKGBMQLCSHFP-KQRAQHLDSA-N 0.000 description 1
- 229950010938 valspodar Drugs 0.000 description 1
- 108010082372 valspodar Proteins 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 229960000241 vandetanib Drugs 0.000 description 1
- UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 description 1
- 229960002730 vapreotide Drugs 0.000 description 1
- 108700029852 vapreotide Proteins 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 229950000578 vatalanib Drugs 0.000 description 1
- YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 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
- 229960003895 verteporfin Drugs 0.000 description 1
- 229950005577 vesnarinone Drugs 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-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
- 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
- 229960004355 vindesine 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
- 229960002066 vinorelbine Drugs 0.000 description 1
- 229960004449 vismodegib Drugs 0.000 description 1
- BPQMGSKTAYIVFO-UHFFFAOYSA-N vismodegib Chemical compound ClC1=CC(S(=O)(=O)C)=CC=C1C(=O)NC1=CC=C(Cl)C(C=2N=CC=CC=2)=C1 BPQMGSKTAYIVFO-UHFFFAOYSA-N 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 208000002003 vulvitis Diseases 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229940053867 xeloda Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- FYQZGCBXYVWXSP-STTFAQHVSA-N zinostatin stimalamer Chemical compound O1[C@H](C)[C@H](O)[C@H](O)[C@@H](NC)[C@H]1OC1C/2=C/C#C[C@H]3O[C@@]3([C@H]3OC(=O)OC3)C#CC\2=C[C@H]1OC(=O)C1=C(C)C=CC2=C(C)C=C(OC)C=C12 FYQZGCBXYVWXSP-STTFAQHVSA-N 0.000 description 1
- 229950009233 zinostatin stimalamer Drugs 0.000 description 1
- 229940072018 zofran Drugs 0.000 description 1
- 229960004276 zoledronic acid Drugs 0.000 description 1
- ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Definitions
- the present invention relates to BET protein-inhibiting, in particular BRD4-inhibitory 3,4-dihydropyrido [2,3-b] pyrazinones with meto-substituted aromatic amino or
- Ether group pharmaceutical agents containing the compounds of the invention and their prophylactic and therapeutic use in hyper-proliferative diseases, especially in tumor diseases. Furthermore, this invention relates to the use of BET protein inhibitors in viral infections, in neurodegenerative diseases, in inflammatory diseases, in atherosclerotic diseases and in male fertility control.
- the human BET family (bromodomain and extra C-terminal domain family) has four members (BRD2, BRD3, BRD4 and BRDT) containing two related bromodomains and one extra-terminal domain (Wu and Chiang, J. Biol. Chem., 2007 , 282: 13141-13145).
- the bromodomains are protein regions that recognize acetylated lysine residues. Such acetylated lysines are often found at the N-terminal end of histones (eg, histone H3 or histone H4) and are features for open chromatin structure and active gene transcription (Kuo and Allis, Bioessays, 1998, 20: 615-626 ).
- bromodomains can recognize additional acetylated proteins.
- BRD4 binds to RelA, resulting in the stimulation of NF- ⁇ B and transcriptional activity of inflammatory genes (Huang et al., Mol. Cell. Biol., 2009, 29: 1375-1387).
- BRD4 also binds to cyclin Tl and forms an active complex important for transcription elongation (Schröder et al., J. Biol. Chem., 2012, 287: 1090-1099).
- the extra-terminal domain of BRD2, BRD3 and BRD4 interacts with several proteins that have a role in chromatin modulation and regulation of gene expression (Rahman et al., Mol. Cell Biol., 2011, 31: 2641-2652).
- BET proteins play an important role in cell growth and cell cycle. Biol. Cell, 2009, 20: 4899-4909; Yang et al., Mol. Cell. Biol., 2008, 28: 967-976).
- a role of BRD4 in the post-mitotic reactivation of gene transcription has been demonstrated (Zhao et al., Nat Cell Biol., 2011, 13: 1295-1304).
- BRD4 is essential for transcription elongation and recruits the elongation complex P-TEFb, which consists of CDK9 and cyclin Tl, resulting in the activation of RNA polymerase II (Yang et al., Mol. Cell, 2005, 19: 535-545; Schröder et al., J.
- BRD2 is involved in the regulation of androgen receptor target genes (Draker et al., PLOS Genetics, 2012, 8, el003047). BRD2 and BRD3 bind to transcribed genes in hyperacetylated chromatin regions and promote transcription by RNA polymerase II (LeRoy et al., Mol. Cell, 2008, 30: 51-60).
- BRD4 Knockdown of BRD4 or inhibition of interaction with acetylated histones in various cell lines results in a Gl residue (Mochizuki et al., J. Biol. Chem., 2008, 283: 9040-9048, Mertz et al. Proc Natl Acad., USA, 2011, 108: 16669-16674). It has also been shown that BRD4 binds to promoter regions of several genes activated in the Gl phase, such as cyclin D1 and D2 (Mochizuki et al., J. Biol. Chem., 2008, 283: 9040-9048 ).
- BRD2 and BRD4 knockout mice die prematurely during embryogenesis (Gyuris et al., Biochim Biophys Acta, 2009, 1789: 413-421, Houzelstein et al., Mol. Cell Biol., 2002, 22: 3794-3802 ).
- Heterozygous BRD4 mice have various growth defects attributable to reduced cell proliferation (Houzelstein et al., Mol. Cell. Biol., 2002, 22: 3794-3802).
- BET proteins play an important role in various tumor types.
- the fusion between the BET proteins BRD3 or BRD4 and NUT results in an aggressive form of squamous cell carcinoma called NUT midline carcinoma (French, Cancer Genet, Cytogenet., 2010, 203: 16 -20).
- the fusion protein prevents cell differentiation and promotes proliferation (Yan et al., J. Biol. Chem., 2011, 286: 27663-27675).
- the growth of derived in vivo models is inhibited by a BRD4 inhibitor (Filippakopoulos et al., Nature, 2010, 468: 1067-1073).
- BRD4 plays an important role in this tumor (Zuber et al., Nature, 2011, 478, 524-528). Reduction of BRD4 expression leads to selective cell cycle arrest and apoptosis. Treatment with a BRD4 inhibitor prevents the proliferation of an AML xenograft in vivo. Further experiments with a BRD4 inhibitor show that BRD4 plays a role in various hematological tumors, such as multiple myeloma (Delmore et al., Cell, 2011, 146, 904-917) and Burkitt's Lymphoma (Mertz et al. Proc. Natl.
- BRD4 also plays an important role in solid tumors, such as lung cancer (Lockwood et al., Proc Natl. Acad., USA, 2012, 109, 19408-19413). Increased expression of BRD4 was detected in multiple myeloma, as well as one
- Amplification of the BRD4 gene has been found in patients with multiple myeloma (Delmore et al., Cell, 2011, 146, 904-917). Amplification of the DNA region containing the BRD4 gene has been detected in primary breast tumors (Kadota et al., Cancer Res, 2009, 69: 7357-7365). Also for BRD2 there is data related to a role in tumors. A transgenic mouse that BRD2, selectively expressed in B cells, develops B-cell lymphomas and leukemias (Greenwall et al., Blood, 2005, 103: 1475-1484).
- BET proteins are also involved in viral infections.
- BRD4 binds to the E2 protein of various papillomaviruses and is important for survival of the viruses in latently infected cells (Wu et al., Genes Dev., 2006, 20: 2383-2396; Vosa et al., J. Viral., 2006 , 80: 8909-8919).
- the herpesvirus responsible for Kaposi's sarcoma interacts with various BET proteins, which is important for disease resistance (Viejo-Borbolla et al., J. Viral., 2005, 79: 13618-13629, You et al , J. Viral., 2006, 80: 8909-8919).
- BRD4 By binding to P-TEFb, BRD4 also plays an important role in the replication of HIV-1 (Bisgrove et al., Proc Natl Acad., USA, 2007, 104: 13690-13695).
- Treatment with a BRD4 inhibitor stimulates the dormant, untreatable reservoir of HIV-1 virus in T cells (Banerjee et al., J. Leukoc, Biol., 2012, 92, 1147-1154). This reactivation could allow new therapeutic routes to AIDS treatment (Zinchenko et al., J. Leukoc Biol., 2012, 92, 1127-1129).
- a critical role of BRD4 in DNA replication of polyomaviruses has also been reported (Wang et al., PLoS Pathog., 2012, 8, doi: 10.1371).
- BET proteins are also involved in inflammatory processes.
- BRD2-hypomorphic mice show reduced inflammation in adipose tissue (Wang et al., Biochem J., 2009, 425: 71-83).
- the infiltration of macrophages into white adipose tissue is also reduced in BRD2-deficient mice (Wang et al., Biochem J., 2009, 425: 71-83).
- BRD4 regulates a number of genes involved in inflammation.
- Macrophages prevent a BRD4 inhibitor from expression of inflammatory genes, such as IL-1 or IL-6 (Nicodeme et al., Nature, 2010, 468: 1119-1123).
- BET proteins are also involved in the regulation of the ApoAl gene (Mirguet et al., Bioorg. Med. Chem. Lett., 2012, 22: 2963-2967).
- the corresponding protein is part of the
- HDL Higher density lipoprotein
- BET protein inhibitors may increase the levels of cholesterol HDL and thus potentially be useful for the treatment of atherosclerosis (Mirgu et al., Bioorg. Med. Chem. Lett., 2012, 22: 2963-2967 ).
- the BET protein BRDT plays an essential role in spermatogenesis through the
- BRDT is involved in the post-meiotic organization of chromatin (Dhar et al., J. Biol. Chem., 2012, 287: 6387-6405).
- In vivo experiments in mice show that treatment with a BET inhibitor that also inhibits BRDT results in a decrease in sperm production and infertility (Matzuk et al., Cell, 2012, 150: 673-684).
- the compounds of the invention in viral infections, in neurodegenerative diseases, in inflammatory diseases, in atherosclerotic diseases and in male fertility control are used.
- BRD4 inhibitors were diazepines. So z. B. phenyl-thieno-triazolo-1,4-diazepines (4-phenyl-6-thieno [3,2- [1,2,4] triazolo [4,3-a] [1,4] diazepines) in
- WO2011 / 143669 (Dana Farber Cancer Institute). Replacement of the thieno by a benzo moiety also results in active inhibitors (J. Med. Chem., 2011, 54, 3827-3838, E. Nicodeme et al., Nature 2010, 468, 1119). Further 4-phenyl-6-thieno [3,2-
- This application relates to 6-substituted 4i7-isoxazolo [5,4-cf] [2] benzazepines and 4i7-isoxazolo [3,4-cf] [2] benzazepines, including those compounds which have optionally substituted phenyl at position 6 and also analogs with alternatives heterocyclic fusion partners instead of the benzo unit, such as thieno or Pyridoazepine.
- Another structural class of BRD4 inhibitors is described as 7-isoxazoloquinolines and related quinolone derivatives (Bioorganic & Medicinal Chemistry Letters 22 (2012) 2963-2967).
- WO2011 / 054845 GaxoSmithKline
- further benzodiazepines are described as BRD4 inhibitors.
- BRD4 inhibitors are also described in the following applications: WO2013 / 030150 - 6H-thieno [3,2-f] [l, 2,4] triazolo [4,3-a] [4,3-a ] [l, 4] diazepines,
- Applicant's application WO 2015/011084 discloses dihydropyridopyazinone derivatives as dual inhibitors of BRD4 and polo-like kinase-1 (PLK-1). In contrast, the compounds according to the invention are substituted 3,4-
- Dihydropyrido [2,3-b] pyrazine-2 (1H) -one derivatives having a meto-substituted aromatic amino or ether group which differ structurally in a variety of forms from the chemotypes of BRD4 inhibitors discussed above. Due to the significant structural differences, it was not to be assumed that the compounds claimed here are also BRD4-inhibitory. It is therefore surprising that the compounds according to the invention have a good inhibitory effect despite the considerable structural differences. Some writings contain structurally similar, but to completely different mechanisms of action and partly also other indications directed connections. Dihydropyridopyrazinones and related bicyclic systems are described in a number of patent applications.
- WO 2013/071217 discloses above all 7,8-dihydropteridin-6 (5H) -one, but also l, 4-dihydropyrido [3,4-b] pyrazine-3 (2H) -one derivatives as inhibitors of kinases, in particular of RSK-1 and RSK-2, as medicaments, inter alia, for the treatment of various
- the compounds disclosed therein differ from the compounds according to the invention inter alia by the obligate aromatic substitution on the nitrogen atom immediately adjacent to the oxo group (N-5 in the dihydropteridones, or N-4 in the dihydropyrido [3,4-b ] pyrazinones).
- WO 2010/085570 (Takeda Pharmaceutical Company) describes poly-ADP-ribose polymerase (PARP) inhibitors derived from a variety of bi- and tricyclic scaffolds and 3,4-dihydropyrido [2,3-b] pyrazine -2 (lH) -one derivatives as drugs for the treatment of various diseases.
- PARP poly-ADP-ribose polymerase
- the example compounds disclosed therein differ from the compounds according to the invention for example by the type and position of the substitution on the pyrido part of the dihydropyridopyrazinone skeleton.
- WO 2006/005510 (Boehringer Ingelheim) describes 1,4-dihydropyrido [3,4-b] pyrazine-3 (2H) -one derivatives as inhibitors of PLK-1 for the treatment of hyperproliferative disorders.
- the position of the pyrido-nitrogen distinguishes the substances disclosed herein from the compounds of the invention.
- WO 2008/117061 (Sterix Ltd) describes a number of bicyclic chemotypes as inhibitors of steroid sulfatase, inter alia, for use in inhibiting the growth of tumors.
- WO 2006/050054, WO 2007/134169 and US 2009/0264384 describe a number of bicyclic chemotypes as inhibitors of tumor necrosis factor alpha (TNF- ⁇ ) as well as of various isoforms of phosphodiesterase for the treatment of inter alia inflammatory diseases.
- TNF- ⁇ tumor necrosis factor alpha
- WO 2012/088314 discloses a series of bicyclic chemotypes as modulators of pyruvate kinase M2.
- WO 2003/020722 and WO 2004/076454 disclose 7,8-dihydropteridine-6 (5H) -ones as inhibitors of specific cell cycle kinases for the treatment of hyperproliferative diseases.
- WO 2006/018182 (Boehringer Ingelheim) describes pharmaceutical preparations of 7,8-dihydropteridine-6 (5H) -ones in combination, inter alia, with various cytostatic agents for the treatment of tumor diseases.
- WO 2006/018185 (Boehringer Ingelheim) describes the use of 7,8-dihydropteridine-6 (5H) -ones for the therapy of various tumor diseases.
- WO 2011/101369 Boehringer Ingelheim
- WO 2011/113293 Jiangsu Hengrui Medicine
- WO 2009/141575 Choroma Therapeutics
- WO 2009/071480 Neviano Medical Sciences
- WO 2006/021378, WO 2006/021379 and WO 2006 / 021548 disclose further 7,8-dihydropteridine-6 (5H) -one derivatives as inhibitors of PLK-1
- WO 2007/022638 (Methylgene Inc.) generally discloses HDAC inhibitors of several chemotypes, however, the structures of the exemplified compounds disclosed differ significantly from the compounds of the present invention.
- WO 1999/050254 describes a series of bicyclic chemotypes as inhibitors of serine proteases for antithrombotic therapy, but these compounds differ markedly by the nature and position of the substituents of the compounds according to the invention.
- C-6 having an aromatic amino group the phenyl group of which in turn is substituted with a para-position amide group
- substituted 3,4-dihydroquinoxaline-2 (1H) -one derivatives are indexed by Chemical Abstracts as "Chemical Library” substances without literature reference [see 4 ⁇ [(3R) -4-cyclopentyl-3-ethyl-1-methyl-2-oxo-1,2] , 3,4-tetrahydro-quinoxalin-6-yl] amino ⁇ -3-methoxy-7V- [2-methyl-l-
- R 2 may be the same or different
- Ci-Cö-alkyl- which is unsubstituted or monosubstituted with Ci-C3-alkoxy, phenyl, Cs-Cs-cycloalkyl, or 4- to 8-membered
- phenyl in turn is unsubstituted or mono-, di- or trisubstituted by identical or different substituents from Ci-C with halo, cyano, 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl , C 1 -C 4 -alkoxy, halogeno-C 1 -C 4 -alkyl, halogeno-C 1 -C 4 -alkoxy-, and
- Cs-Cs-cycloalkyl and 4- to 8-membered heterocycloalkyl are in turn unsubstituted or substituted once or twice, identically or differently, by C 1 -C 3 -alkyl-,
- phenyl or 5- to 6-membered heteroaryl which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with halogen, C 1 -C 3 -alkyl- or 4- to 8-membered heterocycloalkyl-,
- Ci-COE-alkyl which is unsubstituted or is monosubstituted by cyano, Ci-C 3 alkoxy, C 3 alkylamino, phenyl, C 3 -C 8 -cycloalkyl or 4- to 8th- heterocycloalkyl,
- phenyl in turn is unsubstituted or mono-, di- or trisubstituted by identical or different substituents from Ci-C with halo, cyano, 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl , C 1 -C 4 -alkoxy, halogeno-C 1 -C 4 -alkyl, halogeno-C 1 -C 4 -alkoxy-, and
- Cs-Cs-cycloalkyl and 4- to 8-membered heterocycloalkyl are in turn unsubstituted or substituted once or twice, identically or differently, by C 1 -C 3 -alkyl-,
- Ci-C3-alkyl- or Ci-C 4 -alkoxycarbonyl- is Cs-Cs-cycloalkyl- or 4- to 8-membered heterocycloalkyl-, which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with Ci-C3-alkyl- or Ci-C 4 -alkoxycarbonyl-, with the Stipulation that that
- 4- to 8-membered heterocycloalkyl is not bound via a nitrogen atom to the carbonyl or sulfonyl group in R 1 ,
- R 10 and R 11 independently of one another represent hydrogen or unsubstituted or mono- or disubstituted by identical or different hydroxy, oxo, C 1 -C 3 -alkoxy-substituted
- R 12 is C 1 -C 6 -alkyl or phenyl-C 1 -C 3 -alkyl, and their diastereomers, racemates, polymorphs and physiologically tolerated salts, surprisingly inhibit the interaction between BRD 4 and an acetylated histone 4-peptide and thus growth of cancer and tumor cells.
- Preference is given to those compounds of the general formula (I) in which
- A is -NH- or -N (methyl) -
- X is -N- or -CH-
- Y is -N- or -CH-
- n 0, 1 or 2
- phenyl which is unsubstituted or mono-, di- or trisubstituted by identical or different substituents with halogen, cyano, C 1 -C 3 -alkyl, trifluoromethyl, C 1 -C 6 -alkoxy, trifluoromethoxy or -NR 10 R U,
- R 2 is hydrogen, hydroxy, fluorine, chlorine, cyano, methyl, ethyl, methoxy,
- Ethoxy, trifluoromethoxy or phenoxy in which the phenoxy-containing phenyl is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, bromine, cyano, methyl or methoxy, and, if n is 2, R 2 may be the same or different,
- R 3 is methyl or ethyl
- R 4 is hydrogen, methyl or ethyl
- R 5 is hydrogen, methyl or ethyl
- R 6 is C 2 -C 5 alkyl, which is unsubstituted
- phenyl is in turn unsubstituted or mono-, di- or trisubstituted by identical or different substituents with fluorine, chlorine, bromine, cyano,
- Ci-C3-alkyl is Cs-Cs-cycloalkyl or 4- to 8-membered heterocycloalkyl- which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with Ci-C3-alkyl, fluoro-Ci-C3-alkyl- or Ci -C t -alkoxycarbonyl, or
- phenyl or 5- to 6-membered heteroaryl- which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, methyl or 6-membered heterocycloalkyl-,
- 6-membered heterocycloalkyl is in turn unsubstituted or monosubstituted by methyl or ieri-butoxycarbonyl
- Ci-Cö-alkyl- which is unsubstituted or monosubstituted with cyano, Ci-C3-alkoxy, Ci-C3-alkylamino, phenyl or 4- to 8-membered
- phenyl in turn is unsubstituted or mono-, di- or trisubstituted by identical or different substituents with fluorine, chlorine, bromine, cyano, Ci-Cs-alkyl, Ci-C 3 alkoxy, and
- Cs-Cs-cycloalkyl or 4- to 8-membered heterocycloalkyl- which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with Ci-C 3 alkyl or Ci-C t -alkoxycarbonyl, with with the proviso that the 4- to 8-membered heterocycloalkyl is not bound via a nitrogen atom to the sulfonyl group in R 1 ,
- OR 12 stands for C 1 -C 4 -alkyl-
- R 12 is C 1 -C 4 -alkyl or benzyl
- A stands for -NH-
- Y is -N- or -CH-
- n 0 or 1
- phenyl which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, bromine, cyano, methyl, trifluoromethyl or methoxy,
- R 2 is hydrogen, fluorine, chlorine, methyl, methoxy, trifluoromethoxy or phenoxy, in which the phenoxy-containing phenyl is unsubstituted or monosubstituted by fluorine or chlorine,
- R 3 is methyl
- R 4 is methyl or ethyl
- R 5 represents hydrogen
- R 6 is Cs-Cs-alkyl-
- methyl which is monosubstituted with phenyl- or 4- to 6-membered heterocycloalkyl-, wherein phenyl is in turn unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, cyano, methyl or methoxy, and
- phenyl which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine or methyl,
- Ci-C t-alkyl- which is unsubstituted or monosubstituted with cyano
- phenyl in which phenyl is in turn unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, cyano, methyl,
- Y is -N- or -CH-
- n 0 or 1
- phenyl which is unsubstituted or monosubstituted by fluorine, chlorine, cyano, methyl, methoxy,
- R 2 is hydrogen, methyl, methoxy, trifluoromethoxy, phenoxy or para
- R 3 is methyl
- R 4 is methyl
- R 5 represents hydrogen
- R 6 is isopropyl
- tetrahydropyranyl or piperidinyl which are unsubstituted or monosubstituted with methyl, 2,2-difluoroethyl, 2,2,2-trifluorofhyl, 3,3,3-trifluoropropyl or ieri-butoxycarbonyl,
- phenyl which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine or methyl,
- R7 is Ci-Cs-alkyl, trifluoromethyl, allyl, C3-C4 cycloalkyl, or
- A stands for -NH-
- Y is -N- or -CH-
- n 0 or 1
- R 2 is hydrogen, methyl, methoxy, trifluoromethoxy, phenoxy or para
- R 1 and R 2 together with the phenyl ring to which they are attached, for
- R 3 is methyl
- R 4 is methyl
- R 5 represents hydrogen
- R 6 is isopropyl
- R 7 is methyl, ethyl, isopropyl, trifluoromethyl, allyl, cyclopropyl, cyclobutyl or tetrahydropyran-4-yl, and
- R 10 and R 11 together with the nitrogen atom to which they are attached represent N-methylpiperazinyl
- the present invention further relates to compounds of the general formula (I)
- A is -NH-, -N (C 1 -C 3 -alkyl) - or -O-,
- X is -N-, -CH- or -CR 2 -,
- Y is -N-, -CH- or -CR 2 -,
- n 0,1 or 2
- R is hydrogen, hydroxy, halogen, cyano, C 1 -C 3 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, halogen-C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy , Halogeno-C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio or halogeno-C 1 -C 4 -alkylthio, and if n is 2, R 2 may be identical or different,
- R 4 is hydrogen or C 1 -C 3 -alkyl-, is hydrogen or C 1 -C 3 -alkyl-,
- Ci-Cö-alkyl- which is unsubstituted or monosubstituted with C1-C3-alkoxy, phenyl, Cs-Cs-cycloalkyl, or 4- to 8-membered heterocycloalkyl, in which phenyl is in turn unsubstituted or mono-, di- or trisubstituted by identical or different substituents with halogen, cyano, GC 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy , Halogen-C 1 -C 4 -alkyl, halogen-C 1 -C 4 -alkoxy, and
- Cs-Cs-cycloalkyl and 4- to 8-membered heterocycloalkyl are in turn unsubstituted or substituted once or twice, identically or differently, by C 1 -C 3 -alkyl-,
- phenyl or 5- to 6-membered heteroaryl which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with halogen, C1-C3-alkyl or 4- to 8-membered heterocycloalkyl-,
- C 1 -C 6 -alkyl which is unsubstituted or monosubstituted by cyano, C 1 -C 3 -alkoxy, C 1 -C 3 -alkylamino, phenyl, C 3 -C 5 -cycloalkyl or 4 to 8 heterocycloalkyl,
- phenyl in turn is unsubstituted or mono-, di- or trisubstituted by identical or different substituents from Ci-C with halo, cyano, 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl , GC 4 alkoxy, halo-GC 4 alkyl, halo-Ci-C 4 alkoxy, and
- Cs-Cs-cycloalkyl and 4- to 8-membered heterocycloalkyl are in turn unsubstituted or substituted once or twice, identically or differently, by C 1 -C 3 -alkyl-,
- Cs-Cs-cycloalkyl or 4- to 8-membered heterocycloalkyl- which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with Ci-C3-alkyl or Ci-C4-alkoxycarbonyl, with the proviso that the 4- to 8-membered heterocycloalkyl- is not bound via a nitrogen atom to the carbonyl or sulfonyl group in R 1 ,
- OR 12 represents C 1 -C 6 -alkyl- or C 3 -C 8 -cycloalkyl-,
- A is -NH- or -N (methyl) -
- X is -N- or -CH-
- Y stands for -CH-
- n 0,1 or 2
- phenyl which is unsubstituted or mono-, di- or trisubstituted by identical or different substituents with halogen, cyano, C 1 -C 3 -alkyl, trifluoromethyl, C 1 -C 3 -alkoxy, trifluoromethoxy or -NR 10 R U,
- R 2 is hydrogen, hydroxy, fluorine, chlorine, cyano, methyl, methoxy, ethyl or Ethoxy stands, and if n is 2, R 2 may be the same or different, or
- phenyl is in turn unsubstituted or mono-, di- or trisubstituted by identical or different substituents with fluorine, chlorine, bromine, cyano, Ci-C3-alkyl or Ci-C3-alkoxy, and
- phenyl or 5- to 6-membered heteroaryl- which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, methyl or 6-membered heterocycloalkyl-,
- 6-membered heterocycloalkyl is in turn unsubstituted or monosubstituted by methyl or ieri-butoxycarbonyl
- C 1 -C 6 -alkyl which is unsubstituted or monosubstituted by cyano, C 1 -C 3 -alkoxy, C 1 -C 3 -alkylamino, phenyl or 4 to 8-membered
- phenyl in turn is unsubstituted or mono-, di- or trisubstituted by identical or different substituents consisting of fluorine, chlorine, bromine, cyano, Ci- C3 alkyl, Ci-C 3 alkoxy, and
- Cs-Cs-cycloalkyl or 4- to 8-membered heterocycloalkyl- which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with Ci-C3-alkyl- or Ci-C t-alkoxycarbonyl, with the In that the 4- to 8-membered heterocycloalkyl group is not bonded via a nitrogen atom to the carbonyl or sulfonyl group in R 1 ,
- R 9 is C 1 -C 4 -alkyl-
- R 10 and R 11 are independently hydrogen or unsubstituted or simply with
- R 12 is C 1 -C 4 -alkyl or benzyl-
- Y stands for -CH-
- n 0 or 1
- phenyl which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, bromine, cyano, methyl, trifluoromethyl or methoxy,
- oxazolin-2-yl- which is unsubstituted or monosubstituted or disubstituted by methyl, is hydrogen, fluorine, chlorine, methyl or methoxy,
- phenyl is in turn unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, cyano, methyl or methoxy, and
- phenyl which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine or methyl,
- Ci-C t-alkyl- which is unsubstituted or monosubstituted with cyano
- phenyl in which phenyl is in turn unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, cyano, methyl,
- Y stands for -CH-
- n 0 or 1
- phenyl which is unsubstituted or monosubstituted by fluorine, chlorine, cyano, methyl, methoxy,
- R 2 is hydrogen, methyl or methoxy
- R 3 is methyl
- R 4 is methyl
- R 5 represents hydrogen
- R 6 is isopropyl
- phenyl which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine or methyl,
- R 7 is C 1 -C 3 -alkyl- or cyclopropyl-
- R 8 is C 1 -C 8 -alkoxycarbonyl-
- R 9 is Ci-Cs-alkyl-
- X stands for -CH-, stands for -CH-,
- Y stands for -N- or -CH-. Preference is given to compounds of the general formula (I) in which X is -CH- and in which
- Y stands for -N-.
- phenyl which is unsubstituted or mono-, di- or trisubstituted by identical or different substituents with halogen, cyano, C 1 -C 3 -alkyl-, trifluoromethyl-, C 1 -C 3 -alkoxy-,
- phenyl which is unsubstituted or mono-, di- or trisubstituted by identical or different substituents with halogen, cyano, C 1 -C 3 -alkyl-, trifluoromethyl-, C 1 -C 3 -alkoxy-,
- oxazolin-2-yl- which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with Ci-C3-alkyl-.
- R 1 is phenyl which is unsubstituted or mono-, di- or trisubstituted by identical or different substituents with halogen, cyano, C 1 -C 3 -alkyl-, trifluoromethyl , C 1 -C 3 -alkoxy, trifluoromethoxy or -NR 10 R U.
- R 1 is oxazolin-2-yl- which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with C 1 -C 3 -alkyl-.
- phenyl which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, bromine, cyano, methyl, trifluoromethyl or methoxy,
- R 1 is phenyl which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, bromine, cyano, methyltrifluoromethyl or methoxy -.
- R 1 is oxazolin-2-yl- which is unsubstituted or monosubstituted or disubstituted by methyl.
- phenyl which is unsubstituted or monosubstituted by fluorine, chlorine, cyano, methyl, methoxy.
- phenyl which is unsubstituted or monosubstituted by fluorine, chlorine, cyano, methyl, methoxy.
- -NR 10 R U wherein -NR 10 R U is 5- to 6-membered heterocycloalkyl-, which is unsubstituted or monosubstituted with Ci-C 3 alkyl.
- R 2 is hydrogen, hydroxyl, fluorine, chlorine, cyano, methyl, methoxy, ethyl, ethoxy, trifluoromethoxy or phenoxy, in which the radical contained in phenoxy Phenyl is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, bromine, cyano, methyl or methoxy.
- R 2 is hydrogen, hydroxyl, Fluorine, chlorine, cyano, methyl, methoxy, ethyl or ethoxy stands.
- R 2 is hydrogen, fluorine, chlorine, methyl, methoxy, trifluoromethoxy or phenoxy, in which the phenoxy-containing phenyl is unsubstituted or monosubstituted by Fluorine or chlorine.
- R 2 is phenoxy- in which the phenoxy-containing phenyl is unsubstituted or monosubstituted by fluorine or chlorine.
- R 2 is Is hydrogen, methyl, methoxy, trifluoromethoxy, phenoxy or >a-a-fluorophenoxy.
- Ci-C3-alkyl represents C 3 -C 8 -cycloalkyl- or 4- to 8-membered heterocycloalkyl-, which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with Ci-C3-alkyl, fluoro-Ci-C3-alkyl- or Ci-C t-alkoxycarbonyl,
- phenyl or 5- to 6-membered heteroaryl- which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, methyl or 6-membered heterocycloalkyl-,
- 6-membered heterocycloalkyl is in turn unsubstituted or monosubstituted with methyl or ieri-butoxycarbonyl.
- phenyl or 5- to 6-membered heteroaryl- which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, methyl or 6-membered heterocycloalkyl-,
- 6-membered heterocycloalkyl is in turn unsubstituted or simply is substituted with methyl or ieri-butoxycarbonyl.
- R 6 is Cs-Cs-cycloalkyl or 4- to 8-membered heterocycloalkyl- which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with Ci-C 3- alkyl, fluoro-Ci-C 3 alkyl or
- 5- to 6-membered heteroaryl- which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, methyl or 6-membered heterocycloalkyl, in which the 6-membered heterocycloalkyl is in turn unsubstituted or simply is substituted with methyl or ieri-butoxycarbonyl.
- phenyl is in turn unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, cyano, methyl or methoxy, and
- Ci-C3-alkyl is C3-C8-cycloalkyl- or 4- to 6-membered heterocycloalkyl-, which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with Ci-C3-alkyl, fluoro-Ci-C3-alkyl- or Ci -C t -alkoxycarbonyl,
- phenyl which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine or methyl.
- phenyl is in turn unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, cyano, methyl or methoxy, and
- phenyl which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine or methyl.
- phenyl is in turn unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, cyano, methyl or methoxy, and
- Cs-Cs-cycloalkyl- or 4- to 6-membered heterocycloalkyl- which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with C 1 -C 3 -alkyl-, fluoro-C 1 -C 3 -alkyl- or C 1 -C 4 alkoxycarbony 1
- R 6 is phenyl which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine or methyl.
- tetrahydropyranyl or piperidinyl which are unsubstituted or monosubstituted by methyl, 2,2-difluoro-ethyl, 2,2,2-trifluoro-ethyl, 3,3,3-trifluoropropyl or
- phenyl which is unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine or methyl.
- R 6 is tetrahydropyranyl or piperidinyl, which are unsubstituted or monosubstituted by methyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl , 3,3,3-trifluoropropyl or ieri-butoxycarbonyl.
- piperidin-4-yl is tetrahydropyran-4-yl or or piperidin-4-yl, where piperidin-4-yl is unsubstituted or is simply substituted on the nitrogen with methyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl , 3,3,3-trifluoropropyl or uf-butoxycarbonyl,
- piperidin-4-yl is tetrahydropyran-4-yl or piperidin-4-yl, where piperidin-4-yl is unsubstituted or monosubstituted on the nitrogen with methyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl .
- R 7 is C 1 -C 6 -alkyl-, which is unsubstituted or monosubstituted by cyano, C 1 -C 3 -alkoxy, C 1 -C 3 -alkylamino, phenyl or cyano 4- to 8-membered heterocycloalkyl,
- phenyl in turn is unsubstituted or mono-, di- or trisubstituted by identical or different substituents with fluorine, chlorine, bromine, cyano, Ci-C3-alkyl, Ci-C3-alkoxy, and
- Ci-C t-alkoxycarbonyl with the proviso that the 4- to 8-membered heterocycloalkyl is not bound via a nitrogen atom to the carbonyl or sulfonyl group in R 1 .
- R 7 is C 1 -C 6 -alkyl- which is unsubstituted or monosubstituted with cyano, C 1 -C 3 -alkoxy-, C 1 -C 3 -alkylamino-,
- phenyl in turn is unsubstituted or mono-, di- or trisubstituted by identical or different substituents with fluorine, chlorine, bromine, cyano, Ci-C3-alkyl, Ci-C3-alkoxy, and
- Ci-C t-alkoxycarbonyl with the proviso that the 4- to 8-membered heterocycloalkyl is not bound via a nitrogen atom to the carbonyl or sulfonyl group in R 1 .
- R 7 is C 1 -C 6 -alkyl-, which is unsubstituted or monosubstituted by cyano, C 1 -C 3 -alkoxy, C 1 -C 3 -alkylamino, phenyl or cyano 4- to 8-membered heterocycloalkyl,
- 4- to 8-membered heterocycloalkyl is in turn unsubstituted or monosubstituted or disubstituted by identical or different substituents with Ci-C 3 alkyl.
- R 7 is C 3 -C / t-alkenyl or C 3 -C 4 -alkynyl.
- R 7 is Cs-Cs-cycloalkyl or 4- to 8-membered heterocycloalkyl- which are unsubstituted or monosubstituted or disubstituted by identical or different substituents with Ci-C3
- the 4- to 8-membered heterocycloalkyl- is not bound via a nitrogen atom to the carbonyl or sulfonyl group in R 1 -alkyl or Ci-C t -alkoxycarbonyl.
- R 7 is C 1 -C 4 -alkyl- which is unsubstituted or monosubstituted by cyano, phenyl or 5- to 6-membered heterocycloalkyl-,
- phenyl in which phenyl is in turn unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, cyano, methyl,
- R 7 is C 1 -C 4 -alkyl- which is unsubstituted or monosubstituted by cyano, phenyl or 5- to 6-membered heterocycloalkyl-,
- phenyl in which phenyl is in turn unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, cyano, methyl,
- R 7 is C 1 -C 4 -alkyl- which is unsubstituted or monosubstituted by cyano, phenyl or 5- to 6-membered heterocycloalkyl-,
- phenyl in which phenyl is in turn unsubstituted or monosubstituted or disubstituted by identical or different substituents with fluorine, chlorine, cyano, methyl,
- Fluoro-Ci-C 2 alkyl stands. Particular preference is given to compounds of the general formula (I) in which R 7 represents
- C 5 -C 6 cycloalkyl or 5- to 6-membered heterocycloalkyl provided that the 5- to 6-membered heterocycloalkyl is not attached to the carbonyl or sulfonyl group in R 1 via a nitrogen atom.
- Heterocycloalkyl- is not bound via a nitrogen atom to the carbonyl or sulfonyl group in R 1 .
- R 7 is C 1 -C 3 -alkyl, trifluoromethyl, allyl, C 3 -C 4 -cycloalkyl or tetrahydropyranyl.
- R 7 stands for Ci-C 3 alkyl or cyclopropyl.
- R 7 is cyclopropyl, cyclobutyl or tetrahydropyran-4-yl.
- R is hydrogen, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl or -C (0O) OR 12 .
- R 8 is cyano, C 1 -C 4 -alkyl, C 5 -C 12 -cycloalkyl or -C (0O) OR 12 .
- R 8 is cyano, C 1 -C 3 -alkyl or C 1 -C 3 -alkoxycarbonyl.
- R 8 is hydrogen or C 1 -C 3 -alkoxycarbonyl.
- Ci-C 3 alkoxycarbonyl stands.
- R 10 and R 11 independently of one another are hydrogen or unsubstituted or monosubstituted or C 1 -C 3 -alkyl or hydroxy or oxo-substituted heterocycloalkyl-,
- R 10 and R 11 independently of one another are hydrogen or unsubstituted or monosubstituted or C 1 -C 3 -alkyl or hydroxy or oxo-substituted heterocycloalkyl-,
- 5- to 6-membered heterocycloalkyl is in turn unsubstituted or monosubstituted or disubstituted by identical or different substituents with Ci-C3-alkyl-.
- R 10 and R 11 together with the nitrogen atom to which they are bonded, are 4- to 7-membered heterocycloalkyl- which is unsubstituted or mono- or di-twice, the same or is variously substituted with hydroxy, fluorine, oxo, C 1 -C 3 -alkyl, fluoro-C 1 -C 3 -alkyl, cyclopropyl, cyclopropylmethyl, acetyl or ieri-butoxycarbonyl-.
- R and R independently of one another, are hydrogen or C 1 -C 3 -alkyl-
- R 10 and R 11 independently of one another are hydrogen or C 1 -C 3 -alkyl-.
- Heterocycloalkyl- which is unsubstituted or mono- or disubstituted by identical or different substituents with Ci-C 3 alkyl, fluoro-Ci-C3-alkyl or ieri-butoxycarbonyl-.
- Heterocycloalkyl- stand, which is unsubstituted or monosubstituted with Ci-C3-alkyl-.
- Very particular preference is given to compounds of the general formula (I) in which R 10 and R 11, together with the nitrogen atom to which they are attached, represent piperidinyl, piperazinyl or morpholinyl, which is unsubstituted or monosubstituted by methyl -.
- Ci-Cö-alkyl or a Ci-Cö-alkyl group is meant a linear or branched, saturated, monovalent hydrocarbon radical, such. a methyl, ethyl, propyl, butyl, pentyl, hexyl, where-propyl, where-butyl, sec-butyl, ieri-butyl, where-pentyl, 2-methylbutyl, 1- Methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, eo-pentyl, 1,1-dimethylpropyl,
- C 1 -C 4 -alkyl or a C 1 -C 6 -alkyl group is preferably C 1 -C 4 -alkyl, C 2 -C 4 -alkyl or C 2 -C 5 -alkyl, more preferably C 1 -C 3 -alkyl or a methyl, To understand ethyl, propyl or isopropyl radical.
- C 2 -C -alkylene, or a C 2 -C -alkylene group is to be understood as meaning a linear or branched, saturated, divalent hydrocarbon radical, such as, for example, an ethylene, propylene, butylene, pentylene, or propylene -, where-butylene, sec-butylene, ieri-butylene, where-pentylene, 2-methylbutylene, 1-methylbutylene, 1-ethylpropylene, 1,2-dimethylpropylene, eo-pentylene or
- C 2 -C 4 -alkenyl or a C 2 -C 4 -alkenyl group
- C 2 -C 4 -alkynyl or a C 2 -C 4 -alkynyl group
- Ci-C t-alkoxy, or a Ci-C4-alkoxy group is a linear or branched, saturated alkyl ether radical -O-alkyl to understand, such as a methoxy, ethoxy, n-propoxy, isopropoxy or ferric butoxy radical.
- Ci-C / t-alkoxy or a Ci-C t-alkoxy group Ci-C3-alkoxy, particularly preferably a methoxy or ethoxy radical to understand.
- Ci-C t-alkylthio or a Ci-C t-alkylthio group is meant a linear or branched, saturated Alkylthioetherrest -S-alkyl, such as. a methylthio, ethylthio, n-propylthio, isopropylthio, or ierf.-butylfhio radical.
- C 1 -C 4 -alkylthio or a C 1 -C 4 -alkylthio group is understood as meaning C 1 -C 3 -alkylthio, particularly preferably a methylthio and ethylthio radical.
- Ci-C3-alkylamino, or a Ci-C3-alkylamino group is an amino radical having one or two (independently selected) alkyl substituents having 1 to 3 carbon atoms as defined above.
- (C 1 -C 3) -alkylamino is, for example, a monoalkylamino radical having 1 to 3 carbon atoms or a dialkylamino radical having 1 to 3 carbon atoms per molecule
- Examples include:
- the NHNH of the abovementioned sulfoximine may optionally be substituted by C 1 -C 3 -alkyl, C 1 -C 3 -alkylcarbonyl-,
- Oxo may be attached to atoms of suitable valency, for example to a saturated carbon atom or to sulfur.
- the bond to carbon is to form a carbonyl group.
- halogen is meant fluorine, chlorine, bromine or iodine.
- Fluorine, chlorine, bromine or iodine, which is optionally substituted on the phenyl ring, may be in the ortho, meta or ortho position. Preference is given to fluorine and chlorine.
- the preferred position is the meta and / or ara position.
- halogen-Ci-C t-alkyl radical is a Ci-C t-alkyl radical, having at least one
- Halogen substituents preferably having at least one fluorine substituent to understand.
- fluoro-C 1 -C 3 -alkyl radicals for example difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl and pentafluoroethyl.
- perfluorinated alkyl radicals such as trifluoromethyl and pentafluoroethyl.
- phenyl-C 1 -C 3 -alkyl is meant a group which is composed of an optionally substituted phenyl radical and a C 1 -C 3 -alkyl group and which via the C 1 -C 3 -alkyl group to the radical of the molecule is bound.
- Benzyl is preferred.
- a halo-C 1 -C 4 -alkoxy radical is a C 1 -C 4 -alkoxy radical having at least one
- Halogen substituents preferably having at least one fluorine substituent to understand.
- fluoro-C 1 -C 3 -alkoxy radicals for example difluoromethoxy, trifluoromethoxy and 2,2,2-trifluoroethoxy radicals.
- a halogeno-C 1 -C 4 -alkylthio radical is to be understood as meaning a C 1 -C 4 -alkylthio radical having at least one halogen substituent, preferably having at least one fluorine substituent.
- fluorine-C 1 -C 3 -alkylthio radicals in particular trifluoromethylthio radicals.
- a C 1 -C 3 -alkylcarbonyl radical is to be understood as meaning a C 1 -C 3 -alkylC (0O) group. Preference is given to acetyl and propanoyl.
- a C 1 -C 4 -alkoxycarbonyl radical is to be understood as meaning a C 1 -C 4 -alkoxy-C (0O) group.
- Preferred is methoxycarbonyl, ethoxycarbonyl and ferric. Butoxycarbonyl.
- Ci-C4-alkoxy-Ci-C4-alkyl is understood an alkyl group having 4 Ci-C 4 alkoxy substituted Ci-C, such.
- Aryl is understood as meaning an unsaturated fully conjugated system composed of carbon atoms which has 3, 5 or 7 conjugated double bonds, such as, for example, phenyl, naphthyl or phenantryl. Preference is given to phenyl.
- Heteroaryl is to be understood as meaning ring systems which have an aromatic-conjugated ring system and contain at least one and up to five heteroatoms as defined above.
- ring systems may have 5, 6 or 7 ring atoms or, in the case of condensed or benzo-fused ring systems, also combinations of 5- and 6-membered ring systems, 5- and 5-membered ring systems or also 6- and 6-membered ring systems , Examples which may be mentioned are ring systems such as pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furyl, thienyl, oxazolyl, thiazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, oxazinyl, indolyl, benzimidazolyl, indazolyl, benzotriazolyl, benzothiazolyl, Benzoxazolyl, benzofuryl, benzothienyl, quinolinyl, isoquinol
- C3-C6-Cycloalkyl, C3-C5-cycloalkyl or Cs-Cs-cycloalkyl is to be understood as meaning a monocyclic saturated ring system composed exclusively of carbon atoms and having 3 to 6, 3 to 8 atoms or 5 to 8 atoms. Examples are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.
- C t-Cö-cycloalkenyl C t-Cs-cycloalkenyl, or Cs-Cs-cycloalkenyl is a monocyclic, built up exclusively from carbon atoms, mono- or polyunsaturated, non-aromatic ring system with 4 to 6, 4 to 8 atoms, respectively To understand 5 to 8 atoms.
- Examples are cyclobuten-1-yl, cyclopenten-1-yl, cyclohexene-2-yl, cyclohexene-1-yl and cycloocta-2,5-dienyl.
- heterocycloalkyl is meant a 4- to 8-membered monocyclic saturated ring system having from 1 to 3 heteroatoms as defined above, in any combination. Preference is given to 4- to 7-membered heterocycloalkyl groups, particularly preferred are 5- to 6-membered heterocycloalkyl groups.
- Heterocycloalkenyl is a 4- to 8-membered monocyclic, mono- or polyunsaturated, non-aromatic ring system which has 1 to 3 heteroatoms as defined above, in any desired combination. Preference is given to 4- to 7-membered heterocycloalkyl groups, particularly preferred are 5- to 6-membered heterocycloalkyl groups.
- Examples which may be mentioned are 4H-pyranyl, 2H-pyranyl, 2,5-dihydro-1H-pyrrolyl, [1,3] dioxolyl, 4H- [1,3,4] thiadiazinyl, 2,5-dihydrofuranyl, 2,3- Dihydrofuranyl, 2,5-dihydrothiophenyl, 2,3-dihydrothiophenyl, 4,5-dihydrooxazolyl and 4H- [1,4] thiazinyl.
- Compounds of the invention are the compounds of the general formula (I) and their salts, solvates and solvates of the salts, the compounds of the formulas below and their salts, solvates and solvates of the salts of the general formula (I) and of the general formula (I) included, hereinafter referred to as exemplary embodiments
- Salts used in the context of the present invention are physiologically acceptable salts of the compounds according to the invention. However, also included are salts which are not suitable for pharmaceutical applications themselves but can be used, for example, for the isolation or purification of the compounds according to the invention.
- Physiologically acceptable salts of the compounds of the invention include acid addition salts of mineral acids, carboxylic acids and sulfonic acids, e.g. Salts of
- Hydrochloric hydrobromic, sulfuric, phosphoric, methanesulfonic, ethanesulfonic, toluenesulfonic, benzenesulfonic, naphthalenedisulfonic, acetic, trifluoroacetic, propionic, lactic, tartaric, malic, citric, fumaric, maleic and benzoic acids.
- Another object of the present invention are all possible crystalline and polymorphic forms of the compounds of the invention, wherein the polymorphs can be present either as a single polymorph or as a mixture of several polymorphs in all concentration ranges.
- the present invention also relates to pharmaceutical compositions containing the inventive
- Solvates in the context of the invention are those forms of the compounds according to the invention which are in solid or liquid state by coordination with solvent molecules to form a complex. Hydrates are a special form of solvates that coordinate with water. As solvates, hydrates are preferred in the context of the present invention.
- the compounds of the invention may exist in different stereoisomeric forms depending on their structure, i. in the form of configurational isomers or optionally also as conformational isomers.
- the compounds of the invention can am
- Asymmetric center may therefore be present as pure enantiomers, racemates but also as diastereomers or mixtures thereof, if one or more of the substituents described in the formula (I) contains a further asymmetric element, for example a chiral carbon atom.
- the present invention therefore also encompasses diastereomers and their respective mixtures. From such mixtures, the pure stereoisomers can be isolated in a known manner; Preferably, for this purpose, chromatographic methods are used, in particular HPLC chromatography on chiral or achiral phase.
- the enantiomers according to the invention inhibit the different degrees of inhibition
- Another object of the present invention are enantiomeric mixtures of the (3R) - configured compounds of the invention with their (3S) enantiomers, in particular the corresponding racemates and mixtures of enantiomers in which outweighs the (3R) form. If the compounds according to the invention can occur in tautomeric forms, the present invention encompasses all tautomeric forms.
- the present invention also includes all suitable isotopic variants of the compounds of the invention.
- An isotopic variant of a compound according to the invention is understood to mean a compound in which at least one atom within the
- Compound according to the invention is exchanged for another atom of the same atomic number, but with a different atomic mass than the atomic mass usually or predominantly occurring in nature.
- isotopes which can be incorporated into a compound of the invention are those of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine and iodine, such as 2 H (deuterium), 3 H (tritium), U C, 13 C, 14 C, 15 N, 17 O, 18 O, 32 P, 33 P, 33 S, 34 S, 35 S, 36 S, 18 F, 36 C1, 82 Br, 123 1, 124 1, 129 I and 131 L
- Certain isotopic variants of a compound of the invention such as in particular those in which one or more radioactive isotopes are incorporated, may be useful, for example for the study of the mechanism of action or the distribution of active substance in the body; Due to the comparatively easy production and detectability, compounds labeled with 3 H or 14 C isotopes in particular
- Lead such as an extension of the half-life in the body or a
- the compounds according to the invention can act systemically and / or locally.
- they may be applied in a suitable manner, for example orally, parenterally, pulmonarily, nasally, sublingually, lingually, buccally, rectally, dermally, transdermally, conjunctivally, otically or as an implant or stent.
- the compounds according to the invention can be administered in suitable administration forms.
- Suitable for oral administration are all application forms known per se to the person skilled in the art, which can rapidly deliver the compounds according to the invention.
- the compounds according to the invention may in this case be present in crystalline, amorphous or dissolved form, for example in tablets (non-coated or coated tablets, for example with enteric or delayed-dissolving or insoluble coatings which control the release of the compound according to the invention), in the oral cavity rapidly disintegrating tablets , in films / wafers, in films / lyophilisates, in capsules (for example hard or soft gelatin capsules), in dragees, in granules, in pellets, in powders, in emulsions, in suspensions, in aerosols or in solutions.
- the parenteral administration can be done bypassing a resorption step
- intravenously, intraarterially, intracardially, intraspinal or intralumbar or with the involvement of a resorption (for example, intramuscularly, subcutaneously, intracutaneously, percutaneously or intraperitoneally).
- parenteral administration are suitable as application forms u.a.
- Injection and infusion preparations in the form of solutions, suspensions, emulsions, lyophilisates or sterile powders.
- inhalation medicaments ia Powder inhalers, nebulizers
- nasal drops solutions, sprays
- lingual, sublingual or buccal tablets to be applied, films / wafers or capsules, suppositories, ear or
- Ophthalmic preparations vaginal capsules, aqueous suspensions (lotions, shake mixtures), lipophilic suspensions, ointments, creams, transdermal therapeutic systems (such as patches), milk, pastes, foams, scattering powders, implants or stents.
- the compounds according to the invention can be converted into the stated administration forms. This can be done in a manner known to those skilled in the art by mixing with inert, non-toxic, pharmaceutically suitable excipients.
- excipients for example microcrystalline cellulose, lactose, mannitol
- solvents for example liquid polyethylene glycols
- emulsifiers and dispersants or wetting agents for example sodium dodecylsulfate, polyoxysorbitanoleate
- binders for example polyvinylpyrrolidone
- synthetic and natural polymers for example albumin
- Stabilizers for example, antioxidants such as ascorbic acid
- dyes for example, inorganic pigments such as iron oxides
- flavor and / or odoriferous for example, antioxidants such as ascorbic acid
- Stabilizers for example, antioxidants such as ascorbic acid
- dyes for example, inorganic pigments such as iron oxides
- Another object of the present invention are pharmaceutical compositions containing the compounds of the invention, usually together with one or more inert, non-toxic, pharmaceutically suitable excipients and their use for the purposes mentioned above.
- the formulation of the compounds according to the invention into pharmaceutical preparations is carried out in a manner known per se to the person skilled in the art by converting the active substance (s) into the desired administration form with the auxiliaries customary in galenicals.
- excipients for example, vehicles, fillers, disintegrants,
- Binders humectants, lubricants, ab- and adsorbents, diluents, solvents, cosolvents, emulsifiers, solubilizers, flavoring agents,
- the pharmaceutical formulations may be in solid form, for example as tablets, dragees, pills, suppositories, capsules, transdermal systems or in semi-solid form, for example as ointments, creams, gels, suppositories, emulsions or in liquid form, for example as solutions, Tinctures, suspensions or emulsions are present.
- auxiliaries may be, for example, salts, saccharides (mono-, di-, tri-, oligo- and / or polysaccharides), proteins, amino acids, peptides, fats, waxes, oils,
- Hydrocarbons and derivatives thereof, wherein the excipients may be of natural origin or may be obtained synthetically or partially synthetically.
- the compounds according to the invention are suitable for the prophylaxis and / or therapy of hyperproliferative diseases such as, for example, psoriasis, keloids and other skin-related hyperplasias, and for the prophylaxis and / or therapy of benign prostate hyperplasia (BPH), solid tumors and hematological tumors.
- hyperproliferative diseases such as, for example, psoriasis, keloids and other skin-related hyperplasias
- BPH benign prostate hyperplasia
- solid tumors according to the invention for example, tumors of the breast, the respiratory tract, the brain, the reproductive organs, the gastrointestinal tract, the genitourinary tract, the eye, the liver, the skin, the head and neck, the thyroid gland, the parathyroid gland, are treatable Bone and connective tissue and metastases of these tumors.
- multiple myelomas, lymphomas or leukemias are treatable.
- Breast tumors are treatable breast cancers with positive breast cancers
- Non-small cell cancers are treatable as tumors of the respiratory tract
- tumors of the brain are treatable by gliomas, glioblastomas, astrocytomas, meningiomas and medulloblastomas.
- tumors of the male reproductive organs are treatable.
- Prostate carcinomas malignant epididymal tumors, malignant testicular tumors and penile carcinomas.
- tumors of the female reproductive organs are treatable.
- Endometrial carcinoma cervical carcinoma, ovarian carcinoma, vaginal carcinoma and
- Vulvarkarzinome For example, treatable tumors of the gastrointestinal tract are colorectal carcinomas, anal carcinomas, gastric carcinomas, pancreatic carcinomas, esophageal carcinomas.
- Gallbladder carcinomas small bowel carcinomas, salivary gland carcinomas, neuroendocrine tumors and gastrointestinal stromal tumors.
- tumors of the urogenital tract are treatable by bladder carcinomas, renal cell carcinomas, and carcinomas of the renal pelvis and the urinary tract.
- retinoblastomas and intraocular melanomas are treatable as tumors of the eye.
- Treatable hepatocellular carcinomas and cholangiocellular carcinomas are tumors of the liver.
- treatable tumors of the skin are malignant melanomas, basaliomas,
- tumors of the head and neck are treatable with laryngeal carcinomas and carcinomas of the pharynx and oral cavity.
- soft-tissue sarcomas and osteosarcomas are treatable as sarcomas.
- non-Hodgkin's lymphomas For example, non-Hodgkin's lymphomas, Hodgkin's lymphomas, cutaneous lymphomas, central nervous system lymphomas, and AIDS-associated lymphomas are treatable as lymphomas.
- Treatable as leukemias are acute myeloid leukemias, chronic myeloid leukemias, acute lymphatic leukemias, chronic lymphocytic leukemias and hair cell leukemias.
- the compounds according to the invention can be used for the prophylaxis and / or therapy of leukemias, in particular acute myeloid leukemias,
- Prostate cancer especially androgen receptor-positive prostate cancer
- Hormone receptor-positive or BRCA-associated breast carcinoma pancreatic carcinoma, renal cell carcinoma, hepatocellular carcinoma, melanoma and other skin tumors, non-small cell lung carcinoma, endometrial carcinoma and colorectal carcinoma.
- the compounds according to the invention can be used particularly advantageously for the prophylaxis and / or therapy of leukemias, in particular acute myeloid leukemias, prostate carcinomas, in particular androgen receptor-positive prostate carcinomas,
- Breast cancer in particular estrogen receptor-alpha negative breast carcinoma, Melanoma or multiple myeloma.
- the compounds according to the invention are also suitable for the prophylaxis and / or therapy of benign hyperproliferative diseases such as, for example, endometriosis, leiomyoma and benign prostatic hyperplasia.
- benign hyperproliferative diseases such as, for example, endometriosis, leiomyoma and benign prostatic hyperplasia.
- systemic inflammatory diseases in particular LPS-induced endotoxic shock and / or bacteria-induced sepsis.
- the compounds according to the invention are also suitable for the prophylaxis and / or therapy of inflammatory or autoimmune diseases such as, for example: lung diseases associated with inflammatory, allergic and / or proliferative
- Associated processes chronic obstructive pulmonary disease of any genesis, especially bronchial asthma; Bronchitis of different origin; all forms of restrictive lung diseases, especially allergic alveolitis; all forms of pulmonary edema, especially toxic pulmonary edema; Sarcoidoses and granulomatoses, especially Boeck's disease,
- Rheumatic diseases / autoimmune diseases / joint diseases associated with inflammatory, allergic and / or proliferative processes all forms of rheumatic diseases, in particular rheumatoid arthritis, acute rheumatic fever, polymyalgia rheumatica; reactive arthritis; Inflammatory soft tissue diseases of other origin; arthritic symptoms in degenerative joint disease
- Insect bites Insect bites, allergic reactions to drugs, blood derivatives, contrast agents, etc., anaphylactic shock, urticaria, contact dermatitis,
- Vasculitides Panarterilitis nodosa, temporal arteritis, erythema nodosum, - dermatological diseases associated with inflammatory, allergic and / or
- atopic dermatitis Psoriasis; Pityriasis rubra pilaris; erythematous diseases caused by different noxious agents, eg radiation, chemicals, burns etc .; bullous dermatoses; Diseases of the lichenoid Shape circle; pruritus; seborrheic eczema; rosacea; Pemphigus vulgaris; Erythema exudative multiforme; balanitis; vulvitis; Hair loss such as alopecia areata; cutaneous T-cell lymphoma,
- Kidney diseases associated with inflammatory, allergic and / or proliferative processes nephrotic syndrome; all nephritis,
- Liver diseases associated with inflammatory, allergic and / or proliferative processes acute liver cell decay; acute hepatitis of various causes, such as viral, toxic, drug-induced; chronic aggressive and / or chronic intermittent hepatitis,
- Gastrointestinal disorders associated with inflammatory, allergic and / or proliferative processes regional enteritis (Crohn's disease); Ulcerative colitis; Gastritis; reflux esophagitis; Gastroenteritides of other genesis, for example, gluten-sensitive enteropathy (native sprue),
- Proctological diseases associated with inflammatory, allergic and / or proliferative processes analgesic; fissures; Hemorrhoids; idiopathic proctitis,
- Neurological diseases associated with inflammatory, allergic and / or proliferative processes brain edema, especially tumor-related cerebral edema; multiple sclerosis; acute encephalomyelitis; Meningitis; various forms of seizures, such as BNS cramps,
- Blood disorders associated with inflammatory, allergic and / or proliferative processes acquired hemolytic anemia; idiopathic thrombocytopenia,
- Tumor diseases associated with inflammatory, allergic and / or proliferative processes acute lymphoblastic leukemia; malignant lymphomas; Lymphogranulomatosen; lymphosarcoma; extensive metastases, especially in breast, bronchial and prostate cancers,
- Endocrine disorders associated with inflammatory, allergic and / or proliferative Associated processes endocrine orbitopathy; thyrotoxic crisis; Thyreoditis de Quervain; Hashimoto's thyroiditis; Graves' disease,
- Severe states of shock such as anaphylactic shock, systemic shock
- SIRS inflammatory response syndrome
- hypopituitarism acquired secondary adrenal insufficiency, for example, postinfectious, tumors, etc.
- Emesis associated with inflammatory, allergic and / or proliferative processes for example in combination with a 5-HT3 antagonist in cytostatic vomiting, - pain of inflammatory genesis, e.g. Lumbago.
- the compounds according to the invention are also suitable for the treatment of viral
- Diseases such as infections caused by papilloma viruses, herpes viruses, Epstein-Barr viruses, hepatitis B or C viruses, and human immunodeficiency viruses.
- the compounds of the invention are also useful in the treatment of atherosclerosis, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, peripheral vascular disorders, cardiovascular disorders, angina, pectoris, ischemia, stroke, myocardial infarction, angioplasty restenosis, hypertension, thrombosis, obesity, endotoxemia.
- the compounds according to the invention are also suitable for the treatment of
- neurodegenerative diseases such as multiple sclerosis, Alzheimer's disease and Parkinson's disease.
- Another object of the present invention relates to the use of
- Another object of the present invention relates to the use of Compounds according to the invention for the prophylaxis and / or therapy of leukemias, in particular acute myeolemic leukemias, prostate carcinomas, in particular
- Androgen receptor positive prostate carcinomas cervical carcinomas, breast cancers, in particular hormone receptor negative, hormone receptor positive or BRCA associated breast carcinomas, pancreatic carcinomas, renal cell carcinomas, hepatocellular carcinomas, melanomas and other skin tumors, non-small cell lung carcinomas,
- Endometrial carcinomas and colorectal carcinomas are endometrial carcinomas and colorectal carcinomas.
- Another object of the present invention relates to the use of
- Estrogen receptor-alpha negative breast carcinoma melanoma or multiple myeloma.
- Another object of the invention is the use of the compounds of the invention for the manufacture of a medicament.
- Another object of the present invention relates to the use of
- Another object of the present application relates to the use of
- breast cancer in particular hormone receptor-negative, hormone receptor-positive or BRCA-associated breast carcinoma, pancreatic carcinoma, renal cell carcinoma,
- Hepatocellular carcinomas melanomas and other skin tumors, non-small cell lung carcinomas, endometrial carcinomas and colorectal carcinomas.
- Another object of the present invention relates to the use of
- leukemias in particular acute myeloid leukemias, prostate carcinomas, in particular androgen receptor-positive prostate carcinomas, breast carcinomas, in particular estrogen receptor-alpha negative breast carcinomas, melanomas or multiple myelomas.
- Another object of the present invention relates to the use of
- Another object of the present invention relates to the use of
- leukemias in particular acute myeloid leukemias, prostate carcinomas, in particular
- Androgen receptor positive prostate carcinomas cervical carcinomas, breast cancers, in particular hormone receptor negative, hormone receptor positive or BRCA associated breast carcinomas, pancreatic carcinomas, renal cell carcinomas, hepatocellular carcinomas, melanomas and other skin tumors, non-small cell lung carcinomas,
- Endometrial carcinoma and colorectal carcinoma are endometrial carcinoma and colorectal carcinoma.
- Another object of the present invention relates to the use of
- Estrogen receptor-alpha negative breast carcinoma melanoma or multiple myeloma.
- a further subject of the present invention relates to pharmaceutical formulations in the form of tablets containing one of the compounds according to the invention for the prophylaxis and / or therapy of leukemias, in particular acute myeloid leukemias,
- Prostate cancer especially androgen receptor-positive prostate cancer
- Hormone receptor-positive or BRCA-associated breast carcinomas pancreatic carcinomas, renal cell carcinomas, hepatocellular carcinomas, melanomas and other skin tumors, non-small cell lung carcinomas, endometrial carcinomas and colorectal
- a further subject of the present invention relates to pharmaceutical formulations in the form of tablets containing one of the compounds according to the invention for the prophylaxis and / or therapy of leukemias, in particular acute myeloid leukemias,
- Prostate cancer especially androgen receptor-positive prostate cancer
- Breast cancer in particular estrogen receptor-alpha negative breast carcinoma, melanoma or multiple myeloma.
- Another object of the invention relates to the use of the compounds of the invention for the treatment of diseases associated with proliferative processes.
- Another object of the invention relates to the use of the compounds of the invention for the treatment of benign hyperplasia, inflammatory diseases, autoimmune diseases, sepsis, viral infections, vascular diseases and
- the compounds according to the invention can be used alone or as needed in combination with one or more further pharmacologically active substances, as long as they are Combination does not lead to unwanted and unacceptable side effects.
- Another object of the present invention are therefore pharmaceutical compositions containing a compound of the invention and one or more other active ingredients, in particular for the prophylaxis and / or therapy of the aforementioned diseases.
- the compounds of the invention may be combined with known anti-hyperproliferative, cytostatic or cytotoxic chemical and biological substances for the treatment of cancers.
- the combination of the compounds according to the invention with other substances commonly used for cancer therapy or also with radiotherapy is particularly indicated.
- Eflornithine Eligard, Elitek, Ellence, Emend, Enzalutamide, Epirubicin, Epoetin-alfa, Epogen, Epothilone and its Derivatives, Eptaplatin, Ergamisol, Erlotinib, Erythro-Hydroxynonyladenine, Estrace, Estradiol, Estramustine Sodium Phosphate, Ethinylestradiol, Ethyol, Etidronic Acid,
- Etopophos etoposide, everolimus, exatecan, exemestane, fadrozole, farston, fenretinide, filgrastim, finasteride, fligrastim, floxuridine, fluconazole, fludarabine, 5-fluorodeoxyuridine monophosphate, 5-fluorouracil (5-FU), flu-ioxy-imesterone, flutamide , Folotin, Formestan, Fosteabin, Fotemustin, Fulvestrant, Gammagard, Gefitinib, Gemcitabine, Gemtuzumab, Gleevec, Gliadel, Goserelin, Gossypol, Granisetron hydrochloride, Hexamethylmelamine, Histamine dihydrochloride, Histrelin, Holmium-166-DOTPM, Hycamtin, Hydrocorton, erythro Hydroxynonyladenine, hydroxyurea, hydroxyprogesterone caproate, ibandr
- Taxoprexin taxoter, teceleukin, temozolomide, temsirolimus, teniposide, testosterone propionate, testred, thalidomide, thymosin-alpha-1, thioguanine, thiotepa, thyrotropin, tiazorufin,
- Tiludronic acid tipifarnib, tirapazamine, TLK-286, toceranib, topotecan, toremifene,
- Valspodar vandetanib, vapreotide, vatalanib, vemurafinib, verte-porfin, vesnarinone, vinblastine, vincristine, vindesine, vinflumine, vinorelbine, virulizine, vismodegib, xeloda, Z-100, zinecard, zinostatin-stimalamer, zofran, zoledronic acid
- the compounds of the invention can be reacted with antibodies such as e.g.
- Aflibercept alemtuzumab, bevacizumab, brentuximumab, catumaxomab, cetuximab,
- the compounds of the invention can be used in combination with anti-angiogenic therapies such as bevacizumab, axitinib, regorafenib, cediranib, sorafenib, sunitinib, lenalidomide, copanlisib or thalidomide.
- anti-angiogenic therapies such as bevacizumab, axitinib, regorafenib, cediranib, sorafenib, sunitinib, lenalidomide, copanlisib or thalidomide.
- anti-angiogenic therapies such as bevacizumab, axitinib, regorafenib, cediranib, sorafenib, sunitinib, lenalidomide, copanlisib or thalidomide.
- antihormones and steroidal metabolic enzyme inhibitors are particularly suitable because of their favorable side effect profile.
- Combinations with P-TEFb and CDK9 inhibitors are also particularly suitable because of the possible synergistic effects.
- the following objectives can be pursued with the combination of the compounds according to the invention with other cytostatic or cytotoxic agents:
- the compounds of the invention may also be used in conjunction with radiotherapy and / or surgical intervention.
- NMR signals are given with their respective recognizable multiplicity or their combinations.
- s singlet
- d doublet
- t triplet
- q quartet
- qi quintet
- sp septet
- m multiplet
- b broad signal.
- the chemical shifts ⁇ are given in ppm (parts per million).
- (+) - BINAP R) - (+) - 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl (CAS 76189-55-4)
- T3P 2,4,6-tripropyl-l, 3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide
- Substitution reactions or other reactions known to the person skilled in the art include reactions that introduce a functional group that allows further conversion of substituents.
- Suitable protecting groups as well as methods for their introduction and removal are known to those skilled in the art (see, for example, T.W. Greene and P.G.M. Wuts in: Protective Groups in Organic Synthesis, 3rd Edition, Wiley 1999).
- the combination of two or more reaction steps without intermediate workup in a manner known in the art is possible (for example, in so-called “one-pot” reactions).
- Enantiomerengemische for example racemates, or occur as pure enantiomers.
- the enantiomer mixtures mentioned can be prepared by those familiar to the person skilled in the art
- Pyridine derivatives such as 3-amino-2,6-dichloropyridine ((II), CAS No. 62476-56-6).
- nitrogen atom-protected amino acids of the formula (III) in which R 4 and R 5 are defined as in the general formula (I), and in which PG is a protective group such as Boc, Cbz or Fmoc with suitable aminopyridine Derivatives, for example, 3-amino-2,6-dichloropyridine ((II), CAS No. 62476-56-6).
- Coupling reagents such as T3P, TBTU, HATU or DCC used. Conversion of the carboxylic acids to their amides is generally described in reference books such as Compendium of Organic Synthetic Methods, Volume I-VI (Wiley Interscience) or The Practice of Peptides Synthesis ", Bodansky (Springer Verlag) Compounds of the formula (III) are known to the person skilled in the art and are commercially available The compounds of the formula (IV) obtained are then removed by cleavage of the protective group PG on the amine by suitable methods to give the compounds of the formula (V For this purpose, a large number of methods are known which can be found in standard works (see, for example, TW Greene and PGM Wuts in: Protective Groups in Organic Synthesis, 3rd Edition, Wiley 1999) Further conversion to compounds of the formula (VI) with the introduction of the radical R 6 , which is defined as for the general formula (I), can preferably be carried out by the reductive amination known to the person skilled
- Reductant such as sodium triacetoxyborohydride to the secondary amine of formula (VI) transformed.
- the secondary amines of the formula (VI) can be converted by cyclization to give dihydropyridopyrazinones of the formula (VII).
- compounds of formula (VI) in the presence of a suitable base for example a trialkylamine such as triethylamine, A ⁇ -Diisopropylefhylamin or -Dicyclohexylmefhylamin implement at elevated temperature (see also WO2010 / 96426 A2, Example 16).
- 3-Amino-2,6-dichloropyridine ((II), CAS No. 62476-56-6) is reacted with compounds of the formula (IX) in which R 4 and R 5 are defined as for the general formula (I ), and in which LG and LG 'are each independently a leaving group, preferably chlorine or bromine, such as 2-bromopropionyl bromide (CAS 563-76-8).
- a suitable solvent such as dichloromethane or THF
- a base such as methylamine, ⁇ '. ⁇ '-diisopropylcthylamine or pyridine reacted.
- the base can also be used as a solvent.
- the said compounds of the formula (I) are obtained as racemates, provided that R 4 and R 5 are different from one another. If appropriate, these can be separated into the enantiomers using the separation methods familiar to the person skilled in the art, for example preparative U PI .C on a chiral stationary phase.
- arylthiols of the formula (XIII) with appropriate substitution such as 4-methoxythiophenol (CAS 696-63-9) with, for example, alkyl halides R 7 -Hal, in which R 7 is defined as in the general formula (I), for example iodomethane, bromoethane, bromopropane, 2-bromopropane, cyclopropyl bromide or their further homologues with the addition of a base such as sodium, cesium or potassium carbonate, triethylamine or sodium hydride (for example analogously to G.
- a base such as sodium, cesium or potassium carbonate, triethylamine or sodium hydride
- Reagents such as potassium peroxosulfate (Oxone®, CAS 70693-62-8), meta-chloroperbenzoic acid or hydrogen peroxide (eg analogous to JM Zapico, Org. Biomol. Chem., (2011), vol 9, P4587-99).
- AH NH 2
- Y, R 2 , R 7 and n are defined as in the general formula (I)
- XV a reduction of a compound known to those skilled in the art
- XV a radical R 2 represents a nitro group
- Hydrogen are suitable, e.g. Palladium or platinum, which may be fixed on various heterogeneous supports such as activated carbon, alumina or other common carriers, or also e.g. Raney nickel.
- the reduction of the nitro group using a metal or metal salt is often carried out with the addition of an acid such as hydrochloric acid, acetic acid or
- Trifluoroacetic acid are dissolved and by the addition of nitric acid to compounds of formula (XVI) in which X, Y, R 2 , R 7 and n are defined as in the general formula (I) are reacted. These can then be converted, as described, to compounds of the formula (XIIa).
- Compounds of the general formula (XII) in which A is -N (C 1 -C 3 -alkyl) - corresponding to general formula (I) can be prepared by reaction of compounds of the formula (XIIa) generally known to the person skilled in the art with corresponding aldehydes, such as formaldehyde , Acetaldehyde or propionate dehyd and a reducing agent such as Sodium triacetoxyborohydride or sodium cyanoborohydride, or also by reduction with hydrogen and a corresponding catalyst, e.g. Palladium be obtained on activated carbon.
- aldehydes such as formaldehyde , Acetaldehyde or propionate dehyd
- a reducing agent such as Sodium triacetoxyborohydride or sodium cyanoborohydride
- Amines of the general formula (XVII) in which A, X, Y, R 2 , R 10 , R 11 and n are defined as in the general formula (I) are known to the person skilled in the art, are often commercially available or are known from the literature, or can be described with US Pat methods known to those skilled in the art.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Virology (AREA)
- Oncology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Communicable Diseases (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP14173045 | 2014-06-18 | ||
PCT/EP2015/063278 WO2015193219A1 (de) | 2014-06-18 | 2015-06-15 | Bet-proteininhibitorische 3,4-dihydropyrido[2,3-b]pyrazinone mit meta-substituierter aromatischer amino- oder ethergruppe |
Publications (1)
Publication Number | Publication Date |
---|---|
EP3157919A1 true EP3157919A1 (de) | 2017-04-26 |
Family
ID=50972563
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP15729444.8A Withdrawn EP3157919A1 (de) | 2014-06-18 | 2015-06-15 | Bet-proteininhibitorische 3,4-dihydropyrido[2,3-b]pyrazinone mit meta-substituierter aromatischer amino- oder ethergruppe |
Country Status (7)
Country | Link |
---|---|
US (1) | US20170121322A1 (de) |
EP (1) | EP3157919A1 (de) |
JP (1) | JP2017519760A (de) |
CN (1) | CN106573931A (de) |
CA (1) | CA2952526A1 (de) |
HK (1) | HK1232226A1 (de) |
WO (1) | WO2015193219A1 (de) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102017005089A1 (de) | 2016-05-30 | 2017-11-30 | Bayer Pharma Aktiengesellschaft | Substitulerte 3,4-Dihydrochinoxalin-2(1H)-one |
DE102017005091A1 (de) | 2016-05-30 | 2017-11-30 | Bayer Pharma Aktiengesellschaft | Substituierte 3,4-Dihydropyrido[2,3-b]pyrazin-2(1H)-one |
TW202413336A (zh) | 2018-03-08 | 2024-04-01 | 美商英塞特公司 | 作為PI3K-γ抑制劑之胺基吡嗪二醇化合物 |
WO2020010003A1 (en) | 2018-07-02 | 2020-01-09 | Incyte Corporation | AMINOPYRAZINE DERIVATIVES AS PI3K-γ INHIBITORS |
CN115322128B (zh) * | 2022-08-05 | 2024-06-18 | 南京师范大学 | 一种基于烷基卤代物合成C(sp3)-S键的有机硫化合物及其制备方法与应用 |
KR20250008496A (ko) * | 2023-07-07 | 2025-01-14 | 주식회사 티움바이오 | 화합물 및 이를 포함하는 약학 조성물 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SI2496582T1 (sl) * | 2009-11-05 | 2016-04-29 | Glaxosmithkline Llc Corporation Service Company | Benzodiazepinski inhibitor bromodomene |
US9249161B2 (en) * | 2010-12-02 | 2016-02-02 | Constellation Pharmaceuticals, Inc. | Bromodomain inhibitors and uses thereof |
AR084070A1 (es) * | 2010-12-02 | 2013-04-17 | Constellation Pharmaceuticals Inc | Inhibidores del bromodominio y usos de los mismos |
EP2935260A1 (de) * | 2012-12-20 | 2015-10-28 | Bayer Pharma Aktiengesellschaft | Bet-proteininhibitorische dihydropyridopyrazinone |
WO2014095775A1 (de) * | 2012-12-20 | 2014-06-26 | Bayer Pharma Aktiengesellschaft | Bet-proteininhibitorische dihydrochinoxalinone |
US20160176867A1 (en) * | 2013-07-09 | 2016-06-23 | Bayer Pharma Aktiengesellschaft | Modified bet-protein-inhibiting dihydroquinoxalinones and dihydropyridopyrazinones |
-
2015
- 2015-06-15 CA CA2952526A patent/CA2952526A1/en not_active Abandoned
- 2015-06-15 CN CN201580044412.8A patent/CN106573931A/zh active Pending
- 2015-06-15 EP EP15729444.8A patent/EP3157919A1/de not_active Withdrawn
- 2015-06-15 US US15/317,925 patent/US20170121322A1/en not_active Abandoned
- 2015-06-15 WO PCT/EP2015/063278 patent/WO2015193219A1/de active Application Filing
- 2015-06-15 HK HK17105942.9A patent/HK1232226A1/zh unknown
- 2015-06-15 JP JP2016573534A patent/JP2017519760A/ja not_active Withdrawn
Non-Patent Citations (2)
Title |
---|
None * |
See also references of WO2015193219A1 * |
Also Published As
Publication number | Publication date |
---|---|
CN106573931A (zh) | 2017-04-19 |
CA2952526A1 (en) | 2015-12-23 |
HK1232226A1 (zh) | 2018-01-05 |
JP2017519760A (ja) | 2017-07-20 |
WO2015193219A1 (de) | 2015-12-23 |
US20170121322A1 (en) | 2017-05-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP3027614B1 (de) | Substituierte dihydropyrido[3,4-b]pyrazinone als duale inhibitoren von bet-proteinen und polo-like kinasen | |
EP3019493B1 (de) | Modifizierte bet-proteininhibitorische dihydrochinoxalinone und dihydropyridopyrazinone | |
WO2014095775A1 (de) | Bet-proteininhibitorische dihydrochinoxalinone | |
WO2014095774A1 (de) | Bet-proteininhibitorische dihydropyridopyrazinone | |
EP2900672B1 (de) | Bet-proteininhibitorische 5-aryl-triazolo-azepine | |
EP2958923A1 (de) | 4-substituierte pyrrolo- und pyrazolo-diazepine | |
WO2014128070A1 (de) | Pyrrolo- und pyrazolo-triazolodiazepine als bet-proteininhibitoren zur behandlung von hyper-proliferativen erkrankungen | |
WO2014202578A1 (de) | Substituierte phenyl-2,3-benzodiazepine | |
EP3157919A1 (de) | Bet-proteininhibitorische 3,4-dihydropyrido[2,3-b]pyrazinone mit meta-substituierter aromatischer amino- oder ethergruppe | |
WO2015121230A1 (de) | 9-substituierte 2,3-benzodiazepine | |
WO2015121268A1 (de) | 1-phenyl-3h-2,3-benzodiazepine und ihre verwendung als bromodomänen-inhibitoren | |
DE102017005091A1 (de) | Substituierte 3,4-Dihydropyrido[2,3-b]pyrazin-2(1H)-one | |
WO2015193228A1 (de) | Bet-proteininhibitorische 1,4-dihydropyrido[3,4-b]pyrazinone mit para-substituierter aromatischer amino- oder ethergruppe | |
WO2015193217A1 (de) | Bet-proteininhibitorische dihydropyrido[2,3-b]pyrazinon-derivate mit para-substituierter aromatischer amino- oder ethergruppe | |
WO2015121227A1 (de) | 6,9-disubstituierte 1 -phenyl-3h-2,3-benzodiazepine und ihre verwendung als bromodomänen- inhibitoren | |
WO2015121226A1 (de) | 6-substituierte 2,3-benzodiazepine | |
DE102017005089A1 (de) | Substitulerte 3,4-Dihydrochinoxalin-2(1H)-one | |
WO2015193229A1 (de) | Bet-proteininhibitorische 1,4-dihydropyrido[3,4-b]pyrazinone mit meta-substituierter aromatischer amino- oder ethergruppe |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE |
|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE |
|
17P | Request for examination filed |
Effective date: 20170118 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR |
|
AX | Request for extension of the european patent |
Extension state: BA ME |
|
DAV | Request for validation of the european patent (deleted) | ||
DAX | Request for extension of the european patent (deleted) | ||
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: EXAMINATION IS IN PROGRESS |
|
17Q | First examination report despatched |
Effective date: 20180105 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN |
|
18W | Application withdrawn |
Effective date: 20181018 |