JP2014524475A - ピリミド−ピリダジノン化合物及びその使用 - Google Patents
ピリミド−ピリダジノン化合物及びその使用 Download PDFInfo
- Publication number
- JP2014524475A JP2014524475A JP2014527282A JP2014527282A JP2014524475A JP 2014524475 A JP2014524475 A JP 2014524475A JP 2014527282 A JP2014527282 A JP 2014527282A JP 2014527282 A JP2014527282 A JP 2014527282A JP 2014524475 A JP2014524475 A JP 2014524475A
- Authority
- JP
- Japan
- Prior art keywords
- amino
- pyridazin
- phenyl
- oxo
- dihydropyrimido
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- VSGHANRHWUFOHC-UHFFFAOYSA-N 2h-pyrimido[5,4-c]pyridazin-3-one Chemical class N1=CN=CC2=NNC(=O)C=C21 VSGHANRHWUFOHC-UHFFFAOYSA-N 0.000 title abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 193
- 206010061218 Inflammation Diseases 0.000 claims abstract description 53
- 230000004054 inflammatory process Effects 0.000 claims abstract description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 137
- -1 R 46 Chemical compound 0.000 claims description 111
- 125000000623 heterocyclic group Chemical group 0.000 claims description 81
- 229910052799 carbon Inorganic materials 0.000 claims description 56
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 46
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
- 125000001072 heteroaryl group Chemical group 0.000 claims description 41
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
- 150000002367 halogens Chemical class 0.000 claims description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 23
- 230000005764 inhibitory process Effects 0.000 claims description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 13
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 claims description 12
- 125000002950 monocyclic group Chemical group 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 5
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 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 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 101710112791 Tyrosine-protein kinase JAK2 Proteins 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- FQXFKRRYNPIDCF-UHFFFAOYSA-N 2-morpholin-4-yl-4-[4-(piperazin-1-ylmethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one;hydrochloride Chemical compound Cl.C=12C(=O)NN=CC2=NC(N2CCOCC2)=NC=1NC(C=C1)=CC=C1CN1CCNCC1 FQXFKRRYNPIDCF-UHFFFAOYSA-N 0.000 claims description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
- QPMLSUSACCOBDK-UHFFFAOYSA-N diazepane Chemical class C1CCNNCC1 QPMLSUSACCOBDK-UHFFFAOYSA-N 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
- 229920001774 Perfluoroether Polymers 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- UZHXFPYZNTWGCX-UHFFFAOYSA-N methyl 4-[5-oxo-4-[4-(piperazin-1-ylmethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]benzoate;hydrochloride Chemical compound Cl.C1=CC(C(=O)OC)=CC=C1C1=NC(NC=2C=CC(CN3CCNCC3)=CC=2)=C2C(=O)NN=CC2=N1 UZHXFPYZNTWGCX-UHFFFAOYSA-N 0.000 claims description 2
- 150000002780 morpholines Chemical class 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 230000037361 pathway Effects 0.000 claims description 2
- 150000003053 piperidines Chemical class 0.000 claims description 2
- 235000011054 acetic acid Nutrition 0.000 claims 4
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 4
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims 4
- TUCUGMSPHGMPOI-UHFFFAOYSA-N 6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=NC=C2C(=O)NN=CC2=N1 TUCUGMSPHGMPOI-UHFFFAOYSA-N 0.000 claims 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 3
- 125000005605 benzo group Chemical group 0.000 claims 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- 125000004526 pyridazin-2-yl group Chemical group N1N(C=CC=C1)* 0.000 claims 3
- BXACYAKZBAFEIV-UHFFFAOYSA-N 2-[1-[4-[(2-cycloheptyl-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(C2CCCCCC2)=NC2=C1C(=O)NN=C2 BXACYAKZBAFEIV-UHFFFAOYSA-N 0.000 claims 2
- JCVVHKQMKLNYPK-UHFFFAOYSA-N 2-[1-[4-[[2-(2,6-dimethylmorpholin-4-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound C1C(C)OC(C)CN1C1=NC(NC=2C=CC(=CC=2)N2CCC(CC(O)=O)CC2)=C2C(=O)NN=CC2=N1 JCVVHKQMKLNYPK-UHFFFAOYSA-N 0.000 claims 2
- YBTVYOBZIFTKHY-UHFFFAOYSA-N 2-[1-[4-[[2-(3,5-dimethylpiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound C1C(C)CC(C)CN1C1=NC(NC=2C=CC(=CC=2)N2CCC(CC(O)=O)CC2)=C2C(=O)NN=CC2=N1 YBTVYOBZIFTKHY-UHFFFAOYSA-N 0.000 claims 2
- ZLJJGDNOJCDNKD-UHFFFAOYSA-N 2-[1-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-3-yl]acetic acid Chemical compound C1C(CC(=O)O)CCCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 ZLJJGDNOJCDNKD-UHFFFAOYSA-N 0.000 claims 2
- JHCFYMYSDATETA-UHFFFAOYSA-N 2-[1-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1N1CCC(CC#N)CC1 JHCFYMYSDATETA-UHFFFAOYSA-N 0.000 claims 2
- BDIYBAQRVGMTLJ-UHFFFAOYSA-N 2-[1-[5-[[2-[4-(cyanomethyl)piperidin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCC(CC#N)CC2)=NC=1NC(C=N1)=CC=C1N1CCC(CC#N)CC1 BDIYBAQRVGMTLJ-UHFFFAOYSA-N 0.000 claims 2
- JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 claims 2
- 239000005973 Carvone Substances 0.000 claims 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 2
- SMXDYVVLQHNNRX-UHFFFAOYSA-N OC(=O)C1CCN(Cc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCC(C[N+]#[C-])CC3)cc2)CC1 Chemical compound OC(=O)C1CCN(Cc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCC(C[N+]#[C-])CC3)cc2)CC1 SMXDYVVLQHNNRX-UHFFFAOYSA-N 0.000 claims 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 2
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 claims 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims 1
- DQHMEQRQZRKNGU-UHFFFAOYSA-N 1-[4-[(2-cycloheptyl-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(C2CCCCCC2)=NC2=C1C(=O)NN=C2 DQHMEQRQZRKNGU-UHFFFAOYSA-N 0.000 claims 1
- GWYVDNLLCWVVLH-UHFFFAOYSA-N 1-[5-oxo-4-[4-(piperazin-1-ylmethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C1=NC(NC=2C=CC(CN3CCNCC3)=CC=2)=C2C(=O)NN=CC2=N1 GWYVDNLLCWVVLH-UHFFFAOYSA-N 0.000 claims 1
- IGUXJMHNKADNMJ-UHFFFAOYSA-N 1-[5-oxo-4-[4-[[4-(2h-tetrazol-5-yl)piperidin-1-yl]methyl]anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidine-3-carbonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CC(CCC2)C#N)=NC=1NC(C=C1)=CC=C1CN(CC1)CCC1C=1N=NNN=1 IGUXJMHNKADNMJ-UHFFFAOYSA-N 0.000 claims 1
- PCTWVGOAOSCKTF-UHFFFAOYSA-N 1-[5-oxo-4-[4-[[4-(2h-tetrazol-5-ylmethyl)piperidin-1-yl]methyl]anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidine-3-carbonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CC(CCC2)C#N)=NC=1NC(C=C1)=CC=C1CN(CC1)CCC1CC=1N=NNN=1 PCTWVGOAOSCKTF-UHFFFAOYSA-N 0.000 claims 1
- LRYJICZRPINRKO-UHFFFAOYSA-N 1-[5-oxo-4-[4-[[4-(2h-tetrazol-5-ylmethyl)piperidin-1-yl]methyl]anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidine-4-carbonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCC(CC2)C#N)=NC=1NC(C=C1)=CC=C1CN(CC1)CCC1CC=1N=NNN=1 LRYJICZRPINRKO-UHFFFAOYSA-N 0.000 claims 1
- UTQAEKMSXQKRGW-UHFFFAOYSA-N 1-[[4-[(2-cycloheptyl-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC(C=C1)=CC=C1NC1=NC(C2CCCCCC2)=NC2=C1C(=O)NN=C2 UTQAEKMSXQKRGW-UHFFFAOYSA-N 0.000 claims 1
- YIPVVOKGILKIDL-UHFFFAOYSA-N 1-[[4-[(5-oxo-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC(C=C1)=CC=C1NC1C2C(=O)NNCC2NC(C=2C=CC=CC=2)N1 YIPVVOKGILKIDL-UHFFFAOYSA-N 0.000 claims 1
- GFQABYWIGQDNAT-UHFFFAOYSA-N 1-[[4-[[2-(1,4-diazepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC(C=C1)=CC=C1NC1=NC(N2CCNCCC2)=NC2=C1C(=O)NN=C2 GFQABYWIGQDNAT-UHFFFAOYSA-N 0.000 claims 1
- RDRKXVZADSMSRV-UHFFFAOYSA-N 1-[[4-[[2-(4-cyanopiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC(C=C1)=CC=C1NC1=NC(N2CCC(CC2)C#N)=NC2=C1C(=O)NN=C2 RDRKXVZADSMSRV-UHFFFAOYSA-N 0.000 claims 1
- BRTVFTOHSYFRAX-UHFFFAOYSA-N 1-[[4-[[2-[1-(2-cyanoacetyl)piperidin-4-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC(C=C1)=CC=C1NC1=NC(C2CCN(CC2)C(=O)CC#N)=NC2=C1C(=O)NN=C2 BRTVFTOHSYFRAX-UHFFFAOYSA-N 0.000 claims 1
- RHEJAFIJMIXTRZ-UHFFFAOYSA-N 1-[[4-[[2-[4-(2-cyanoacetyl)piperazin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC(C=C1)=CC=C1NC1=NC(N2CCN(CC2)C(=O)CC#N)=NC2=C1C(=O)NN=C2 RHEJAFIJMIXTRZ-UHFFFAOYSA-N 0.000 claims 1
- GODQDEZAPIGXQP-UHFFFAOYSA-N 1-[[4-[[2-[4-(cyanomethyl)piperazin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC(C=C1)=CC=C1NC1=NC(N2CCN(CC#N)CC2)=NC2=C1C(=O)NN=C2 GODQDEZAPIGXQP-UHFFFAOYSA-N 0.000 claims 1
- ZQVDOALFJLMVJY-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yl)-4-[4-(piperazin-1-ylmethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one;hydrochloride Chemical compound Cl.C=12C(=O)NN=CC2=NC(C=2C=C3OCOC3=CC=2)=NC=1NC(C=C1)=CC=C1CN1CCNCC1 ZQVDOALFJLMVJY-UHFFFAOYSA-N 0.000 claims 1
- PWQYFIGYNKXMGO-UHFFFAOYSA-N 2-(2,6-dimethylmorpholin-4-yl)-4-[4-(piperazin-1-ylmethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1C(C)OC(C)CN1C1=NC(NC=2C=CC(CN3CCNCC3)=CC=2)=C2C(=O)NN=CC2=N1 PWQYFIGYNKXMGO-UHFFFAOYSA-N 0.000 claims 1
- QZYIENPQSUGNJJ-UHFFFAOYSA-N 2-(2,6-dimethylmorpholin-4-yl)-4-[4-[4-(2-hydroxy-2-methylpropanoyl)piperidin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1C(C)OC(C)CN1C1=NC(NC=2C=CC(=CC=2)N2CCC(CC2)C(=O)C(C)(C)O)=C2C(=O)NN=CC2=N1 QZYIENPQSUGNJJ-UHFFFAOYSA-N 0.000 claims 1
- FOKIZMPMKWLBFN-UHFFFAOYSA-N 2-(2,6-dimethylpiperidin-1-yl)-4-[4-(piperazin-1-ylmethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound CC1CCCC(C)N1C1=NC(NC=2C=CC(CN3CCNCC3)=CC=2)=C2C(=O)NN=CC2=N1 FOKIZMPMKWLBFN-UHFFFAOYSA-N 0.000 claims 1
- PQBUWKLREGFKPV-UHFFFAOYSA-N 2-(2,6-dimethylpiperidin-1-yl)-4-[4-[4-(2-hydroxy-2-methylpropanoyl)piperazin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound CC1CCCC(C)N1C1=NC(NC=2C=CC(=CC=2)N2CCN(CC2)C(=O)C(C)(C)O)=C2C(=O)NN=CC2=N1 PQBUWKLREGFKPV-UHFFFAOYSA-N 0.000 claims 1
- ALGAGCOMWWNTFS-UHFFFAOYSA-N 2-(2-methylpiperidin-1-yl)-4-[4-(piperazin-1-ylmethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound CC1CCCCN1C1=NC(NC=2C=CC(CN3CCNCC3)=CC=2)=C2C(=O)NN=CC2=N1 ALGAGCOMWWNTFS-UHFFFAOYSA-N 0.000 claims 1
- LMNBXWZFGDZDPQ-UHFFFAOYSA-N 2-(3,5-dimethylpiperidin-1-yl)-4-[4-(piperazin-1-ylmethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1C(C)CC(C)CN1C1=NC(NC=2C=CC(CN3CCNCC3)=CC=2)=C2C(=O)NN=CC2=N1 LMNBXWZFGDZDPQ-UHFFFAOYSA-N 0.000 claims 1
- SWNARPWGNMZKTR-UHFFFAOYSA-N 2-(3,5-dimethylpiperidin-1-yl)-4-[4-[4-(2-hydroxy-2-methylpropanoyl)piperidin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1C(C)CC(C)CN1C1=NC(NC=2C=CC(=CC=2)N2CCC(CC2)C(=O)C(C)(C)O)=C2C(=O)NN=CC2=N1 SWNARPWGNMZKTR-UHFFFAOYSA-N 0.000 claims 1
- GEIUOZVZDHABJA-UHFFFAOYSA-N 2-(4-ethylpiperazin-1-yl)-4-[4-(piperazin-1-ylmethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one;hydrochloride Chemical compound Cl.C1CN(CC)CCN1C1=NC(NC=2C=CC(CN3CCNCC3)=CC=2)=C2C(=O)NN=CC2=N1 GEIUOZVZDHABJA-UHFFFAOYSA-N 0.000 claims 1
- KFHYJLQWOOBWIW-UHFFFAOYSA-N 2-(4-methylpiperidin-1-yl)-4-[4-(2-piperazin-1-ylethoxy)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one;hydrochloride Chemical compound Cl.C1CC(C)CCN1C1=NC(NC=2C=CC(OCCN3CCNCC3)=CC=2)=C2C(=O)NN=CC2=N1 KFHYJLQWOOBWIW-UHFFFAOYSA-N 0.000 claims 1
- IZJDDAXLNVWKQV-UHFFFAOYSA-N 2-(6-azaspiro[2.5]octan-6-yl)-4-(4-morpholin-4-ylanilino)-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCC3(CC3)CC2)=NC=1NC(C=C1)=CC=C1N1CCOCC1 IZJDDAXLNVWKQV-UHFFFAOYSA-N 0.000 claims 1
- ODVAGCHOBKZNJO-UHFFFAOYSA-N 2-(azepan-1-yl)-4-(2h-benzotriazol-5-ylamino)-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound N=1C(NC=2C=C3N=NNC3=CC=2)=C2C(=O)NN=CC2=NC=1N1CCCCCC1 ODVAGCHOBKZNJO-UHFFFAOYSA-N 0.000 claims 1
- XWTPGDYKOXRGGS-UHFFFAOYSA-N 2-(azepan-1-yl)-4-(4-fluoroanilino)-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=CC(F)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 XWTPGDYKOXRGGS-UHFFFAOYSA-N 0.000 claims 1
- RQVSTZRYEAVRET-UHFFFAOYSA-N 2-(azepan-1-yl)-4-(4-methylsulfonylanilino)-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 RQVSTZRYEAVRET-UHFFFAOYSA-N 0.000 claims 1
- MLWMQOQVMDQGDC-UHFFFAOYSA-N 2-(azepan-1-yl)-4-(4-morpholin-4-ylanilino)-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1N1CCOCC1 MLWMQOQVMDQGDC-UHFFFAOYSA-N 0.000 claims 1
- FNMSNCOGAKUVDX-UHFFFAOYSA-N 2-(azepan-1-yl)-4-(4-piperidin-4-yloxyanilino)-6h-pyrimido[4,5-d]pyridazin-5-one;hydrochloride Chemical compound Cl.C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1OC1CCNCC1 FNMSNCOGAKUVDX-UHFFFAOYSA-N 0.000 claims 1
- ISAKNYJSENHFTQ-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[3-(hydroxymethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound OCC1=CC=CC(NC=2C=3C(=O)NN=CC=3N=C(N=2)N2CCCCCC2)=C1 ISAKNYJSENHFTQ-UHFFFAOYSA-N 0.000 claims 1
- PLNZRHOWESHDLZ-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(1-hydroxy-2-methylpropan-2-yl)oxyanilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=CC(OC(C)(CO)C)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 PLNZRHOWESHDLZ-UHFFFAOYSA-N 0.000 claims 1
- CZMLJVGPETYKEJ-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(2-ethyltetrazol-5-yl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound CCN1N=NC(C=2C=CC(NC=3C=4C(=O)NN=CC=4N=C(N=3)N3CCCCCC3)=CC=2)=N1 CZMLJVGPETYKEJ-UHFFFAOYSA-N 0.000 claims 1
- OAKFEOPDFIPHNK-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(2-hydroxyethoxy)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=CC(OCCO)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 OAKFEOPDFIPHNK-UHFFFAOYSA-N 0.000 claims 1
- RXIZXXKJRDEVMI-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(2-hydroxyethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=CC(CCO)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 RXIZXXKJRDEVMI-UHFFFAOYSA-N 0.000 claims 1
- MESFFTSCLYFQNJ-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(2-methoxyethoxy)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=CC(OCCOC)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 MESFFTSCLYFQNJ-UHFFFAOYSA-N 0.000 claims 1
- YKKVLDDNAYHXNZ-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(2-morpholin-4-ylethoxy)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1OCCN1CCOCC1 YKKVLDDNAYHXNZ-UHFFFAOYSA-N 0.000 claims 1
- RYZDJZFSIODRQX-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(2-piperazin-1-ylethoxy)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1OCCN1CCNCC1 RYZDJZFSIODRQX-UHFFFAOYSA-N 0.000 claims 1
- FWSXXCBEKWMASQ-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(2-piperazin-1-ylethoxy)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one;hydrochloride Chemical compound Cl.C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1OCCN1CCNCC1 FWSXXCBEKWMASQ-UHFFFAOYSA-N 0.000 claims 1
- LFMMFFXSMFPZCC-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(2-piperazin-1-ylethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1CCN1CCNCC1 LFMMFFXSMFPZCC-UHFFFAOYSA-N 0.000 claims 1
- TWQCCZUFZBJSER-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(3-hydroxypiperidin-1-yl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1C(O)CCCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 TWQCCZUFZBJSER-UHFFFAOYSA-N 0.000 claims 1
- RQGSMFTVLOIWDI-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(3-hydroxypropoxy)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=CC(OCCCO)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 RQGSMFTVLOIWDI-UHFFFAOYSA-N 0.000 claims 1
- HKNMOTLQXYDGCC-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(3-hydroxypropyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=CC(CCCO)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 HKNMOTLQXYDGCC-UHFFFAOYSA-N 0.000 claims 1
- RIHAPCPVSFCDSQ-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(3-piperazin-1-ylpropoxy)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1OCCCN1CCNCC1 RIHAPCPVSFCDSQ-UHFFFAOYSA-N 0.000 claims 1
- BGYRXGQWAZXEDS-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(3-piperazin-1-ylpropyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1CCCN1CCNCC1 BGYRXGQWAZXEDS-UHFFFAOYSA-N 0.000 claims 1
- PLMRZLPLJGKPMQ-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(4,4-difluoropiperidin-1-yl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CC(F)(F)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 PLMRZLPLJGKPMQ-UHFFFAOYSA-N 0.000 claims 1
- MUKBSXUWZHPJBE-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(4-hydroxypiperidin-1-yl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CC(O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 MUKBSXUWZHPJBE-UHFFFAOYSA-N 0.000 claims 1
- JUFNJDGTOSTABG-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-(morpholine-4-carbonyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=1C=C(NC=2C=3C(=O)NN=CC=3N=C(N=2)N2CCCCCC2)C=CC=1C(=O)N1CCOCC1 JUFNJDGTOSTABG-UHFFFAOYSA-N 0.000 claims 1
- UEUZWOPDWCJLFL-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(1,4-diazepan-1-yl)ethoxy]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1OCCN1CCCNCC1 UEUZWOPDWCJLFL-UHFFFAOYSA-N 0.000 claims 1
- ZLKXZPXDOZIMOT-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(3-oxopiperazin-1-yl)ethoxy]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CNC(=O)CN1CCOC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 ZLKXZPXDOZIMOT-UHFFFAOYSA-N 0.000 claims 1
- LQQOXQAYDYXSRD-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(4-ethylpiperazin-1-yl)-2-oxoethoxy]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(CC)CCN1C(=O)COC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 LQQOXQAYDYXSRD-UHFFFAOYSA-N 0.000 claims 1
- DCSJUPXLDMJOJR-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(4-ethylpiperazin-1-yl)ethoxy]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(CC)CCN1CCOC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 DCSJUPXLDMJOJR-UHFFFAOYSA-N 0.000 claims 1
- WGDFDNOMSGBBJS-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(4-ethylpiperazin-1-yl)ethyl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(CC)CCN1CCC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 WGDFDNOMSGBBJS-UHFFFAOYSA-N 0.000 claims 1
- LBWDZKUIXZGMRC-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(4-hydroxy-4-methylpiperidin-1-yl)ethoxy]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CC(C)(O)CCN1CCOC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 LBWDZKUIXZGMRC-UHFFFAOYSA-N 0.000 claims 1
- OGSQWLDZPCKFBL-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(4-hydroxy-4-methylpiperidin-1-yl)ethyl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CC(C)(O)CCN1CCC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 OGSQWLDZPCKFBL-UHFFFAOYSA-N 0.000 claims 1
- HYHWPPVSNVMQKG-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(4-hydroxypiperidin-1-yl)ethoxy]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CC(O)CCN1CCOC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 HYHWPPVSNVMQKG-UHFFFAOYSA-N 0.000 claims 1
- CQCJOABXZPVPFA-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(4-hydroxypiperidin-1-yl)ethyl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CC(O)CCN1CCC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 CQCJOABXZPVPFA-UHFFFAOYSA-N 0.000 claims 1
- RSVRQLHDWFVQCL-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(4-methylpiperazin-1-yl)-2-oxoethoxy]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(C)CCN1C(=O)COC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 RSVRQLHDWFVQCL-UHFFFAOYSA-N 0.000 claims 1
- DECWCGJHVBGDPC-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(4-methylpiperazin-1-yl)ethoxy]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(C)CCN1CCOC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 DECWCGJHVBGDPC-UHFFFAOYSA-N 0.000 claims 1
- PYLOBWHIDAVZTO-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(diethylamino)ethoxy]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 PYLOBWHIDAVZTO-UHFFFAOYSA-N 0.000 claims 1
- GBMAQXAAFUMFMD-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(dimethylamino)ethoxy]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=CC(OCCN(C)C)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 GBMAQXAAFUMFMD-UHFFFAOYSA-N 0.000 claims 1
- ARFUBOBMDOPZSH-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-(hydroxymethyl)-6-azaspiro[2.5]octan-6-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound OCC1CC11CCN(C=2C=CC(NC=3C=4C(=O)NN=CC=4N=C(N=3)N3CCCCCC3)=CC=2)CC1 ARFUBOBMDOPZSH-UHFFFAOYSA-N 0.000 claims 1
- CISVPDHPAHVGKD-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-[4-(2-hydroxyethyl)piperazin-1-yl]ethoxy]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(CCO)CCN1CCOC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 CISVPDHPAHVGKD-UHFFFAOYSA-N 0.000 claims 1
- OOWPOJNZCSHXJD-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-[4-(2-hydroxyethyl)piperazin-1-yl]ethyl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(CCO)CCN1CCC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 OOWPOJNZCSHXJD-UHFFFAOYSA-N 0.000 claims 1
- NXPMVEXTFYJLLS-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[2-[di(propan-2-yl)amino]ethoxy]anilino]-6-methanimidoylpyrimidine-5-carboxamide Chemical compound C1=CC(OCCN(C(C)C)C(C)C)=CC=C1NC1=NC(N2CCCCCC2)=NC(C=N)=C1C(N)=O NXPMVEXTFYJLLS-UHFFFAOYSA-N 0.000 claims 1
- BAPVGKRYXAZESI-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[3-(2-hydroxyethyl)piperidin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1C(CCO)CCCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 BAPVGKRYXAZESI-UHFFFAOYSA-N 0.000 claims 1
- YTBOWIHSWMFGMZ-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[3-(4-hydroxypiperidin-1-yl)propyl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CC(O)CCN1CCCC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 YTBOWIHSWMFGMZ-UHFFFAOYSA-N 0.000 claims 1
- AUCSMJREAGEEBJ-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[4-(2-fluoroethyl)piperazin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(CCF)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 AUCSMJREAGEEBJ-UHFFFAOYSA-N 0.000 claims 1
- CNPKPHSSRROGJX-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[4-(2-fluoroethyl)piperidin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CC(CCF)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 CNPKPHSSRROGJX-UHFFFAOYSA-N 0.000 claims 1
- AGWDZMOUZQZVIK-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[4-(2-hydroxy-2-methylpropanoyl)piperazin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(C(=O)C(C)(O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 AGWDZMOUZQZVIK-UHFFFAOYSA-N 0.000 claims 1
- QBRFMRDBOKTIJD-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[4-(2-hydroxyethyl)-1,4-diazepan-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(CCO)CCCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 QBRFMRDBOKTIJD-UHFFFAOYSA-N 0.000 claims 1
- HMJOHRRHAANVNT-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[4-(2-hydroxyethyl)piperazin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(CCO)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 HMJOHRRHAANVNT-UHFFFAOYSA-N 0.000 claims 1
- YJRXHACLAZOJMV-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[4-(2-hydroxyethyl)piperidin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CC(CCO)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 YJRXHACLAZOJMV-UHFFFAOYSA-N 0.000 claims 1
- OHKAPGVTPJBHMW-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[4-(2-hydroxypropan-2-yl)piperidin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CC(C(C)(O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 OHKAPGVTPJBHMW-UHFFFAOYSA-N 0.000 claims 1
- ZWDHHDQLIIZORJ-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[4-(2-methoxyethyl)piperazin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(CCOC)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 ZWDHHDQLIIZORJ-UHFFFAOYSA-N 0.000 claims 1
- XSPVBRTUDJLQHT-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[4-(2h-tetrazol-5-ylmethyl)piperidin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1N(CC1)CCC1CC=1N=NNN=1 XSPVBRTUDJLQHT-UHFFFAOYSA-N 0.000 claims 1
- CIXIYNWZBIBNPJ-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[4-(3-hydroxypropyl)piperazin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(CCCO)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 CIXIYNWZBIBNPJ-UHFFFAOYSA-N 0.000 claims 1
- JNGDMXQJQQFQCZ-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[4-(3-hydroxypropyl)piperidin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CC(CCCO)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 JNGDMXQJQQFQCZ-UHFFFAOYSA-N 0.000 claims 1
- OYAPELWSINUPOM-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[4-(hydroxymethyl)piperidin-1-yl]anilino]-6-methanimidoylpyrimidine-5-carboxamide Chemical compound N1=C(N2CCCCCC2)N=C(C=N)C(C(=O)N)=C1NC(C=C1)=CC=C1N1CCC(CO)CC1 OYAPELWSINUPOM-UHFFFAOYSA-N 0.000 claims 1
- IOOLIHWRFJAGAW-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[[4-(2h-tetrazol-5-yl)piperidin-1-yl]methyl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1CN(CC1)CCC1C=1N=NNN=1 IOOLIHWRFJAGAW-UHFFFAOYSA-N 0.000 claims 1
- LSJRPFVCHIAVPU-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[[4-(2h-tetrazol-5-ylmethyl)piperidin-1-yl]methyl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1CN(CC1)CCC1CC=1N=NNN=1 LSJRPFVCHIAVPU-UHFFFAOYSA-N 0.000 claims 1
- UNOYSHGDZLAVLK-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[4-[bis(2-hydroxyethyl)amino]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=CC(N(CCO)CCO)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 UNOYSHGDZLAVLK-UHFFFAOYSA-N 0.000 claims 1
- GVZMVIZFLAHGSP-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[[6-(2-piperazin-1-ylethoxy)pyridin-3-yl]amino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=N1)=CC=C1OCCN1CCNCC1 GVZMVIZFLAHGSP-UHFFFAOYSA-N 0.000 claims 1
- YURDXNFXINHACP-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[[6-(3-hydroxypiperidin-1-yl)pyridin-3-yl]amino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1C(O)CCCN1C(N=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 YURDXNFXINHACP-UHFFFAOYSA-N 0.000 claims 1
- RXIKMJWFBQWPGA-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[[6-(4-ethylpiperazin-1-yl)pyridin-3-yl]amino]-6-methanimidoylpyrimidine-5-carboxamide Chemical compound C1CN(CC)CCN1C(N=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC(C=N)=C1C(N)=O RXIKMJWFBQWPGA-UHFFFAOYSA-N 0.000 claims 1
- GFKWHZAGPDLSPU-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[[6-(4-hydroxypiperidin-1-yl)pyridin-3-yl]amino]-6-methanimidoylpyrimidine-5-carboxamide Chemical compound N1=C(N2CCCCCC2)N=C(C=N)C(C(=O)N)=C1NC(C=N1)=CC=C1N1CCC(O)CC1 GFKWHZAGPDLSPU-UHFFFAOYSA-N 0.000 claims 1
- DIGIWXYCKRCHGB-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[[6-[4-(2-hydroxy-2-methylpropanoyl)piperazin-1-yl]pyridin-3-yl]amino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(C(=O)C(C)(O)C)CCN1C(N=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 DIGIWXYCKRCHGB-UHFFFAOYSA-N 0.000 claims 1
- YYZHLVMUOGPGFH-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[[6-[4-(2-hydroxyethyl)piperidin-1-yl]pyridin-3-yl]amino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CC(CCO)CCN1C(N=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 YYZHLVMUOGPGFH-UHFFFAOYSA-N 0.000 claims 1
- XDZRLVAWZMEKTN-UHFFFAOYSA-N 2-(azepan-1-yl)-4-[[6-[4-(2h-tetrazol-5-ylmethyl)piperidin-1-yl]pyridin-3-yl]amino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=N1)=CC=C1N(CC1)CCC1CC=1N=NNN=1 XDZRLVAWZMEKTN-UHFFFAOYSA-N 0.000 claims 1
- HSXOWAZAWNXKBH-UHFFFAOYSA-N 2-(azepan-1-yl)-4-methanimidoyl-6-(4-piperazin-1-ylanilino)pyrimidine-5-carboxamide Chemical compound N1=C(N2CCCCCC2)N=C(C=N)C(C(=O)N)=C1NC(C=C1)=CC=C1N1CCNCC1 HSXOWAZAWNXKBH-UHFFFAOYSA-N 0.000 claims 1
- PLMLSHIYJOCZES-UHFFFAOYSA-N 2-(azepan-1-yl)-4-methanimidoyl-6-[(6-piperazin-1-ylpyridin-3-yl)amino]pyrimidine-5-carboxamide Chemical compound N1=C(N2CCCCCC2)N=C(C=N)C(C(=O)N)=C1NC(C=N1)=CC=C1N1CCNCC1 PLMLSHIYJOCZES-UHFFFAOYSA-N 0.000 claims 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 claims 1
- XYRIWKWYDIPEIS-UHFFFAOYSA-N 2-[1-(2-isocyanoacetyl)piperidin-4-yl]-4-[4-[[4-(2H-tetrazol-5-ylmethyl)piperidin-1-yl]methyl]anilino]-6H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(C(C[N+]#[C-])=O)CCC1C1=NC(NC=2C=CC(CN3CCC(CC4=NNN=N4)CC3)=CC=2)=C2C(=O)NN=CC2=N1 XYRIWKWYDIPEIS-UHFFFAOYSA-N 0.000 claims 1
- CIRUZMRIKHTPOG-UHFFFAOYSA-N 2-[1-[2-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenoxy]ethyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1CCOC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 CIRUZMRIKHTPOG-UHFFFAOYSA-N 0.000 claims 1
- SXDILXCFYORZFS-UHFFFAOYSA-N 2-[1-[2-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]piperidin-1-yl]ethyl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(CC1)CCN1CCN1CCC(CC#N)CC1 SXDILXCFYORZFS-UHFFFAOYSA-N 0.000 claims 1
- ONWQCRZBUOXITQ-UHFFFAOYSA-N 2-[1-[3-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenoxy]propyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1CCCOC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 ONWQCRZBUOXITQ-UHFFFAOYSA-N 0.000 claims 1
- BMCOMLYRWROTIC-UHFFFAOYSA-N 2-[1-[4-(3,4-dimethoxyanilino)-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=C(OC)C(OC)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 BMCOMLYRWROTIC-UHFFFAOYSA-N 0.000 claims 1
- VOCWEMFHZLOTHJ-UHFFFAOYSA-N 2-[1-[4-(3,5-dimethoxyanilino)-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound COC1=CC(OC)=CC(NC=2C=3C(=O)NN=CC=3N=C(N=2)N2CCC(CC#N)CC2)=C1 VOCWEMFHZLOTHJ-UHFFFAOYSA-N 0.000 claims 1
- BCUZROOCSCJNDI-UHFFFAOYSA-N 2-[1-[4-(3-methoxyanilino)-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound COC1=CC=CC(NC=2C=3C(=O)NN=CC=3N=C(N=2)N2CCC(CC#N)CC2)=C1 BCUZROOCSCJNDI-UHFFFAOYSA-N 0.000 claims 1
- YKIWKCHKWQGGES-UHFFFAOYSA-N 2-[1-[4-(4-fluoroanilino)-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(F)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 YKIWKCHKWQGGES-UHFFFAOYSA-N 0.000 claims 1
- MVXVCMDMYHRBPV-UHFFFAOYSA-N 2-[1-[4-(4-methylsulfonylanilino)-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(S(=O)(=O)C)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 MVXVCMDMYHRBPV-UHFFFAOYSA-N 0.000 claims 1
- MYWVHKINECQIOO-UHFFFAOYSA-N 2-[1-[4-[(5-oxo-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C(C=C1)=CC=C1NC1C2C(=O)NNCC2NC(C=2C=CC=CC=2)N1 MYWVHKINECQIOO-UHFFFAOYSA-N 0.000 claims 1
- KGMKDNMNJDEGKW-UHFFFAOYSA-N 2-[1-[4-[(5-oxo-2-phenyl-6h-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(C=2C=CC=CC=2)=NC=1NC(C=C1)=CC=C1N1CCC(CC#N)CC1 KGMKDNMNJDEGKW-UHFFFAOYSA-N 0.000 claims 1
- ZZIPKXKOZASFNH-UHFFFAOYSA-N 2-[1-[4-[3-(hydroxymethyl)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound OCC1=CC=CC(NC=2C=3C(=O)NN=CC=3N=C(N=2)N2CCC(CC#N)CC2)=C1 ZZIPKXKOZASFNH-UHFFFAOYSA-N 0.000 claims 1
- NSXLMTSVPFZQNQ-UHFFFAOYSA-N 2-[1-[4-[4-(1-hydroxy-2-methylpropan-2-yl)oxyanilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(OC(C)(CO)C)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 NSXLMTSVPFZQNQ-UHFFFAOYSA-N 0.000 claims 1
- JZNSOSHUGJVPCI-UHFFFAOYSA-N 2-[1-[4-[4-(2-aminoethoxy)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(OCCN)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 JZNSOSHUGJVPCI-UHFFFAOYSA-N 0.000 claims 1
- XMFADZKTTRIXAE-UHFFFAOYSA-N 2-[1-[4-[4-(2-ethyltetrazol-5-yl)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound CCN1N=NC(C=2C=CC(NC=3C=4C(=O)NN=CC=4N=C(N=3)N3CCC(CC#N)CC3)=CC=2)=N1 XMFADZKTTRIXAE-UHFFFAOYSA-N 0.000 claims 1
- QKCMDGMFYDDNIU-UHFFFAOYSA-N 2-[1-[4-[4-(2-hydroxyethoxy)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(OCCO)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 QKCMDGMFYDDNIU-UHFFFAOYSA-N 0.000 claims 1
- SLWNSBACHGTCSL-UHFFFAOYSA-N 2-[1-[4-[4-(2-hydroxyethyl)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(CCO)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 SLWNSBACHGTCSL-UHFFFAOYSA-N 0.000 claims 1
- JLVJXSSGBIIFAL-UHFFFAOYSA-N 2-[1-[4-[4-(2-methoxyethoxy)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(OCCOC)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 JLVJXSSGBIIFAL-UHFFFAOYSA-N 0.000 claims 1
- STUXZVYNMDRZHE-UHFFFAOYSA-N 2-[1-[4-[4-(3-fluoropropyl)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(CCCF)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 STUXZVYNMDRZHE-UHFFFAOYSA-N 0.000 claims 1
- KBTZBNSTRFVKHX-UHFFFAOYSA-N 2-[1-[4-[4-(3-hydroxypropoxy)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(OCCCO)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 KBTZBNSTRFVKHX-UHFFFAOYSA-N 0.000 claims 1
- LHSAEXHLZCPBIR-UHFFFAOYSA-N 2-[1-[4-[4-(3-hydroxypropyl)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(CCCO)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 LHSAEXHLZCPBIR-UHFFFAOYSA-N 0.000 claims 1
- MEUIVFUNEDFODR-UHFFFAOYSA-N 2-[1-[4-[4-(4,4-difluoropiperidin-1-yl)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CC(F)(F)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 MEUIVFUNEDFODR-UHFFFAOYSA-N 0.000 claims 1
- CRTWTCGXTBFBRC-UHFFFAOYSA-N 2-[1-[4-[4-(4-ethyl-3-oxopiperazin-1-yl)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1C(=O)N(CC)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 CRTWTCGXTBFBRC-UHFFFAOYSA-N 0.000 claims 1
- DGDKLFRWILUTRT-UHFFFAOYSA-N 2-[1-[4-[4-(4-fluoropiperidin-1-yl)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CC(F)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 DGDKLFRWILUTRT-UHFFFAOYSA-N 0.000 claims 1
- ZZXDCXDYBQNAQO-UHFFFAOYSA-N 2-[1-[4-[4-(4-methoxypiperidin-1-yl)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CC(OC)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 ZZXDCXDYBQNAQO-UHFFFAOYSA-N 0.000 claims 1
- AYVBENXNEMWXMU-UHFFFAOYSA-N 2-[1-[4-[4-(4-methylpiperazin-1-yl)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 AYVBENXNEMWXMU-UHFFFAOYSA-N 0.000 claims 1
- NMQCMGVCKWRENS-UHFFFAOYSA-N 2-[1-[4-[4-(difluoromethoxy)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(OC(F)F)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 NMQCMGVCKWRENS-UHFFFAOYSA-N 0.000 claims 1
- NPSWKSAWDLUJLR-UHFFFAOYSA-N 2-[1-[4-[4-(hydroxymethyl)anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(CO)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 NPSWKSAWDLUJLR-UHFFFAOYSA-N 0.000 claims 1
- LLENPOKVIGSYRZ-UHFFFAOYSA-N 2-[1-[4-[4-[2-(4-hydroxy-4-methylpiperidin-1-yl)ethoxy]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CC(C)(O)CCN1CCOC(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 LLENPOKVIGSYRZ-UHFFFAOYSA-N 0.000 claims 1
- NLXLMINLOOVCET-UHFFFAOYSA-N 2-[1-[4-[4-[2-(4-methylpiperazin-1-yl)-2-oxoethoxy]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CN(C)CCN1C(=O)COC(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 NLXLMINLOOVCET-UHFFFAOYSA-N 0.000 claims 1
- CISLRSNPHVRCJG-UHFFFAOYSA-N 2-[1-[4-[4-[2-(diethylamino)ethoxy]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 CISLRSNPHVRCJG-UHFFFAOYSA-N 0.000 claims 1
- FDTCETNNEBMDSI-UHFFFAOYSA-N 2-[1-[4-[4-[2-(hydroxymethyl)-6-azaspiro[2.5]octan-6-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound OCC1CC11CCN(C=2C=CC(NC=3C=4C(=O)NN=CC=4N=C(N=3)N3CCC(CC#N)CC3)=CC=2)CC1 FDTCETNNEBMDSI-UHFFFAOYSA-N 0.000 claims 1
- UZVNTRNYZHBBRQ-UHFFFAOYSA-N 2-[1-[4-[4-[2-[4-(2-hydroxyethyl)piperazin-1-yl]ethyl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CN(CCO)CCN1CCC(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 UZVNTRNYZHBBRQ-UHFFFAOYSA-N 0.000 claims 1
- IAQFWBGWLCTRFN-UHFFFAOYSA-N 2-[1-[4-[4-[2-[4-(hydroxymethyl)piperidin-1-yl]ethoxy]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CC(CO)CCN1CCOC(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 IAQFWBGWLCTRFN-UHFFFAOYSA-N 0.000 claims 1
- GYZLMNXPXAYBMK-UHFFFAOYSA-N 2-[1-[4-[4-[3-(2-hydroxyethyl)piperidin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1C(CCO)CCCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 GYZLMNXPXAYBMK-UHFFFAOYSA-N 0.000 claims 1
- HCWZVRZKAROHBM-UHFFFAOYSA-N 2-[1-[4-[4-[3-(hydroxymethyl)piperidin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1C(CO)CCCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 HCWZVRZKAROHBM-UHFFFAOYSA-N 0.000 claims 1
- IQXLJBQAZJZPOZ-UHFFFAOYSA-N 2-[1-[4-[4-[4-(2,3-dihydroxypropyl)piperazin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CN(CC(O)CO)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 IQXLJBQAZJZPOZ-UHFFFAOYSA-N 0.000 claims 1
- AOSXWJLOQOHZLF-UHFFFAOYSA-N 2-[1-[4-[4-[4-(2-aminoethyl)piperazin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CN(CCN)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 AOSXWJLOQOHZLF-UHFFFAOYSA-N 0.000 claims 1
- VJANWUOQIRLQLV-UHFFFAOYSA-N 2-[1-[4-[4-[4-(2-fluoroethyl)piperazin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CN(CCF)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 VJANWUOQIRLQLV-UHFFFAOYSA-N 0.000 claims 1
- XVNUWBXCLRWCLO-UHFFFAOYSA-N 2-[1-[4-[4-[4-(2-fluoroethyl)piperidin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CC(CCF)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 XVNUWBXCLRWCLO-UHFFFAOYSA-N 0.000 claims 1
- VNEOFSRZUQNVIU-UHFFFAOYSA-N 2-[1-[4-[4-[4-(2-hydroxyethyl)-1,4-diazepan-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CN(CCO)CCCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 VNEOFSRZUQNVIU-UHFFFAOYSA-N 0.000 claims 1
- RUXLYAGOXLTHIG-UHFFFAOYSA-N 2-[1-[4-[4-[4-(2-hydroxyethyl)piperazin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CN(CCO)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 RUXLYAGOXLTHIG-UHFFFAOYSA-N 0.000 claims 1
- VGWZWARUYOJGFS-UHFFFAOYSA-N 2-[1-[4-[4-[4-(2-hydroxyethyl)piperidin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CC(CCO)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 VGWZWARUYOJGFS-UHFFFAOYSA-N 0.000 claims 1
- LXSFMSJRSBGNET-UHFFFAOYSA-N 2-[1-[4-[4-[4-(2-hydroxypropan-2-yl)piperidin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CC(C(C)(O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 LXSFMSJRSBGNET-UHFFFAOYSA-N 0.000 claims 1
- QKALHAYRECPYNX-UHFFFAOYSA-N 2-[1-[4-[4-[4-(2-methoxyethyl)piperazin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CN(CCOC)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 QKALHAYRECPYNX-UHFFFAOYSA-N 0.000 claims 1
- FYJRMCOKVMYLQJ-UHFFFAOYSA-N 2-[1-[4-[4-[4-(3-hydroxypropyl)piperazin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CN(CCCO)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 FYJRMCOKVMYLQJ-UHFFFAOYSA-N 0.000 claims 1
- RDEDVVUPPSUAIU-UHFFFAOYSA-N 2-[1-[4-[4-[4-(cyanomethyl)piperazin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCC(CC#N)CC2)=NC=1NC(C=C1)=CC=C1N1CCN(CC#N)CC1 RDEDVVUPPSUAIU-UHFFFAOYSA-N 0.000 claims 1
- HXAZIDNOTNMKQS-UHFFFAOYSA-N 2-[1-[4-[4-[4-(hydroxymethyl)piperidin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CC(CO)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 HXAZIDNOTNMKQS-UHFFFAOYSA-N 0.000 claims 1
- CLCVYZZSOVSICV-UHFFFAOYSA-N 2-[1-[4-[4-[4-[2-(dimethylamino)ethyl]piperazin-1-yl]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CN(CCN(C)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 CLCVYZZSOVSICV-UHFFFAOYSA-N 0.000 claims 1
- YORPJVFFCMACGV-UHFFFAOYSA-N 2-[1-[4-[4-[bis(2-hydroxyethyl)amino]anilino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(N(CCO)CCO)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 YORPJVFFCMACGV-UHFFFAOYSA-N 0.000 claims 1
- KYCAKYXRRPCJQX-UHFFFAOYSA-N 2-[1-[4-[[2-(1,4-diazepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCNCCC2)=NC2=C1C(=O)NN=C2 KYCAKYXRRPCJQX-UHFFFAOYSA-N 0.000 claims 1
- NZRYFJRBXZZVSO-UHFFFAOYSA-N 2-[1-[4-[[2-(2,6-dimethylmorpholin-4-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetonitrile Chemical compound C1C(C)OC(C)CN1C1=NC(NC=2C=CC(=CC=2)N2CCC(CC#N)CC2)=C2C(=O)NN=CC2=N1 NZRYFJRBXZZVSO-UHFFFAOYSA-N 0.000 claims 1
- RGEYYDDEXORXFI-UHFFFAOYSA-N 2-[1-[4-[[2-(2,6-dimethylpiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound CC1CCCC(C)N1C1=NC(NC=2C=CC(=CC=2)N2CCC(CC(O)=O)CC2)=C2C(=O)NN=CC2=N1 RGEYYDDEXORXFI-UHFFFAOYSA-N 0.000 claims 1
- XUINSQVJJOKGFK-UHFFFAOYSA-N 2-[1-[4-[[2-(2,6-dimethylpiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetonitrile Chemical compound CC1CCCC(C)N1C1=NC(NC=2C=CC(=CC=2)N2CCC(CC#N)CC2)=C2C(=O)NN=CC2=N1 XUINSQVJJOKGFK-UHFFFAOYSA-N 0.000 claims 1
- HSLWFLOZNCYFDT-UHFFFAOYSA-N 2-[1-[4-[[2-(2-methylpiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound CC1CCCCN1C1=NC(NC=2C=CC(=CC=2)N2CCC(CC(O)=O)CC2)=C2C(=O)NN=CC2=N1 HSLWFLOZNCYFDT-UHFFFAOYSA-N 0.000 claims 1
- JSIZZJFYHMAVQZ-UHFFFAOYSA-N 2-[1-[4-[[2-(2-methylpiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetonitrile Chemical compound CC1CCCCN1C1=NC(NC=2C=CC(=CC=2)N2CCC(CC#N)CC2)=C2C(=O)NN=CC2=N1 JSIZZJFYHMAVQZ-UHFFFAOYSA-N 0.000 claims 1
- NJDZYNQTLIHVQV-UHFFFAOYSA-N 2-[1-[4-[[2-(3,5-dimethylpiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetonitrile Chemical compound C1C(C)CC(C)CN1C1=NC(NC=2C=CC(=CC=2)N2CCC(CC#N)CC2)=C2C(=O)NN=CC2=N1 NJDZYNQTLIHVQV-UHFFFAOYSA-N 0.000 claims 1
- CCMRPIXGONWHJS-UHFFFAOYSA-N 2-[1-[4-[[2-(3-cyanopiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(N2CC(CCC2)C#N)=NC2=C1C(=O)NN=C2 CCMRPIXGONWHJS-UHFFFAOYSA-N 0.000 claims 1
- NONFSTXUUVMGBF-UHFFFAOYSA-N 2-[1-[4-[[2-(3-methoxyphenyl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetonitrile Chemical compound COC1=CC=CC(C=2N=C3C(C(NN=C3)=O)=C(NC=3C=CC(=CC=3)N3CCC(CC#N)CC3)N=2)=C1 NONFSTXUUVMGBF-UHFFFAOYSA-N 0.000 claims 1
- ITORKKLKAZVJBF-UHFFFAOYSA-N 2-[1-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]-2-methylpropanoic acid Chemical compound C1CC(C(C)(C)C(O)=O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 ITORKKLKAZVJBF-UHFFFAOYSA-N 0.000 claims 1
- PGHYLBCWLPGZDH-UHFFFAOYSA-N 2-[1-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 PGHYLBCWLPGZDH-UHFFFAOYSA-N 0.000 claims 1
- IJBKDGMSEDAMBN-UHFFFAOYSA-N 2-[1-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]cyclopropane-1-carboxylic acid Chemical compound OC(=O)C1CC1C1CCN(C=2C=CC(NC=3C=4C(=O)NN=CC=4N=C(N=3)N3CCCCCC3)=CC=2)CC1 IJBKDGMSEDAMBN-UHFFFAOYSA-N 0.000 claims 1
- LENHGPBRXMASGO-UHFFFAOYSA-N 2-[1-[4-[[2-(azocan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCCC2)=NC2=C1C(=O)NN=C2 LENHGPBRXMASGO-UHFFFAOYSA-N 0.000 claims 1
- SYHVUACYJMSJSS-UHFFFAOYSA-N 2-[1-[4-[[2-[1-(2-cyanoacetyl)piperidin-4-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(C2CCN(CC2)C(=O)CC#N)=NC2=C1C(=O)NN=C2 SYHVUACYJMSJSS-UHFFFAOYSA-N 0.000 claims 1
- UXNLRBOFQOPLMF-UHFFFAOYSA-N 2-[1-[4-[[2-[4-(2-cyanoacetyl)piperazin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCN(CC2)C(=O)CC#N)=NC2=C1C(=O)NN=C2 UXNLRBOFQOPLMF-UHFFFAOYSA-N 0.000 claims 1
- BUWCWAIGJUCVTA-UHFFFAOYSA-N 2-[1-[4-[[2-[4-(2-cyanopropan-2-yl)piperidin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound C1CC(C(C)(C#N)C)CCN1C1=NC(NC=2C=CC(=CC=2)N2CCC(CC(O)=O)CC2)=C2C(=O)NN=CC2=N1 BUWCWAIGJUCVTA-UHFFFAOYSA-N 0.000 claims 1
- GIVBOIPQEJTHPU-UHFFFAOYSA-N 2-[1-[4-[[2-[4-(cyanomethyl)piperazin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCN(CC#N)CC2)=NC2=C1C(=O)NN=C2 GIVBOIPQEJTHPU-UHFFFAOYSA-N 0.000 claims 1
- CAADRCABWYRLNQ-UHFFFAOYSA-N 2-[1-[4-[[2-[4-(cyanomethyl)piperidin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-3-yl]acetic acid Chemical compound C1C(CC(=O)O)CCCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 CAADRCABWYRLNQ-UHFFFAOYSA-N 0.000 claims 1
- VJJUMDMQKUYLKE-UHFFFAOYSA-N 2-[1-[4-[[2-[4-(cyanomethyl)piperidin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 VJJUMDMQKUYLKE-UHFFFAOYSA-N 0.000 claims 1
- FUZONMXIBGUQPR-UHFFFAOYSA-N 2-[1-[4-[[2-[cyclohexyl(methyl)amino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetic acid Chemical compound N=1C(NC=2C=CC(=CC=2)N2CCC(CC(O)=O)CC2)=C(C(NN=C2)=O)C2=NC=1N(C)C1CCCCC1 FUZONMXIBGUQPR-UHFFFAOYSA-N 0.000 claims 1
- VFUVXZYJTJMVTP-UHFFFAOYSA-N 2-[1-[4-[[2-[di(propan-2-yl)amino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]acetonitrile Chemical compound C1=NNC(=O)C=2C1=NC(N(C(C)C)C(C)C)=NC=2NC(C=C1)=CC=C1N1CCC(CC#N)CC1 VFUVXZYJTJMVTP-UHFFFAOYSA-N 0.000 claims 1
- AJXVRZSFKIWMPE-UHFFFAOYSA-N 2-[1-[4-[[6-(3-hydroxypiperidin-1-yl)pyridin-3-yl]amino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1C(O)CCCN1C(N=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 AJXVRZSFKIWMPE-UHFFFAOYSA-N 0.000 claims 1
- KAZVWDLCKKDSPA-UHFFFAOYSA-N 2-[1-[4-[[6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1CN(C)CCN1C(N=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 KAZVWDLCKKDSPA-UHFFFAOYSA-N 0.000 claims 1
- OOLXTNYZCCEZJE-UHFFFAOYSA-N 2-[1-[5-[(5-oxo-2-phenyl-6h-pyrimido[4,5-d]pyridazin-4-yl)amino]pyridin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(C=2C=CC=CC=2)=NC=1NC(C=N1)=CC=C1N1CCC(CC#N)CC1 OOLXTNYZCCEZJE-UHFFFAOYSA-N 0.000 claims 1
- CXIFWMGGQKUFBH-UHFFFAOYSA-N 2-[1-[5-[[2-(2,6-dimethylmorpholin-4-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]piperidin-4-yl]acetic acid Chemical compound C1C(C)OC(C)CN1C1=NC(NC=2C=NC(=CC=2)N2CCC(CC(O)=O)CC2)=C2C(=O)NN=CC2=N1 CXIFWMGGQKUFBH-UHFFFAOYSA-N 0.000 claims 1
- SEDAOMWWLUBEOH-UHFFFAOYSA-N 2-[1-[5-[[2-(2,6-dimethylpiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]piperidin-4-yl]acetic acid Chemical compound CC1CCCC(C)N1C1=NC(NC=2C=NC(=CC=2)N2CCC(CC(O)=O)CC2)=C2C(=O)NN=CC2=N1 SEDAOMWWLUBEOH-UHFFFAOYSA-N 0.000 claims 1
- IYDSLTRZBAYIHH-UHFFFAOYSA-N 2-[1-[5-[[2-(2-methylpiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]piperidin-4-yl]acetic acid Chemical compound CC1CCCCN1C1=NC(NC=2C=NC(=CC=2)N2CCC(CC(O)=O)CC2)=C2C(=O)NN=CC2=N1 IYDSLTRZBAYIHH-UHFFFAOYSA-N 0.000 claims 1
- LNDYJUHBPAYKST-UHFFFAOYSA-N 2-[1-[5-[[2-(3,5-dimethylpiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]piperidin-4-yl]acetic acid Chemical compound C1C(C)CC(C)CN1C1=NC(NC=2C=NC(=CC=2)N2CCC(CC(O)=O)CC2)=C2C(=O)NN=CC2=N1 LNDYJUHBPAYKST-UHFFFAOYSA-N 0.000 claims 1
- OVBVNXVTONKYRW-UHFFFAOYSA-N 2-[1-[5-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C(N=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 OVBVNXVTONKYRW-UHFFFAOYSA-N 0.000 claims 1
- SINXYUJLCYIKMA-UHFFFAOYSA-N 2-[1-[5-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=N1)=CC=C1N1CCC(CC#N)CC1 SINXYUJLCYIKMA-UHFFFAOYSA-N 0.000 claims 1
- UJFNGXNNRFLOJF-UHFFFAOYSA-N 2-[1-[5-[[2-[4-(cyanomethyl)piperidin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]piperidin-3-yl]acetic acid Chemical compound C1C(CC(=O)O)CCCN1C(N=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 UJFNGXNNRFLOJF-UHFFFAOYSA-N 0.000 claims 1
- SFVSAJFMIQDDRE-UHFFFAOYSA-N 2-[1-[5-[[2-[4-(cyanomethyl)piperidin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C(N=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 SFVSAJFMIQDDRE-UHFFFAOYSA-N 0.000 claims 1
- SYJVDLBYTZZQRX-UHFFFAOYSA-N 2-[1-[5-[[2-[di(propan-2-yl)amino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]piperidin-4-yl]acetic acid Chemical compound C1=NNC(=O)C=2C1=NC(N(C(C)C)C(C)C)=NC=2NC(C=N1)=CC=C1N1CCC(CC(O)=O)CC1 SYJVDLBYTZZQRX-UHFFFAOYSA-N 0.000 claims 1
- AEWNGOHLUNPQEQ-UHFFFAOYSA-N 2-[1-[5-oxo-4-(3,4,5-trimethoxyanilino)-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound COC1=C(OC)C(OC)=CC(NC=2C=3C(=O)NN=CC=3N=C(N=2)N2CCC(CC#N)CC2)=C1 AEWNGOHLUNPQEQ-UHFFFAOYSA-N 0.000 claims 1
- AOMSNALEFNZLAY-UHFFFAOYSA-N 2-[1-[5-oxo-4-(4-piperazin-1-ylanilino)-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCC(CC#N)CC2)=NC=1NC(C=C1)=CC=C1N1CCNCC1 AOMSNALEFNZLAY-UHFFFAOYSA-N 0.000 claims 1
- LFWPPUMWYUVLEU-UHFFFAOYSA-N 2-[1-[5-oxo-4-[(2-oxo-1,3-dihydrobenzimidazol-5-yl)amino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=C2NC(=O)NC2=CC=C1NC(C=1C(=O)NN=CC=1N=1)=NC=1N1CCC(CC#N)CC1 LFWPPUMWYUVLEU-UHFFFAOYSA-N 0.000 claims 1
- FJJYDXLMPWBGSK-UHFFFAOYSA-N 2-[1-[5-oxo-4-[(6-piperazin-1-ylpyridin-3-yl)amino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCC(CC#N)CC2)=NC=1NC(C=N1)=CC=C1N1CCNCC1 FJJYDXLMPWBGSK-UHFFFAOYSA-N 0.000 claims 1
- RYGOOQDQGBYSJO-UHFFFAOYSA-N 2-[1-[5-oxo-4-[4-(2-piperazin-1-ylethoxy)anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCC(CC#N)CC2)=NC=1NC(C=C1)=CC=C1OCCN1CCNCC1 RYGOOQDQGBYSJO-UHFFFAOYSA-N 0.000 claims 1
- FRTDJFPREPWBPC-UHFFFAOYSA-N 2-[1-[5-oxo-4-[4-(2-piperidin-4-ylethoxy)anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCC(CC#N)CC2)=NC=1NC(C=C1)=CC=C1OCCC1CCNCC1 FRTDJFPREPWBPC-UHFFFAOYSA-N 0.000 claims 1
- ODNKDIDXPUIXMO-UHFFFAOYSA-N 2-[1-[5-oxo-4-[4-(3-piperazin-1-ylpropyl)anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCC(CC#N)CC2)=NC=1NC(C=C1)=CC=C1CCCN1CCNCC1 ODNKDIDXPUIXMO-UHFFFAOYSA-N 0.000 claims 1
- BFUHTWSWTXIEJC-UHFFFAOYSA-N 2-[1-[5-oxo-4-[4-(piperazin-1-ylmethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetic acid;hydrochloride Chemical compound Cl.C1CC(CC(=O)O)CCN1C1=NC(NC=2C=CC(CN3CCNCC3)=CC=2)=C2C(=O)NN=CC2=N1 BFUHTWSWTXIEJC-UHFFFAOYSA-N 0.000 claims 1
- QXCHIHIQFOYQGH-UHFFFAOYSA-N 2-[1-[5-oxo-4-[4-(trifluoromethoxy)anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 QXCHIHIQFOYQGH-UHFFFAOYSA-N 0.000 claims 1
- OWDALGIWVSYEOC-UHFFFAOYSA-N 2-[1-[5-oxo-4-[4-[4-(2h-tetrazol-5-ylmethyl)piperidin-1-yl]anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCC(CC#N)CC2)=NC=1NC(C=C1)=CC=C1N(CC1)CCC1CC=1N=NNN=1 OWDALGIWVSYEOC-UHFFFAOYSA-N 0.000 claims 1
- GZCXKYVYBYNSMV-UHFFFAOYSA-N 2-[1-[5-oxo-4-[4-[[4-(2h-tetrazol-5-yl)piperidin-1-yl]methyl]anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCC(CC#N)CC2)=NC=1NC(C=C1)=CC=C1CN(CC1)CCC1C=1N=NNN=1 GZCXKYVYBYNSMV-UHFFFAOYSA-N 0.000 claims 1
- LUBWRHMWWIENQO-UHFFFAOYSA-N 2-[1-[5-oxo-4-[4-[[4-(2h-tetrazol-5-ylmethyl)piperidin-1-yl]methyl]anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-4-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCC(CC#N)CC2)=NC=1NC(C=C1)=CC=C1CN(CC1)CCC1CC=1N=NNN=1 LUBWRHMWWIENQO-UHFFFAOYSA-N 0.000 claims 1
- CCTORJYQUOCRBG-UHFFFAOYSA-N 2-[1-[[4-[(2-cycloheptyl-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]methyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1CC(C=C1)=CC=C1NC1=NC(C2CCCCCC2)=NC2=C1C(=O)NN=C2 CCTORJYQUOCRBG-UHFFFAOYSA-N 0.000 claims 1
- ULYXVCBTKBLXJO-UHFFFAOYSA-N 2-[1-[[4-[[2-(3-cyanopiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]methyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1CC(C=C1)=CC=C1NC1=NC(N2CC(CCC2)C#N)=NC2=C1C(=O)NN=C2 ULYXVCBTKBLXJO-UHFFFAOYSA-N 0.000 claims 1
- CMPDWEQQDRGLNH-UHFFFAOYSA-N 2-[1-[[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]methyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1CC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 CMPDWEQQDRGLNH-UHFFFAOYSA-N 0.000 claims 1
- FIDJTOZKPQHRHQ-UHFFFAOYSA-N 2-[1-[[4-[[2-[1-(2-cyanoacetyl)piperidin-4-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]methyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1CC(C=C1)=CC=C1NC1=NC(C2CCN(CC2)C(=O)CC#N)=NC2=C1C(=O)NN=C2 FIDJTOZKPQHRHQ-UHFFFAOYSA-N 0.000 claims 1
- SKWJPUZGIZAAJN-UHFFFAOYSA-N 2-[1-[[4-[[2-[4-(2-cyanoacetyl)piperazin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]methyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1CC(C=C1)=CC=C1NC1=NC(N2CCN(CC2)C(=O)CC#N)=NC2=C1C(=O)NN=C2 SKWJPUZGIZAAJN-UHFFFAOYSA-N 0.000 claims 1
- CRFPFKVKCCTUQG-UHFFFAOYSA-N 2-[1-[[4-[[2-[4-(cyanomethyl)piperazin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]methyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1CC(C=C1)=CC=C1NC1=NC(N2CCN(CC#N)CC2)=NC2=C1C(=O)NN=C2 CRFPFKVKCCTUQG-UHFFFAOYSA-N 0.000 claims 1
- VSJNCJFJORMKKU-UHFFFAOYSA-N 2-[4-(cyanomethyl)piperidin-1-yl]-4-[4-(4-ethylpiperazin-1-yl)anilino]-6-methanimidoylpyrimidine-5-carboxamide Chemical compound C1CN(CC)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC(C=N)=C1C(N)=O VSJNCJFJORMKKU-UHFFFAOYSA-N 0.000 claims 1
- LOHLQMZDHKALKA-UHFFFAOYSA-N 2-[4-(cyanomethyl)piperidin-1-yl]-4-[4-[2-(4-ethylpiperazin-1-yl)ethyl]anilino]-6-methanimidoylpyrimidine-5-carboxamide Chemical compound C1CN(CC)CCN1CCC(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC(C=N)=C1C(N)=O LOHLQMZDHKALKA-UHFFFAOYSA-N 0.000 claims 1
- OVQIQNNRBIZJJN-UHFFFAOYSA-N 2-[4-(cyanomethyl)piperidin-1-yl]-4-[4-[4-(2-hydroxy-2-methylpropanoyl)piperazin-1-yl]anilino]-6-methanimidoylpyrimidine-5-carboxamide Chemical compound C1CN(C(=O)C(C)(O)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC(C=N)=C1C(N)=O OVQIQNNRBIZJJN-UHFFFAOYSA-N 0.000 claims 1
- WWQRRHZTBFDFJY-UHFFFAOYSA-N 2-[4-(cyanomethyl)piperidin-1-yl]-4-[[6-[4-(2-diazenyl-2-iminoethyl)piperidin-1-yl]pyridin-3-yl]amino]-6-methanimidoylpyrimidine-5-carboxamide Chemical compound N1=C(N2CCC(CC#N)CC2)N=C(C=N)C(C(=O)N)=C1NC(C=N1)=CC=C1N1CCC(CC(=N)N=N)CC1 WWQRRHZTBFDFJY-UHFFFAOYSA-N 0.000 claims 1
- IKJGJDKBIUHBPU-UHFFFAOYSA-N 2-[4-(morpholin-4-ylmethyl)phenyl]-4-[4-(piperazin-1-ylmethyl)anilino]-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C12C(=O)NNCC2NC(C=2C=CC(CN3CCOCC3)=CC=2)NC1NC(C=C1)=CC=C1CN1CCNCC1 IKJGJDKBIUHBPU-UHFFFAOYSA-N 0.000 claims 1
- FBASVZLYAFUGQZ-UHFFFAOYSA-N 2-[4-[2-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenoxy]ethyl]piperazin-1-yl]-2-methylpropanenitrile Chemical compound C1CN(C(C)(C#N)C)CCN1CCOC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 FBASVZLYAFUGQZ-UHFFFAOYSA-N 0.000 claims 1
- FTUTYOPDMHSCDE-UHFFFAOYSA-N 2-[4-[4-[(5-oxo-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]cyclohexyl]acetic acid Chemical compound C1CC(CC(=O)O)CCC1C(C=C1)=CC=C1NC1C2C(=O)NNCC2NC(C=2C=CC=CC=2)N1 FTUTYOPDMHSCDE-UHFFFAOYSA-N 0.000 claims 1
- RBSRPNFTFMGELL-UHFFFAOYSA-N 2-[4-[4-[(5-oxo-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]piperazin-1-yl]acetic acid Chemical compound C1CN(CC(=O)O)CCN1C(C=C1)=CC=C1NC1C2C(=O)NNCC2NC(C=2C=CC=CC=2)N1 RBSRPNFTFMGELL-UHFFFAOYSA-N 0.000 claims 1
- FISOYMNWGMVMAG-UHFFFAOYSA-N 2-[4-[4-[(5-oxo-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]piperidin-1-yl]acetic acid Chemical compound C1CN(CC(=O)O)CCC1C(C=C1)=CC=C1NC1C2C(=O)NNCC2NC(C=2C=CC=CC=2)N1 FISOYMNWGMVMAG-UHFFFAOYSA-N 0.000 claims 1
- CXXPNTGGRNQRLO-UHFFFAOYSA-N 2-[4-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenoxy]piperidin-1-yl]acetic acid Chemical compound C1CN(CC(=O)O)CCC1OC(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 CXXPNTGGRNQRLO-UHFFFAOYSA-N 0.000 claims 1
- RRPYHFCTYGYGDP-UHFFFAOYSA-N 2-[4-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperazin-1-yl]-2-methylpropanamide Chemical compound C1CN(C(C)(C)C(N)=O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 RRPYHFCTYGYGDP-UHFFFAOYSA-N 0.000 claims 1
- BUHQHAKCQJVJNR-UHFFFAOYSA-N 2-[4-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperazin-1-yl]-2-methylpropanenitrile Chemical compound C1CN(C(C)(C#N)C)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 BUHQHAKCQJVJNR-UHFFFAOYSA-N 0.000 claims 1
- PGWIMNRICNCIBR-UHFFFAOYSA-N 2-[4-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperazin-1-yl]-2-methylpropanoic acid Chemical compound C1CN(C(C)(C)C(O)=O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 PGWIMNRICNCIBR-UHFFFAOYSA-N 0.000 claims 1
- GYAKIFQKEUIRSB-UHFFFAOYSA-N 2-[4-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperazin-1-yl]acetic acid Chemical compound C1CN(CC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 GYAKIFQKEUIRSB-UHFFFAOYSA-N 0.000 claims 1
- JAJPXOXMPWOKPD-UHFFFAOYSA-N 2-[4-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperazin-1-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCCC2)=NC=1NC(C=C1)=CC=C1N1CCN(CC#N)CC1 JAJPXOXMPWOKPD-UHFFFAOYSA-N 0.000 claims 1
- CHDJUUAJRMMYHT-UHFFFAOYSA-N 2-[4-[4-[[5-carbamoyl-2-[4-(cyanomethyl)piperidin-1-yl]-6-methanimidoylpyrimidin-4-yl]amino]phenyl]piperazin-1-yl]-2-methylpropanoic acid Chemical compound C1CN(C(C)(C)C(O)=O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC(C=N)=C1C(N)=O CHDJUUAJRMMYHT-UHFFFAOYSA-N 0.000 claims 1
- YKMKSKQQPHLCCJ-UHFFFAOYSA-N 2-[4-[5-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]piperazin-1-yl]acetic acid Chemical compound C1CN(CC(=O)O)CCN1C(N=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 YKMKSKQQPHLCCJ-UHFFFAOYSA-N 0.000 claims 1
- QEHHYYYDYIPNSU-UHFFFAOYSA-N 2-[4-[5-oxo-4-[4-(2-piperazin-1-ylethoxy)anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperazin-1-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCN(CC#N)CC2)=NC=1NC(C=C1)=CC=C1OCCN1CCNCC1 QEHHYYYDYIPNSU-UHFFFAOYSA-N 0.000 claims 1
- YKFWNMINHNBPDH-UHFFFAOYSA-N 2-[4-[5-oxo-4-[4-[[4-(2h-tetrazol-5-yl)piperidin-1-yl]methyl]anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperazin-1-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCN(CC#N)CC2)=NC=1NC(C=C1)=CC=C1CN(CC1)CCC1C=1N=NNN=1 YKFWNMINHNBPDH-UHFFFAOYSA-N 0.000 claims 1
- QGWGYGGLMYLUIC-UHFFFAOYSA-N 2-[4-[5-oxo-4-[4-[[4-(2h-tetrazol-5-ylmethyl)piperidin-1-yl]methyl]anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperazin-1-yl]acetonitrile Chemical compound C=12C(=O)NN=CC2=NC(N2CCN(CC#N)CC2)=NC=1NC(C=C1)=CC=C1CN(CC1)CCC1CC=1N=NNN=1 QGWGYGGLMYLUIC-UHFFFAOYSA-N 0.000 claims 1
- YNBDBXIEAYCZCT-UHFFFAOYSA-N 2-[5-[4-[[2-(azepan-1-yl)-5-carbamoyl-6-methanimidoylpyrimidin-4-yl]amino]phenyl]tetrazol-2-yl]acetic acid Chemical compound N1=C(N2CCCCCC2)N=C(C=N)C(C(=O)N)=C1NC(C=C1)=CC=C1C=1N=NN(CC(O)=O)N=1 YNBDBXIEAYCZCT-UHFFFAOYSA-N 0.000 claims 1
- UBHBYSLTIFKEQZ-UHFFFAOYSA-N 2-[di(propan-2-yl)amino]-4-[4-(piperazin-1-ylmethyl)anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=NNC(=O)C=2C1=NC(N(C(C)C)C(C)C)=NC=2NC(C=C1)=CC=C1CN1CCNCC1 UBHBYSLTIFKEQZ-UHFFFAOYSA-N 0.000 claims 1
- IBZQMGVSEURXBS-UHFFFAOYSA-N 2-cycloheptyl-4-[4-[[4-(2h-tetrazol-5-ylmethyl)piperidin-1-yl]methyl]anilino]-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(C2CCCCCC2)=NC=1NC(C=C1)=CC=C1CN(CC1)CCC1CC=1N=NNN=1 IBZQMGVSEURXBS-UHFFFAOYSA-N 0.000 claims 1
- YZINQLLBHOCDGX-UHFFFAOYSA-N 2-methyl-2-[1-[4-[(5-oxo-2-phenyl-6h-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]piperidin-4-yl]propanenitrile Chemical compound C1CC(C(C)(C#N)C)CCN1C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=NC2=C1C(=O)NN=C2 YZINQLLBHOCDGX-UHFFFAOYSA-N 0.000 claims 1
- ODGXBLJUBMENDM-UHFFFAOYSA-N 2-methyl-2-[1-[4-[(5-oxo-2-phenyl-6h-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]piperidin-4-yl]propanoic acid Chemical compound C1CC(C(C)(C)C(O)=O)CCN1C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=NC2=C1C(=O)NN=C2 ODGXBLJUBMENDM-UHFFFAOYSA-N 0.000 claims 1
- BJTVZYGZPOJXBU-UHFFFAOYSA-N 2-phenyl-4-(4-piperazin-1-ylanilino)-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C12C(=O)NNCC2NC(C=2C=CC=CC=2)NC1NC(C=C1)=CC=C1N1CCNCC1 BJTVZYGZPOJXBU-UHFFFAOYSA-N 0.000 claims 1
- LGHYCNLIBKDMJF-UHFFFAOYSA-N 2-phenyl-4-[4-(2-piperazin-1-ylethoxy)anilino]-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C12C(=O)NNCC2NC(C=2C=CC=CC=2)NC1NC(C=C1)=CC=C1OCCN1CCNCC1 LGHYCNLIBKDMJF-UHFFFAOYSA-N 0.000 claims 1
- DEJRBJRLVAFXHD-UHFFFAOYSA-N 2-phenyl-4-[4-(piperazin-1-ylmethyl)anilino]-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C12C(=O)NNCC2NC(C=2C=CC=CC=2)NC1NC(C=C1)=CC=C1CN1CCNCC1 DEJRBJRLVAFXHD-UHFFFAOYSA-N 0.000 claims 1
- XNOMOWJZGMEILF-UHFFFAOYSA-N 2-phenyl-4-[[1-(2-piperazin-1-ylethyl)pyrazol-4-yl]amino]-6h-pyrimido[4,5-d]pyridazin-5-one;hydrochloride Chemical compound Cl.C=12C(=O)NN=CC2=NC(C=2C=CC=CC=2)=NC=1NC(=C1)C=NN1CCN1CCNCC1 XNOMOWJZGMEILF-UHFFFAOYSA-N 0.000 claims 1
- FPSCWKHRIRPRNQ-UHFFFAOYSA-N 3-[1-[4-[(5-oxo-2-phenyl-6h-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]piperidin-4-yl]propanoic acid Chemical compound C1CC(CCC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=NC2=C1C(=O)NN=C2 FPSCWKHRIRPRNQ-UHFFFAOYSA-N 0.000 claims 1
- LERGMBDKQPLVFB-UHFFFAOYSA-N 3-[1-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]propanoic acid Chemical compound C1CC(CCC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 LERGMBDKQPLVFB-UHFFFAOYSA-N 0.000 claims 1
- WFSPIPHKSHGGFT-UHFFFAOYSA-N 3-[1-[4-[[2-[4-(cyanomethyl)piperidin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperidin-4-yl]propanoic acid Chemical compound C1CC(CCC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 WFSPIPHKSHGGFT-UHFFFAOYSA-N 0.000 claims 1
- YFBIHTBFBBFRFC-UHFFFAOYSA-N 3-[4-[4-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]piperazin-1-yl]propanoic acid Chemical compound C1CN(CCC(=O)O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 YFBIHTBFBBFRFC-UHFFFAOYSA-N 0.000 claims 1
- ZBQUWXBJCNZQRD-UHFFFAOYSA-N 3-[4-[4-[[5-carbamoyl-2-[4-(cyanomethyl)piperidin-1-yl]-6-methanimidoylpyrimidin-4-yl]amino]phenyl]piperazin-1-yl]propanoic acid Chemical compound N1=C(N2CCC(CC#N)CC2)N=C(C=N)C(C(=O)N)=C1NC(C=C1)=CC=C1N1CCN(CCC(O)=O)CC1 ZBQUWXBJCNZQRD-UHFFFAOYSA-N 0.000 claims 1
- JKTGTIZLZMFIRN-UHFFFAOYSA-N 3-[4-[5-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]piperazin-1-yl]-3-oxopropanenitrile Chemical compound C1CN(C(CC#N)=O)CCN1C(N=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC2=C1C(=O)NN=C2 JKTGTIZLZMFIRN-UHFFFAOYSA-N 0.000 claims 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 1
- UDYSBBDEDMNXOU-UHFFFAOYSA-N 3-oxo-3-[4-[5-oxo-4-[4-[[4-(2h-tetrazol-5-yl)piperidin-1-yl]methyl]anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperazin-1-yl]propanenitrile Chemical compound C1CN(C(CC#N)=O)CCN1C1=NC(NC=2C=CC(CN3CCC(CC3)C3=NNN=N3)=CC=2)=C2C(=O)NN=CC2=N1 UDYSBBDEDMNXOU-UHFFFAOYSA-N 0.000 claims 1
- JJMXVZQBAVVQAC-UHFFFAOYSA-N 3-oxo-3-[4-[5-oxo-4-[4-[[4-(2h-tetrazol-5-yl)piperidin-1-yl]methyl]anilino]-6h-pyrimido[4,5-d]pyridazin-2-yl]piperidin-1-yl]propanenitrile Chemical compound C1CN(C(CC#N)=O)CCC1C1=NC(NC=2C=CC(CN3CCC(CC3)C3=NNN=N3)=CC=2)=C2C(=O)NN=CC2=N1 JJMXVZQBAVVQAC-UHFFFAOYSA-N 0.000 claims 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- LHLYRQXNLDJBEA-UHFFFAOYSA-N 4-(4-carbamimidoylanilino)-2-[4-(cyanomethyl)piperidin-1-yl]-6-methanimidoylpyrimidine-5-carboxamide Chemical compound C1=CC(C(=N)N)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC(C=N)=C1C(N)=O LHLYRQXNLDJBEA-UHFFFAOYSA-N 0.000 claims 1
- LAFDLDWISTZONW-UHFFFAOYSA-N 4-(4-morpholin-4-ylanilino)-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C12C(=O)NNCC2NC(C=2C=CC=CC=2)NC1NC(C=C1)=CC=C1N1CCOCC1 LAFDLDWISTZONW-UHFFFAOYSA-N 0.000 claims 1
- BDKCJURYCPGCFH-UHFFFAOYSA-N 4-[4-(2-aminoethoxy)anilino]-2-(azepan-1-yl)-6-methanimidoylpyrimidine-5-carboxamide Chemical compound C1=CC(OCCN)=CC=C1NC1=NC(N2CCCCCC2)=NC(C=N)=C1C(N)=O BDKCJURYCPGCFH-UHFFFAOYSA-N 0.000 claims 1
- HPAVHRZUPZTCJR-UHFFFAOYSA-N 4-[4-(2-morpholin-4-ylethoxy)anilino]-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C12C(=O)NNCC2NC(C=2C=CC=CC=2)NC1NC(C=C1)=CC=C1OCCN1CCOCC1 HPAVHRZUPZTCJR-UHFFFAOYSA-N 0.000 claims 1
- VWYIJHIVDASGPH-UHFFFAOYSA-N 4-[4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)anilino]-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C12C(=O)NNCC2NC(C=2C=CC=CC=2)NC1NC(C=C1)=CC=C1N(CC1)CCC21COC2 VWYIJHIVDASGPH-UHFFFAOYSA-N 0.000 claims 1
- VQXWOWIEIYQDJA-UHFFFAOYSA-N 4-[4-(2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl)anilino]-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C12C(=O)NNCC2NC(C=2C=CC=CC=2)NC1NC(C=C1)=CC=C1CN(CC1)CCC21COC2 VQXWOWIEIYQDJA-UHFFFAOYSA-N 0.000 claims 1
- BLPCSYNEEROVPD-UHFFFAOYSA-N 4-[4-(2-oxo-1,7-diazaspiro[3.5]nonan-7-yl)anilino]-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound N1C(=O)CC11CCN(C=2C=CC(NC3C4C(=O)NNCC4NC(N3)C=3C=CC=CC=3)=CC=2)CC1 BLPCSYNEEROVPD-UHFFFAOYSA-N 0.000 claims 1
- AYRPBKTYPBQYSK-UHFFFAOYSA-N 4-[4-(4-ethylpiperazin-1-yl)anilino]-2-[4-(trifluoromethoxy)phenyl]-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(CC)CCN1C(C=C1)=CC=C1NC1C2C(=O)NNCC2NC(C=2C=CC(OC(F)(F)F)=CC=2)N1 AYRPBKTYPBQYSK-UHFFFAOYSA-N 0.000 claims 1
- BEBYZOYXFUTCAH-UHFFFAOYSA-N 4-[4-(4-ethylpiperazin-1-yl)anilino]-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(CC)CCN1C(C=C1)=CC=C1NC1C2C(=O)NNCC2NC(C=2C=CC=CC=2)N1 BEBYZOYXFUTCAH-UHFFFAOYSA-N 0.000 claims 1
- ICQWIHBLXGBATD-UHFFFAOYSA-N 4-[4-(morpholin-4-ylmethyl)anilino]-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C12C(=O)NNCC2NC(C=2C=CC=CC=2)NC1NC(C=C1)=CC=C1CN1CCOCC1 ICQWIHBLXGBATD-UHFFFAOYSA-N 0.000 claims 1
- VWXRNRYGLAGGLW-UHFFFAOYSA-N 4-[4-(morpholine-4-carbonyl)anilino]-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=1C=C(NC2C3C(=O)NNCC3NC(N2)C=2C=CC=CC=2)C=CC=1C(=O)N1CCOCC1 VWXRNRYGLAGGLW-UHFFFAOYSA-N 0.000 claims 1
- MGJNCBCDNVORJM-UHFFFAOYSA-N 4-[4-[(4-ethylpiperazin-1-yl)methyl]anilino]-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(CC)CCN1CC(C=C1)=CC=C1NC1C2C(=O)NNCC2NC(C=2C=CC=CC=2)N1 MGJNCBCDNVORJM-UHFFFAOYSA-N 0.000 claims 1
- GNOPSCBEOSUMGK-UHFFFAOYSA-N 4-[4-[2-(1,4-diazepan-1-yl)ethoxy]anilino]-2-piperidin-1-yl-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCC2)=NC=1NC(C=C1)=CC=C1OCCN1CCCNCC1 GNOPSCBEOSUMGK-UHFFFAOYSA-N 0.000 claims 1
- KAFYDCJMMMLHRA-UHFFFAOYSA-N 4-[4-[2-(4-hydroxypiperidin-1-yl)ethoxy]anilino]-2-piperidin-1-yl-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CC(O)CCN1CCOC(C=C1)=CC=C1NC1=NC(N2CCCCC2)=NC2=C1C(=O)NN=C2 KAFYDCJMMMLHRA-UHFFFAOYSA-N 0.000 claims 1
- BIVYYJSAAKYTHI-UHFFFAOYSA-N 4-[4-[4-(2-aminoacetyl)piperazin-1-yl]anilino]-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(C(=O)CN)CCN1C(C=C1)=CC=C1NC1C2C(=O)NNCC2NC(C=2C=CC=CC=2)N1 BIVYYJSAAKYTHI-UHFFFAOYSA-N 0.000 claims 1
- AYQCDTBDEQAVSX-UHFFFAOYSA-N 4-[4-[4-(2-aminoacetyl)piperazin-1-yl]anilino]-2-phenyl-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1CN(C(=O)CN)CCN1C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=NC2=C1C(=O)NN=C2 AYQCDTBDEQAVSX-UHFFFAOYSA-N 0.000 claims 1
- ONKUJXAJVUMXKJ-UHFFFAOYSA-N 4-[4-[4-(2-hydroxy-2-methylpropanoyl)piperidin-1-yl]anilino]-2-(2-methylpiperidin-1-yl)-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound CC1CCCCN1C1=NC(NC=2C=CC(=CC=2)N2CCC(CC2)C(=O)C(C)(C)O)=C2C(=O)NN=CC2=N1 ONKUJXAJVUMXKJ-UHFFFAOYSA-N 0.000 claims 1
- BJBOLFNHMLVZRT-UHFFFAOYSA-N 4-[4-[4-(3-hydroxypropyl)piperidin-1-yl]anilino]-2-[4-(isocyanomethyl)piperidin-1-yl]-6-methanimidoylpyrimidine-5-carboxamide Chemical compound NC(=O)C1=C(C=N)N=C(N=C1NC1=CC=C(C=C1)N1CCC(CCCO)CC1)N1CCC(C[N+]#[C-])CC1 BJBOLFNHMLVZRT-UHFFFAOYSA-N 0.000 claims 1
- NJLDZCNGRFGZMB-RBUKOAKNSA-N 4-[4-[[(2s,5s)-5-(hydroxymethyl)-1,4-dioxan-2-yl]methoxy]anilino]-2-phenyl-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1O[C@@H](CO)CO[C@@H]1COC(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=NC2=C1C(=O)NN=C2 NJLDZCNGRFGZMB-RBUKOAKNSA-N 0.000 claims 1
- DRPFCKWXHLVXLR-UHFFFAOYSA-N 4-[4-[bis(2-hydroxyethyl)amino]anilino]-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-5-one Chemical compound C1=CC(N(CCO)CCO)=CC=C1NC1C2C(=O)NNCC2NC(C=2C=CC=CC=2)N1 DRPFCKWXHLVXLR-UHFFFAOYSA-N 0.000 claims 1
- OOBNVERUJKKRBQ-UHFFFAOYSA-N 4-[[1-(2-morpholin-4-ylethyl)pyrazol-4-yl]amino]-2-phenyl-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(C=2C=CC=CC=2)=NC=1NC(=C1)C=NN1CCN1CCOCC1 OOBNVERUJKKRBQ-UHFFFAOYSA-N 0.000 claims 1
- UEPCIYPCSUUHKN-UHFFFAOYSA-N 4-[[6-(2-piperazin-1-ylethoxy)pyridin-3-yl]amino]-2-piperidin-1-yl-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(N2CCCCC2)=NC=1NC(C=N1)=CC=C1OCCN1CCNCC1 UEPCIYPCSUUHKN-UHFFFAOYSA-N 0.000 claims 1
- QMURQZVMMZFUEJ-UHFFFAOYSA-N 4-[[6-[4-(2-cyanoacetyl)piperazin-1-yl]pyridin-3-yl]amino]-2-[4-(cyanomethyl)piperidin-1-yl]-6-methanimidoylpyrimidine-5-carboxamide Chemical compound N1=C(N2CCC(CC#N)CC2)N=C(C=N)C(C(=O)N)=C1NC(C=N1)=CC=C1N1CCN(C(=O)CC#N)CC1 QMURQZVMMZFUEJ-UHFFFAOYSA-N 0.000 claims 1
- JTDBIHBPFWSBCG-UHFFFAOYSA-N 6-[4-[(5-oxo-2-pyridin-4-yl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]-6-azaspiro[2.5]octane-2-carboxylic acid Chemical compound OC(=O)C1CC11CCN(C=2C=CC(NC3C4C(=O)NNCC4NC(N3)C=3C=CN=CC=3)=CC=2)CC1 JTDBIHBPFWSBCG-UHFFFAOYSA-N 0.000 claims 1
- FHUNUEAFOCKJBZ-UHFFFAOYSA-N 6-[4-[(5-oxo-2-thiophen-3-yl-6h-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]-6-azaspiro[2.5]octane-2-carboxylic acid Chemical compound OC(=O)C1CC11CCN(C=2C=CC(NC=3C=4C(=O)NN=CC=4N=C(N=3)C3=CSC=C3)=CC=2)CC1 FHUNUEAFOCKJBZ-UHFFFAOYSA-N 0.000 claims 1
- VDNZSMASXFMFQB-UHFFFAOYSA-N 6-[4-[[2-(1,4-diazepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]-6-azaspiro[2.5]octane-2-carboxylic acid Chemical compound OC(=O)C1CC11CCN(C=2C=CC(NC=3C=4C(=O)NN=CC=4N=C(N=3)N3CCNCCC3)=CC=2)CC1 VDNZSMASXFMFQB-UHFFFAOYSA-N 0.000 claims 1
- LACMQPQIGPVYDG-UHFFFAOYSA-N 6-[4-[[2-(1,4-diazepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]-6-azaspiro[2.5]octane-2-carboxylic acid;hydrochloride Chemical compound Cl.OC(=O)C1CC11CCN(C=2C=CC(NC=3C=4C(=O)NN=CC=4N=C(N=3)N3CCNCCC3)=CC=2)CC1 LACMQPQIGPVYDG-UHFFFAOYSA-N 0.000 claims 1
- YNXLQJKBYQYQPC-UHFFFAOYSA-N 6-[4-[[2-(2,6-dimethylmorpholin-4-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]-6-azaspiro[2.5]octane-2-carboxylic acid Chemical compound C1C(C)OC(C)CN1C1=NC(NC=2C=CC(=CC=2)N2CCC3(C(C3)C(O)=O)CC2)=C2C(=O)NN=CC2=N1 YNXLQJKBYQYQPC-UHFFFAOYSA-N 0.000 claims 1
- AOJDOBPLUQSZLO-UHFFFAOYSA-N 6-[4-[[2-(2,6-dimethylpiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]-6-azaspiro[2.5]octane-2-carboxylic acid Chemical compound CC1CCCC(C)N1C1=NC(NC=2C=CC(=CC=2)N2CCC3(C(C3)C(O)=O)CC2)=C2C(=O)NN=CC2=N1 AOJDOBPLUQSZLO-UHFFFAOYSA-N 0.000 claims 1
- PRIOUYKKTCCFQE-UHFFFAOYSA-N 6-[4-[[2-(3,5-dimethylpiperidin-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]-6-azaspiro[2.5]octane-2-carboxylic acid Chemical compound C1C(C)CC(C)CN1C1=NC(NC=2C=CC(=CC=2)N2CCC3(C(C3)C(O)=O)CC2)=C2C(=O)NN=CC2=N1 PRIOUYKKTCCFQE-UHFFFAOYSA-N 0.000 claims 1
- XDMRJVMWLLUDFU-UHFFFAOYSA-N 6-[4-[[2-(4-methoxyphenyl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]-6-azaspiro[2.5]octane-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1=NC(NC=2C=CC(=CC=2)N2CCC3(C(C3)C(O)=O)CC2)=C2C(=O)NN=CC2=N1 XDMRJVMWLLUDFU-UHFFFAOYSA-N 0.000 claims 1
- RKTRDBZCPLJMMO-UHFFFAOYSA-N 6-[4-[[2-[1-(2-cyanoacetyl)piperidin-4-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]-6-azaspiro[2.5]octane-2-carboxylic acid Chemical compound OC(=O)C1CC11CCN(C=2C=CC(NC=3C=4C(=O)NN=CC=4N=C(N=3)C3CCN(CC3)C(=O)CC#N)=CC=2)CC1 RKTRDBZCPLJMMO-UHFFFAOYSA-N 0.000 claims 1
- KXHXYVVYIYEMJQ-UHFFFAOYSA-N 6-[4-[[2-[4-(2-cyanoacetyl)piperazin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]-6-azaspiro[2.5]octane-2-carboxylic acid Chemical compound OC(=O)C1CC11CCN(C=2C=CC(NC=3C=4C(=O)NN=CC=4N=C(N=3)N3CCN(CC3)C(=O)CC#N)=CC=2)CC1 KXHXYVVYIYEMJQ-UHFFFAOYSA-N 0.000 claims 1
- CQLNPNVGEIUICM-UHFFFAOYSA-N 6-[4-[[2-[di(propan-2-yl)amino]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]-6-azaspiro[2.5]octane-2-carboxylic acid Chemical compound C1=NNC(=O)C=2C1=NC(N(C(C)C)C(C)C)=NC=2NC(C=C1)=CC=C1N(CC1)CCC21CC2C(O)=O CQLNPNVGEIUICM-UHFFFAOYSA-N 0.000 claims 1
- GXWLYDJPYDIHSY-UHFFFAOYSA-N 6-[5-[[2-(azepan-1-yl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]-6-azaspiro[2.5]octane-2-carboxylic acid Chemical compound OC(=O)C1CC11CCN(C=2N=CC(NC=3C=4C(=O)NN=CC=4N=C(N=3)N3CCCCCC3)=CC=2)CC1 GXWLYDJPYDIHSY-UHFFFAOYSA-N 0.000 claims 1
- BJFPPTIKXSPLBJ-UHFFFAOYSA-N 6-[5-[[2-[4-(cyanomethyl)piperidin-1-yl]-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]pyridin-2-yl]-6-azaspiro[2.5]octane-2-carboxylic acid Chemical compound OC(=O)C1CC11CCN(C=2N=CC(NC=3C=4C(=O)NN=CC=4N=C(N=3)N3CCC(CC#N)CC3)=CC=2)CC1 BJFPPTIKXSPLBJ-UHFFFAOYSA-N 0.000 claims 1
- PTUKLDQLWKNNAW-UHFFFAOYSA-N C1CCCN(CC1)C2=NC(=NC3=CC=C(C=C3)C4=NNN=N4)C5C(=N2)C=NNC5=O Chemical compound C1CCCN(CC1)C2=NC(=NC3=CC=C(C=C3)C4=NNN=N4)C5C(=N2)C=NNC5=O PTUKLDQLWKNNAW-UHFFFAOYSA-N 0.000 claims 1
- GVPNHYBTDCFFQC-UHFFFAOYSA-N C1CN(CCC1CC#N)C2=NC(=NC3=CC4=NNN=C4C=C3)C5C(=N2)C=NNC5=O Chemical compound C1CN(CCC1CC#N)C2=NC(=NC3=CC4=NNN=C4C=C3)C5C(=N2)C=NNC5=O GVPNHYBTDCFFQC-UHFFFAOYSA-N 0.000 claims 1
- PAODDNHMDUDXDP-UHFFFAOYSA-N C1CN(CCC1CC#N)C2=NC(=NC3=CC=C(C=C3)C4=NNN=N4)C5C(=N2)C=NNC5=O Chemical compound C1CN(CCC1CC#N)C2=NC(=NC3=CC=C(C=C3)C4=NNN=N4)C5C(=N2)C=NNC5=O PAODDNHMDUDXDP-UHFFFAOYSA-N 0.000 claims 1
- XJBMJCWJHJEDHL-UHFFFAOYSA-N CC(C)(C)OC1=CC=C(C=C1)NC2=NC(=NC3=C2C(=O)NN=C3)N4CCCCCC4 Chemical compound CC(C)(C)OC1=CC=C(C=C1)NC2=NC(=NC3=C2C(=O)NN=C3)N4CCCCCC4 XJBMJCWJHJEDHL-UHFFFAOYSA-N 0.000 claims 1
- HJPYZKBFJLKISF-UHFFFAOYSA-N CC(C)(CO)N1CCCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1 Chemical compound CC(C)(CO)N1CCCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1 HJPYZKBFJLKISF-UHFFFAOYSA-N 0.000 claims 1
- QTTQLTVLCSCZGW-UHFFFAOYSA-N CC(C)(CO)N1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound CC(C)(CO)N1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 QTTQLTVLCSCZGW-UHFFFAOYSA-N 0.000 claims 1
- GRTWUVFZPDHHBE-UHFFFAOYSA-N CC(C)(O)C(=O)N1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cn1 Chemical compound CC(C)(O)C(=O)N1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cn1 GRTWUVFZPDHHBE-UHFFFAOYSA-N 0.000 claims 1
- BXSSEDHTYPNHHF-UHFFFAOYSA-N CC(C)(O)C(=O)N1CCN(CCOc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CC1 Chemical compound CC(C)(O)C(=O)N1CCN(CCOc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CC1 BXSSEDHTYPNHHF-UHFFFAOYSA-N 0.000 claims 1
- NYTZWBPMTLQAGU-UHFFFAOYSA-N CC(C)(O)C(=O)N1CCN(Cc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CC1 Chemical compound CC(C)(O)C(=O)N1CCN(Cc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CC1 NYTZWBPMTLQAGU-UHFFFAOYSA-N 0.000 claims 1
- MCCFNNCQIKPCPL-UHFFFAOYSA-N CC(C)(Oc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1)C(O)=O Chemical compound CC(C)(Oc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1)C(O)=O MCCFNNCQIKPCPL-UHFFFAOYSA-N 0.000 claims 1
- HXHJYKQABDZRHS-UHFFFAOYSA-N CC(C)N(C(C)C)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 Chemical compound CC(C)N(C(C)C)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 HXHJYKQABDZRHS-UHFFFAOYSA-N 0.000 claims 1
- YFUMCIDGKJQPHM-UHFFFAOYSA-N CC1CCN(CC1)C1NC2CNNC(=O)C2C(Nc2ccc(cc2)N2CCC3(CC3C(O)=O)CC2)N1 Chemical compound CC1CCN(CC1)C1NC2CNNC(=O)C2C(Nc2ccc(cc2)N2CCC3(CC3C(O)=O)CC2)N1 YFUMCIDGKJQPHM-UHFFFAOYSA-N 0.000 claims 1
- HSGDXRVWVFVQTK-UHFFFAOYSA-N CC1CN(CC(C)O1)C1NC2CNNC(=O)C2C(Nc2ccc(OCCN3CCNCC3)cc2)N1 Chemical compound CC1CN(CC(C)O1)C1NC2CNNC(=O)C2C(Nc2ccc(OCCN3CCNCC3)cc2)N1 HSGDXRVWVFVQTK-UHFFFAOYSA-N 0.000 claims 1
- TUTFNPABZUDEDO-UHFFFAOYSA-N CCN1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound CCN1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 TUTFNPABZUDEDO-UHFFFAOYSA-N 0.000 claims 1
- WRHUNZBDGQTZCQ-UHFFFAOYSA-N CCN1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCOCC2)cc1 Chemical compound CCN1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCOCC2)cc1 WRHUNZBDGQTZCQ-UHFFFAOYSA-N 0.000 claims 1
- XZTOZJRPCPUFAP-UHFFFAOYSA-N CCN1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)c2ccsc2)cc1 Chemical compound CCN1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)c2ccsc2)cc1 XZTOZJRPCPUFAP-UHFFFAOYSA-N 0.000 claims 1
- TWZZHKWCDDACEG-UHFFFAOYSA-N CCN1CCN(CC1=O)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound CCN1CCN(CC1=O)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 TWZZHKWCDDACEG-UHFFFAOYSA-N 0.000 claims 1
- IFCCDROOCUODJG-UHFFFAOYSA-N CCOC1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 Chemical compound CCOC1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 IFCCDROOCUODJG-UHFFFAOYSA-N 0.000 claims 1
- DSJVFHSOFHJLRM-UHFFFAOYSA-N CN(C)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 Chemical compound CN(C)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 DSJVFHSOFHJLRM-UHFFFAOYSA-N 0.000 claims 1
- NCCTZQWZDPWCMA-UHFFFAOYSA-N CN(C1CCCCC1)C1NC2CNNC(=O)C2C(Nc2ccc(OCCN3CCNCC3)cc2)N1 Chemical compound CN(C1CCCCC1)C1NC2CNNC(=O)C2C(Nc2ccc(OCCN3CCNCC3)cc2)N1 NCCTZQWZDPWCMA-UHFFFAOYSA-N 0.000 claims 1
- OMTKHPLIWHPSRI-UHFFFAOYSA-N CN(C1CCCCC1)C1NC2CNNC(=O)C2C(Nc2ccc(cc2)N2CCC3(CC3C(O)=O)CC2)N1 Chemical compound CN(C1CCCCC1)C1NC2CNNC(=O)C2C(Nc2ccc(cc2)N2CCC3(CC3C(O)=O)CC2)N1 OMTKHPLIWHPSRI-UHFFFAOYSA-N 0.000 claims 1
- WDWCSHCMZSLJLB-UHFFFAOYSA-N CN1CCN(CC1)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 Chemical compound CN1CCN(CC1)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 WDWCSHCMZSLJLB-UHFFFAOYSA-N 0.000 claims 1
- DREFZNQBMLOWPM-UHFFFAOYSA-N CN1CCN(CC1)C2=NC=C(C=C2)N=C3C4C(=NC(=N3)N5CCCCCC5)C=NNC4=O Chemical compound CN1CCN(CC1)C2=NC=C(C=C2)N=C3C4C(=NC(=N3)N5CCCCCC5)C=NNC4=O DREFZNQBMLOWPM-UHFFFAOYSA-N 0.000 claims 1
- GZUITUFAEIMKBH-UHFFFAOYSA-N CN1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound CN1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 GZUITUFAEIMKBH-UHFFFAOYSA-N 0.000 claims 1
- PYBBOPDZNIDKDC-UHFFFAOYSA-N CN1CCN(Cc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CC1 Chemical compound CN1CCN(Cc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CC1 PYBBOPDZNIDKDC-UHFFFAOYSA-N 0.000 claims 1
- DJWRZXRZLINUKZ-UHFFFAOYSA-N COC(=O)c1ccc(cc1)C1NC2CNNC(=O)C2C(Nc2ccc(cc2)N2CCOCC2)N1 Chemical compound COC(=O)c1ccc(cc1)C1NC2CNNC(=O)C2C(Nc2ccc(cc2)N2CCOCC2)N1 DJWRZXRZLINUKZ-UHFFFAOYSA-N 0.000 claims 1
- ZIZIUXVWGIHOFM-UHFFFAOYSA-N COC(C=CC=C1)=C1C(N=C1NC2=CC=C(C(C3)(C33CCNCC3)C(O)=O)C=C2)=NC(C=NN2)=C1C2=O Chemical compound COC(C=CC=C1)=C1C(N=C1NC2=CC=C(C(C3)(C33CCNCC3)C(O)=O)C=C2)=NC(C=NN2)=C1C2=O ZIZIUXVWGIHOFM-UHFFFAOYSA-N 0.000 claims 1
- OLRFKTACNKOFCK-UHFFFAOYSA-N COC1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound COC1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 OLRFKTACNKOFCK-UHFFFAOYSA-N 0.000 claims 1
- WSCZNTJXVHSQRB-UHFFFAOYSA-N COC1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 Chemical compound COC1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 WSCZNTJXVHSQRB-UHFFFAOYSA-N 0.000 claims 1
- UGJVATUASBILCP-UHFFFAOYSA-N COc1cc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc(OC)c1 Chemical compound COc1cc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc(OC)c1 UGJVATUASBILCP-UHFFFAOYSA-N 0.000 claims 1
- UPOWHTUNPMRRBZ-UHFFFAOYSA-N COc1cc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc(OC)c1OC Chemical compound COc1cc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc(OC)c1OC UPOWHTUNPMRRBZ-UHFFFAOYSA-N 0.000 claims 1
- GCKXEWDRLVZKAN-UHFFFAOYSA-N COc1ccc(cc1)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 Chemical compound COc1ccc(cc1)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 GCKXEWDRLVZKAN-UHFFFAOYSA-N 0.000 claims 1
- JFMISSJSNKKMSQ-UHFFFAOYSA-N COc1cccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)c1 Chemical compound COc1cccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)c1 JFMISSJSNKKMSQ-UHFFFAOYSA-N 0.000 claims 1
- CBEQKTNHSFJORM-UHFFFAOYSA-N COc1cccc(c1)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 Chemical compound COc1cccc(c1)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 CBEQKTNHSFJORM-UHFFFAOYSA-N 0.000 claims 1
- JEHPUSNSQFJOQY-UHFFFAOYSA-N COc1cccc(c1)C1NC2CNNC(=O)C2C(Nc2ccc(OCCN3CCNCC3)cc2)N1 Chemical compound COc1cccc(c1)C1NC2CNNC(=O)C2C(Nc2ccc(OCCN3CCNCC3)cc2)N1 JEHPUSNSQFJOQY-UHFFFAOYSA-N 0.000 claims 1
- GNLCEHNTCIXUFJ-UHFFFAOYSA-N COc1cccc(c1)C1NC2CNNC(=O)C2C(Nc2ccc(cc2)N2CCC3(CC3C(O)=O)CC2)N1 Chemical compound COc1cccc(c1)C1NC2CNNC(=O)C2C(Nc2ccc(cc2)N2CCC3(CC3C(O)=O)CC2)N1 GNLCEHNTCIXUFJ-UHFFFAOYSA-N 0.000 claims 1
- SNSWAGOZMXZARN-UHFFFAOYSA-N COc1ccccc1C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 Chemical compound COc1ccccc1C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 SNSWAGOZMXZARN-UHFFFAOYSA-N 0.000 claims 1
- DVLGBAMRHNZUMN-UHFFFAOYSA-N Clc1ccc(cc1)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 Chemical compound Clc1ccc(cc1)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 DVLGBAMRHNZUMN-UHFFFAOYSA-N 0.000 claims 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- VFKRSIXWSXWTCM-UHFFFAOYSA-N FC(F)(F)Oc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound FC(F)(F)Oc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 VFKRSIXWSXWTCM-UHFFFAOYSA-N 0.000 claims 1
- XOCAOVZYGJLMNT-UHFFFAOYSA-N N#CC(C=O)N(CC1)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC(C=NN2)=C1C2=O Chemical compound N#CC(C=O)N(CC1)CCN1C(C=C1)=CC=C1NC1=NC(N2CCCCCC2)=NC(C=NN2)=C1C2=O XOCAOVZYGJLMNT-UHFFFAOYSA-N 0.000 claims 1
- XAQQADQBGFQXAC-UHFFFAOYSA-N N#CCC(CC1)CCN1C(N=C1NC(C=C2)=CC=C2N(CC2)CCN2C(C=O)C#N)=NC(C=NN2)=C1C2=O Chemical compound N#CCC(CC1)CCN1C(N=C1NC(C=C2)=CC=C2N(CC2)CCN2C(C=O)C#N)=NC(C=NN2)=C1C2=O XAQQADQBGFQXAC-UHFFFAOYSA-N 0.000 claims 1
- BQYKQMOSEZCTTG-UHFFFAOYSA-N N-[2-(dimethylamino)ethyl]-N-methyl-4-[(5-oxo-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-4-yl)amino]benzamide Chemical compound C1=CC(C(=O)N(C)CCN(C)C)=CC=C1NC1C2C(=O)NNCC2NC(C=2C=CC=CC=2)N1 BQYKQMOSEZCTTG-UHFFFAOYSA-N 0.000 claims 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims 1
- SPPCRSLIKDZRMS-UHFFFAOYSA-N O=C(N1CCNCC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound O=C(N1CCNCC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 SPPCRSLIKDZRMS-UHFFFAOYSA-N 0.000 claims 1
- PHGHWWYILWZXPH-UHFFFAOYSA-N O=C1CC2(CCN(CC2)C2NC3CNNC(=O)C3C(Nc3ccc(CN4CCNCC4)cc3)N2)CC(=O)N1 Chemical compound O=C1CC2(CCN(CC2)C2NC3CNNC(=O)C3C(Nc3ccc(CN4CCNCC4)cc3)N2)CC(=O)N1 PHGHWWYILWZXPH-UHFFFAOYSA-N 0.000 claims 1
- GYZAPVRUISTWBR-UHFFFAOYSA-N O=C1CN(CCN1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound O=C1CN(CCN1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 GYZAPVRUISTWBR-UHFFFAOYSA-N 0.000 claims 1
- AJDNSILYAJFCLN-UHFFFAOYSA-N O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)N1CCC(CC1)[N+]#[C-] Chemical compound O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)N1CCC(CC1)[N+]#[C-] AJDNSILYAJFCLN-UHFFFAOYSA-N 0.000 claims 1
- JJFVUVSNXZBDQP-UHFFFAOYSA-N O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)N1CCCC1 Chemical compound O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)N1CCCC1 JJFVUVSNXZBDQP-UHFFFAOYSA-N 0.000 claims 1
- FPKKZSSQDWXERD-UHFFFAOYSA-N O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)N1CCCCC1 Chemical compound O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)N1CCCCC1 FPKKZSSQDWXERD-UHFFFAOYSA-N 0.000 claims 1
- HEUPAFWTKGTXMM-UHFFFAOYSA-N O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)N1CCCCCC1 Chemical compound O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)N1CCCCCC1 HEUPAFWTKGTXMM-UHFFFAOYSA-N 0.000 claims 1
- NVVCGECDFWCUNR-UHFFFAOYSA-N O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)N1CCCNCC1 Chemical compound O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)N1CCCNCC1 NVVCGECDFWCUNR-UHFFFAOYSA-N 0.000 claims 1
- RERIMGBKMBJDAG-UHFFFAOYSA-N O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)N1CCNCC1 Chemical compound O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)N1CCNCC1 RERIMGBKMBJDAG-UHFFFAOYSA-N 0.000 claims 1
- RJSXQOCTTAEMCO-UHFFFAOYSA-N O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)c1ccsc1 Chemical compound O=C1NNCC2NC(NC(Nc3ccc(CN4CCNCC4)cc3)C12)c1ccsc1 RJSXQOCTTAEMCO-UHFFFAOYSA-N 0.000 claims 1
- PCBWTPZEPXIWHY-UHFFFAOYSA-N O=C1NNCC2NC(NC(Nc3ccc(OCCC4CCNCC4)cc3)C12)N1CCCCCC1 Chemical compound O=C1NNCC2NC(NC(Nc3ccc(OCCC4CCNCC4)cc3)C12)N1CCCCCC1 PCBWTPZEPXIWHY-UHFFFAOYSA-N 0.000 claims 1
- GCKCYGHKZLZDOT-UHFFFAOYSA-N O=C1NNCC2NC(NC(Nc3ccc(OCCN4CCNCC4)cc3)C12)N1CCC(CC1)[N+]#[C-] Chemical compound O=C1NNCC2NC(NC(Nc3ccc(OCCN4CCNCC4)cc3)C12)N1CCC(CC1)[N+]#[C-] GCKCYGHKZLZDOT-UHFFFAOYSA-N 0.000 claims 1
- KZOVVORFWGZGPB-UHFFFAOYSA-N O=C1NNCC2NC(NC(Nc3ccc(OCCN4CCNCC4)cc3)C12)N1CCCCC1 Chemical compound O=C1NNCC2NC(NC(Nc3ccc(OCCN4CCNCC4)cc3)C12)N1CCCCC1 KZOVVORFWGZGPB-UHFFFAOYSA-N 0.000 claims 1
- LNMDYFPQFHVIIC-UHFFFAOYSA-N O=C1NNCC2NC(NC(Nc3ccc(OCCN4CCNCC4)cc3)C12)N1CCOCC1 Chemical compound O=C1NNCC2NC(NC(Nc3ccc(OCCN4CCNCC4)cc3)C12)N1CCOCC1 LNMDYFPQFHVIIC-UHFFFAOYSA-N 0.000 claims 1
- MQQRCURXIYRFLY-UHFFFAOYSA-N OC(=O)C1CC11CCC(CC1)c1ccc(NC2NC(NC3CCCCC3)NC3CNNC(=O)C23)cc1 Chemical compound OC(=O)C1CC11CCC(CC1)c1ccc(NC2NC(NC3CCCCC3)NC3CNNC(=O)C23)cc1 MQQRCURXIYRFLY-UHFFFAOYSA-N 0.000 claims 1
- LWTSLRSZELDWFH-UHFFFAOYSA-N OC(=O)C1CC11CCC(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCC2)cc1 Chemical compound OC(=O)C1CC11CCC(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCC2)cc1 LWTSLRSZELDWFH-UHFFFAOYSA-N 0.000 claims 1
- AGDVQMJYQYXDHD-UHFFFAOYSA-N OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)C2CCCCCC2)cc1 Chemical compound OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)C2CCCCCC2)cc1 AGDVQMJYQYXDHD-UHFFFAOYSA-N 0.000 claims 1
- OGYIBXUVUUHXEP-UHFFFAOYSA-N OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC2)[N+]#[C-])cc1 Chemical compound OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC2)[N+]#[C-])cc1 OGYIBXUVUUHXEP-UHFFFAOYSA-N 0.000 claims 1
- BYWMDYZJFAYSLM-UHFFFAOYSA-N OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(C[N+]#[C-])CC2)cc1 Chemical compound OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(C[N+]#[C-])CC2)cc1 BYWMDYZJFAYSLM-UHFFFAOYSA-N 0.000 claims 1
- SKXVGPFJOWCXQU-UHFFFAOYSA-N OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 SKXVGPFJOWCXQU-UHFFFAOYSA-N 0.000 claims 1
- JKZGNPXJZIIQSJ-UHFFFAOYSA-N OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1F Chemical compound OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1F JKZGNPXJZIIQSJ-UHFFFAOYSA-N 0.000 claims 1
- YTUHQBCSPLAFDE-UHFFFAOYSA-N OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCCC2)cc1 Chemical compound OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCCC2)cc1 YTUHQBCSPLAFDE-UHFFFAOYSA-N 0.000 claims 1
- IETBGTSQKUXVRU-UHFFFAOYSA-N OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCN(C[N+]#[C-])CC2)cc1 Chemical compound OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCN(C[N+]#[C-])CC2)cc1 IETBGTSQKUXVRU-UHFFFAOYSA-N 0.000 claims 1
- MYOYPRMWLHPTFF-UHFFFAOYSA-N OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCOCC2)cc1 Chemical compound OC(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCOCC2)cc1 MYOYPRMWLHPTFF-UHFFFAOYSA-N 0.000 claims 1
- NZBNTCDXOPENLR-UHFFFAOYSA-N OC(=O)C1CC11CCN(CCOc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CC1 Chemical compound OC(=O)C1CC11CCN(CCOc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CC1 NZBNTCDXOPENLR-UHFFFAOYSA-N 0.000 claims 1
- KKDBQMDEFGFUPO-UHFFFAOYSA-N OC(=O)C1CCN(CCOc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CC1 Chemical compound OC(=O)C1CCN(CCOc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CC1 KKDBQMDEFGFUPO-UHFFFAOYSA-N 0.000 claims 1
- ITZWDHUUXWCUHN-UHFFFAOYSA-N OC(=O)CC1CCC(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound OC(=O)CC1CCC(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 ITZWDHUUXWCUHN-UHFFFAOYSA-N 0.000 claims 1
- IGVIDESRTMGKJI-UHFFFAOYSA-N OC(=O)CCCOc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound OC(=O)CCCOc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 IGVIDESRTMGKJI-UHFFFAOYSA-N 0.000 claims 1
- SHKRXALTOSPPHE-UHFFFAOYSA-N OC(=O)CCc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1 Chemical compound OC(=O)CCc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1 SHKRXALTOSPPHE-UHFFFAOYSA-N 0.000 claims 1
- GBXVZIPWUBBETG-UHFFFAOYSA-N OC(=O)CCc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound OC(=O)CCc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 GBXVZIPWUBBETG-UHFFFAOYSA-N 0.000 claims 1
- UTHVPVRSQDTCML-UHFFFAOYSA-N OC(=O)CN1CCC(CC1)Oc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1 Chemical compound OC(=O)CN1CCC(CC1)Oc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1 UTHVPVRSQDTCML-UHFFFAOYSA-N 0.000 claims 1
- KVLQQOKXBJSYIJ-UHFFFAOYSA-N OC(=O)CN1CCCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCC2)cc1 Chemical compound OC(=O)CN1CCCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCC2)cc1 KVLQQOKXBJSYIJ-UHFFFAOYSA-N 0.000 claims 1
- KVZPNYWAXPMBLT-UHFFFAOYSA-N OC(=O)CN1CCCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound OC(=O)CN1CCCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 KVZPNYWAXPMBLT-UHFFFAOYSA-N 0.000 claims 1
- LEZOPGWYWZHLFT-UHFFFAOYSA-N OC(=O)CN1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1 Chemical compound OC(=O)CN1CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1 LEZOPGWYWZHLFT-UHFFFAOYSA-N 0.000 claims 1
- JHIYFQSCOFGXQQ-UHFFFAOYSA-N OC(=O)CN1CCN(CCOc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CC1 Chemical compound OC(=O)CN1CCN(CCOc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CC1 JHIYFQSCOFGXQQ-UHFFFAOYSA-N 0.000 claims 1
- SDEYRFBSYRXCQH-HLOUMQLKSA-N OC(=O)[C@H]1CO[C@H](COc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CO1 Chemical compound OC(=O)[C@H]1CO[C@H](COc2ccc(NC3NC(NC4CNNC(=O)C34)N3CCCCCC3)cc2)CO1 SDEYRFBSYRXCQH-HLOUMQLKSA-N 0.000 claims 1
- LPJRZLGURJLACT-UHFFFAOYSA-N OC(=O)c1ccc(cc1)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 Chemical compound OC(=O)c1ccc(cc1)C1NC2CNNC(=O)C2C(Nc2ccc(CN3CCNCC3)cc2)N1 LPJRZLGURJLACT-UHFFFAOYSA-N 0.000 claims 1
- FSSQFUCXYAXPNN-UHFFFAOYSA-N OC(C(C1)(C11CCNCC1)C(C=C1)=CC=C1NC1=NC(C(C=C2)=CC=C2F)=NC(C=NN2)=C1C2=O)=O Chemical compound OC(C(C1)(C11CCNCC1)C(C=C1)=CC=C1NC1=NC(C(C=C2)=CC=C2F)=NC(C=NN2)=C1C2=O)=O FSSQFUCXYAXPNN-UHFFFAOYSA-N 0.000 claims 1
- MHCDEAZCPKWYOH-UHFFFAOYSA-N OC1CCCN(C1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1 Chemical compound OC1CCCN(C1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1 MHCDEAZCPKWYOH-UHFFFAOYSA-N 0.000 claims 1
- IUOPXHZLRMSXBS-UHFFFAOYSA-N OCC1CCCN(C1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound OCC1CCCN(C1)c1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 IUOPXHZLRMSXBS-UHFFFAOYSA-N 0.000 claims 1
- NOUJFTNYQZKOTJ-UHFFFAOYSA-N OCCN1CCC(CC1)Oc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1 Chemical compound OCCN1CCC(CC1)Oc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCC(CC#N)CC2)cc1 NOUJFTNYQZKOTJ-UHFFFAOYSA-N 0.000 claims 1
- DWGCHYVQIRPGJA-UHFFFAOYSA-N OCc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 Chemical compound OCc1ccc(NC2NC(NC3CNNC(=O)C23)N2CCCCCC2)cc1 DWGCHYVQIRPGJA-UHFFFAOYSA-N 0.000 claims 1
- SYKBEUPCNDWPFH-UHFFFAOYSA-M P(=O)(ON1N=CC2=C(C1=O)C(=NC(=N2)N1CCC(CC1)CC#N)NC1=CC=C(C=C1)N1CCC(CC1)O)(OC)[O-].[Na+] Chemical compound P(=O)(ON1N=CC2=C(C1=O)C(=NC(=N2)N1CCC(CC1)CC#N)NC1=CC=C(C=C1)N1CCC(CC1)O)(OC)[O-].[Na+] SYKBEUPCNDWPFH-UHFFFAOYSA-M 0.000 claims 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims 1
- AKXHGIZHOIWBRS-UHFFFAOYSA-M [O-]C(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)c2ccccc2)cc1 Chemical compound [O-]C(=O)C1CC11CCN(CC1)c1ccc(NC2NC(NC3CNNC(=O)C23)c2ccccc2)cc1 AKXHGIZHOIWBRS-UHFFFAOYSA-M 0.000 claims 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims 1
- 229940092714 benzenesulfonic acid Drugs 0.000 claims 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- 125000004310 dioxan-2-yl group Chemical group [H]C1([H])OC([H])([H])C([H])(*)OC1([H])[H] 0.000 claims 1
- IIPMXKWCRYWFSW-UHFFFAOYSA-N ethyl 6-[4-[(5-oxo-2-phenyl-2,3,4,4a,6,7,8,8a-octahydro-1H-pyrimido[4,5-d]pyridazin-4-yl)amino]phenyl]-6-azaspiro[2.5]octane-2-carboxylate Chemical compound CCOC(=O)C1CC11CCN(C=2C=CC(NC3C4C(=O)NNCC4NC(N3)C=3C=CC=CC=3)=CC=2)CC1 IIPMXKWCRYWFSW-UHFFFAOYSA-N 0.000 claims 1
- 239000001530 fumaric acid Substances 0.000 claims 1
- 235000011087 fumaric acid Nutrition 0.000 claims 1
- NLFLXLJXEIUQDL-UHFFFAOYSA-N gusacitinib Chemical compound C1CC(O)CCN1C(C=C1)=CC=C1NC1=NC(N2CCC(CC#N)CC2)=NC2=C1C(=O)NN=C2 NLFLXLJXEIUQDL-UHFFFAOYSA-N 0.000 claims 1
- IRXWIGPNZAGTAI-UHFFFAOYSA-N hydroxymethyl 6-[4-[[2-(azepan-1-yl)-5-carbamoyl-6-methanimidoylpyrimidin-4-yl]amino]phenyl]-6-azaspiro[2.5]octane-2-carboxylate Chemical compound N1=C(N2CCCCCC2)N=C(C=N)C(C(=O)N)=C1NC(C=C1)=CC=C1N(CC1)CCC21CC2C(=O)OCO IRXWIGPNZAGTAI-UHFFFAOYSA-N 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 239000004310 lactic acid Substances 0.000 claims 1
- 235000014655 lactic acid Nutrition 0.000 claims 1
- 239000011976 maleic acid Substances 0.000 claims 1
- 239000001630 malic acid Substances 0.000 claims 1
- 235000011090 malic acid Nutrition 0.000 claims 1
- 229960002510 mandelic acid Drugs 0.000 claims 1
- 229940098779 methanesulfonic acid Drugs 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 claims 1
- 229910017604 nitric acid Inorganic materials 0.000 claims 1
- POTQIHURRUDRCG-UHFFFAOYSA-N nonanoic acid;hydrochloride Chemical compound Cl.CCCCCCCCC(O)=O POTQIHURRUDRCG-UHFFFAOYSA-N 0.000 claims 1
- 235000019260 propionic acid Nutrition 0.000 claims 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims 1
- 239000011975 tartaric acid Substances 0.000 claims 1
- 235000002906 tartaric acid Nutrition 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 20
- 239000000203 mixture Substances 0.000 description 51
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 0 *c1ncc(*=C)cc1 Chemical compound *c1ncc(*=C)cc1 0.000 description 30
- 125000003545 alkoxy group Chemical group 0.000 description 25
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- 239000000758 substrate Substances 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 241001465754 Metazoa Species 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 238000002347 injection Methods 0.000 description 14
- 239000007924 injection Substances 0.000 description 14
- 208000009386 Experimental Arthritis Diseases 0.000 description 13
- 108091000080 Phosphotransferase Proteins 0.000 description 13
- 102000020233 phosphotransferase Human genes 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 150000001721 carbon Chemical group 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 206010030113 Oedema Diseases 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 230000001404 mediated effect Effects 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 239000002775 capsule Substances 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 230000011664 signaling Effects 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 241000282414 Homo sapiens Species 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 239000000969 carrier Substances 0.000 description 9
- 125000001188 haloalkyl group Chemical group 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- 108010019437 Janus Kinase 2 Proteins 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
- 239000000427 antigen Substances 0.000 description 8
- 125000002619 bicyclic group Chemical group 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 7
- 150000001299 aldehydes Chemical class 0.000 description 7
- 125000004103 aminoalkyl group Chemical group 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 102000007478 beta-N-Acetylhexosaminidases Human genes 0.000 description 7
- 108010085377 beta-N-Acetylhexosaminidases Proteins 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 108010016672 Syk Kinase Proteins 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000002168 alkylating agent Substances 0.000 description 6
- 229940100198 alkylating agent Drugs 0.000 description 6
- 125000003368 amide group Chemical group 0.000 description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 230000003053 immunization Effects 0.000 description 6
- 238000002649 immunization Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000002674 ointment Substances 0.000 description 6
- 238000007248 oxidative elimination reaction Methods 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000001356 surgical procedure Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 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 5
- 230000004913 activation Effects 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 5
- 150000001448 anilines Chemical class 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 5
- 206010003246 arthritis Diseases 0.000 description 5
- 239000007894 caplet Substances 0.000 description 5
- 125000005518 carboxamido group Chemical group 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 229940125773 compound 10 Drugs 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 5
- 229960000485 methotrexate Drugs 0.000 description 5
- 150000007530 organic bases Chemical class 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 102000009438 IgE Receptors Human genes 0.000 description 4
- 108010073816 IgE Receptors Proteins 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 102100038183 Tyrosine-protein kinase SYK Human genes 0.000 description 4
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 239000010432 diamond Substances 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 230000005802 health problem Effects 0.000 description 4
- 210000003630 histaminocyte Anatomy 0.000 description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical group IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 4
- 230000003040 nociceptive effect Effects 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical group ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 108060006633 protein kinase Proteins 0.000 description 4
- CCOXWRVWKFVFDG-UHFFFAOYSA-N pyrimidine-2-carbaldehyde Chemical compound O=CC1=NC=CC=N1 CCOXWRVWKFVFDG-UHFFFAOYSA-N 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 230000009278 visceral effect Effects 0.000 description 4
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 3
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 3
- XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 3
- SQSBWXVYOZWNJH-UHFFFAOYSA-N 4-methylsulfanyl-2-phenyl-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound N=1C=2C=NNC(=O)C=2C(SC)=NC=1C1=CC=CC=C1 SQSBWXVYOZWNJH-UHFFFAOYSA-N 0.000 description 3
- MITGKKFYIJJQGL-UHFFFAOYSA-N 9-(4-chlorobenzoyl)-6-methylsulfonyl-2,3-dihydro-1H-carbazol-4-one Chemical compound ClC1=CC=C(C(=O)N2C3=CC=C(C=C3C=3C(CCCC2=3)=O)S(=O)(=O)C)C=C1 MITGKKFYIJJQGL-UHFFFAOYSA-N 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 206010051728 Bone erosion Diseases 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- 102000000503 Collagen Type II Human genes 0.000 description 3
- 108010041390 Collagen Type II Proteins 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 102000042838 JAK family Human genes 0.000 description 3
- 108091082332 JAK family Proteins 0.000 description 3
- 102000015617 Janus Kinases Human genes 0.000 description 3
- 108010024121 Janus Kinases Proteins 0.000 description 3
- 241000872931 Myoporum sandwicense Species 0.000 description 3
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 3
- 108010058846 Ovalbumin Proteins 0.000 description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 102000000551 Syk Kinase Human genes 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 206010053614 Type III immune complex mediated reaction Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- SOIFLUNRINLCBN-UHFFFAOYSA-N ammonium thiocyanate Chemical compound [NH4+].[S-]C#N SOIFLUNRINLCBN-UHFFFAOYSA-N 0.000 description 3
- 230000002917 arthritic effect Effects 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 210000003651 basophil Anatomy 0.000 description 3
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 239000012320 chlorinating reagent Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 229940125810 compound 20 Drugs 0.000 description 3
- 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 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- 108010067755 dinitrophenyl-bovine serum albumin Proteins 0.000 description 3
- OYRKAFJVRIJXIS-UHFFFAOYSA-N ethyl 2-chloro-4-methyl-6-[4-[[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]methyl]anilino]pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)N=C(Cl)N=C1NC(C=C1)=CC=C1CN1CCN(C(=O)OC(C)(C)C)CC1 OYRKAFJVRIJXIS-UHFFFAOYSA-N 0.000 description 3
- CDZIZNTXUNQQDP-UHFFFAOYSA-N ethyl 4-methyl-6-methylsulfanyl-2-phenylpyrimidine-5-carboxylate Chemical compound N1=C(SC)C(C(=O)OCC)=C(C)N=C1C1=CC=CC=C1 CDZIZNTXUNQQDP-UHFFFAOYSA-N 0.000 description 3
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)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)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 3
- 239000005414 inactive ingredient Substances 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 3
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 229940092253 ovalbumin Drugs 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 2
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 2
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 2
- ZOJWBYYWJVERJS-UHFFFAOYSA-N 4-(4-morpholin-4-ylanilino)-2-phenyl-6h-pyrimido[4,5-d]pyridazin-5-one Chemical compound C=12C(=O)NN=CC2=NC(C=2C=CC=CC=2)=NC=1NC(C=C1)=CC=C1N1CCOCC1 ZOJWBYYWJVERJS-UHFFFAOYSA-N 0.000 description 2
- HSHNITRMYYLLCV-UHFFFAOYSA-N 4-methylumbelliferone Chemical compound C1=C(O)C=CC2=C1OC(=O)C=C2C HSHNITRMYYLLCV-UHFFFAOYSA-N 0.000 description 2
- YQZITMLBTHTMFV-UHFFFAOYSA-N C(=O)O.C(C)SC#N Chemical compound C(=O)O.C(C)SC#N YQZITMLBTHTMFV-UHFFFAOYSA-N 0.000 description 2
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 2
- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 238000001061 Dunnett's test Methods 0.000 description 2
- 102000009109 Fc receptors Human genes 0.000 description 2
- 108010087819 Fc receptors Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 2
- 208000007514 Herpes zoster Diseases 0.000 description 2
- 102000009490 IgG Receptors Human genes 0.000 description 2
- 108010073807 IgG Receptors Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000007920 Neurogenic Inflammation Diseases 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 2
- 235000011613 Pinus brutia Nutrition 0.000 description 2
- 241000018646 Pinus brutia Species 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 description 2
- 108010046882 ZAP-70 Protein-Tyrosine Kinase Proteins 0.000 description 2
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 2
- 125000005157 alkyl carboxy group Chemical group 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 125000004069 aziridinyl group Chemical group 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 229940125797 compound 12 Drugs 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 229940126142 compound 16 Drugs 0.000 description 2
- 229940126086 compound 21 Drugs 0.000 description 2
- 229940125833 compound 23 Drugs 0.000 description 2
- 229940125846 compound 25 Drugs 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 229910003460 diamond Inorganic materials 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- NLEBIOOXCVAHBD-QKMCSOCLSA-N dodecyl beta-D-maltoside Chemical compound O[C@@H]1[C@@H](O)[C@H](OCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 NLEBIOOXCVAHBD-QKMCSOCLSA-N 0.000 description 2
- 238000001952 enzyme assay Methods 0.000 description 2
- OXHHCTICZZKBAA-VOTSOKGWSA-N ethyl (z)-3-amino-2-(ethoxycarbonylcarbamothioyl)but-2-enoate Chemical compound CCOC(=O)NC(=S)C(=C(\C)N)\C(=O)OCC OXHHCTICZZKBAA-VOTSOKGWSA-N 0.000 description 2
- NBLFZEOAMBXUEI-UHFFFAOYSA-N ethyl 2,4-dichloro-6-methylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)N=C(Cl)N=C1Cl NBLFZEOAMBXUEI-UHFFFAOYSA-N 0.000 description 2
- AXMITKLWOIYLEA-UHFFFAOYSA-N ethyl 2-[bis(methylsulfanyl)methylidene]-3-oxobutanoate Chemical compound CCOC(=O)C(C(C)=O)=C(SC)SC AXMITKLWOIYLEA-UHFFFAOYSA-N 0.000 description 2
- JIELNZYVNVUXLF-UHFFFAOYSA-N ethyl 4-formyl-6-[4-[[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]methyl]anilino]-2-morpholin-4-ylpyrimidine-5-carboxylate Chemical compound N1=C(N2CCOCC2)N=C(C=O)C(C(=O)OCC)=C1NC(C=C1)=CC=C1CN1CCN(C(=O)OC(C)(C)C)CC1 JIELNZYVNVUXLF-UHFFFAOYSA-N 0.000 description 2
- XRECDTDZWNRMHN-UHFFFAOYSA-N ethyl 4-formyl-6-methylsulfanyl-2-phenylpyrimidine-5-carboxylate Chemical compound N1=C(C=O)C(C(=O)OCC)=C(SC)N=C1C1=CC=CC=C1 XRECDTDZWNRMHN-UHFFFAOYSA-N 0.000 description 2
- HQOXGQMLMVPYIB-UHFFFAOYSA-N ethyl 4-methyl-6-[4-[[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]methyl]anilino]-2-morpholin-4-ylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)N=C(N2CCOCC2)N=C1NC(C=C1)=CC=C1CN1CCN(C(=O)OC(C)(C)C)CC1 HQOXGQMLMVPYIB-UHFFFAOYSA-N 0.000 description 2
- FKWPOCBDNMHKCV-UHFFFAOYSA-N ethyl 6-methyl-2-oxo-4-sulfanylidene-1h-pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(=O)NC1=S FKWPOCBDNMHKCV-UHFFFAOYSA-N 0.000 description 2
- 229960003699 evans blue Drugs 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000007888 film coating Substances 0.000 description 2
- 238000009501 film coating Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 238000011694 lewis rat Methods 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000001473 noxious effect Effects 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 210000001428 peripheral nervous system Anatomy 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000007388 punch biopsy Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 2
- 238000007390 skin biopsy Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 230000000392 somatic effect Effects 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000012089 stop solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 210000001258 synovial membrane Anatomy 0.000 description 2
- COLDGLCAIJJUMB-UHFFFAOYSA-N tert-butyl 4-[[4-[[2-(4-methoxycarbonylphenyl)-5-oxo-6h-pyrimido[4,5-d]pyridazin-4-yl]amino]phenyl]methyl]piperazine-1-carboxylate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NC(NC=2C=CC(CN3CCN(CC3)C(=O)OC(C)(C)C)=CC=2)=C2C(=O)NN=CC2=N1 COLDGLCAIJJUMB-UHFFFAOYSA-N 0.000 description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 2
- 208000025883 type III hypersensitivity disease Diseases 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- 239000004034 viscosity adjusting agent Substances 0.000 description 2
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- TWYYFYNJOJGNFP-CUXYNZQBSA-N (2s,4r,5s,6s)-2-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-2-carbamoyl-4-[[(e,4s,6s)-4,6-dimethyloct-2-enoyl]oxymethyl]-5-hydroxy-1,3-dioxane-4,5,6-tricarboxylic acid Chemical compound O1[C@H](C(O)=O)[C@](C(O)=O)(O)[C@](COC(=O)/C=C/[C@@H](C)C[C@@H](C)CC)(C(O)=O)O[C@]1(C(N)=O)CCC(=C)[C@@H](OC(C)=O)[C@H](C)CC1=CC=CC=C1 TWYYFYNJOJGNFP-CUXYNZQBSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- MLKHXLFEYOOYEY-NVNXTCNLSA-N (3z)-3-[(1-methylindol-3-yl)methylidene]-2-oxo-1h-indole-5-sulfonamide Chemical compound C12=CC=CC=C2N(C)C=C1\C=C/1C2=CC(S(N)(=O)=O)=CC=C2NC\1=O MLKHXLFEYOOYEY-NVNXTCNLSA-N 0.000 description 1
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 1
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 1
- OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 description 1
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 1
- MWZDIEIXRBWPLG-UHFFFAOYSA-N 1-methyl-1,2,4-triazole Chemical compound CN1C=NC=N1 MWZDIEIXRBWPLG-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- FGYADSCZTQOAFK-UHFFFAOYSA-N 1-methylbenzimidazole Chemical compound C1=CC=C2N(C)C=NC2=C1 FGYADSCZTQOAFK-UHFFFAOYSA-N 0.000 description 1
- OMAFFHIGWTVZOH-UHFFFAOYSA-N 1-methyltetrazole Chemical compound CN1C=NN=N1 OMAFFHIGWTVZOH-UHFFFAOYSA-N 0.000 description 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 description 1
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 1
- UKHJNJFJCGBKSF-UHFFFAOYSA-N 2,5-diazabicyclo[2.2.1]heptane Chemical compound C1NC2CNC1C2 UKHJNJFJCGBKSF-UHFFFAOYSA-N 0.000 description 1
- DJWDAKFSDBOQJK-UHFFFAOYSA-N 2,5-diazabicyclo[2.2.2]octane Chemical compound C1NC2CCC1NC2 DJWDAKFSDBOQJK-UHFFFAOYSA-N 0.000 description 1
- UBUBIMQAMCKQCX-UHFFFAOYSA-N 2,5-dioxa-8-azabicyclo[2.2.2]octane Chemical compound C1OC2CNC1OC2 UBUBIMQAMCKQCX-UHFFFAOYSA-N 0.000 description 1
- KCDXWVLANOYMJG-UHFFFAOYSA-N 2,6-dioxa-8-azabicyclo[2.2.2]octane Chemical compound C1OC2CNC1CO2 KCDXWVLANOYMJG-UHFFFAOYSA-N 0.000 description 1
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
- JNYWVERKQKRXSL-UHFFFAOYSA-N 2-oxa-5-azabicyclo[2.2.2]octane Chemical compound C1NC2CCC1OC2 JNYWVERKQKRXSL-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- YVHBSYTYLQYTOU-UHFFFAOYSA-N 3,6-diazabicyclo[3.1.1]heptane Chemical compound C1NCC2CC1N2 YVHBSYTYLQYTOU-UHFFFAOYSA-N 0.000 description 1
- AYNOATFQHAEZHR-UHFFFAOYSA-N 3,6-dioxa-8-azabicyclo[3.2.1]octane Chemical compound C1OCC2COC1N2 AYNOATFQHAEZHR-UHFFFAOYSA-N 0.000 description 1
- LKDJYZBKCVSODK-UHFFFAOYSA-N 3,8-diazabicyclo[3.2.1]octane Chemical compound C1NCC2CCC1N2 LKDJYZBKCVSODK-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- BXMGZQQTBBJSPP-UHFFFAOYSA-N 3-oxa-6-azabicyclo[3.1.1]heptane Chemical compound C1OCC2CC1N2 BXMGZQQTBBJSPP-UHFFFAOYSA-N 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- FFGRBWANQMLTQI-UHFFFAOYSA-N 3H-1,2,4-triazole Chemical compound C1N=CN=N1 FFGRBWANQMLTQI-UHFFFAOYSA-N 0.000 description 1
- WNYFVEFUHMDIRQ-UHFFFAOYSA-N 4-(morpholin-4-ylmethyl)aniline Chemical compound C1=CC(N)=CC=C1CN1CCOCC1 WNYFVEFUHMDIRQ-UHFFFAOYSA-N 0.000 description 1
- WCDLCPLAAKUJNY-UHFFFAOYSA-N 4-[4-[3-(1h-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenyl]morpholine Chemical compound C1COCCN1C1=CC=C(C2=CN3N=CC(=C3N=C2)C2=CNN=C2)C=C1 WCDLCPLAAKUJNY-UHFFFAOYSA-N 0.000 description 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- HYJHBSPJETTWEH-UHFFFAOYSA-N 6-oxa-3,8-diazabicyclo[3.2.1]octane Chemical compound C1NCC2COC1N2 HYJHBSPJETTWEH-UHFFFAOYSA-N 0.000 description 1
- WDJAQSJMDRFZIX-UHFFFAOYSA-N 6-oxa-3-azabicyclo[3.1.1]heptane Chemical compound C1NCC2CC1O2 WDJAQSJMDRFZIX-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 208000030507 AIDS Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical group OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 208000016557 Acute basophilic leukemia Diseases 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 241001550224 Apha Species 0.000 description 1
- 208000000104 Arthus reaction Diseases 0.000 description 1
- 108091008875 B cell receptors Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 102100031658 C-X-C chemokine receptor type 5 Human genes 0.000 description 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 1
- 125000005915 C6-C14 aryl group Chemical group 0.000 description 1
- SBHYYJLJUMMJMM-UHFFFAOYSA-N CC(C)(C)OC(N1CCN(Cc(cc2)ccc2N)CC1)=[U] Chemical compound CC(C)(C)OC(N1CCN(Cc(cc2)ccc2N)CC1)=[U] SBHYYJLJUMMJMM-UHFFFAOYSA-N 0.000 description 1
- RBNQYCJLTCBHCG-UHFFFAOYSA-N CCOC(C(C(C)=N)C(NC(OCC)=O)=S)=O Chemical compound CCOC(C(C(C)=N)C(NC(OCC)=O)=S)=O RBNQYCJLTCBHCG-UHFFFAOYSA-N 0.000 description 1
- FGJCTKUGXHFAPK-UHFFFAOYSA-N CCOC([ClH]C)=O Chemical compound CCOC([ClH]C)=O FGJCTKUGXHFAPK-UHFFFAOYSA-N 0.000 description 1
- VSRCRHIFCPVDAA-WAYWQWQTSA-N CC[O](C)C(/C=C(/C)\N)=O Chemical compound CC[O](C)C(/C=C(/C)\N)=O VSRCRHIFCPVDAA-WAYWQWQTSA-N 0.000 description 1
- ARJAQOIDIXTGAG-UHFFFAOYSA-N COC(c(cc1)ccc1-c(nc1C=NN2)nc(Nc3ccc(CN4CCNCC4)cc3)c1C2=O)=O Chemical compound COC(c(cc1)ccc1-c(nc1C=NN2)nc(Nc3ccc(CN4CCNCC4)cc3)c1C2=O)=O ARJAQOIDIXTGAG-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010051290 Central nervous system lesion Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- YSWHPLCDIMUKFE-QWRGUYRKSA-N Glu-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 YSWHPLCDIMUKFE-QWRGUYRKSA-N 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 101000922405 Homo sapiens C-X-C chemokine receptor type 5 Proteins 0.000 description 1
- 101000883515 Homo sapiens Chitinase-3-like protein 1 Proteins 0.000 description 1
- 101001090688 Homo sapiens Lymphocyte cytosolic protein 2 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 208000005615 Interstitial Cystitis Diseases 0.000 description 1
- 208000003618 Intervertebral Disc Displacement Diseases 0.000 description 1
- 206010050296 Intervertebral disc protrusion Diseases 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 230000004163 JAK-STAT signaling pathway Effects 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 102100034709 Lymphocyte cytosolic protein 2 Human genes 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- UQFQONCQIQEYPJ-UHFFFAOYSA-N N-methylpyrazole Chemical compound CN1C=CC=N1 UQFQONCQIQEYPJ-UHFFFAOYSA-N 0.000 description 1
- 206010029174 Nerve compression Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 239000007990 PIPES buffer Substances 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 241001504519 Papio ursinus Species 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102100038394 Platelet glycoprotein VI Human genes 0.000 description 1
- 101710194982 Platelet glycoprotein VI Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 206010036376 Postherpetic Neuralgia Diseases 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
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 102000014400 SH2 domains Human genes 0.000 description 1
- 108050003452 SH2 domains Proteins 0.000 description 1
- 208000010040 Sprains and Strains Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 206010043269 Tension headache Diseases 0.000 description 1
- 208000008548 Tension-Type Headache Diseases 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102000000887 Transcription factor STAT Human genes 0.000 description 1
- 108050007918 Transcription factor STAT Proteins 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 230000007488 abnormal function Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001351 alkyl iodides Chemical group 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
- 230000002456 anti-arthritic effect Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 229940124411 anti-hiv antiviral agent Drugs 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- LZCZIHQBSCVGRD-UHFFFAOYSA-N benzenecarboximidamide;hydron;chloride Chemical class [Cl-].NC(=[NH2+])C1=CC=CC=C1 LZCZIHQBSCVGRD-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 125000002529 biphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C12)* 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 229940096529 carboxypolymethylene Drugs 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 229940125851 compound 27 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000003271 compound fluorescence assay Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000002316 cosmetic surgery Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- QCDXQRIWSOOHJL-UHFFFAOYSA-N ethyl 2-(4-methoxycarbonylphenyl)-4-methyl-6-[4-[[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]methyl]anilino]pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)N=C(C=2C=CC(=CC=2)C(=O)OC)N=C1NC(C=C1)=CC=C1CN1CCN(C(=O)OC(C)(C)C)CC1 QCDXQRIWSOOHJL-UHFFFAOYSA-N 0.000 description 1
- IUZVFVLCBUAQEB-UHFFFAOYSA-N ethyl 4-[2-(dimethylamino)ethenyl]-6-[4-[[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]methyl]anilino]-2-morpholin-4-ylpyrimidine-5-carboxylate Chemical compound CCOC(=O)c1c(Nc2ccc(CN3CCN(CC3)C(=O)OC(C)(C)C)cc2)nc(nc1C=CN(C)C)N1CCOCC1 IUZVFVLCBUAQEB-UHFFFAOYSA-N 0.000 description 1
- CXRWJABHKXXVHQ-UHFFFAOYSA-N ethyl 4-formyl-2-(4-methoxycarbonylphenyl)-6-[4-[[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]methyl]anilino]pyrimidine-5-carboxylate Chemical compound N1=C(C=2C=CC(=CC=2)C(=O)OC)N=C(C=O)C(C(=O)OCC)=C1NC(C=C1)=CC=C1CN1CCN(C(=O)OC(C)(C)C)CC1 CXRWJABHKXXVHQ-UHFFFAOYSA-N 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- BDTDECDAHYOJRO-UHFFFAOYSA-N ethyl n-(sulfanylidenemethylidene)carbamate Chemical compound CCOC(=O)N=C=S BDTDECDAHYOJRO-UHFFFAOYSA-N 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000009033 hematopoietic malignancy Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000054350 human CHI3L1 Human genes 0.000 description 1
- LIAWOTKNAVAKCX-UHFFFAOYSA-N hydrazine;dihydrochloride Chemical compound Cl.Cl.NN LIAWOTKNAVAKCX-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 108091008915 immune receptors Proteins 0.000 description 1
- 102000027596 immune receptors Human genes 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 208000018937 joint inflammation Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 239000012022 methylating agents Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002991 molded plastic Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000002346 musculoskeletal system Anatomy 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000018791 negative regulation of catalytic activity Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000012057 packaged powder Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000032696 parturition Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 210000004224 pleura Anatomy 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000007674 radiofrequency ablation Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-N sodium;2-hydroxybenzoic acid Chemical compound [Na+].OC(=O)C1=CC=CC=C1O ABBQHOQBGMUPJH-UHFFFAOYSA-N 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- ZTYRRWNDQSVOCL-UHFFFAOYSA-N tert-butyl 4-[(4-aminophenyl)methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC1=CC=C(N)C=C1 ZTYRRWNDQSVOCL-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VOVUARRWDCVURC-UHFFFAOYSA-N thiirane Chemical compound C1CS1 VOVUARRWDCVURC-UHFFFAOYSA-N 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 235000014107 unsaturated dietary fats Nutrition 0.000 description 1
- 208000000143 urethritis Diseases 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Abstract
Description
の化合物を提供する。
本発明は、組織傷害、損傷又は病態により引き起される炎症を低減するか又は排除できる化合物及びその医薬組成物を提供する。本発明はさらに、プロテインキナーゼ阻害機構を通して機能する化合物及び組成物を提供する。
式中、R1は、NR4R5、任意に置換されたC1−C6アルコキシ、任意に置換されたC6−C14アリール、任意に置換されたヘテロアリール、任意に置換された3−10員の単環式又はニ環式シクロアルキル、又は任意に置換された3−10員の単環式又はニ環式へテロシクリルである。一態様によれば、3−4員のシクロアルキル及びヘテロシクリルは飽和である。別の態様によれば、前記シクロアルキル又はヘテロシクリルの同じ炭素原子上の水素原子は、任意に置換された3−6員のシクロアルキル又はヘテロシクリルにより任意に置換され、スピロシクロアルキル又はスピロシクリルが形成される。さらなる態様によれば、前記シクロアルキル又はヘテロシクリルの同じ原子上の水素原子は、Oにより任意に置換され、オキソ置換基が形成される。
である。
である。
ix.さらに追加の実施形態によれば、R1は、下記構造:
である。
xi.さらなる実施形態によれば、R1はヘテロアリールである。
a.一実施形態によれば、R2は、C(O)NR4R5により置換されたフェニルである。
c.さらなる実施形態によれば、R2は、NR4R5により置換されたフェニルである。
のヘテロシクリルが形成される。
i.さらに別の実施形態によれば、R2は、NR4R5又は(C1−C6アルキル)NR4R5により置換されたフェニルであり、そしてR4及びR5は結合され、下記構造:
のヘテロシクリルが形成される。
k.さらなる実施形態によれば、R2は、NR4R5又は(C1−C6アルキル)NR4R5により置換されたフェニルであり、そしてR4及びR5が一緒になり、下記構造:
のヘテロシクリルが形成される。
n.さらに別の実施形態によれば、R2は、(C1−C6アルキル)NR4R5により置換されたフェニルである。
q.さらなる実施形態によれば、R2は、(C1−C6アルキル)NR4R5により置換されたフェニルであり、そしてR4及びR5は結合され、任意に置換された6員の環が形成される。
が形成される。
が形成される。
が形成される。
w.さらなる実施形態によれば、R2は、NR4R5により置換されたヘテロアリールである。
z.別の実施形態によれば、R2は、下記構造:
である。
ee.さらに別の実施形態によれば、R2は、下記構造:
である。
である。
である。
である。
である。
ll.別の実施形態によれば、R2は、−O−(C1−C6アルキル)−ヘテロ環により置換されたアリールである。
組成物はまた、適切な量の式(I)の化合物を含有するよう細分割され得る。例えば、単位剤形は、パッケージされた組成物、例えば小包化された粉末、バイアル、アンプル、予備充填された注射器又は液体含有サシエットであり得る。
このアッセイの目的は、Sykキナーゼ酵素を阻害する化合物の能力を、放射分析法により試験することであった。
脾臓チロシンキナーゼ(Syk)は、炎症及びアレルギー応答において極めて重要な役割を果たす細胞質タンパク質チロシンキナーゼである。Sykは、肥満細胞、好塩基球及びマクロファージにおいてIgE及びIgG受容体介在性シグナル伝達を引き起こし、脱顆粒化及びサイトカイン放出を導く。Skyの異常機能がまた、造血器悪性腫瘍のいくつかの場合に関与している。
誘導倍率=陽性対照/基質対照における放射能計数(補正前の値)。
%阻害率=100−{化合物を含む反応についてのCPM * 100}/(陽性対照についてのCPM)
State Kinetics of Spleen Tyrosine Kinase Investigated by a Real Time Fluorescence Assay", Biochemistry (2007) 46: 15103-15114(参照により本明細書に組込まれる)を参照のこと。
このアッセイの目的は、JAK2(Janusキナーゼ)活性を阻害するそれらの能力について、時間分析蛍光共鳴エネルギー転換(TR−FRET)酵素アッセイ法により化合物をスクリーンすることであった。それらの研究においてSyk及びJAK2を阻害する化合物が、炎症の処置において実質的に使用され得る。
JAK2(Janusキナーゼ2)は、JAK−STAT経路を介してサイトカイン介在性シグナルを伝達する細胞内非受容体チロシンキナーゼのファミリーである。それらのキナーゼは、約130Kdaの見掛け分子量を有する。それらは、当初、「単なる別のキナーゼ(just another kinase)」1及び2と命名されたが(それらは、キナーゼのPCRに基づくスクリーンにおける多数の発見のうち単なる2つあったので)、しかし最終的には、「Janusキナーゼ」として公表された。JAKは、ほぼ同一のリン酸−トランスファードメインを有する。1つのドメインはキナーゼ活性を示したが、ところが他のドメインは最初のキナーゼ活性を負に調節する。それらは、種々のサイトカイン、成長因子及びインターフェロンのための極めて重要なシグナル伝達物質である。
ブランクに2μlの10%DMSO、陽性対照ウェルに基質対照、及び試験ウェルに試験化合物を添加した。ブランク及び基質対照ウェルに13μlのアッセイ緩衝液、及び陽性及び試験ウェルに13μlの酵素緩衝液を添加した。反応混合物を、プレートシェーカー上で、室温で30分間インキュベートした。Ultra Light-pGT 基質 (5μl) [U Light TM 色素により標識されたpoly Glu-Tyr (4:1)、チロシンキナーゼ基質]及びATPミックスを、すべてのウェルに添加した。反応プレートを、プレートシェーカー上で、室温で60分間インキュベートした。緩衝液中に、40mMのEDTA(10μl)を添加することにより、反応を停止した。10μlの抗体を、すべてのウェルに添加した。プレートを、Wallac(登録商標)1420 Multilabel Counter Victor 3 計測器 (Ex:340 nm 、Em:615 & 665 nm)により読取った。以下のの計算を行った:
F@ 615値−緩衝液ブランク
比率: (F@665緩衝液ブランク/F@615緩衝液ブランク)* 10000
F@665/F@615−基質ブランクの比率
%活性= (試験サンプル/陽性対照) * 100
%阻害率= (100−%活性)
このアッセイの目的は、RBL2H3細胞における免疫複合体介在性脱顆粒化の間のβ−ヘキソサミニダーゼ放出に対する化合物の効果を、蛍光法により試験することであった。
免疫グロブリン受容体を介して自己抗原と反応する自己抗体及びそれらの免疫複合体(IC)は、炎症及び慢性炎症疾患、例えばリウマチ様関節炎において広く関与して来た。肥満細胞及び好塩基球上で発現される免疫グロブリンE(IgE)、FcεRIに対して高親和性受容体の活性化が、それらのアレルギー応答の開始において中心的役割を果たす。ICによる受容体の凝集に続いて、肥満細胞は、種々の有能な生物学的活性分子、例えばサイトカイン、脂質由来のメディエーター、アミン、プロテアーゼ及びプロテオグリカンを放出する。DNP−BSAによる刺激に基づいての抗DNP(抗ジニトロフェニル)IgE処理RBL2H3細胞は、β−ヘキソサミニダーゼを包含する種々の前炎症分子の放出を介在するFczR1架橋を導く。
(i)プロトコールA:24ウェル型
RBL2H3細胞を、5%CO2を含む哺乳類細胞培養CO2インキュベーターにおいて37℃で、10%FBSを含むMEM完全培地において、70−80%コンフルエンスで維持した。2×105個の細胞/ウェルを、1mlの完全培地に播種し、そして細胞付着のために5時間インキュベートした。完全培地を、増感剤として1.2μg/mlの抗DNPラットIgEを含む無血清MEM培地1mlと交換し、そしてさらに、5%CO2下で37℃で一晩インキュベートした。次の日、細胞を、無血清培地により洗浄し、そしてさらに、37℃及び5%CO2下で45分間、種々の濃度の試験化合物(0.1%DMSO中)により処理した。細胞をさらに、5μg/mlのDNP−BSAにより60分間、刺激した。プレートを1000rpmで5分間、遠心分離し、そして25μlの培養上清液を、各アッセイウェルから96ウェルブラックコーティングされたプレート中に移した。25μlのβ−NAG基質を、この混合物に添加し、そして室温で30分間インキュベートした。反応を100μlの停止溶液により停止し、そして蛍光をモニターした。(励起355nm;発光460nm)。Sanderson, (2010), Cellular Immunology, 262(1): 28-34 and Silverman, (2006) MCB, 26(5): 1826-1838(参照により本明細書に組込まれる)を参照のこと。
%β−ヘキソサミニダーゼ放出率=[(試験化合物−DMSO対照)/(IgE対照−DMSO対照)]×100
RBL2H3細胞を、5%CO2を含む哺乳類細胞培養CO2インキュベーターにおいて37℃で、70−80%コンフルエンスで、10%FBSを含むMEM完全培地において維持した。5×104個の細胞/ウェルを、増感剤として0.3μg/mlの抗DNPラットIgEを含む完全培地200μlにおいて、37℃及び5%CO2下でプレートした。次の日、細胞をPIPES緩衝液により37℃で10分間、2度洗浄し、そして無血清MEM培地を補充した。細胞を種々の濃度の試験化合物(0.5%DMSO中)により、37℃及び5%CO2下で15分間、処理した。細胞をさらに、0.1μg/mlのDNP−BSAにより45分間、刺激した。プレートを2000rpmで5分間、回転し、そして25μlの培養上清液を、96ウェルブラックコーティング中に各アッセイウェルから移した。5μlのβ−NAG基質を添加し、そして室温で30分間インキュベートした。基質のインキュベーションの後、150μlの停止溶液を添加し、そして蛍光をモニターした。(励起355nm;発光450nm)。Yamamoto, JPET, 306(3): 1 174-1181 (2003) and Taylor, MCB, 15(8): 4149-4157 (1995)(参照により本明細書に組込まれる)を参照のこと。
A.序説
コラーゲン誘発関節炎(CIA)は、フロイントアジュバント中、II型コラーゲン(cII)による免疫化に続いて、感受性動物において誘発され得るヒトリウマチ様関節炎(RA)の十分に特徴づけられたモデルである。CIAは、ヒトRAのいくつかの特徴、例えば重度の腫張/関節の炎症、滑膜過形成、軟膏破壊及び骨侵食を示す。CIAの病理生理学は、関節滑膜におけるT細胞の高められた浸潤により、及びまた、T細胞欠失マウスにおけるCIAの減衰により明らかなように、T細胞成分から成る。CIA進行は、疾病動物におけるcII抗体の循環、及びまた、xidマウス/B細胞欠損マウス/CXCR5ヌルマウスにおける疾病の発症の阻害により明らかなように、B細胞成分も含む。Pine, "Inflammation and bone erosion are suppressed in models of rheumatoid arthritis following treatment with a novel Syk inhibitor", Clin. Immunol., 2007, 124(3):244-57; Xiong cha, "Suppression of the onset and progression of collagen- induced arthritis in rats by QFGJS, a preparation from an anti-arthritic Chinese herbal formula", J. Ethnopharmacology (2007) 1 10:39-48;及び Stolina, "The evolving systemic and local biomarker milieu at different stages of disease progression in rat collagen induced arthritis", Biomarkers (2008) 13(7-8):692-712(参照により本明細書に組込まれる)を参照のこと。
(i)CIAの誘発
雌ルイスラット(一群当たり8匹、生後6−8週)を、1.2mg/mlの最終濃度で、完全フロイントアジュバント(Sigma:Cat#5881)により乳化されたII型コラーゲン(免疫化等級のII型; Chondrex; Cat #20021)により1日目に免疫化した。初回免疫化のために、動物の尾の付け根に、300μgのcII(0.25ml/ラット)を注射した。不完全フロイントアジュバント(Sigma、Cat#F5506)(0.25ml/ラット)により乳化された同じII型コラーゲンの追加の免疫注射を、8日目、動物(100g)の尾の付け根に行った。追加免疫注射中の最終CII濃度は、0.4μg/mlであった。
1以上の関節炎評点を有する動物を群分けし、試験化合物(30mg/kg)又はメトトレキサート(0.5mg/kg)の投与を、12日目〜14日目の間で開始し、そしてそれらのそれぞれの化合物の毎日の投与を、10日間、続けた。
浮腫:足体積を、CIAの誘発の前(基礎測定値)及び投与期間の1、3、6及び9日目、動物についてのプレチスモメーターにより測定した。両後足の体積を測定し、そして浮腫を、基本平均から減算することにより計算した。
(i)計算
浮腫の%阻害率を、下記式により、対照に関して計算した:
異なった群の平均を、一元配置分散分析法(one way ANOVA)、続いてダネット試験(Dunnett’s test)を用いて、対照と比較した。
A.序説
アルサス反応は、局部III型過敏性反応の一種である。III型過敏性反応は、免疫複合体−介在性であり、そして主に血管壁、漿膜(胸膜、心膜、滑膜)、及び糸球体における抗原/抗体複合体の沈着を包含する。これは、抗体の皮内注射の後、抗原/抗体複合体の形成を包含する。動物が抗原及び色素により前もって注射されている(循環抗原を有する)場合、アルサス反応が起こる。これは、皮膚の血管における免疫複合体の沈着に起因する局部血管炎として現れる。PMNの補体及び補充の活性化が結果として起き、皮膚に炎症反応及び色素の血管外漏出をもたらす。この複雑な工程を阻害できる化合物は、広範囲の炎症及び自己免疫疾患への治療的含意を有することができる。Pine, "Inflammation and bone erosion are suppressed in models of rheumatoid arthritis following treatment with a novel Syk inhibitor"; Clin. Immunol. (2007) 124 (3): 244-57;及びSylvia, "R-406, an Orally Available Spleen Tyrosine Kinase Inhibitor Blocks Fc Receptor Signaling and Reduces Immune Complex-Mediated Inflammation", JPET 319:998-1008, 2006(参照により本明細書に組込まれる)を参照のこと。
雌c57BL/6マウスに、1%エバンスブルー(EB)を含むPBS中、0.1%オボアルブミン(OVA)である抗原を、イソフルラン麻酔(2.5mg/25gの体重のマウス)下で10ml/kgの濃度で静脈内注射した。抗原注射の10分後、動物に、ウサギ抗OVA IgG(25ml/部位で50μg)(Polysciences;Cat #23744)を、背中の2つの毛剃された部位の皮内に注射した。動物にまた、負の対照として機能するよう、背中の2つの底及び反対の部位の皮内に、リン酸緩衝生理食塩水(PBS、25μl)を注射した。マウスを、抗原(オボアルブミン)攻撃の4時間後、頚椎脱臼により安楽死させた。皮膚組織を、透明なプラスチックシート上に浮腫領域をトレーシングすることにより評価した。注射部位のパンチ生検を採取した。
(i)溢出領域
浮腫をスケールにより手動的に測定した。各動物について、2つの直径を採取し、そして平均した。
注射部位のパンチ生検(10mmの皮膚生検パンチを用いて)を、2mlの硫酸ナトリウム:アセトン混合物(0.6+1.4ml)において、室温で16−18時間インキュベートした。上清液を、消化された組織から、4000rpmでの10分間の遠心分離により除き、濾過し、そして610nmで分光光度的に読取った。
色素漏れの%阻害率を、下記式により、対照に関して計算した:
ODの%阻害率={1−[処置された動物における平均OD/対照動物における平均OD]}×100
浮腫領域の%阻害率={1−[処置された動物における平均浮腫領域/対照動物における平均浮腫領域]}×100
異なった群の平均を、一元配置分散分析法(one way ANOVA)、続いてダネット試験(Dunnett’s test)を用いて、対照と比較した。
Claims (65)
- 式(I)の化合物:
R1は、NR4R5、任意に置換されたC1〜C6アルコキシ、任意に置換されたC6〜C14アリール、任意に置換されたヘテロアリール、任意に置換された3〜10員の単環式又は二環式シクロアルキル、又は任意に置換された3〜10員の単環式又は二環式へテロシクリルであり、ここで
(i)3〜4員のシクロアルキル及びヘテロシクリルは飽和であり;
(ii)前記シクロアルキル又はヘテロシクリルの同じ炭素原子上の水素原子は、任意に置換された3〜6員のシクロアルキル又はヘテロシクリルにより任意に置換されて、スピロシクロアルキル又はスピロシクリルを形成し;そして
(iii)前記シクロアルキル又はヘテロシクリルの同じ原子上の水素原子は、Oにより任意に置換されて、オキソ置換基を形成し;
R2は、任意に置換されたフェニル、−O−(C1〜C6アルキル)−任意に置換されたフェニル、又は任意に置換された5〜6員のヘテロアリールであり、但し、R2が4−ピリジルである場合、その4−ピリジルは2位でカルボニル置換基を欠いており;
R4及びR5は、
(a)H、C1〜C6アルキル、C1〜C6ヒドロキシアルキル、C3〜C8シクロアルキル及び−(C1〜C6アルキル)N(C1〜C6アルキル)(C1−C6アルキル)からなる群から独立して選択され;
(b)結合して任意に置換された3〜8員のヘテロシクリルを形成し、ここで
(bi)前記ヘテロシクリルの同じ炭素原子上の水素原子は、任意に置換された3〜6員のシクロアルキル又はヘテロシクリルにより任意に置換されて、スピロシクロアルキル又はスピロシクリルを形成し;そして
(bii)前記へテロシクリル(b)、シクロアルキル(bi)又はヘテロシクリル(bi)の同じ原子上の水素原子は、Oにより任意に置換されて、オキソ置換基を形成する)
又はその医薬的に許容される塩若しくはエステル。 - R2が、C(O)NR4R5により置換されたフェニルである、請求項1に記載の化合物。
- R2が、NR4R5により置換されたフェニルである、請求項1に記載の化合物。
- R2が、(C1〜C6アルキル)NR4R5により置換されたフェニルである、請求項1に記載の化合物。
- R4及びR5が、それらが結合される窒素原子と一緒になって、6員の環を形成する、請求項4又は5に記載の化合物。
- R4及びR5が結合して、以下の構造:
R10、R11、R12及びR13は独立して、H又はC1〜C6アルキルであり;
R14は、ハロゲン、OH、C(O)OH、C1〜C6アルコキシ、(C1〜C6アルキル)ハロゲン、(C1〜C6アルキル)C(O)OH、C1〜C6ヒドロキシアルキル、C3〜C8シクロアルキル、(C1〜C6)アルキル)C(O)NH2、(C1〜C6アルキル)C(O)NH(C1〜C6ヒドロキシアルキル)、(C1〜C6アルキル)C(O)N(C1〜C6ヒドロキシアルキル)2、(C1〜C6アルキル)CN、(C1〜C6アルキル)ヘテロアリール、又はヘテロアリールであり;そして
R18は、C1〜C6ヒドロキシアルキル、又はC1〜C6アルキル−C(O)OHである)
のヘテロシクリルを形成する、請求項6に記載の化合物。 - R4及びR5が結合して、任意に置換されたピペリジン又はジアゼパンを形成する、請求項1に記載の化合物。
- R4及びR5が一緒になり、以下の構造:
R10、R11、R12及びR13は独立して、H又はC1〜C6アルキルであり;
Yは、O又はNR9であり;そして
R9は、H、C1〜C6アルキル、OH、C(O)OH、C1〜C6ヒドロキシアルキル、(C1〜C6アルキル)NH2、(C1〜C6アルキル)N(C1〜C6アルキル)(C1〜C6アルキル)、(C1〜C6アルキル)(C1〜C6アルコキシ)、C(O)(C1〜C6アルキル)NH2、(C1〜C6アルキル)C(O)OH、C(O)(C1〜C6ヒドロキシアルキル)、C(O)(C1〜C6アルキル)CN、(C1〜C6アルキル)CN、(C1〜C6アルキル)ハロゲン、又は(C1〜C6アルキル)O(C1〜C6アルキル)C(O)(C1〜C6アルキル)NH2であり;ここで
同じ炭素原子に結合される2つの水素原子は任意には、=Oにより置換される)
のヘテロシクリルを形成する、請求項4又は5に記載の化合物。 - R4及びR5が一緒になり、任意に置換されたモルホリン又はピペラジンを形成する、請求項4又は5に記載の化合物。
- R2が、(C1〜C6アルキル)NR4R5により置換されたフェニルである、請求項1に記載の化合物。
- R4及びR5が、(C1〜C6ヒドロキシアルキル)である、請求項15に記載の化合物。
- R4及びR5が結合して、任意に置換された6員の環を形成する、請求項15に記載の化合物。
- R2が、(C1〜C6アルキル)NR4R5により置換されたヘテロアリールである、請求項1に記載の化合物。
- R2が、NR4R5により置換されたヘテロアリールである、請求項1に記載の化合物。
- 前記へテロアリールがピリジンである、請求項24に記載の化合物。
- R2が、1又は2以上のC1〜C6アルコキシ、(C1〜C6アルキル)ハロゲン、C1〜C6トリフルオロアルコキシ、(C1〜C6アルキル)C(O)OH、ハロゲン、任意に置換されたC3〜C8シクロアルキル、任意に置換されたヘテロシクリル、任意に置換されたヘテロアリール、−0−(C1〜C6アルキル)C(O)OH、−O−(C1〜C6アルキル)−NR4R5、−O−(任意に置換されたヘテロ環)、−O(C1〜C6アルキル)−N(C1〜C6アルキル)(C1〜C6アルキル)、−O−(C1〜C6アルキル)NH2、C1〜C6ヒドロキシアルキル、−O−(C1〜C6ヒドロキシアルキル)、O−(C1〜C6アルキル)−C(O)OH、−C1〜C6アルコキシ-C1〜C6アルコキシ、O−(ヘテロ環)-(C1〜C6ヒドロキシアルキル)、SO2−(C1〜C6アルキル)、又は−(C1〜C6アルキル)−(C1〜C6アルコキシ)-ハロゲンにより置換されたフェニルである、請求項1に記載の化合物。
- R2が−O−(C1〜C6アルキル)NR4R5である、請求項1に記載の化合物。
- R2が、−O−(C1〜C6アルキル)−ヘテロ環により置換されたアリールである、請求項1に記載の化合物。
- R1が、N(C1〜C6アルキル)(C1〜C6アルキル)又はC1〜C6アルコキシである、請求項1に記載の化合物。
- R1が、N(CH(CH3)2)2、N(CH3)2、OCH2CH3又はOCH3である、請求項41に記載の化合物。
- R1が任意に置換されたフェニルである、請求項1に記載の化合物。
- R1が、任意に置換された5〜9員の飽和ヘテロシクリルである、請求項1に記載の化合物。
- R1がヘテロアリールである、請求項1に記載の化合物。
- R1が、チオフェン、ベンゾオキソール、又はピリジンである、請求項51に記載の化合物。
- R1が単環式C3〜C8シクロアルキルである、請求項1に記載の化合物。
- R1がシクロヘプチル又はシクロヘキシルであり、両者が任意には、−N(C1〜C6アルキル)(C1〜C6アルキル)により置換される、請求項53に記載の化合物。
- R1がC(O)(C1〜C6アルキル)CNにより置換されたピペリジンである、請求項1に記載の化合物。
- 酸の塩である、請求項1〜56のいずれか一項に記載の化合物。
- 前記酸が、酢酸、プロピオン酸、乳酸、クエン酸、酒石酸、コハク酸、フマル酸、マレイン酸、マロン酸、マンデル酸、リンゴ酸、フタル酸、塩酸、臭化水素酸、リン酸、硝酸、硫酸、メタンスルホン酸、ナフタレンスルホン酸、ベンゼンスルホン酸、トルエンスルホン酸、トリフルオロ酢酸、カンファースルホン酸からなる群から選択される、請求項57に記載の化合物。
- 4−(4−モルホリノフェニルアミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
メチル4−(5−オキソ−4−(4−(ピペラジン−l−イルメチル)フェニルアミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ベンゾエート 塩酸塩;
2−モルホリノ−4−(4−(ピペラジン−l−イルメチル)フェニルアミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン 塩酸塩;
4−(4−(モルホリノメチル)フェニルアミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−(4−(4−エチルピペラジン−l−イル)フェニルアミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−(4−((4−エチルピペラジン−l−イル)メチル)フェニルアミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−フェニル−4−(4−(ピペラジン−l−イルメチル)フェニルアミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン 塩酸塩;
2−フェニル−4−(4−(ピペラジン−l−イル)フェニルアミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−(4−(モルホリン−4−カルボニル)フェニルアミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−(4−(ビス(2−ヒドロキシエチル)アミノ)フェニルアミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−(4−(4−(2−アミノアセチル)ピペラジン−l−イル)フェニルアミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン 塩酸塩;
2−(4−(4−(5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イルアミノ)フェニル)ピペラジン−1−イル)酢酸;
l−(4−(5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イルアミノ)フェニル)ピペリジン−4−カルボン酸;
4−(4−(4−(2−アミノアセチル)ピペラジン−l−イル)フェニルアミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
N−(2−(ジメチルアミノ)エチル)−N−メチル−4−(5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イルアミノ)ベンズアミド;
4−(4−(2−オキソ−l,7−ジアザスピロ[3.5]ノナン−7−イル)フェニルアミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−(4−(2−オキサ−7−アザスピロ[3.5]ノナン−7−イル)フェニルアミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−(4−モルホリノフェニルアミノ)−2−(6−アザスピロ[2.5]オクタン−6−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
6−(4−(5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イルアミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
エチル6−(4−(5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イルアミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸塩;
6−(4−(5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イルアミノ)ベンジル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
ナトリウム 6−(4−(5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イルアミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸塩;
4−(4−(2−オキサ−7−アザスピロ[3.5]ノナン−7−イルメチル)フェニルアミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−(4−(ピペラジン−1−イルメチル)フェニルアミノ)−2−(チオフェン−3−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン 塩酸塩;
6−(5−オキソ−4−(4−(ピペラジン−l−イルメチル)フェニルアミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)−6−アザスピロ[2.5]オクタン−1−カルボン酸 塩酸塩;
4−(4−(4−エチルピペラジン−1−イル)フェニルアミノ)−2−モルホリノピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−(5−オキソ−4−(4−(ピペラジン−1−イルメチル)フェニルアミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)安息香酸 塩酸塩;
4−(4−(4−エチルピペラジン−1−イル)フェニルアミノ)−2−(4−(トリフルオロメトキシ)フェニル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
メチル 4−(4−(4−モルホリノフェニルアミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ベンゾエート;
4−(4−(ピペラジン−1−イルメチル)フェニルアミノ)−2−(ピペリジン−1−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン 塩酸塩;
2−(3−メトキシフェニル)−4−(4−(ピペラジン−1−イルメチル)フェニルアミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン 塩酸塩;
2−(ピペラジン−1−イル)−4−(4−(ピペラジン−1−イルメチル)フェニルアミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン 二塩酸塩;
2−(ベンゾ[d][1,3]ジオキソール−5−イル)−4−(4−(ピペラジン−1−イルメチル)フェニルアミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン 塩酸塩;
2−(1−(4−(5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イルアミノ)フェニル)ピペリジン−4−イル)酢酸;
1−(4−(5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イルアミノ)ベンジル)ピペリジン−4−カルボン酸;
2−(2−メトキシフェニル)−4−(4−(ピペラジン−1−イルメチル)フェニルアミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン 塩酸塩;
4−(4−(4−エチルピペラジン−1−イル)フェニルアミノ)−2−(チオフェン−3−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン 塩酸塩;
9−(5−オキソ−4−(4−(ピペラジン−l−イルメチル)フェニルアミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)−3,9−ジアザスピロ[5.5]ウンデカン−2,4−ジオン塩酸塩;
6−(4−(5−オキソ−2−(チオフェン−3−イル)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イルアミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
2−(4−クロロフェニル)−4−(4−(ピペラジン−l−イルメチル)フェニルアミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
2−(4−メトキシフェニル)−4−(4−(ピペラジン−l−イルメチル)フェニルアミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
6−(4−((2−モルホリノ−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
2−(l−(5−オキソ−4−((4−(ピペラジン−l−イルメチル)フェニル)アミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)酢酸 塩酸塩;
2−(1−オキシドチオモルホリノ)−4−((4−(ピペラジン−1−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
2−(4−メチルピペラジン−1−イル)−4−((4−(ピペラジン−1−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
6−(4−((2−(4−メトキシフェニル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
6−(4−((2−(3−メトキシフェニル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
4−((4−(ピペラジン−l−イルメチル)フェニル)アミノ)−2−(ピロリジン−l−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
2−(ジメチルアミノ)−4−((4−(ピペラジン−l−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
2−エトキシ−4−((4−(ピペラジン−l−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
1−(5−オキソ−4−((4−(ピペラジン−l−イルメチル)フェニル)アミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−カルボン酸 塩酸塩;
2−(アゼパン−1−イル)−4−((4−(ピペラジン−1−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
6−(4−((2−(2−メトキシフェニル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
2−(ジイソプロピルアミノ)−4−((4−(ピペラジン−1−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
2−(4−(モルホリノメチル)フェニル)−4−((4−(ピペラジン−1−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
1−(5−オキソ−4−((4−(ピペラジン−l−イルメチル)フェニル)アミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−カルボニトリル 塩酸塩;
2−(4−エチルピペラジン−1−イル)−4−((4−(ピペラジン−1−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
4−((l−(2−モルホリノエチル)−lH−ピラゾール−4−イル)アミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1,4−ジアゼパン−1−イル)−4−((4−(ピペラジン−1−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン 二塩酸塩;
2−(アゼパン−l−イル)−4−((4−モルホリノフェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−メトキシ4−((4−(ピペラジン−l−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
6−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
2−フェニル−4−((1−(2−(ピペラジン−1−イル)エチル)−1H−ピラゾール−4−イル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
4−((1−(2−(4−メチルピペラジン−1−イル)エチル)−1H−ピラゾール−4−イル)アミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−((1−(2−(4−エチルピペラジン−1−イル)エチル)−1H−ピラゾール−4−イル)アミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
6−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
2−(アゼパン−l−イル)−4−((3,4,5−トリメトキシフェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−l−イル)−4−((4−(モルホリン−4−カルボニル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
2−(l−(4−((2−(4−(シアノメチル)ピペラジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
2−(l−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
6−(4−((2−(l,4−ジアゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸 塩酸塩;
6−(4−((2−(4−(シアノメチル)ピペラジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
6−(4−((2−(4−シアノピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
2−(l−(4−((2−(4−シアノピペリジンl−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
1−(4−((2−(4−シアノピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−カルボン酸;
2−(l−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−イル)酢酸;
1−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−カルボン酸;
6−(4−((2−シクロヘキシル−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
2−(l−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)アセトニトリル;
6−(4−((2−シクロヘプチル−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
2−(l−(4−((5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)アセトニトリル;
4−((4−((4−(2−ヒドロキシ−2−メチルプロパノイル)ピペラジン−1−イル)メチル)フェニル)アミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−((4−(2−ヒドロキシ−2−メチルプロパノイル)ピペラジン−1−イル)メチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−((4−メチルピペラジン−1−イル)メチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(4−(4−((5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−1−イル)酢酸;
2−(4−(4−((5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)シクロヘキシル)酢酸;
2−(l−(4−((2−(アゾカン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
2−(アゼパン−l−イル)−4−((4−(2−(ピペラジン−l−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
2−(l−(4−((2−シクロヘプチル−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
2−(4−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)シクロヘキシル)酢酸;
4−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェノキシ)ブタン酸;
2−(アゼパン−l−イル)−4−((4−(2−モルホリノエトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−((4−(2−モルホリノエトキシ)フェニル)アミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−(2−(4−メチルピペラジン−1−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(2−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェノキシ)エチル)ピペリジン−4−イル)酢酸;
2−(l−(5−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペリジン−4−イル)アセトニトリル;
1−(2−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェノキシ)エチル)ピペリジン−4−カルボン酸;
2−(l−(5−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペリジン−4−イル)アセトアミド;
2−(l−(4−((2−(4−(2−シアノプロパン−2−イル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
2−(l−(5−((5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(5−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(ピペラジン−1−カルボニル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
2−(l−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)アセトアミド;
2−(4−(2−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェノキシ)エチル)ピペラジン−1−イル)酢酸;
2−(アゼパン−l−イル)−4−((4−(2−(ピペラジン−l−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(5−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペリジン−4−イル)酢酸;
2−(l−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)−N−(2−ヒドロキシエチル)アセトアミド;
2−(アゼパン−1−イル)−4−((4−(((2S,5S)−5−(ヒドロキシメチル)−l,4−ジオキサン−2−イル)メトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(4−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペラジン−1−イル)−2−メチルプロパンニトリル;
2−(4−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペラジン−1−イル)−2−メチルプロパンアミド;
2−(l−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)アセトニトリル;
2−(l−(5−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(2−(4−(2−ヒドロキシ−2−メチルプロパノイル)ピペラジン−1−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(5−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペリジン−4−イル)酢酸;
2−(l−(4−((2−(3,5−ジメチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
2−(l−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)−N,N−ビス(2−ヒドロキシエチル)アセトアミド;
2−メチル−2−(l−(4−((5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)プロパンニトリル;
2−(4−(2−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェノキシ)エチル)ピペラジン−l−イル)−2−メチルプロパンニトリル;
2−(l−(4−((2−(2,6−ジメチルモルホリノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
4−((4−(((2S,5S)−5−(ヒドロキシメチル)−l,4−ジオキサン−2−イル)メトキシ)フェニル)アミノ)−2−フェニルピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−((lS,4S)−4−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)シクロヘキシル)酢酸;
(2R,5S)−5−((4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェノキシ)メチル)−1,4−ジオキサン−2−カルボン酸;
2−(4−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペラジン−1−イル)酢酸;
2−(l−(3−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェノキシ)プロピル)ピペリジン−4−イル)酢酸;
6−(4−((2−(シクロヘキシルアミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)スピロ[2.5]オクタン−1−カルボン酸;
6−(4−((5−オキソ−2−(ピペリジン−l−イル)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)スピロ[2.5]オクタン−1−カルボン酸;
2−((lR,4R)−4−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)シクロヘキシル)酢酸;
3−(l−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)プロパン酸;
2−(l−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)シクロプロパンカルボン酸;
3−(l−(4−((5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)プロパン酸;
6−(4−((2−(4−フルオロフェニル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
6−(5−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
6−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)−2−フルオロフェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
2−(アゼパン−l−イル)−4−((4−(3−(ピペラジン−l−イル)プロポキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
6−(5−((5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
6−(4−((5−オキソ−2−(ピリジン−4−イル)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
2−(アゼパン−1−イル)−4−((4−(4−(2−ヒドロキシプロパン−2−イル)ピペリジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(4−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペラジン−1−イル)−2−メチルプロパン酸;
6−(4−((2−(アゾカン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
2−(l−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)−2−メチルプロパン酸;
2−メチル−2−(l−(4−((5−オキソ−2−フェニル−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)プロパン酸;
2−(2,6−ジメチルピペリジン−1−イル)−4−((4−(ピペラジン−1−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((2−(2,6−ジメチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
6−(4−((2−(2,6−ジメチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
2−(l−(4−((2−(2,6−ジメチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)アセトニトリル;
2−(2,6−ジメチルピペリジン−1−イル)−4−((4−(4−(2−ヒドロキシ−2−メチルプロパノイル)ピペラジン−l−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(5−((2−(2,6−ジメチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペリジン−4−イル)酢酸;
2−(3,5−ジメチルピペリジン−1−イル)−4−((4−(ピペラジン−1−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((2−(3,5−ジメチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
6−(4−((2−(3,5−ジメチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
2−(l−(4−((2−(3,5−ジメチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)アセトニトリル;
2−(3,5−ジメチルピペリジン−1−イル)−4−((4−(4−(2−ヒドロキシ−2−メチルプロパノイル)ピペリジン−l−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(5−((2−(3,5−ジメチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペリジン−4−イル)酢酸;
2−(2,6−ジメチルモルホリノ)−4−((4−(ピペラジン−l−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((2−(2,6−ジメチルモルホリノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
6−(4−((2−(2,6−ジメチルモルホリノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
2−(l−(4−((2−(2,6−ジメチルモルホリノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)アセトニトリル;
2−(2,6−ジメチルモルホリノ)−4−((4−(4−(2−ヒドロキシ−2−メチルプロパノイル)ピペリジン−l−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(5−((2−(2,6−ジメチルモルホリノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペリジン−4−イル)酢酸;
2−(ジイソプロピルアミノ)−4−((4−(ピペラジン−1−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((2−(ジイソプロピルアミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
6−(4−((2−(ジイソプロピルアミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
2−(l−(4−((2−(ジイソプロピルアミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)アセトニトリル;
2−(ジイソプロピルアミノ)−4−((4−(4−(2−ヒドロキシ−2−メチルプロパノイル)ピペリジン−l−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(5−((2−(ジイソプロピルアミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペリジン−4−イル)酢酸;
2−(2−メチルピペリジン−1−イル)−4−((4−(ピペラジン−1−イルメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((2−(2−メチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
6−(4−((2−(2−メチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
2−(l−(4−((2−(2−メチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)アセトニトリル;
4−((4−(4−(2−ヒドロキシ−2−メチルプロパノイル)ピペリジン−l−イル)フェニル)アミノ)−2−(2−メチルピペリジン−1−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(5−((2−(2−メチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペリジン−4−イル)酢酸;
l−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−カルボン酸;
1−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−カルボン酸;
4−((4−((4−(2H−テトラゾール−5−イル)ピペリジン−l−イル)メチル)フェニル)アミノ)−2−(アゼパン−l−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−((4−((4−((2H−テトラゾール−5−イル)メチル)ピペリジン−l−イル)メチル)フェニル)アミノ)−2−(アゼパン−l−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((2−シクロヘプチル−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
1−(4−((2−シクロヘプチル−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−カルボン酸;
6−(4−((2−(3−シアノピペリジンl−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
2−(l−(4−((2−(3−シアノピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
l−(4−((2−(3−シアノピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−カルボン酸;
l−(4−((2−(3−シアノピペリジンl−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−カルボン酸;
1−(4−((4−((4−(2H−テトラゾール−5−イル)ピペリジン−l−イル)メチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−3−カルボニトリル;
2−(l−(4−((2−(3−シアノピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−イル)酢酸;
1 −(4−((4−((4−((2H−テトラゾール−5−イル)メチル)ピペリジン−1−イル)メチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−3−カルボニトリル;
1−(4−((2−シクロヘプチル−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−カルボン酸;
4−((4−((4−(2H−テトラゾール−5−イル)ピペリジン−l−イル)メチル)フェニル)アミノ)−2−シクロヘプチルピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((2−シクロヘプチル−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−イル)酢酸;
4−((4−((4−((2H−テトラゾール−5−イル)メチル)ピペリジン−l−イル)メチル)フェニル)アミノ)−2−シクロヘプチルピリミド[4,5−d]ピリダジン−5(6H)−オン;
l−(4−((2−(4−シアノピペリジンl−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−カルボン酸;
l−(4−((4−((4−(2H−テトラゾール−5−イル)ピペリジン−l−イル)メチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−カルボニトリル;
1−(4−((4−((4−((2H−テトラゾール−5−イル)メチル)ピペリジン−1−イル)メチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−カルボニトリル;
1−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−カルボン酸;
2−(l−(4−((4−((4−(2H−テトラゾール−5−イル)ピペリジン−l−イル)メチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(1−(4−((4−((4−((2H−テトラゾール−5−イル)メチル)ピペリジン−1−イル)メチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
l−(4−((2−(4−(シアノメチル)ピペラジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−カルボン酸;
1−(4−((2−(4−(シアノメチル)ピペラジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−カルボン酸;
2−(4−(4−((4−((4−(2H−テトラゾール−5−イル)ピペリジン−l−イル)メチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペラジン−l−イル)アセトニトリル;
2−(l−(4−((2−(4−(シアノメチル)ピペラジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−イル)酢酸;
2−(4−(4−((4−((4−((2H−テトラゾール−5−イル)メチル)ピペリジン−1−イル)メチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペラジン−l−イル)アセトニトリル;
6−(4−((2−(l,4−ジアゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
2−(l−(4−((2−(l,4−ジアゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
l−(4−((2−(l,4−ジアゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−カルボン酸;
1−(4−((2−(l,4−ジアゼパンl−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−カルボン酸;
6−(4−((2−(4−(2−シアノアセチル)ピペラジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
2−(l−(4−((2−(4−(2−シアノアセチル)ピペラジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
l−(4−((2−(4−(2−シアノアセチル)ピペラジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−カルボン酸;
1−(4−((2−(4−(2−シアノアセチル)ピペラジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−カルボン酸;
3−(4−(4−((4−((4−(2H−テトラゾール−5−イル)ピペリジン−l−イル)メチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペラジン−l−イル)−3−オキソプロパンニトリル;
2−(l−(4−((2−(4−(2−シアノアセチル)ピペラジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−イル)酢酸;
4−((4−((4−((2H−テトラゾール−5−イル)メチル)ピペリジン−l−イル)メチル)フェニル)アミノ)−2−(4−(2−イソシアノアセチル)ピペラジン−l−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
6−(4−((2−(l−(2−シアノアセチル)ピペリジン−4−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
2−(l−(4−((2−(l−(2−シアノアセチル)ピペリジン−4−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
l−(4−((2−(l−(2−シアノアセチル)ピペリジン−4−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−カルボン酸;
1−(4−((2−(l−(2−シアノアセチル)ピペリジン−4−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−カルボン酸;
3−(4−(4−((4−((4−(2H−テトラゾール−5−イル)ピペリジン−l−イル)メチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−l−イル)−3−オキソプロパンニトリル;
2−(l−(4−((2−(l−(2−シアノアセチル)ピペリジン−4−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ベンジル)ピペリジン−4−イル)酢酸;
4−((4−((4−((2H−テトラゾール−5−イル)メチル)ピペリジン−l−イル)メチル)フェニル)アミノ)−2−(l−(2−イソシアノアセチル)ピペリジン−4−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(4−(5−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペラジン−1−イル)酢酸;
2−(4−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−1,4−ジアゼパン−1−イル)酢酸;
2−(l−(4−((4−(4−(2−ヒドロキシプロパン−2−イル)ピペリジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
3−(l−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)プロパン酸;
6−(5−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)−6−アザスピロ[2.5]オクタン−1−カルボン酸;
1−(5−オキソ−4−((4−(2−(ピペラジン−l−イル)エトキシ)フェニル)アミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−カルボニトリル;
2−(l−(5−オキソ−4−((4−(2−(ピペラジン−l−イル)エトキシ)フェニル)アミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(2−(4−エチルピペラジン−1−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−フェニル−4−((4−(2−(ピペラジン−l−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−((4−(2−(ピペラジン−1−イル)エトキシ)フェニル)アミノ)−2−(ピペリジン−1−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(4−(4−((5−オキソ−2−(ピペリジン−1−イル)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−1,4−ジアゼパン−1−イル)酢酸;
6−(4−((2−(4−メチルピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
2−(4−メチルピペリジン−1−イル)−4−((4−(2−(ピペラジン−1−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
2−(アゼパン−1−イル)−4−((4−(2−(3−オキソピペラジン−1−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
6−(2−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェノキシ)エチル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
2−(アゼパン−l−イル)−4−((4−(2−(ジエチルアミノ)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(シクロヘキシル(メチル)アミノ)−4−((4−(2−(ピペラジン−l−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((2−(シクロヘキシル(メチル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)酢酸;
2−(4−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペラジン−1−イル)酢酸;
2−(l−(4−((2−(3−メトキシフェニル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−4−イル)アセトニトリル;
4−((4−(2−(1,4−ジアゼパン−1−イル)エトキシ)フェニル)アミノ)−2−(アゼパン−1−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−(3−オキソピペラジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(3−メトキシフェニル)−4−((4−(2−(ピペラジン−l−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−l−イル)−4−((4−(2−(ジメチルアミノ)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−l−イル)−4−((4−(2−(ピペリジン−4−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(5−オキソ−4−((4−(2−(ピペリジン−4−イル)エトキシ)フェニル)アミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
6−(4−((2−(シクロヘキシル(メチル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−l−カルボン酸;
4−((4−(2−(1,4−ジアゼパン−1−イル)エトキシ)フェニル)アミノ)−2−(ピペリジン−1−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−(2−(4−ヒドロキシピペリジン−1−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−l−イル)−4−((4−(3−(ピペラジン−l−イル)プロピル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(5−オキソ−4−((4−(3−(ピペラジン−1−イル)プロピル)フェニル)アミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(4−エチル−3−オキソピペラジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−モルホリノ−4−((4−(2−(ピペラジン−l−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(2,6−ジメチルモルホリノ)−4−((4−(2−(ピペラジン−l−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(4−((4−(4−エチル−3−オキソピペラジン−1−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(3−(4−ヒドロキシピペリジン−1−イル)プロピル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−(4−エチルピペラジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−((6−(2−(ピペラジン−1−イル)エトキシ)ピリジン−3−イル)アミノ)−2−(ピペリジン−1−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((6−(2−(ピペラジン−1−イル)エトキシ)ピリジン−3−イル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−((4−(2−(4−ヒドロキシピペリジン−1−イル)エトキシ)フェニル)アミノ)−2−(ピペリジン−1−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−(2−(4−ヒドロキシ−4−メチルピペリジン−1−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(2−(4−ヒドロキシ−4−メチルピペリジン−l−イル)エトキシ)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(4−ヒドロキシピペリジン−l−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(4−((4−(4−エチルピペラジン−1−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(2−(ジイソプロピルアミノ)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(4−ヒドロキシピペリジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(4−(2−ヒドロキシエチル)ピペラジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(4−(2−ヒドロキシエチル)ピペラジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(ピペラジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(5−オキソ−4−((4−(ピペラジン−l−イル)フェニル)アミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(4−(3−ヒドロキシプロピル)ピペリジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−(4−(2−ヒドロキシエチル)ピペリジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(4−(2−ヒドロキシエチル)ピペリジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(4−((4−(2−(4−エチルピペラジン−l−イル)エチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(2−(ピペラジン−l−イル)エチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
4−((4−(2−アミノエトキシ)フェニル)アミノ)−2−(アゼパン−l−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(2−アミノエトキシ)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(2−(4−ヒドロキシピペリジン−1−イル)エチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−(4−(ヒドロキシメチル)ピペリジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−(2−(4−(ヒドロキシメチル)ピペリジン−1−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(2−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピペリジン−1−イル)エチル)ピペリジン−4−イル)アセトニトリル;
2−(1−(4−((4−(4−(3−ヒドロキシプロピル)ピペリジン−1−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(4−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペラジン−1−イル)アセトニトリル;
2−(l−(4−((4−(4−(シアノメチル)ピペラジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
3−(4−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペラジン−1−イル)プロパン酸;
2−(アゼパン−1−イル)−4−((4−(2−(4−エチルピペラジン−1−イル)エチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−(2−(4−ヒドロキシ−4−メチルピペリジン−1−イル)エチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−(2−(4−(2−ヒドロキシエチル)ピペラジン−1−イル)エチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(2−(4−(2−ヒドロキシエチル)ピペラジン−l−イル)エチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(4−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペラジン−1−イル)−2−メチルプロパン酸;
2−(アゼパン−1−イル)−4−((4−(4−(2−ヒドロキシ−2−メチルプロパノイル)ピペラジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
3−(4−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペラジン−1−イル)−3−オキソプロパンニトリル;
2−(l−(4−((4−(4−(ヒドロキシメチル)ピペリジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((6−(4−ヒドロキシピペリジン−1−イル)ピリジン−3−イル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(2−(4−(ヒドロキシメチル)ピペリジン−l−イル)エトキシ)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
(ホスホノオキシ)メチル 6−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−6−アザスピロ[2.5]オクタン−1−カルボン酸塩;
3−(4−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペラジン−1−イル)プロパン酸;
2−(アゼパン−l−イル)−4−((6−(ピペラジン−l−イル)ピリジン−3−イル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−(2−(2−ヒドロキシエチル)−2H−テトラゾール−5−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(4−((4−(4−(2−ヒドロキシ−2−メチルプロパノイル)ピペラジン−1−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(4−((4−(2−(ジエチルアミノ)エトキシ)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(2−エチル−2H−テトラゾール−5−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(2−エチル−2H−テトラゾール−5−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
4−((4−(2H−テトラゾール−5−イル)フェニル)アミノ)−2−(アゼパン−l−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((6−(4−エチルピペラジンl−イル)ピリジン−3−イル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((6−(4−エチルピペラジン−1−イル)ピリジン−3−イル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(4−(5−オキソ−4−((4−(2−(ピペラジン−l−イル)エトキシ)フェニル)アミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペラジン−l−イル)アセトニトリル;
2−(l−(5−オキソ−4−((6−(ピペラジン−l−イル)ピリジン−3−イル)アミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−3−イル)酢酸;
2−(l−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−3−イル)酢酸;
3−(4−(5−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペラジン−1−イル)−3−オキソプロパンニトリル;
2−(5−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−2H−テトラゾール−2−イル)酢酸;
2− (アゼパン−1−イル)−4−((6−(4−(2−ヒドロキシエチル)ピペリジン−1−イル)ピリジン−3−イル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
3−(4−(5−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペラジン−1−イル)−3−オキソプロパンニトリル;
2−(アゼパン−1−イル)−4−((6−(4−(2−ヒドロキシ−2−メチルプロパノイル)ピペラジン−1−イル)ピリジン−3−イル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−(2−(4−(2−ヒドロキシエチル)ピペラジン−1−イル)エトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
3−(4−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペラジン−1−イル)−3−オキソプロパンニトリル;
2−(5−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)−2H−テトラゾール−2−イル)酢酸;
2−(アゼパン−1−イル)−4−((6−(4−メチルピペラジン−1−イル)ピリジン−3−イル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(4−((6−(4−メチルピペラジン−1−イル)ピリジン−3−イル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
4−((4−(4−((2H−テトラゾール−5−イル)メチル)ピペリジン−l−イル)フェニル)アミノ)−2−(アゼパン−l−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(4−((4−(2H−テトラゾール−5−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(4−((4−(4−((2H−テトラゾール−5−イル)メチル)ピペリジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(4−メチルピペラジン−l−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(4−メチルピペラジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(5−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)ピリジン−2−イル)ピペリジン−3−イル)酢酸;
2−(l−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)ピペリジン−3−イル)酢酸;
2−(1−(4−((6−(4−(2−ヒドロキシ−2−メチルプロパノイル)ピペラジン−1−イル)ピリジン−3−イル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
4−((6−(4−((2H−テトラゾール−5−イル)メチル)ピペリジン−l−イル)ピリジン−3−イル)アミノ)−2−(アゼパン−l−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(4−((6−(4−((2H−テトラゾール−5−イル)メチル)ピペリジン−1−イル)ピリジン−3−イル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(4−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェノキシ)ピペリジン−1−イル)酢酸;
2−(アゼパン−1−イル)−4−((4−(4−(2−メトキシエチル)ピペラジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(4−(2−メトキシエチル)ピペラジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(4−((4−(4−(2−アミノエチル)ピペラジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(l−(ヒドロキシメチル)−6−アザスピロ[2.5]オクタン−6−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(l−(ヒドロキシメチル)−6−アザスピロ[2.5]オクタン−6−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(4−(3−ヒドロキシプロピル)ピペラジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(4−(3−ヒドロキシプロピル)ピペラジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(4−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェノキシ)ピペリジン−1−イル)酢酸;
2−(アゼパン−1−イル)−4−((4−(4−(2−ヒドロキシエチル)−1,4−ジアゼパン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(4−((4−(4−(2−ヒドロキシエチル)−1,4−ジアゼパン−1−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(4−(1−ヒドロキシ−2−メチルプロパン−2−イル)ピペラジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(4−((4−(4−(1−ヒドロキシ−2−メチルプロパン−2−イル)ピペラジン−1−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(4−(2−(ジメチルアミノ)エチル)ピペラジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(4−(2−(ジメチルアミノ)エチル)ピペラジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(2−(4−エチルピペラジン−1−イル)−2−オキソエトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(2−(4−エチルピペラジン−l−イル)−2−オキソエトキシ)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(4−((4−(2−(4−メチルピペラジン−l−イル)−2−オキソエトキシ)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(3−(2−ヒドロキシエチル)ピペリジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−(4−(2,3−ジヒドロキシプロピル)ピペラジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(4−(2,3−ジヒドロキシプロピル)ピペラジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(4−(2−フルオロエチル)ピペラジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(4−(2−フルオロエチル)ピペラジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((6−(3−ヒドロキシピペリジン−l−イル)ピリジン−3−イル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((6−(3−ヒドロキシピペリジン−l−イル)ピリジン−3−イル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(4,4−ジフルオロピペリジン−l−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(4−((4−(4,4−ジフルオロピペリジン−1−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(3−ヒドロキシピペリジン−l−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(4−((4−(3−ヒドロキシピペリジン−1−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(2−(4−メチルピペラジン−1−イル)−2−オキソエトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(4−((4−(3−(ヒドロキシメチル)ピペリジン−1−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(3−(ヒドロキシメチル)ピペリジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(3−(2−ヒドロキシエチル)ピペリジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(4−((4−(4−メトキシピペリジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(4−メトキシピペリジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−l−イル)−4−((4−(4−フルオロピペリジン−l−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(4−フルオロピペリジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(1−(4−((4−((1−(2−ヒドロキシエチル)ピペリジン−4−イル)オキシ)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(ピペリジン−4−イルオキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン塩酸塩;
2−(l−(4−((4−(2−ヒドロキシエトキシ)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(2−ヒドロキシエトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(3−ヒドロキシプロポキシ)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(3−ヒドロキシプロポキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(4−((4−(4−(1−ヒドロキシ−2−メチルプロパン−2−イル)−1,4−ジアゼパン−1−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−(4−(2−フルオロエチル)ピペリジン−1−イル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(4−(2−フルオロエチル)ピペリジン−l−イル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(4−((3,5−ジメトキシフェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(5−オキソ−4−((4−(トリフルオロメトキシ)フェニル)アミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((3,5−ジメトキシフェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−l−イル)−4−((4−(トリフルオロメトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
3−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)プロパン酸;
3−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェニル)プロパン酸;
2−(アゼパン−l−イル)−4−((4−(ビス(2−ヒドロキシエチル)アミノ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(ビス(2−ヒドロキシエチル)アミノ)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(3−ヒドロキシプロピル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(3−ヒドロキシプロピル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((3−(ヒドロキシメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((3−(ヒドロキシメチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(4−((4−フルオロフェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−フルオロフェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(アゼパン−1−イル)−4−((4−((1−ヒドロキシ−2−メチルプロパン−2−イル)オキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−((1−ヒドロキシ−2−メチルプロパン−2−イル)オキシ)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(4−((2−(アゼパン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェノキシ)−2−メチルプロパン酸;
2−(4−((2−(4−(シアノメチル)ピペリジン−l−イル)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−4−イル)アミノ)フェノキシ)−2−メチルプロパン酸;
2−(アゼパン−l−イル)−4−((3,4−ジメトキシフェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((3,4−ジメトキシフェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((3−メトキシフェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((3−メトキシフェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(2−ヒドロキシエチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(2−ヒドロキシエチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(2−メトキシエトキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(2−メトキシエトキシ)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(5−オキソ−4−((3,4,5−トリメトキシフェニル)アミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−(ベンゾ[d][l,3]ジオキソール−5−イルアミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−(ベンゾ[d][l,3]ジオキソール−5−イルアミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−1−イル)−4−((4−((1−(2−ヒドロキシエチル)ピペリジン−4−イル)オキシ)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
ナトリウム (2−(4−(シアノメチル)ピペリジン−1−イル)−4−((4−(4−ヒドロキシピペリジン−1−イル)フェニル)アミノ)−5−オキソピリミド[4,5−d]ピリダジン−6(5H)−イル)メチルホスフェート;
2−(アゼパン−l−イル)−4−((4−(ヒドロキシメチル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(l−(4−((4−(ヒドロキシメチル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(4−((4−(メチルスルホニル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(アゼパン−l−イル)−4−((4−(メチルスルホニル)フェニル)アミノ)ピリミド[4,5−d]ピリダジン−5(6H)−オン;
2−(1−(4−((1H−ベンゾ[d][1,2,3]トリアゾール−5−イル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(5−オキソ−4−((2−オキソ−2,3−ジヒドロ−lH−ベンゾ[d]イミダゾール−5−イル)アミノ)−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(4−((4−(3−フルオロプロピル)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;
2−(l−(4−((4−(ジフルオロメトキシ)フェニル)アミノ)−5−オキソ−5,6−ジヒドロピリミド[4,5−d]ピリダジン−2−イル)ピペリジン−4−イル)アセトニトリル;及び
4−((1H−ベンゾ[d][1,2,3]トリアゾール−5−イル)アミノ)−2−(アゼパン−1−イル)ピリミド[4,5−d]ピリダジン−5(6H)−オン
である、請求項1に記載の化合物。 - 請求項1〜59のいずれか一項に記載の化合物、及び医薬的に許容される担体を含む医薬組成物。
- 請求項1〜59のいずれか一項に記載の化合物を含むキット。
- JAK−2及びSykの共調節における使用のための請求項1〜59のいずれか一項に記載の化合物又はその医薬的に許容される塩。
- 前記共調節が、JAK−2/Syk経路の阻害を含む、請求項62に記載の化合物。
- JAK−2/Sykを阻害することにより治療できる状態の処置における使用のための請求項1〜59のいずれか一項に記載の化合物又はその医薬的に許容される塩。
- 炎症の低減における使用のための請求項1〜59のいずれか一項に記載の化合物又はその医薬的に許容される塩。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161526525P | 2011-08-23 | 2011-08-23 | |
US61/526,525 | 2011-08-23 | ||
PCT/US2012/051980 WO2013028818A1 (en) | 2011-08-23 | 2012-08-23 | Pyrimido- pyridazinone compounds and use thereof |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2014524475A true JP2014524475A (ja) | 2014-09-22 |
JP2014524475A5 JP2014524475A5 (ja) | 2015-10-15 |
JP5993010B2 JP5993010B2 (ja) | 2016-09-14 |
Family
ID=46829884
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014527282A Active JP5993010B2 (ja) | 2011-08-23 | 2012-08-23 | ピリミド−ピリダジノン化合物及びその使用 |
Country Status (13)
Country | Link |
---|---|
US (5) | US8729079B2 (ja) |
EP (4) | EP3404029A3 (ja) |
JP (1) | JP5993010B2 (ja) |
CN (2) | CN103974955B (ja) |
BR (1) | BR112014003981A2 (ja) |
CA (1) | CA2846187A1 (ja) |
DK (2) | DK3392252T3 (ja) |
ES (1) | ES2690971T3 (ja) |
FI (1) | FI3392252T3 (ja) |
IL (1) | IL231082A (ja) |
MX (1) | MX361458B (ja) |
PL (1) | PL2748166T3 (ja) |
WO (1) | WO2013028818A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020518565A (ja) * | 2017-04-28 | 2020-06-25 | アサナ バイオサイエンシズ,リミティド ライアビリティ カンパニー | アトピー性皮膚炎の治療及び原薬の安定性を向上するための製剤、方法、キット、及び剤形 |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2690971T3 (es) * | 2011-08-23 | 2018-11-23 | Asana Biosciences, Llc | Compuestos pirimido-piridazinona y uso de los mismos |
AR106830A1 (es) * | 2015-12-04 | 2018-02-21 | Asana Biosciences Llc | Usos de piridazinonas para tratar el cáncer |
WO2018187294A1 (en) * | 2017-04-03 | 2018-10-11 | Asana Biosciences, Llc | Pyrimido-pyridazinone compound combinations, methods, kits and formulations thereof |
CN111961035B (zh) * | 2019-05-20 | 2022-11-01 | 南京科技职业学院 | 一类含有羟基异喹啉类结构的化合物、药物组合物以及其应用 |
WO2021027943A1 (zh) * | 2019-08-14 | 2021-02-18 | 正大天晴药业集团南京顺欣制药有限公司 | 哒嗪酮并嘧啶类衍生物及其医药用途 |
CN113583026A (zh) * | 2020-04-30 | 2021-11-02 | 杭州英创医药科技有限公司 | 一类含有稠合三环结构的化合物 |
TW202202498A (zh) * | 2020-07-01 | 2022-01-16 | 大陸商四川海思科製藥有限公司 | 一種並環雜環衍生物及其在醫藥上的應用 |
WO2023122662A1 (en) * | 2021-12-22 | 2023-06-29 | The Regents Of The University Of California | Covalently binding inhibitors of g12s, g12d and/or g12e mutants of k-ras gtpase |
WO2023164024A1 (en) * | 2022-02-23 | 2023-08-31 | Teva Pharmaceuticals International Gmbh | Solid state forms of gusacitinib |
WO2023192989A2 (en) * | 2022-04-01 | 2023-10-05 | Azkarra Therapeutics, Inc. | Phthalazinone compounds as parp7 inhibitors |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS4948695A (ja) * | 1972-05-12 | 1974-05-11 | ||
JP2011510990A (ja) * | 2008-02-01 | 2011-04-07 | アイアールエム・リミテッド・ライアビリティ・カンパニー | キナーゼ阻害剤としての化合物および組成物 |
WO2011053861A1 (en) * | 2009-10-29 | 2011-05-05 | Genosco | Kinase inhibitors |
WO2011079105A1 (en) * | 2009-12-23 | 2011-06-30 | Abbott Laboratories | Novel thienopyrrole compounds |
Family Cites Families (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE756508A (fr) * | 1969-09-24 | 1971-03-01 | Takeda Chemical Industries Ltd | Derives de pyrimidopyridazine |
JPS4948695U (ja) | 1972-07-29 | 1974-04-27 | ||
JPS50101387A (ja) * | 1974-01-16 | 1975-08-11 | ||
CA1052046A (en) | 1974-01-21 | 1979-04-03 | American Cyanamid Company | Unsymmetrically substituted 1,4-dioxane-2,5-diones |
US5369086A (en) | 1993-04-28 | 1994-11-29 | Zeneca Limited | N-benzotriazoles |
IL112249A (en) | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
JPH0948695A (ja) | 1995-08-02 | 1997-02-18 | Toshiba Ceramics Co Ltd | シリコン単結晶の製造方法 |
JP2002504550A (ja) | 1998-02-25 | 2002-02-12 | ファルマシア・アンド・アップジョン・カンパニー | 抗微生物剤として有用な置換アミノメチルイソオキサゾリン誘導体 |
OA11674A (en) | 1998-11-10 | 2005-01-12 | Janssen Pharmaceutica Nv | HIV Replication inhibiting pyrimidines. |
CA2422054C (en) * | 2000-09-22 | 2011-01-11 | Akzo Nobel Nv | Bicyclic heteroaromatic compounds |
CN1649848A (zh) | 2001-04-30 | 2005-08-03 | 葛兰素集团有限公司 | 作为促肾上腺皮质激素释放因子(crf)拮抗剂的稠合嘧啶衍生物 |
AU2003212634A1 (en) | 2002-03-11 | 2003-09-22 | Zetiq Technologies Ltd. | Compounds useful in the treatment of cancer |
US7517886B2 (en) | 2002-07-29 | 2009-04-14 | Rigel Pharmaceuticals, Inc. | Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds |
CN1894234A (zh) | 2003-03-25 | 2007-01-10 | 武田药品工业株式会社 | 二肽基肽酶抑制剂 |
CN102358738A (zh) | 2003-07-30 | 2012-02-22 | 里格尔药品股份有限公司 | 2,4-嘧啶二胺化合物及其预防和治疗自体免疫疾病的用途 |
WO2005080377A1 (ja) | 2004-02-20 | 2005-09-01 | Kirin Beer Kabushiki Kaisha | TGFβ阻害活性を有する化合物およびそれを含んでなる医薬組成物 |
TW200626574A (en) | 2004-09-30 | 2006-08-01 | Tibotec Pharm Ltd | HIV inhibiting 5-heterocyclyl pyrimidines |
PL1830869T3 (pl) | 2004-12-24 | 2013-11-29 | Novartis Ag | Sposób leczenia lub profilaktyki |
MX2007011850A (es) | 2005-03-25 | 2007-10-03 | Tibotec Pharm Ltd | Inhibidores heterobiciclicos de virus de hepatitis c. |
CN101189234B (zh) | 2005-03-25 | 2011-08-17 | 泰博特克药品有限公司 | Hcv的杂二环抑制剂 |
KR20080000584A (ko) | 2005-04-29 | 2008-01-02 | 얀센 파마슈티카 엔.브이. | 카나비노이드 수용체 길항제로서의 벤조트리아졸 유도체 |
EP1970373A1 (en) * | 2005-12-02 | 2008-09-17 | Mitsubishi Tanabe Pharma Corporation | Alicyclic heterocyclic compound |
US20070161670A1 (en) | 2006-01-09 | 2007-07-12 | Bristol-Myers Squibb Company | Process for the preparation of substituted heterocycles |
WO2007125405A2 (en) | 2006-05-01 | 2007-11-08 | Pfizer Products Inc. | Substituted 2-amino-fused heterocyclic compounds |
GB0625196D0 (en) | 2006-12-18 | 2007-01-24 | 7Tm Pharma As | Modulators of cannabinoid receptor |
HUE027641T2 (en) * | 2006-12-28 | 2016-11-28 | Abbvie Inc | Poly (ADP-ribose) polymerase inhibitors |
EA018441B1 (ru) | 2007-03-14 | 2013-08-30 | ЭКСЕЛИКСИС ПАТЕНТ КОМПАНИ ЭлЭлСи | Ингибиторы пути хеджхога |
CA2737217A1 (en) * | 2008-09-30 | 2010-04-08 | Astrazeneca Ab | Heterocyclic jak kinase inhibitors |
TW201016676A (en) | 2008-10-03 | 2010-05-01 | Astrazeneca Ab | Heterocyclic derivatives and methods of use thereof |
US20100216827A1 (en) | 2008-10-21 | 2010-08-26 | Metabolex, Inc. | Aryl gpr120 receptor agonists and uses thereof |
US8440662B2 (en) | 2010-10-31 | 2013-05-14 | Endo Pharmaceuticals, Inc. | Substituted quinazoline and pyrido-pyrimidine derivatives |
ES2690971T3 (es) * | 2011-08-23 | 2018-11-23 | Asana Biosciences, Llc | Compuestos pirimido-piridazinona y uso de los mismos |
WO2014022728A1 (en) | 2012-08-02 | 2014-02-06 | Endo Pharmaceuticals, Inc | Substituted 5 - (quinazolin - 2 - yl) pyrimidin- 2 -amine derivatives useful as pi3k/mtor inhibitors for the treatment of cancer |
AR106830A1 (es) * | 2015-12-04 | 2018-02-21 | Asana Biosciences Llc | Usos de piridazinonas para tratar el cáncer |
CA3060316A1 (en) * | 2017-04-28 | 2018-11-01 | Asana Biosciences, Llc | Formulations, methods, kits, and dosage forms for treating atopic dermatitis and for improved stability of an active pharmaceutical ingredient |
-
2012
- 2012-08-23 ES ES12756865T patent/ES2690971T3/es active Active
- 2012-08-23 CN CN201280051788.8A patent/CN103974955B/zh active Active
- 2012-08-23 MX MX2014002112A patent/MX361458B/es active IP Right Grant
- 2012-08-23 US US13/592,511 patent/US8729079B2/en active Active
- 2012-08-23 DK DK18175788.1T patent/DK3392252T3/da active
- 2012-08-23 EP EP18182723.9A patent/EP3404029A3/en not_active Withdrawn
- 2012-08-23 PL PL12756865T patent/PL2748166T3/pl unknown
- 2012-08-23 JP JP2014527282A patent/JP5993010B2/ja active Active
- 2012-08-23 EP EP23201319.3A patent/EP4327886A2/en active Pending
- 2012-08-23 EP EP12756865.7A patent/EP2748166B1/en active Active
- 2012-08-23 BR BR112014003981A patent/BR112014003981A2/pt not_active IP Right Cessation
- 2012-08-23 CN CN201810492306.1A patent/CN108707151B/zh active Active
- 2012-08-23 DK DK12756865.7T patent/DK2748166T3/en active
- 2012-08-23 FI FIEP18175788.1T patent/FI3392252T3/fi active
- 2012-08-23 WO PCT/US2012/051980 patent/WO2013028818A1/en active Application Filing
- 2012-08-23 EP EP18175788.1A patent/EP3392252B1/en active Active
- 2012-08-23 CA CA2846187A patent/CA2846187A1/en active Pending
-
2014
- 2014-02-23 IL IL231082A patent/IL231082A/en active IP Right Grant
- 2014-04-03 US US14/244,183 patent/US9382277B2/en active Active
-
2016
- 2016-04-25 US US15/137,950 patent/US10183944B2/en active Active
-
2018
- 2018-11-30 US US16/206,395 patent/US10647720B2/en active Active
-
2020
- 2020-02-25 US US16/800,111 patent/US20200190095A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS4948695A (ja) * | 1972-05-12 | 1974-05-11 | ||
JP2011510990A (ja) * | 2008-02-01 | 2011-04-07 | アイアールエム・リミテッド・ライアビリティ・カンパニー | キナーゼ阻害剤としての化合物および組成物 |
WO2011053861A1 (en) * | 2009-10-29 | 2011-05-05 | Genosco | Kinase inhibitors |
WO2011079105A1 (en) * | 2009-12-23 | 2011-06-30 | Abbott Laboratories | Novel thienopyrrole compounds |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020518565A (ja) * | 2017-04-28 | 2020-06-25 | アサナ バイオサイエンシズ,リミティド ライアビリティ カンパニー | アトピー性皮膚炎の治療及び原薬の安定性を向上するための製剤、方法、キット、及び剤形 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5993010B2 (ja) | ピリミド−ピリダジノン化合物及びその使用 | |
TWI398252B (zh) | 吡咯并嘧啶化合物及其用途 | |
AU2022206702B2 (en) | Phenyl-2-hydroxy-acetylamino-2-methyl-phenyl compounds | |
KR20190114910A (ko) | 상피세포 성장인자 수용체 돌연변이 저해 효과를 갖는 신규 설폰아마이드 유도체 | |
US20080221092A1 (en) | Heterobicyclic metalloprotease inhibitors | |
CN105283454A (zh) | 作为ras/raf/mek/erk和pi3k/akt/pten/mtor通路双重抑制剂的喹唑啉和氮杂喹唑啉 | |
JP2016526545A (ja) | スルホキシイミン置換キナゾリンならびにmnk1および/またはmnk2キナーゼ阻害薬としてのその使用 | |
WO2015058661A1 (zh) | Bcr-abl激酶抑制剂及其应用 | |
WO2021239133A1 (zh) | 作为axl抑制剂的嘧啶类化合物 | |
KR20210120054A (ko) | Akt 억제제 | |
WO2023279938A1 (zh) | 2,6,8-多取代咪唑并[1,2-a]吡嗪及其合成方法和应用 | |
WO2018187294A1 (en) | Pyrimido-pyridazinone compound combinations, methods, kits and formulations thereof | |
US8889870B2 (en) | Kinase inhibitors | |
US9820989B2 (en) | Method of treating conditions with kinase inhibitors | |
CN101553476A (zh) | 作为有丝***驱动蛋白抑制剂的二唑和噻二唑衍生物及其使用方法 | |
JP2023521172A (ja) | キナーゼ阻害剤 | |
JP7477846B2 (ja) | Nを含むヘテロアリール誘導体およびこれを有効成分として含むがんの予防または治療用薬学的組成物 | |
CA3218374A1 (en) | Macrocyclic compounds and uses thereof | |
CN101374842A (zh) | 作为药物剂的氮杂卓并吲哚衍生物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150824 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150824 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20160303 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160322 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160622 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160719 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160818 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5993010 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |