BRPI0720457A2 - Compostos citoesqueletais ativos inibidores de rho quinase, composição e uso - Google Patents

Info

Publication number

BRPI0720457A2

BRPI0720457A2 BRPI0720457-4A BRPI0720457A BRPI0720457A2 BR PI0720457 A2 BRPI0720457 A2 BR PI0720457A2 BR PI0720457 A BRPI0720457 A BR PI0720457A BR PI0720457 A2 BRPI0720457 A2 BR PI0720457A2

Authority

BR

Brazil

Prior art keywords

compound

piperidin

indazol

ylamino

methyl

Prior art date

2006-12-18

Links

• Espacenet
• Global Dossier
• Discuss

• 239000000203 mixture Substances 0.000 title description 32
• 239000003112 inhibitor Substances 0.000 title description 4
• 239000003590 rho kinase inhibitor Substances 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims description 355
• -1 1H-indazol-5-ylamino Chemical group 0.000 claims description 218
• AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 claims description 131
• 125000001072 heteroaryl group Chemical group 0.000 claims description 107
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 98
• 125000000217 alkyl group Chemical group 0.000 claims description 92
• 125000001424 substituent group Chemical group 0.000 claims description 87
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 83
• 125000000623 heterocyclic group Chemical group 0.000 claims description 83
• 125000000304 alkynyl group Chemical group 0.000 claims description 82
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 74
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 69
• 125000003342 alkenyl group Chemical group 0.000 claims description 67
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 63
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 62
• 125000003118 aryl group Chemical group 0.000 claims description 53
• 229910052757 nitrogen Inorganic materials 0.000 claims description 53
• 125000005843 halogen group Chemical group 0.000 claims description 45
• 125000005842 heteroatom Chemical group 0.000 claims description 45
• 125000005018 aryl alkenyl group Chemical group 0.000 claims description 41
• 230000004410 intraocular pressure Effects 0.000 claims description 37
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
• 229910052760 oxygen Inorganic materials 0.000 claims description 30
• 239000001301 oxygen Substances 0.000 claims description 30
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 29
• 229910052717 sulfur Inorganic materials 0.000 claims description 26
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 24
• 208000010412 Glaucoma Diseases 0.000 claims description 21
• 125000005015 aryl alkynyl group Chemical group 0.000 claims description 21
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 19
• 125000004434 sulfur atom Chemical group 0.000 claims description 18
• 230000002401 inhibitory effect Effects 0.000 claims description 17
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 17
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
• 125000002015 acyclic group Chemical group 0.000 claims description 16
• 229910052799 carbon Inorganic materials 0.000 claims description 16
• 239000012530 fluid Substances 0.000 claims description 16
• 238000002360 preparation method Methods 0.000 claims description 16
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 15
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
• 108010043137 Actomyosin Proteins 0.000 claims description 13
• 230000003993 interaction Effects 0.000 claims description 13
• 101100533877 Hypocrea jecorina (strain QM6a) sor8 gene Proteins 0.000 claims description 12
• 230000033115 angiogenesis Effects 0.000 claims description 12
• 125000005356 cycloalkylalkenyl group Chemical group 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 12
• DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 12
• 150000002367 halogens Chemical class 0.000 claims description 11
• 239000003795 chemical substances by application Substances 0.000 claims description 10
• 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 10
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
• 229910052736 halogen Inorganic materials 0.000 claims description 9
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
• 230000037390 scarring Effects 0.000 claims description 9
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 8
• DTVYNUOOZIKEEX-UHFFFAOYSA-N 5-aminoisoquinoline Chemical compound N1=CC=C2C(N)=CC=CC2=C1 DTVYNUOOZIKEEX-UHFFFAOYSA-N 0.000 claims description 8
• 208000002177 Cataract Diseases 0.000 claims description 8
• 206010047163 Vasospasm Diseases 0.000 claims description 8
• 125000005349 heteroarylcycloalkyl group Chemical group 0.000 claims description 8
• 229910052739 hydrogen Inorganic materials 0.000 claims description 8
• 125000002950 monocyclic group Chemical group 0.000 claims description 8
• 125000004043 oxo group Chemical group O=* 0.000 claims description 8
• 230000000923 atherogenic effect Effects 0.000 claims description 7
• 150000001721 carbon Chemical group 0.000 claims description 7
• 238000000605 extraction Methods 0.000 claims description 7
• 238000002513 implantation Methods 0.000 claims description 7
• 230000010412 perfusion Effects 0.000 claims description 7
• 229940079593 drug Drugs 0.000 claims description 6
• PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 claims description 5
• 208000008516 Capsule Opacification Diseases 0.000 claims description 4
• IHCQSKFOQWOBBA-UZLBHIALSA-N (2r)-1-[3-[[(3s)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]propan-2-ol Chemical compound C[C@@H](O)COC1=CC=CC(CN2C[C@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 IHCQSKFOQWOBBA-UZLBHIALSA-N 0.000 claims description 3
• OXZZTYUKEITHSD-WOJBJXKFSA-N (2r)-3-[3-[[(3r)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]propane-1,2-diol Chemical compound OC[C@@H](O)COC1=CC=CC(CN2C[C@@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 OXZZTYUKEITHSD-WOJBJXKFSA-N 0.000 claims description 3
• BPRCQSXHYHFFRW-GOSISDBHSA-N 2-[3-[[(3r)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=CC(CN2C[C@@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 BPRCQSXHYHFFRW-GOSISDBHSA-N 0.000 claims description 3
• QPEIXLYASHZHRM-GOSISDBHSA-N 2-[3-[[(3r)-3-(1h-indazol-5-ylamino)pyrrolidin-1-yl]methyl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(CN2C[C@@H](CC2)NC=2C=C3C=NNC3=CC=2)=C1 QPEIXLYASHZHRM-GOSISDBHSA-N 0.000 claims description 3
• PDNRANQFZBPQEF-IBGZPJMESA-N 2-[3-[[(3s)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(CN2C[C@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 PDNRANQFZBPQEF-IBGZPJMESA-N 0.000 claims description 3
• YXVDBONDQPTXQM-UHFFFAOYSA-N 2-[3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]acetamide Chemical compound NC(=O)COC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 YXVDBONDQPTXQM-UHFFFAOYSA-N 0.000 claims description 3
• QPEIXLYASHZHRM-UHFFFAOYSA-N 2-[3-[[3-(1h-indazol-5-ylamino)pyrrolidin-1-yl]methyl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(CN2CC(CC2)NC=2C=C3C=NNC3=CC=2)=C1 QPEIXLYASHZHRM-UHFFFAOYSA-N 0.000 claims description 3
• HRCKLYFDWWYCLS-UHFFFAOYSA-N 2-[3-[[3-(isoquinolin-5-ylamino)pyrrolidin-1-yl]methyl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(CN2CC(CC2)NC=2C3=CC=NC=C3C=CC=2)=C1 HRCKLYFDWWYCLS-UHFFFAOYSA-N 0.000 claims description 3
• UDCBPDAHRGAKOJ-UHFFFAOYSA-N 2-[3-[[4-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(CN2CCC(CC2)NC=2C=C3C=NNC3=CC=2)=C1 UDCBPDAHRGAKOJ-UHFFFAOYSA-N 0.000 claims description 3
• CIHPIJHUAGKONW-UHFFFAOYSA-N 2-[4-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]ethanol Chemical compound C1=CC(OCCO)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 CIHPIJHUAGKONW-UHFFFAOYSA-N 0.000 claims description 3
• BXCXZISLTZBGJO-UHFFFAOYSA-N 2-[6-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]-2,3-dihydroindol-1-yl]ethanol Chemical compound C1=C2NN=CC2=CC(NC2CCCN(C2)CC2=CC=C3CCN(C3=C2)CCO)=C1 BXCXZISLTZBGJO-UHFFFAOYSA-N 0.000 claims description 3
• GGWYWWPWWDQMKJ-UHFFFAOYSA-N 3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]benzamide Chemical compound NC(=O)C1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 GGWYWWPWWDQMKJ-UHFFFAOYSA-N 0.000 claims description 3
• GDLBRGNBENEOGY-UHFFFAOYSA-N 3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]benzonitrile Chemical compound N#CC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 GDLBRGNBENEOGY-UHFFFAOYSA-N 0.000 claims description 3
• KKQFDOMDTGXQMM-UHFFFAOYSA-N 3-[[3-(1h-indazol-5-ylamino)pyrrolidin-1-yl]methyl]benzonitrile Chemical compound N#CC1=CC=CC(CN2CC(CC2)NC=2C=C3C=NNC3=CC=2)=C1 KKQFDOMDTGXQMM-UHFFFAOYSA-N 0.000 claims description 3
• LFXXHSZZBJKJJF-UHFFFAOYSA-N 4-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 LFXXHSZZBJKJJF-UHFFFAOYSA-N 0.000 claims description 3
• 239000002775 capsule Substances 0.000 claims description 3
• ZOHRKOKZKGNCNH-OAQYLSRUSA-N n-[(3r)-1-[(3-cyclopropylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C([C@@H](CC1)NC=2C3=CC=NC=C3C=CC=2)N1CC(C=1)=CC=CC=1C1CC1 ZOHRKOKZKGNCNH-OAQYLSRUSA-N 0.000 claims description 3
• LMORZGYOIOJSPZ-OAQYLSRUSA-N n-[(3r)-1-[(4-cyclopropylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C([C@@H](CC1)NC=2C3=CC=NC=C3C=CC=2)N1CC(C=C1)=CC=C1C1CC1 LMORZGYOIOJSPZ-OAQYLSRUSA-N 0.000 claims description 3
• DPZSYTMLVCLGRU-GOSISDBHSA-N n-[(3r)-1-[(4-methylsulfanylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(SC)=CC=C1CN1C[C@H](NC=2C=C3C=NNC3=CC=2)CCC1 DPZSYTMLVCLGRU-GOSISDBHSA-N 0.000 claims description 3
• IQUZIVDCVRBBFR-GOSISDBHSA-N n-[(3r)-1-[(4-methylsulfanylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C1=CC(SC)=CC=C1CN1C[C@H](NC=2C3=CC=NC=C3C=CC=2)CC1 IQUZIVDCVRBBFR-GOSISDBHSA-N 0.000 claims description 3
• ZOHRKOKZKGNCNH-NRFANRHFSA-N n-[(3s)-1-[(3-cyclopropylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C([C@H](CC1)NC=2C3=CC=NC=C3C=CC=2)N1CC(C=1)=CC=CC=1C1CC1 ZOHRKOKZKGNCNH-NRFANRHFSA-N 0.000 claims description 3
• IQUZIVDCVRBBFR-SFHVURJKSA-N n-[(3s)-1-[(4-methylsulfanylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C1=CC(SC)=CC=C1CN1C[C@@H](NC=2C3=CC=NC=C3C=CC=2)CC1 IQUZIVDCVRBBFR-SFHVURJKSA-N 0.000 claims description 3
• QUJOREAGMCLAOO-UHFFFAOYSA-N n-[1-[(4-cyclopropylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1CCC(NC=2C=C3C=NNC3=CC=2)CN1CC(C=C1)=CC=C1C1CC1 QUJOREAGMCLAOO-UHFFFAOYSA-N 0.000 claims description 3
• XPXJREKHQWNIQZ-UHFFFAOYSA-N n-[1-[(4-cyclopropylsulfanylphenyl)methyl]piperidin-3-yl]isoquinolin-5-amine Chemical compound C1CCC(NC=2C3=CC=NC=C3C=CC=2)CN1CC(C=C1)=CC=C1SC1CC1 XPXJREKHQWNIQZ-UHFFFAOYSA-N 0.000 claims description 3
• DQNYJGMBMWJKJV-UHFFFAOYSA-N n-[1-[(4-ethenylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(C=C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 DQNYJGMBMWJKJV-UHFFFAOYSA-N 0.000 claims description 3
• DMQNUCUGOVADJT-UHFFFAOYSA-N n-[1-[(4-methylsulfanylphenyl)methyl]piperidin-3-yl]isoquinolin-5-amine Chemical compound C1=CC(SC)=CC=C1CN1CC(NC=2C3=CC=NC=C3C=CC=2)CCC1 DMQNUCUGOVADJT-UHFFFAOYSA-N 0.000 claims description 3
• XSYWGPNWBBDYPP-UHFFFAOYSA-N n-[1-[(4-methylsulfonylphenyl)methyl]piperidin-3-yl]isoquinolin-5-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1CC(NC=2C3=CC=NC=C3C=CC=2)CCC1 XSYWGPNWBBDYPP-UHFFFAOYSA-N 0.000 claims description 3
• IERPXRYTDDRYGB-UHFFFAOYSA-N n-[1-[(4-methylsulfonylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1CC(NC=2C3=CC=NC=C3C=CC=2)CC1 IERPXRYTDDRYGB-UHFFFAOYSA-N 0.000 claims description 3
• LNAVORGTPYZRDM-UHFFFAOYSA-N n-[1-[[3-(aminomethyl)phenyl]methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound NCC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 LNAVORGTPYZRDM-UHFFFAOYSA-N 0.000 claims description 3
• HUVLXAMZMWMEAO-UHFFFAOYSA-N n-[2-[3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]ethyl]acetamide Chemical compound CC(=O)NCCOC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 HUVLXAMZMWMEAO-UHFFFAOYSA-N 0.000 claims description 3
• UVIWSVMESNYYMT-UHFFFAOYSA-N n-[2-chloro-5-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]methanesulfonamide Chemical compound C1=C(Cl)C(NS(=O)(=O)C)=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 UVIWSVMESNYYMT-UHFFFAOYSA-N 0.000 claims description 3
• ATFSXSWVVPUEBE-UHFFFAOYSA-N n-[3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]-n-methylmethanesulfonamide Chemical compound CS(=O)(=O)N(C)C1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 ATFSXSWVVPUEBE-UHFFFAOYSA-N 0.000 claims description 3
• CPVFJCZYQSPUEE-UHFFFAOYSA-N n-[3-[[3-(1h-indazol-5-ylamino)pyrrolidin-1-yl]methyl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(CN2CC(CC2)NC=2C=C3C=NNC3=CC=2)=C1 CPVFJCZYQSPUEE-UHFFFAOYSA-N 0.000 claims description 3
• CDKZHWZCXRRPDX-UHFFFAOYSA-N n-[[3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]methyl]acetamide Chemical compound CC(=O)NCC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 CDKZHWZCXRRPDX-UHFFFAOYSA-N 0.000 claims description 3
• IHCQSKFOQWOBBA-OXQOHEQNSA-N (2r)-1-[3-[[(3r)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]propan-2-ol Chemical compound C[C@@H](O)COC1=CC=CC(CN2C[C@@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 IHCQSKFOQWOBBA-OXQOHEQNSA-N 0.000 claims description 2
• OXZZTYUKEITHSD-VQTJNVASSA-N (2r)-3-[3-[[(3s)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]propane-1,2-diol Chemical compound OC[C@@H](O)COC1=CC=CC(CN2C[C@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 OXZZTYUKEITHSD-VQTJNVASSA-N 0.000 claims description 2
• OXZZTYUKEITHSD-UXHICEINSA-N (2s)-3-[3-[[(3r)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]propane-1,2-diol Chemical compound OC[C@H](O)COC1=CC=CC(CN2C[C@@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 OXZZTYUKEITHSD-UXHICEINSA-N 0.000 claims description 2
• RZQREJCXFJBPJW-HSZRJFAPSA-N 2-[3-[[(3r)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]-1-(4-methylpiperazin-1-yl)ethanone Chemical compound C1CN(C)CCN1C(=O)COC1=CC=CC(CN2C[C@@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 RZQREJCXFJBPJW-HSZRJFAPSA-N 0.000 claims description 2
• PDNRANQFZBPQEF-LJQANCHMSA-N 2-[3-[[(3r)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(CN2C[C@@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 PDNRANQFZBPQEF-LJQANCHMSA-N 0.000 claims description 2
• QPEIXLYASHZHRM-SFHVURJKSA-N 2-[3-[[(3s)-3-(1h-indazol-5-ylamino)pyrrolidin-1-yl]methyl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(CN2C[C@H](CC2)NC=2C=C3C=NNC3=CC=2)=C1 QPEIXLYASHZHRM-SFHVURJKSA-N 0.000 claims description 2
• BPRCQSXHYHFFRW-UHFFFAOYSA-N 2-[3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 BPRCQSXHYHFFRW-UHFFFAOYSA-N 0.000 claims description 2
• PDNRANQFZBPQEF-UHFFFAOYSA-N 2-[3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 PDNRANQFZBPQEF-UHFFFAOYSA-N 0.000 claims description 2
• GCWJCJSCGSLPQM-UHFFFAOYSA-N 2-[5-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]-2-methylphenoxy]ethanol Chemical compound C1=C(OCCO)C(C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 GCWJCJSCGSLPQM-UHFFFAOYSA-N 0.000 claims description 2
• XEQSNPVXRPAPMJ-NRFANRHFSA-N 2-[6-[[(3s)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]indol-1-yl]ethanol Chemical compound C1=C2NN=CC2=CC(N[C@H]2CCCN(C2)CC2=CC=C3C=CN(C3=C2)CCO)=C1 XEQSNPVXRPAPMJ-NRFANRHFSA-N 0.000 claims description 2
• IGNAVGHLKLQNRU-UHFFFAOYSA-N 2-[6-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]indol-1-yl]acetic acid Chemical compound C1=C2NN=CC2=CC(NC2CCCN(C2)CC2=CC=C3C=CN(C3=C2)CC(=O)O)=C1 IGNAVGHLKLQNRU-UHFFFAOYSA-N 0.000 claims description 2
• HFFGJIJZKRLHOZ-UHFFFAOYSA-N 2-ethynyl-5-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenol Chemical compound C1=C(C#C)C(O)=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 HFFGJIJZKRLHOZ-UHFFFAOYSA-N 0.000 claims description 2
• IUBQYUTWCSGHJN-UHFFFAOYSA-N 3-[4-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]prop-2-yn-1-ol Chemical compound C1=CC(C#CCO)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 IUBQYUTWCSGHJN-UHFFFAOYSA-N 0.000 claims description 2
• JSQRFMBGAVZKFV-UHFFFAOYSA-N 3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 JSQRFMBGAVZKFV-UHFFFAOYSA-N 0.000 claims description 2
• IBZCJNIYGGMRCN-UHFFFAOYSA-N 4-[4-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]but-3-yn-1-ol Chemical compound C1=CC(C#CCCO)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 IBZCJNIYGGMRCN-UHFFFAOYSA-N 0.000 claims description 2
• YCNQEIDRNDLZLW-UHFFFAOYSA-N ethyl 2-[3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]acetate Chemical compound CCOC(=O)COC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 YCNQEIDRNDLZLW-UHFFFAOYSA-N 0.000 claims description 2
• SPMSXTGVXFPBBK-LJQANCHMSA-N n-[(3r)-1-[(4-cyclopropylsulfanylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C([C@@H](CC1)NC=2C3=CC=NC=C3C=CC=2)N1CC(C=C1)=CC=C1SC1CC1 SPMSXTGVXFPBBK-LJQANCHMSA-N 0.000 claims description 2
• FQZNIWQVFRJDOJ-HXUWFJFHSA-N n-[(3r)-1-[(4-ethynylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(C#C)=CC=C1CN1C[C@H](NC=2C=C3C=NNC3=CC=2)CCC1 FQZNIWQVFRJDOJ-HXUWFJFHSA-N 0.000 claims description 2
• SPMSXTGVXFPBBK-IBGZPJMESA-N n-[(3s)-1-[(4-cyclopropylsulfanylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C([C@H](CC1)NC=2C3=CC=NC=C3C=CC=2)N1CC(C=C1)=CC=C1SC1CC1 SPMSXTGVXFPBBK-IBGZPJMESA-N 0.000 claims description 2
• FQZNIWQVFRJDOJ-FQEVSTJZSA-N n-[(3s)-1-[(4-ethynylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(C#C)=CC=C1CN1C[C@@H](NC=2C=C3C=NNC3=CC=2)CCC1 FQZNIWQVFRJDOJ-FQEVSTJZSA-N 0.000 claims description 2
• DPZSYTMLVCLGRU-SFHVURJKSA-N n-[(3s)-1-[(4-methylsulfanylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(SC)=CC=C1CN1C[C@@H](NC=2C=C3C=NNC3=CC=2)CCC1 DPZSYTMLVCLGRU-SFHVURJKSA-N 0.000 claims description 2
• QQPGUHWCZXHDEH-UHFFFAOYSA-N n-[1-[(3-cyclopropylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1CCC(NC=2C=C3C=NNC3=CC=2)CN1CC(C=1)=CC=CC=1C1CC1 QQPGUHWCZXHDEH-UHFFFAOYSA-N 0.000 claims description 2
• ISVDVUHFFNAXRM-UHFFFAOYSA-N n-[1-[(3-ethynylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C#CC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 ISVDVUHFFNAXRM-UHFFFAOYSA-N 0.000 claims description 2
• NGHLZEZXRFLFJC-UHFFFAOYSA-N n-[1-[(3-methylsulfanylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound CSC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 NGHLZEZXRFLFJC-UHFFFAOYSA-N 0.000 claims description 2
• DLTBJFNKVNSDQJ-UHFFFAOYSA-N n-[1-[(4-ethylsulfanylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(SCC)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 DLTBJFNKVNSDQJ-UHFFFAOYSA-N 0.000 claims description 2
• DPZSYTMLVCLGRU-UHFFFAOYSA-N n-[1-[(4-methylsulfanylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(SC)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 DPZSYTMLVCLGRU-UHFFFAOYSA-N 0.000 claims description 2
• BMTAHBGHVDJLDW-UHFFFAOYSA-N n-[1-[(4-morpholin-4-ylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1CCC(NC=2C=C3C=NNC3=CC=2)CN1CC(C=C1)=CC=C1N1CCOCC1 BMTAHBGHVDJLDW-UHFFFAOYSA-N 0.000 claims description 2
• SOXNYIWWQIFJRI-UHFFFAOYSA-N n-[1-[(4-pyrrolidin-1-ylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1CCC(NC=2C=C3C=NNC3=CC=2)CN1CC(C=C1)=CC=C1N1CCCC1 SOXNYIWWQIFJRI-UHFFFAOYSA-N 0.000 claims description 2
• WAVNRZBIYVZRSB-UHFFFAOYSA-N n-[1-[(4-thiophen-2-ylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1CCC(NC=2C=C3C=NNC3=CC=2)CN1CC(C=C1)=CC=C1C1=CC=CS1 WAVNRZBIYVZRSB-UHFFFAOYSA-N 0.000 claims description 2
• QPQXUWYBRBDMKL-UHFFFAOYSA-N n-[1-[[3-(2-aminoethoxy)phenyl]methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound NCCOC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 QPQXUWYBRBDMKL-UHFFFAOYSA-N 0.000 claims description 2
• AIEDMXUFXQBODU-UHFFFAOYSA-N n-[1-[[4-(2-cyclopropylethynyl)phenyl]methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1CCC(NC=2C=C3C=NNC3=CC=2)CN1CC(C=C1)=CC=C1C#CC1CC1 AIEDMXUFXQBODU-UHFFFAOYSA-N 0.000 claims description 2
• CWXOVADRAJYZRV-UHFFFAOYSA-N n-[1-[[4-(methylsulfonylmethyl)phenyl]methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(CS(=O)(=O)C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 CWXOVADRAJYZRV-UHFFFAOYSA-N 0.000 claims description 2
• DSSHWWLYALEYJS-HXUWFJFHSA-N n-[3-[[(3r)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]ethanesulfonamide Chemical compound CCS(=O)(=O)NC1=CC=CC(CN2C[C@@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 DSSHWWLYALEYJS-HXUWFJFHSA-N 0.000 claims description 2
• VYDWBAYBPOUUPX-LJQANCHMSA-N n-[3-[[(3r)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(CN2C[C@@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 VYDWBAYBPOUUPX-LJQANCHMSA-N 0.000 claims description 2
• CPVFJCZYQSPUEE-GOSISDBHSA-N n-[3-[[(3r)-3-(1h-indazol-5-ylamino)pyrrolidin-1-yl]methyl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(CN2C[C@@H](CC2)NC=2C=C3C=NNC3=CC=2)=C1 CPVFJCZYQSPUEE-GOSISDBHSA-N 0.000 claims description 2
• CNFJHJMGGNMYDX-HXUWFJFHSA-N n-[3-[[(3r)-3-(isoquinolin-5-ylamino)pyrrolidin-1-yl]methyl]phenyl]ethanesulfonamide Chemical compound CCS(=O)(=O)NC1=CC=CC(CN2C[C@@H](CC2)NC=2C3=CC=NC=C3C=CC=2)=C1 CNFJHJMGGNMYDX-HXUWFJFHSA-N 0.000 claims description 2
• DSSHWWLYALEYJS-FQEVSTJZSA-N n-[3-[[(3s)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]ethanesulfonamide Chemical compound CCS(=O)(=O)NC1=CC=CC(CN2C[C@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 DSSHWWLYALEYJS-FQEVSTJZSA-N 0.000 claims description 2
• DSSHWWLYALEYJS-UHFFFAOYSA-N n-[3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]ethanesulfonamide Chemical compound CCS(=O)(=O)NC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 DSSHWWLYALEYJS-UHFFFAOYSA-N 0.000 claims description 2
• VYDWBAYBPOUUPX-UHFFFAOYSA-N n-[3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 VYDWBAYBPOUUPX-UHFFFAOYSA-N 0.000 claims description 2
• UNHJXKXHKIFADV-UHFFFAOYSA-N n-[4-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 UNHJXKXHKIFADV-UHFFFAOYSA-N 0.000 claims description 2
• RNANERPNWMVVAB-UHFFFAOYSA-N n-[4-[[3-(1h-indazol-5-ylamino)pyrrolidin-1-yl]methyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CC1 RNANERPNWMVVAB-UHFFFAOYSA-N 0.000 claims description 2
• LBXZGQULVZGSNR-UHFFFAOYSA-N n-[4-[[3-(isoquinolin-5-ylamino)piperidin-1-yl]methyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1CN1CC(NC=2C3=CC=NC=C3C=CC=2)CCC1 LBXZGQULVZGSNR-UHFFFAOYSA-N 0.000 claims description 2
• YCCKDGUXWPCDCH-UHFFFAOYSA-N n-[4-[[3-(isoquinolin-5-ylamino)pyrrolidin-1-yl]methyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1CN1CC(NC=2C3=CC=NC=C3C=CC=2)CC1 YCCKDGUXWPCDCH-UHFFFAOYSA-N 0.000 claims description 2
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 3
• XWCDUEYGMIPYND-JOCHJYFZSA-N 2-[3-[[(3r)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]-1-morpholin-4-ylethanone Chemical compound C=1C=CC(CN2C[C@@H](CCC2)NC=2C=C3C=NNC3=CC=2)=CC=1OCC(=O)N1CCOCC1 XWCDUEYGMIPYND-JOCHJYFZSA-N 0.000 claims 1
• CVQXJHBUWUKUAE-JOCHJYFZSA-N 2-[3-[[(3r)-3-(isoquinolin-5-ylamino)pyrrolidin-1-yl]methyl]phenoxy]-1-morpholin-4-ylethanone Chemical compound C=1C=CC(CN2C[C@@H](CC2)NC=2C3=CC=NC=C3C=CC=2)=CC=1OCC(=O)N1CCOCC1 CVQXJHBUWUKUAE-JOCHJYFZSA-N 0.000 claims 1
• UPWDVLSJGHGBFP-GOSISDBHSA-N 2-[3-[[(3r)-3-(isoquinolin-5-ylamino)pyrrolidin-1-yl]methyl]phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=CC(CN2C[C@@H](CC2)NC=2C3=CC=NC=C3C=CC=2)=C1 UPWDVLSJGHGBFP-GOSISDBHSA-N 0.000 claims 1
• QBXDKOPEYCIHQK-UHFFFAOYSA-N 2-[5-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]indol-1-yl]acetic acid Chemical compound C1=C2NN=CC2=CC(NC2CCCN(C2)CC=2C=C3C=CN(C3=CC=2)CC(=O)O)=C1 QBXDKOPEYCIHQK-UHFFFAOYSA-N 0.000 claims 1
• PBBCVKDKPWRTSW-UHFFFAOYSA-N 2-[5-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]indol-1-yl]ethanol Chemical compound C1=C2NN=CC2=CC(NC2CCCN(C2)CC=2C=C3C=CN(C3=CC=2)CCO)=C1 PBBCVKDKPWRTSW-UHFFFAOYSA-N 0.000 claims 1
• XEQSNPVXRPAPMJ-OAQYLSRUSA-N 2-[6-[[(3r)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]indol-1-yl]ethanol Chemical compound C1=C2NN=CC2=CC(N[C@@H]2CCCN(C2)CC2=CC=C3C=CN(C3=C2)CCO)=C1 XEQSNPVXRPAPMJ-OAQYLSRUSA-N 0.000 claims 1
• XEQSNPVXRPAPMJ-UHFFFAOYSA-N 2-[6-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]indol-1-yl]ethanol Chemical compound C1=C2NN=CC2=CC(NC2CCCN(C2)CC2=CC=C3C=CN(C3=C2)CCO)=C1 XEQSNPVXRPAPMJ-UHFFFAOYSA-N 0.000 claims 1
• LWKUYNWGILHOCX-UHFFFAOYSA-N 3-[3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenoxy]propan-1-ol Chemical compound OCCCOC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 LWKUYNWGILHOCX-UHFFFAOYSA-N 0.000 claims 1
• HGIRVGIKIQKKOC-UHFFFAOYSA-N 3-[[3-(isoquinolin-5-ylamino)piperidin-1-yl]methyl]benzonitrile Chemical compound N#CC1=CC=CC(CN2CC(CCC2)NC=2C3=CC=NC=C3C=CC=2)=C1 HGIRVGIKIQKKOC-UHFFFAOYSA-N 0.000 claims 1
• DJUWCELEOPHKCD-UHFFFAOYSA-N 3-[[3-(isoquinolin-5-ylamino)pyrrolidin-1-yl]methyl]benzonitrile Chemical compound N#CC1=CC=CC(CN2CC(CC2)NC=2C3=CC=NC=C3C=CC=2)=C1 DJUWCELEOPHKCD-UHFFFAOYSA-N 0.000 claims 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 1
• MIMFSAOPASEOEY-HXUWFJFHSA-N n-[(3r)-1-[(4-ethynylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C1=CC(C#C)=CC=C1CN1C[C@H](NC=2C3=CC=NC=C3C=CC=2)CC1 MIMFSAOPASEOEY-HXUWFJFHSA-N 0.000 claims 1
• OLGYHXPKEZCVEP-UHFFFAOYSA-N n-[1-[(3-methylsulfonylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound CS(=O)(=O)C1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 OLGYHXPKEZCVEP-UHFFFAOYSA-N 0.000 claims 1
• NWQAWCOYBNUWPT-UHFFFAOYSA-N n-[1-[(4-cyclopropylphenyl)methyl]piperidin-3-yl]isoquinolin-5-amine Chemical compound C1CCC(NC=2C3=CC=NC=C3C=CC=2)CN1CC(C=C1)=CC=C1C1CC1 NWQAWCOYBNUWPT-UHFFFAOYSA-N 0.000 claims 1
• XOGZXGLZHJWWDZ-UHFFFAOYSA-N n-[1-[(4-cyclopropylsulfanylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1CCC(NC=2C=C3C=NNC3=CC=2)CN1CC(C=C1)=CC=C1SC1CC1 XOGZXGLZHJWWDZ-UHFFFAOYSA-N 0.000 claims 1
• FQZNIWQVFRJDOJ-UHFFFAOYSA-N n-[1-[(4-ethynylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(C#C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 FQZNIWQVFRJDOJ-UHFFFAOYSA-N 0.000 claims 1
• DLFCOOXTMLTEEG-UHFFFAOYSA-N n-[1-[(4-methylsulfonylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 DLFCOOXTMLTEEG-UHFFFAOYSA-N 0.000 claims 1
• XKFGCNGELSXIMD-UHFFFAOYSA-N n-[1-[(4-methylsulfonylphenyl)methyl]pyrrolidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CC1 XKFGCNGELSXIMD-UHFFFAOYSA-N 0.000 claims 1
• LDHMTLKGXAMHJD-UHFFFAOYSA-N n-[1-[[3-(methylsulfonylmethyl)phenyl]methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound CS(=O)(=O)CC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 LDHMTLKGXAMHJD-UHFFFAOYSA-N 0.000 claims 1
• LFRWJOOFIZGJRS-UHFFFAOYSA-N n-[1-[[4-(aminomethyl)phenyl]methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(CN)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 LFRWJOOFIZGJRS-UHFFFAOYSA-N 0.000 claims 1
• PKCSBJKNGDETTE-UHFFFAOYSA-N n-[1-[[4-(methylsulfanylmethyl)phenyl]methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(CSC)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 PKCSBJKNGDETTE-UHFFFAOYSA-N 0.000 claims 1
• YKVGSJWLOZXWNB-UHFFFAOYSA-N n-[1-[[4-[(dimethylamino)methyl]phenyl]methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(CN(C)C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 YKVGSJWLOZXWNB-UHFFFAOYSA-N 0.000 claims 1
• QRMMOYFBMFFTSZ-UHFFFAOYSA-N n-[1-[[4-[3-(dimethylamino)propoxy]phenyl]methyl]pyrrolidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(OCCCN(C)C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CC1 QRMMOYFBMFFTSZ-UHFFFAOYSA-N 0.000 claims 1
• VYDWBAYBPOUUPX-IBGZPJMESA-N n-[3-[[(3s)-3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(CN2C[C@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 VYDWBAYBPOUUPX-IBGZPJMESA-N 0.000 claims 1
• CPVFJCZYQSPUEE-SFHVURJKSA-N n-[3-[[(3s)-3-(1h-indazol-5-ylamino)pyrrolidin-1-yl]methyl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(CN2C[C@H](CC2)NC=2C=C3C=NNC3=CC=2)=C1 CPVFJCZYQSPUEE-SFHVURJKSA-N 0.000 claims 1
• ZRMHZVWQKSOWAN-IBGZPJMESA-N n-[3-[[(3s)-3-(isoquinolin-5-ylamino)pyrrolidin-1-yl]methyl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(CN2C[C@H](CC2)NC=2C3=CC=NC=C3C=CC=2)=C1 ZRMHZVWQKSOWAN-IBGZPJMESA-N 0.000 claims 1
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 304
• 238000005160 1H NMR spectroscopy Methods 0.000 description 166
• 238000000034 method Methods 0.000 description 117
• 238000006243 chemical reaction Methods 0.000 description 61
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 43
• 125000004432 carbon atom Chemical group C* 0.000 description 29
• 239000000243 solution Substances 0.000 description 28
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
• 125000003282 alkyl amino group Chemical group 0.000 description 26
• 238000010511 deprotection reaction Methods 0.000 description 26
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 26
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 24
• 210000004027 cell Anatomy 0.000 description 23
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 22
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 22
• 230000003436 cytoskeletal effect Effects 0.000 description 21
• 235000019439 ethyl acetate Nutrition 0.000 description 19
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 150000001299 aldehydes Chemical class 0.000 description 18
• 210000001742 aqueous humor Anatomy 0.000 description 18
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 16
• 125000003545 alkoxy group Chemical group 0.000 description 15
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 14
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 14
• 229940122975 Rho-associated kinase inhibitor Drugs 0.000 description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
• 150000003839 salts Chemical class 0.000 description 13
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 12
• 239000007787 solid Substances 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
• 108010085238 Actins Proteins 0.000 description 11
• 102000007469 Actins Human genes 0.000 description 11
• 238000005859 coupling reaction Methods 0.000 description 11
• 239000012074 organic phase Substances 0.000 description 11
• 238000012360 testing method Methods 0.000 description 11
• 241001465754 Metazoa Species 0.000 description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
• 238000009472 formulation Methods 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• 238000011282 treatment Methods 0.000 description 10
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 201000010099 disease Diseases 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 8
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
• 230000008878 coupling Effects 0.000 description 8
• 238000010168 coupling process Methods 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• 230000005764 inhibitory process Effects 0.000 description 8
• 229920006395 saturated elastomer Polymers 0.000 description 8
• 239000000741 silica gel Substances 0.000 description 8
• 229910002027 silica gel Inorganic materials 0.000 description 8
• 239000011593 sulfur Substances 0.000 description 8
• 206010030348 Open-Angle Glaucoma Diseases 0.000 description 7
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
• 238000003556 assay Methods 0.000 description 7
• 239000007810 chemical reaction solvent Substances 0.000 description 7
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 7
• 239000008194 pharmaceutical composition Substances 0.000 description 7
• NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 6
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• 238000005481 NMR spectroscopy Methods 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 125000004429 atom Chemical group 0.000 description 6
• 239000003638 chemical reducing agent Substances 0.000 description 6
• 238000004587 chromatography analysis Methods 0.000 description 6
• 229960004979 fampridine Drugs 0.000 description 6
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 6
• 201000006366 primary open angle glaucoma Diseases 0.000 description 6
• 238000006467 substitution reaction Methods 0.000 description 6
• 238000001356 surgical procedure Methods 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 210000001519 tissue Anatomy 0.000 description 6
• 230000000699 topical effect Effects 0.000 description 6
• DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 5
• 101000669921 Homo sapiens Rho-associated protein kinase 2 Proteins 0.000 description 5
• 102100039314 Rho-associated protein kinase 2 Human genes 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 229940125782 compound 2 Drugs 0.000 description 5
• 239000003937 drug carrier Substances 0.000 description 5
• 239000000499 gel Substances 0.000 description 5
• 239000001257 hydrogen Substances 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 239000012528 membrane Substances 0.000 description 5
• 230000004048 modification Effects 0.000 description 5
• 238000012986 modification Methods 0.000 description 5
• 230000003287 optical effect Effects 0.000 description 5
• 239000003755 preservative agent Substances 0.000 description 5
• UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
• 235000017557 sodium bicarbonate Nutrition 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 239000012453 solvate Substances 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• RIFXIGDBUBXKEI-UHFFFAOYSA-N tert-butyl 3-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(=O)C1 RIFXIGDBUBXKEI-UHFFFAOYSA-N 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• 230000029663 wound healing Effects 0.000 description 5
• LXGJEYHEYBEAMM-UHFFFAOYSA-N 2,2-dimethyl-1-[5-(piperidin-3-ylamino)indazol-1-yl]propan-1-one Chemical compound C=1C=C2N(C(=O)C(C)(C)C)N=CC2=CC=1NC1CCCNC1 LXGJEYHEYBEAMM-UHFFFAOYSA-N 0.000 description 4
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
• 229960000583 acetic acid Drugs 0.000 description 4
• 238000013459 approach Methods 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• 125000005518 carboxamido group Chemical group 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• 125000004122 cyclic group Chemical group 0.000 description 4
• 150000004985 diamines Chemical class 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 4
• 229960002949 fluorouracil Drugs 0.000 description 4
• 230000006870 function Effects 0.000 description 4
• 150000004677 hydrates Chemical class 0.000 description 4
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
• 235000019341 magnesium sulphate Nutrition 0.000 description 4
• 229960004857 mitomycin Drugs 0.000 description 4
• 239000003921 oil Substances 0.000 description 4
• 235000019198 oils Nutrition 0.000 description 4
• 230000035699 permeability Effects 0.000 description 4
• 125000003386 piperidinyl group Chemical group 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• 230000004224 protection Effects 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 4
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
• QRVYABWJVXXOTN-UHFFFAOYSA-N 4-methylsulfanylbenzaldehyde Chemical compound CSC1=CC=C(C=O)C=C1 QRVYABWJVXXOTN-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 201000004569 Blindness Diseases 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
• 206010036346 Posterior capsule opacification Diseases 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 206010052428 Wound Diseases 0.000 description 3
• 208000027418 Wounds and injury Diseases 0.000 description 3
• 230000004075 alteration Effects 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 229960000686 benzalkonium chloride Drugs 0.000 description 3
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• 150000007942 carboxylates Chemical class 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 230000021164 cell adhesion Effects 0.000 description 3
• 238000002782 cell morphology assay Methods 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 230000001276 controlling effect Effects 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 230000001419 dependent effect Effects 0.000 description 3
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
• 210000002889 endothelial cell Anatomy 0.000 description 3
• ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 210000001650 focal adhesion Anatomy 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 230000002427 irreversible effect Effects 0.000 description 3
• 229940043355 kinase inhibitor Drugs 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 238000002483 medication Methods 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• HOTGJYAYVQJOMO-LLVKDONJSA-N n-[(3r)-pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C1NCC[C@H]1NC1=CC=CC2=CN=CC=C12 HOTGJYAYVQJOMO-LLVKDONJSA-N 0.000 description 3
• HOTGJYAYVQJOMO-NSHDSACASA-N n-[(3s)-pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C1NCC[C@@H]1NC1=CC=CC2=CN=CC=C12 HOTGJYAYVQJOMO-NSHDSACASA-N 0.000 description 3
• QOYNRBLJACVNTD-UHFFFAOYSA-N n-[1-[[3-(trifluoromethyl)phenyl]methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound FC(F)(F)C1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 QOYNRBLJACVNTD-UHFFFAOYSA-N 0.000 description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
• 230000000144 pharmacologic effect Effects 0.000 description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
• 230000002980 postoperative effect Effects 0.000 description 3
• 239000002244 precipitate Substances 0.000 description 3
• 230000002335 preservative effect Effects 0.000 description 3
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
• 125000004076 pyridyl group Chemical group 0.000 description 3
• 230000008707 rearrangement Effects 0.000 description 3
• 108010041788 rho-Associated Kinases Proteins 0.000 description 3
• 102000000568 rho-Associated Kinases Human genes 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 3
• 230000004393 visual impairment Effects 0.000 description 3
• DPZNOMCNRMUKPS-UHFFFAOYSA-N 1,3-Dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1 DPZNOMCNRMUKPS-UHFFFAOYSA-N 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 2
• RZPNBOIDKHKPQD-UHFFFAOYSA-N 1-[4-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 RZPNBOIDKHKPQD-UHFFFAOYSA-N 0.000 description 2
• HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
• VDEVCBVUHZCKCU-FQEVSTJZSA-N 2-[3-[[(3s)-3-(isoquinolin-5-ylamino)piperidin-1-yl]methyl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(CN2C[C@H](CCC2)NC=2C3=CC=NC=C3C=CC=2)=C1 VDEVCBVUHZCKCU-FQEVSTJZSA-N 0.000 description 2
• WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
• PXNZHWOGIVAURZ-UHFFFAOYSA-N 4-(4-aminophenyl)-1,2,5-oxadiazol-3-amine Chemical compound NC1=NON=C1C1=CC=C(N)C=C1 PXNZHWOGIVAURZ-UHFFFAOYSA-N 0.000 description 2
• ZEFURAOTBQBPON-UHFFFAOYSA-N 4-(4-nitrophenyl)-1,2,5-oxadiazol-3-amine Chemical compound NC1=NON=C1C1=CC=C([N+]([O-])=O)C=C1 ZEFURAOTBQBPON-UHFFFAOYSA-N 0.000 description 2
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
• FUXNTHGNLGWQIQ-UHFFFAOYSA-N 5-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]-2-methylphenol Chemical compound C1=C(O)C(C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 FUXNTHGNLGWQIQ-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
• 201000002862 Angle-Closure Glaucoma Diseases 0.000 description 2
• 125000006847 BOC protecting group Chemical group 0.000 description 2
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
• 206010028980 Neoplasm Diseases 0.000 description 2
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-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
• 208000017442 Retinal disease Diseases 0.000 description 2
• 206010038923 Retinopathy Diseases 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• 206010047555 Visual field defect Diseases 0.000 description 2
• NVXGZQGKWLMDKQ-UHFFFAOYSA-N [4-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenyl]methanol Chemical compound C1=CC(CO)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 NVXGZQGKWLMDKQ-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
• 125000002252 acyl group Chemical group 0.000 description 2
• 125000004442 acylamino group Chemical group 0.000 description 2
• 206010064930 age-related macular degeneration Diseases 0.000 description 2
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 2
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 2
• 125000004414 alkyl thio group Chemical group 0.000 description 2
• 125000004103 aminoalkyl group Chemical group 0.000 description 2
• 230000000340 anti-metabolite Effects 0.000 description 2
• 229940100197 antimetabolite Drugs 0.000 description 2
• 239000002256 antimetabolite Substances 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 235000006708 antioxidants Nutrition 0.000 description 2
• 230000006907 apoptotic process Effects 0.000 description 2
• 125000004104 aryloxy group Chemical group 0.000 description 2
• METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 230000004397 blinking Effects 0.000 description 2
• 238000006664 bond formation reaction Methods 0.000 description 2
• 239000007975 buffered saline Substances 0.000 description 2
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 229940125904 compound 1 Drugs 0.000 description 2
• 239000006184 cosolvent Substances 0.000 description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 210000004292 cytoskeleton Anatomy 0.000 description 2
• 125000004663 dialkyl amino group Chemical group 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 239000003623 enhancer Substances 0.000 description 2
• 210000002919 epithelial cell Anatomy 0.000 description 2
• 210000003560 epithelium corneal Anatomy 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
• 125000004438 haloalkoxy group Chemical group 0.000 description 2
• 125000005553 heteroaryloxy group Chemical group 0.000 description 2
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• 230000007774 longterm Effects 0.000 description 2
• 208000002780 macular degeneration Diseases 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
• 239000004530 micro-emulsion Substances 0.000 description 2
• 230000005012 migration Effects 0.000 description 2
• 238000013508 migration Methods 0.000 description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
• 230000004660 morphological change Effects 0.000 description 2
• XDTIVYIDZRYAGC-UHFFFAOYSA-N n-(1-benzylpiperidin-3-yl)pyridin-4-amine Chemical compound C=1C=CC=CC=1CN(C1)CCCC1NC1=CC=NC=C1 XDTIVYIDZRYAGC-UHFFFAOYSA-N 0.000 description 2
• HHDLBGHLDFIDKP-LJQANCHMSA-N n-[(3r)-1-(1-benzothiophen-5-ylmethyl)piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=C2SC=CC2=CC(CN2C[C@@H](CCC2)NC=2C=C3C=NNC3=CC=2)=C1 HHDLBGHLDFIDKP-LJQANCHMSA-N 0.000 description 2
• NVDYRDZHCINQQB-MRXNPFEDSA-N n-[(3r)-1-[(3,4-difluorophenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=C(F)C(F)=CC=C1CN1C[C@H](NC=2C=C3C=NNC3=CC=2)CCC1 NVDYRDZHCINQQB-MRXNPFEDSA-N 0.000 description 2
• UGWBCYQPCXKMGF-GOSISDBHSA-N n-[(3r)-1-[(4-chlorophenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C1=CC(Cl)=CC=C1CN1C[C@H](NC=2C3=CC=NC=C3C=CC=2)CC1 UGWBCYQPCXKMGF-GOSISDBHSA-N 0.000 description 2
• DNUAUADEIBLJGT-GOSISDBHSA-N n-[(3r)-1-benzylpiperidin-3-yl]-1h-indazol-5-amine Chemical compound C([C@@H](CCC1)NC=2C=C3C=NNC3=CC=2)N1CC1=CC=CC=C1 DNUAUADEIBLJGT-GOSISDBHSA-N 0.000 description 2
• LMORZGYOIOJSPZ-NRFANRHFSA-N n-[(3s)-1-[(4-cyclopropylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C([C@H](CC1)NC=2C3=CC=NC=C3C=CC=2)N1CC(C=C1)=CC=C1C1CC1 LMORZGYOIOJSPZ-NRFANRHFSA-N 0.000 description 2
• UCJIXVPTONWDEH-SFHVURJKSA-N n-[(3s)-1-[(4-methoxyphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(OC)=CC=C1CN1C[C@@H](NC=2C=C3C=NNC3=CC=2)CCC1 UCJIXVPTONWDEH-SFHVURJKSA-N 0.000 description 2
• JLWTUPLIJAHTKE-IBGZPJMESA-N n-[(3s)-1-[(4-methylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(C)=CC=C1CN1C[C@@H](NC=2C=C3C=NNC3=CC=2)CCC1 JLWTUPLIJAHTKE-IBGZPJMESA-N 0.000 description 2
• UQCGQZYLCBENSJ-IBGZPJMESA-N n-[(3s)-1-[(4-methylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C1=CC(C)=CC=C1CN1C[C@@H](NC=2C3=CC=NC=C3C=CC=2)CC1 UQCGQZYLCBENSJ-IBGZPJMESA-N 0.000 description 2
• BYGZNIYIFZDUNZ-XRIOVQLTSA-N n-[(3s)-pyrrolidin-3-yl]-1h-indazol-5-amine;dihydrochloride Chemical compound Cl.Cl.C1NCC[C@@H]1NC1=CC=C(NN=C2)C2=C1 BYGZNIYIFZDUNZ-XRIOVQLTSA-N 0.000 description 2
• ATNOGRXONZLRGS-UHFFFAOYSA-N n-[1-[(2,3-dimethylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound CC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1C ATNOGRXONZLRGS-UHFFFAOYSA-N 0.000 description 2
• CLCMIAAQLBZPHZ-UHFFFAOYSA-N n-[1-[(3-cyclopropylphenyl)methyl]piperidin-3-yl]isoquinolin-5-amine Chemical compound C1CCC(NC=2C3=CC=NC=C3C=CC=2)CN1CC(C=1)=CC=CC=1C1CC1 CLCMIAAQLBZPHZ-UHFFFAOYSA-N 0.000 description 2
• KTQNVPQFJGMQDM-UHFFFAOYSA-N n-[1-[[3-(trifluoromethyl)phenyl]methyl]piperidin-3-yl]isoquinolin-5-amine Chemical compound FC(F)(F)C1=CC=CC(CN2CC(CCC2)NC=2C3=CC=NC=C3C=CC=2)=C1 KTQNVPQFJGMQDM-UHFFFAOYSA-N 0.000 description 2
• JVACKTOSODNYNH-FQEVSTJZSA-N n-[3-[[(3s)-3-(isoquinolin-5-ylamino)piperidin-1-yl]methyl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(CN2C[C@H](CCC2)NC=2C3=CC=NC=C3C=CC=2)=C1 JVACKTOSODNYNH-FQEVSTJZSA-N 0.000 description 2
• ALCJHEHAIODSCG-UHFFFAOYSA-N n-piperidin-3-ylisoquinolin-5-amine Chemical compound C1CCNCC1NC1=CC=CC2=CN=CC=C12 ALCJHEHAIODSCG-UHFFFAOYSA-N 0.000 description 2
• HOTGJYAYVQJOMO-UHFFFAOYSA-N n-pyrrolidin-3-ylisoquinolin-5-amine Chemical compound C1NCCC1NC1=CC=CC2=CN=CC=C12 HOTGJYAYVQJOMO-UHFFFAOYSA-N 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 230000004112 neuroprotection Effects 0.000 description 2
• 239000012299 nitrogen atmosphere Substances 0.000 description 2
• RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
• 230000035790 physiological processes and functions Effects 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 229940002612 prodrug Drugs 0.000 description 2
• 239000000651 prodrug Substances 0.000 description 2
• NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
• XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 238000003756 stirring Methods 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 125000005415 substituted alkoxy group Chemical group 0.000 description 2
• 125000000547 substituted alkyl group Chemical group 0.000 description 2
• 125000003107 substituted aryl group Chemical group 0.000 description 2
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• AKQXKEBCONUWCL-UHFFFAOYSA-N tert-butyl 3-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(N)C1 AKQXKEBCONUWCL-UHFFFAOYSA-N 0.000 description 2
• JSOMVCDXPUXKIC-UHFFFAOYSA-N tert-butyl 3-oxopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)C1 JSOMVCDXPUXKIC-UHFFFAOYSA-N 0.000 description 2
• LPQZERIRKRYGGM-UHFFFAOYSA-N tert-butyl pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1 LPQZERIRKRYGGM-UHFFFAOYSA-N 0.000 description 2
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 239000012929 tonicity agent Substances 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 210000001585 trabecular meshwork Anatomy 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• 230000000007 visual effect Effects 0.000 description 2
• QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 1
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
• MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
• ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
• GLTHODFTRSIXMR-BTJKTKAUSA-N 1-(5-aminoindazol-1-yl)-2,2-dimethylpropan-1-one;(z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.NC1=CC=C2N(C(=O)C(C)(C)C)N=CC2=C1 GLTHODFTRSIXMR-BTJKTKAUSA-N 0.000 description 1
• WINUIRRWEIPYSH-UHFFFAOYSA-N 1-[(4-methylsulfonylphenyl)methyl]piperidine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1CCCCC1 WINUIRRWEIPYSH-UHFFFAOYSA-N 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• NZVZVGPYTICZBZ-UHFFFAOYSA-N 1-benzylpiperidine Chemical compound C=1C=CC=CC=1CN1CCCCC1 NZVZVGPYTICZBZ-UHFFFAOYSA-N 0.000 description 1
• LVUQCTGSDJLWCE-UHFFFAOYSA-N 1-benzylpyrrolidin-2-one Chemical compound O=C1CCCN1CC1=CC=CC=C1 LVUQCTGSDJLWCE-UHFFFAOYSA-N 0.000 description 1
• WLDBFHWXAVBMAN-UHFFFAOYSA-N 1-bromoindazole Chemical compound C1=CC=C2N(Br)N=CC2=C1 WLDBFHWXAVBMAN-UHFFFAOYSA-N 0.000 description 1
• PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
• KYWXRBNOYGGPIZ-UHFFFAOYSA-N 1-morpholin-4-ylethanone Chemical compound CC(=O)N1CCOCC1 KYWXRBNOYGGPIZ-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
• TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
• XBTOSRUBOXQWBO-UHFFFAOYSA-N 1h-indazol-5-amine Chemical compound NC1=CC=C2NN=CC2=C1 XBTOSRUBOXQWBO-UHFFFAOYSA-N 0.000 description 1
• QPTCSNDPDWGXLB-UHFFFAOYSA-N 2,2-dimethyl-1-(5-nitroindazol-1-yl)propan-1-one Chemical compound [O-][N+](=O)C1=CC=C2N(C(=O)C(C)(C)C)N=CC2=C1 QPTCSNDPDWGXLB-UHFFFAOYSA-N 0.000 description 1
• SELLOUCVOPBGBM-UHFFFAOYSA-N 2,2-dimethyl-1-[5-(pyrrolidin-3-ylamino)indazol-1-yl]propan-1-one Chemical compound C=1C=C2N(C(=O)C(C)(C)C)N=CC2=CC=1NC1CCNC1 SELLOUCVOPBGBM-UHFFFAOYSA-N 0.000 description 1
• DRQIWUHMLKABMY-UHFFFAOYSA-N 2,2-dimethyl-1-[5-[[1-(3-methylsulfanylbenzoyl)piperidin-3-yl]amino]indazol-1-yl]propan-1-one Chemical compound CSC1=CC=CC(C(=O)N2CC(CCC2)NC=2C=C3C=NN(C3=CC=2)C(=O)C(C)(C)C)=C1 DRQIWUHMLKABMY-UHFFFAOYSA-N 0.000 description 1
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical compound CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
• JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
• VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
• PXNJGLAVKOXITN-UHFFFAOYSA-N 2-(4-nitrophenyl)acetonitrile Chemical compound [O-][N+](=O)C1=CC=C(CC#N)C=C1 PXNJGLAVKOXITN-UHFFFAOYSA-N 0.000 description 1
• HUHGPYXAVBJSJV-UHFFFAOYSA-N 2-[3,5-bis(2-hydroxyethyl)-1,3,5-triazinan-1-yl]ethanol Chemical compound OCCN1CN(CCO)CN(CCO)C1 HUHGPYXAVBJSJV-UHFFFAOYSA-N 0.000 description 1
• VDEVCBVUHZCKCU-HXUWFJFHSA-N 2-[3-[[(3r)-3-(isoquinolin-5-ylamino)piperidin-1-yl]methyl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(CN2C[C@@H](CCC2)NC=2C3=CC=NC=C3C=CC=2)=C1 VDEVCBVUHZCKCU-HXUWFJFHSA-N 0.000 description 1
• HRCKLYFDWWYCLS-LJQANCHMSA-N 2-[3-[[(3r)-3-(isoquinolin-5-ylamino)pyrrolidin-1-yl]methyl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(CN2C[C@@H](CC2)NC=2C3=CC=NC=C3C=CC=2)=C1 HRCKLYFDWWYCLS-LJQANCHMSA-N 0.000 description 1
• HRCKLYFDWWYCLS-IBGZPJMESA-N 2-[3-[[(3s)-3-(isoquinolin-5-ylamino)pyrrolidin-1-yl]methyl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(CN2C[C@H](CC2)NC=2C3=CC=NC=C3C=CC=2)=C1 HRCKLYFDWWYCLS-IBGZPJMESA-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
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• LIUCHRXQRHVSJI-UHFFFAOYSA-N 3-(2-hydroxyethoxy)benzaldehyde Chemical compound OCCOC1=CC=CC(C=O)=C1 LIUCHRXQRHVSJI-UHFFFAOYSA-N 0.000 description 1
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
• OUVFWXFHWPYQQY-UHFFFAOYSA-N 3-(ethyliminomethylideneamino)-n,n-dimethylpropan-1-amine;hydroiodide Chemical compound I.CCN=C=NCCCN(C)C OUVFWXFHWPYQQY-UHFFFAOYSA-N 0.000 description 1
• YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 1
• ZEAHQEHAYJCLND-UHFFFAOYSA-N 3-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]phenol Chemical compound OC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 ZEAHQEHAYJCLND-UHFFFAOYSA-N 0.000 description 1
• MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
• DSKKEOXRMGSCSN-UHFFFAOYSA-N 3-aminopiperidine-1-carboxylic acid Chemical compound NC1CCCN(C(O)=O)C1 DSKKEOXRMGSCSN-UHFFFAOYSA-N 0.000 description 1
• MKSTXMDSWOHKOR-UHFFFAOYSA-N 3-aminopyrrolidine-1-carboxylic acid Chemical compound NC1CCN(C(O)=O)C1 MKSTXMDSWOHKOR-UHFFFAOYSA-N 0.000 description 1
• PZGADOOBMVLBJE-UHFFFAOYSA-N 3-methylsulfanylbenzoic acid Chemical compound CSC1=CC=CC(C(O)=O)=C1 PZGADOOBMVLBJE-UHFFFAOYSA-N 0.000 description 1
• VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
• JIIYCIBCUFLMNE-UHFFFAOYSA-N 4-[1-[(4-benzylpiperidin-3-yl)amino]cyclohexa-2,4-dien-1-yl]-1,2,5-oxadiazol-3-amine Chemical compound NC1=NON=C1C1(NC2C(CCNC2)CC=2C=CC=CC=2)C=CC=CC1 JIIYCIBCUFLMNE-UHFFFAOYSA-N 0.000 description 1
• VUSFUCQSQHXOOJ-UHFFFAOYSA-N 4-[1-[(4-benzylpyrrolidin-3-yl)amino]cyclohexa-2,4-dien-1-yl]-1,2,5-oxadiazol-3-amine Chemical compound NC1=NON=C1C1(NC2C(CNC2)CC=2C=CC=CC=2)C=CC=CC1 VUSFUCQSQHXOOJ-UHFFFAOYSA-N 0.000 description 1
• YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
• QQMSBYSCOLLGQD-UHFFFAOYSA-N 4-[4-(piperidin-3-ylamino)phenyl]-1,2,5-oxadiazol-3-amine Chemical compound NC1=NON=C1C(C=C1)=CC=C1NC1CNCCC1 QQMSBYSCOLLGQD-UHFFFAOYSA-N 0.000 description 1
• MWMKHPBXSMBPLY-UHFFFAOYSA-N 4-[4-[(1-benzylpiperidin-3-yl)amino]phenyl]-1,2,5-oxadiazol-3-amine Chemical compound NC1=NON=C1C(C=C1)=CC=C1NC1CN(CC=2C=CC=CC=2)CCC1 MWMKHPBXSMBPLY-UHFFFAOYSA-N 0.000 description 1
• VWFVJDFMHCLBMS-UHFFFAOYSA-N 4-[4-[(1-benzylpyrrolidin-3-yl)amino]phenyl]-1,2,5-oxadiazol-3-amine Chemical compound NC1=NON=C1C(C=C1)=CC=C1NC1CN(CC=2C=CC=CC=2)CC1 VWFVJDFMHCLBMS-UHFFFAOYSA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 1
• GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 1
• IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
• YZCJAYGUDYIBGT-UHFFFAOYSA-N 5-[[3-(1h-indazol-5-ylamino)piperidin-1-yl]methyl]-2-iodophenol Chemical compound C1=C(I)C(O)=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 YZCJAYGUDYIBGT-UHFFFAOYSA-N 0.000 description 1
• SOSQXTINASWATM-UHFFFAOYSA-N 5-bromo-1-(oxan-2-yl)indazole Chemical compound N1=CC2=CC(Br)=CC=C2N1C1CCCCO1 SOSQXTINASWATM-UHFFFAOYSA-N 0.000 description 1
• STVHMYNPQCLUNJ-UHFFFAOYSA-N 5-bromo-1h-indazole Chemical compound BrC1=CC=C2NN=CC2=C1 STVHMYNPQCLUNJ-UHFFFAOYSA-N 0.000 description 1
• DWWCFKBYGWPOTQ-UHFFFAOYSA-N 5-bromo-2-[(4-methoxyphenyl)methyl]indazole Chemical compound C1=CC(OC)=CC=C1CN1N=C2C=CC(Br)=CC2=C1 DWWCFKBYGWPOTQ-UHFFFAOYSA-N 0.000 description 1
• CYJZJGYYTFQQBY-UHFFFAOYSA-N 5-bromoisoquinoline Chemical compound N1=CC=C2C(Br)=CC=CC2=C1 CYJZJGYYTFQQBY-UHFFFAOYSA-N 0.000 description 1
• NVKJOXRVEKMMHS-UHFFFAOYSA-N 5-nitro-1,2,4-triazol-3-one Chemical compound [O-][N+](=O)C1=NC(=O)N=N1 NVKJOXRVEKMMHS-UHFFFAOYSA-N 0.000 description 1
• WSGURAYTCUVDQL-UHFFFAOYSA-N 5-nitro-1h-indazole Chemical compound [O-][N+](=O)C1=CC=C2NN=CC2=C1 WSGURAYTCUVDQL-UHFFFAOYSA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-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
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
• KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
• 238000012935 Averaging Methods 0.000 description 1
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
• 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
• NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 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
• 102100034460 Cytosolic iron-sulfur assembly component 3 Human genes 0.000 description 1
• 101710095809 Cytosolic iron-sulfur assembly component 3 Proteins 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 1
• 206010016717 Fistula Diseases 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 108010024636 Glutathione Proteins 0.000 description 1
• JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
• 229920002683 Glycosaminoglycan Polymers 0.000 description 1
• 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
• 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
• 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
• 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
• PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
• QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
• 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
• 239000004166 Lanolin Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 1
• 206010029113 Neovascularisation Diseases 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
• 206010030043 Ocular hypertension Diseases 0.000 description 1
• 206010061323 Optic neuropathy Diseases 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 206010033372 Pain and discomfort Diseases 0.000 description 1
• 235000019482 Palm oil Nutrition 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• 229920001214 Polysorbate 60 Polymers 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• 208000035965 Postoperative Complications Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
• 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
• 229920002385 Sodium hyaluronate Polymers 0.000 description 1
• 229920002125 Sokalan® Polymers 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
• UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical class [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 229960004308 acetylcysteine Drugs 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 150000001266 acyl halides Chemical class 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 238000011360 adjunctive therapy Methods 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 238000005576 amination reaction Methods 0.000 description 1
• 229960003116 amyl nitrite Drugs 0.000 description 1
• 230000002491 angiogenic effect Effects 0.000 description 1
• 210000002159 anterior chamber Anatomy 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
• 230000002686 anti-diuretic effect Effects 0.000 description 1
• 230000001399 anti-metabolic effect Effects 0.000 description 1
• 229940124538 antidiuretic agent Drugs 0.000 description 1
• 239000003160 antidiuretic agent Substances 0.000 description 1
• 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 description 1
• 239000003080 antimitotic agent Substances 0.000 description 1
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
• 230000004509 aqueous humor production Effects 0.000 description 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
• MVXVYAKCVDQRLW-UHFFFAOYSA-N azain Natural products C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 1
• RVSPCRWXESLLJY-UHFFFAOYSA-N azane;1h-indazole Chemical class N.C1=CC=C2C=NNC2=C1 RVSPCRWXESLLJY-UHFFFAOYSA-N 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
• 229960001950 benzethonium chloride Drugs 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 239000002876 beta blocker Substances 0.000 description 1
• 229940097320 beta blocking agent Drugs 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
• 239000000227 bioadhesive Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 239000012888 bovine serum Substances 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
• 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
• CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
• 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
• 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 239000006143 cell culture medium Substances 0.000 description 1
• 230000009087 cell motility Effects 0.000 description 1
• 230000025611 cell-substrate adhesion Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 229960003260 chlorhexidine Drugs 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
• 238000004140 cleaning Methods 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 239000008139 complexing agent Substances 0.000 description 1
• 238000011109 contamination Methods 0.000 description 1
• 230000008602 contraction Effects 0.000 description 1
• 210000004087 cornea Anatomy 0.000 description 1
• 210000000399 corneal endothelial cell Anatomy 0.000 description 1
• 201000000159 corneal neovascularization Diseases 0.000 description 1
• 239000007819 coupling partner Substances 0.000 description 1
• 125000006165 cyclic alkyl group Chemical group 0.000 description 1
• 125000000000 cycloalkoxy group Chemical group 0.000 description 1
• 125000005357 cycloalkylalkynyl group Chemical group 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• 229960002433 cysteine Drugs 0.000 description 1
• 230000021953 cytokinesis Effects 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 238000007872 degassing Methods 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• GMLFPSKPTROTFV-UHFFFAOYSA-N dimethylborane Chemical compound CBC GMLFPSKPTROTFV-UHFFFAOYSA-N 0.000 description 1
• 230000008034 disappearance Effects 0.000 description 1
• WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 description 1
• CJYQQUPRURWLOW-YDLUHMIOSA-M dmsc Chemical compound [Na+].OP(=O)=O.OP(=O)=O.OP(=O)=O.[O-]P(=O)=O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O CJYQQUPRURWLOW-YDLUHMIOSA-M 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 239000008151 electrolyte solution Substances 0.000 description 1
• 229940021013 electrolyte solution Drugs 0.000 description 1
• 230000013020 embryo development Effects 0.000 description 1
• 230000003511 endothelial effect Effects 0.000 description 1
• 210000000871 endothelium corneal Anatomy 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 208000030533 eye disease Diseases 0.000 description 1
• 210000000744 eyelid Anatomy 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 239000012065 filter cake Substances 0.000 description 1
• 238000009093 first-line therapy Methods 0.000 description 1
• 230000003890 fistula Effects 0.000 description 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
• 238000002875 fluorescence polarization Methods 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 235000003969 glutathione Nutrition 0.000 description 1
• 229960003180 glutathione Drugs 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 125000005312 heteroarylalkynyl group Chemical group 0.000 description 1
• 125000004366 heterocycloalkenyl group Chemical group 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 230000001631 hypertensive effect Effects 0.000 description 1
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 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
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
• 229940011051 isopropyl acetate Drugs 0.000 description 1
• OSILBMSORKFRTB-UHFFFAOYSA-N isoquinolin-1-amine Chemical compound C1=CC=C2C(N)=NC=CC2=C1 OSILBMSORKFRTB-UHFFFAOYSA-N 0.000 description 1
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
• GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• GQWYWHOHRVVHAP-DHKPLNAMSA-N jaspamide Chemical compound C1([C@@H]2NC(=O)[C@@H](CC=3C4=CC=CC=C4NC=3Br)N(C)C(=O)[C@H](C)NC(=O)[C@@H](C)C/C(C)=C/[C@H](C)C[C@@H](OC(=O)C2)C)=CC=C(O)C=C1 GQWYWHOHRVVHAP-DHKPLNAMSA-N 0.000 description 1
• GQWYWHOHRVVHAP-UHFFFAOYSA-N jasplakinolide Natural products C1C(=O)OC(C)CC(C)C=C(C)CC(C)C(=O)NC(C)C(=O)N(C)C(CC=2C3=CC=CC=C3NC=2Br)C(=O)NC1C1=CC=C(O)C=C1 GQWYWHOHRVVHAP-UHFFFAOYSA-N 0.000 description 1
• 108010052440 jasplakinolide Proteins 0.000 description 1
• 238000000021 kinase assay Methods 0.000 description 1
• TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
• 235000019388 lanolin Nutrition 0.000 description 1
• 229940039717 lanolin Drugs 0.000 description 1
• NSHPHXHGRHSMIK-JRIKCGFMSA-N latrunculin B Chemical compound C([C@H]1[C@@]2(O)C[C@H]3C[C@H](O2)CC[C@@H](\C=C/CC\C(C)=C/C(=O)O3)C)SC(=O)N1 NSHPHXHGRHSMIK-JRIKCGFMSA-N 0.000 description 1
• NSHPHXHGRHSMIK-IWQSFCKSSA-N latrunculin B Natural products C[C@H]1CC[C@@H]2C[C@@H](C[C@@](O)(O2)[C@@H]3CSC(=O)N3)OC(=O)C=C(C)/CCC=C/1 NSHPHXHGRHSMIK-IWQSFCKSSA-N 0.000 description 1
• DDVBPZROPPMBLW-ZJBINBEQSA-N latrunculin a Chemical compound C([C@H]1[C@@]2(O)C[C@H]3C[C@H](O2)CC[C@@H](/C=C\C=C/CC\C(C)=C/C(=O)O3)C)SC(=O)N1 DDVBPZROPPMBLW-ZJBINBEQSA-N 0.000 description 1
• DDVBPZROPPMBLW-UHFFFAOYSA-N latrunculin-A Natural products O1C(=O)C=C(C)CCC=CC=CC(C)CCC(O2)CC1CC2(O)C1CSC(=O)N1 DDVBPZROPPMBLW-UHFFFAOYSA-N 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 231100001231 less toxic Toxicity 0.000 description 1
• 230000002197 limbic effect Effects 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 230000004904 long-term response Effects 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 238000013160 medical therapy Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical class C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
• 239000004005 microsphere Substances 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
• GLPNDMBVKNMSLG-UHFFFAOYSA-N n-(1-benzylazepan-4-yl)isoquinolin-5-amine Chemical compound C1CCC(NC=2C3=CC=NC=C3C=CC=2)CCN1CC1=CC=CC=C1 GLPNDMBVKNMSLG-UHFFFAOYSA-N 0.000 description 1
• DNUAUADEIBLJGT-UHFFFAOYSA-N n-(1-benzylpiperidin-3-yl)-1h-indazol-5-amine Chemical compound C1CCC(NC=2C=C3C=NNC3=CC=2)CN1CC1=CC=CC=C1 DNUAUADEIBLJGT-UHFFFAOYSA-N 0.000 description 1
• YRCNFZIFNSAAQU-UHFFFAOYSA-N n-(1-benzylpyrrolidin-3-yl)isoquinolin-5-amine Chemical compound C1CC(NC=2C3=CC=NC=C3C=CC=2)CN1CC1=CC=CC=C1 YRCNFZIFNSAAQU-UHFFFAOYSA-N 0.000 description 1
• FHLWBDTURRAKOU-HXUWFJFHSA-N n-[(3r)-1-[(2,4-dimethylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound CC1=CC(C)=CC=C1CN1C[C@H](NC=2C=C3C=NNC3=CC=2)CCC1 FHLWBDTURRAKOU-HXUWFJFHSA-N 0.000 description 1
• AISNTYHVCJKWMX-GOSISDBHSA-N n-[(3r)-1-[(4-bromophenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(Br)=CC=C1CN1C[C@H](NC=2C=C3C=NNC3=CC=2)CCC1 AISNTYHVCJKWMX-GOSISDBHSA-N 0.000 description 1
• GXRPIGJWZJONKF-HXUWFJFHSA-N n-[(3r)-1-[(4-ethylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(CC)=CC=C1CN1C[C@H](NC=2C=C3C=NNC3=CC=2)CCC1 GXRPIGJWZJONKF-HXUWFJFHSA-N 0.000 description 1
• JLWTUPLIJAHTKE-LJQANCHMSA-N n-[(3r)-1-[(4-methylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(C)=CC=C1CN1C[C@H](NC=2C=C3C=NNC3=CC=2)CCC1 JLWTUPLIJAHTKE-LJQANCHMSA-N 0.000 description 1
• UQCGQZYLCBENSJ-LJQANCHMSA-N n-[(3r)-1-[(4-methylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C1=CC(C)=CC=C1CN1C[C@H](NC=2C3=CC=NC=C3C=CC=2)CC1 UQCGQZYLCBENSJ-LJQANCHMSA-N 0.000 description 1
• DZCXFGNWECEITN-LLVKDONJSA-N n-[(3r)-piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1CCNC[C@@H]1NC1=CC=C(NN=C2)C2=C1 DZCXFGNWECEITN-LLVKDONJSA-N 0.000 description 1
• ALCJHEHAIODSCG-GFCCVEGCSA-N n-[(3r)-piperidin-3-yl]isoquinolin-5-amine Chemical compound C1CCNC[C@@H]1NC1=CC=CC2=CN=CC=C12 ALCJHEHAIODSCG-GFCCVEGCSA-N 0.000 description 1
• NVDYRDZHCINQQB-INIZCTEOSA-N n-[(3s)-1-[(3,4-difluorophenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=C(F)C(F)=CC=C1CN1C[C@@H](NC=2C=C3C=NNC3=CC=2)CCC1 NVDYRDZHCINQQB-INIZCTEOSA-N 0.000 description 1
• JQCWNEXLKSGUJQ-SFHVURJKSA-N n-[(3s)-1-[(4-chlorophenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(Cl)=CC=C1CN1C[C@@H](NC=2C=C3C=NNC3=CC=2)CCC1 JQCWNEXLKSGUJQ-SFHVURJKSA-N 0.000 description 1
• XHCMXEUIYRCOOX-IDMXKUIJSA-N n-[(3s)-piperidin-3-yl]-1h-indazol-5-amine;dihydrochloride Chemical compound Cl.Cl.C1CCNC[C@H]1NC1=CC=C(NN=C2)C2=C1 XHCMXEUIYRCOOX-IDMXKUIJSA-N 0.000 description 1
• ALCJHEHAIODSCG-LBPRGKRZSA-N n-[(3s)-piperidin-3-yl]isoquinolin-5-amine Chemical compound C1CCNC[C@H]1NC1=CC=CC2=CN=CC=C12 ALCJHEHAIODSCG-LBPRGKRZSA-N 0.000 description 1
• PLAYNEJTZXFWOI-UHFFFAOYSA-N n-[1-(1-benzofuran-5-ylmethyl)piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=C2OC=CC2=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 PLAYNEJTZXFWOI-UHFFFAOYSA-N 0.000 description 1
• PBHMZFQBWANQMI-UHFFFAOYSA-N n-[1-(1h-indol-5-ylmethyl)piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=C2NC=CC2=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 PBHMZFQBWANQMI-UHFFFAOYSA-N 0.000 description 1
• QNBWBURSLYDEDL-UHFFFAOYSA-N n-[1-(1h-indol-6-ylmethyl)piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=C2C=CNC2=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 QNBWBURSLYDEDL-UHFFFAOYSA-N 0.000 description 1
• SFATVUFGJJLYSY-UHFFFAOYSA-N n-[1-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)piperidin-3-yl]-1h-indazol-5-amine Chemical compound O1CCOC2=CC(CN3CC(CCC3)NC=3C=C4C=NNC4=CC=3)=CC=C21 SFATVUFGJJLYSY-UHFFFAOYSA-N 0.000 description 1
• FHLWBDTURRAKOU-UHFFFAOYSA-N n-[1-[(2,4-dimethylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound CC1=CC(C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 FHLWBDTURRAKOU-UHFFFAOYSA-N 0.000 description 1
• DJENEJYAILABCR-UHFFFAOYSA-N n-[1-[(2,5-dibromophenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound BrC1=CC=C(Br)C(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 DJENEJYAILABCR-UHFFFAOYSA-N 0.000 description 1
• XGAOBHWQHSZCKT-UHFFFAOYSA-N n-[1-[(2-methoxyphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound COC1=CC=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 XGAOBHWQHSZCKT-UHFFFAOYSA-N 0.000 description 1
• HMBSLPNVVKIQGR-UHFFFAOYSA-N n-[1-[(3,4-dichlorophenyl)methyl]piperidin-3-yl]isoquinolin-5-amine Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1CC(NC=2C3=CC=NC=C3C=CC=2)CCC1 HMBSLPNVVKIQGR-UHFFFAOYSA-N 0.000 description 1
• DMPFVMAOEFGDNT-UHFFFAOYSA-N n-[1-[(3,4-dichlorophenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1CC(NC=2C3=CC=NC=C3C=CC=2)CC1 DMPFVMAOEFGDNT-UHFFFAOYSA-N 0.000 description 1
• UXMYPZHYVIRZFL-UHFFFAOYSA-N n-[1-[(3-amino-4-chlorophenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=C(Cl)C(N)=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 UXMYPZHYVIRZFL-UHFFFAOYSA-N 0.000 description 1
• RKFCSIVIFMVTFQ-UHFFFAOYSA-N n-[1-[(3-bromophenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound BrC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 RKFCSIVIFMVTFQ-UHFFFAOYSA-N 0.000 description 1
• SXUKHUQRLXBBJH-UHFFFAOYSA-N n-[1-[(3-ethoxyphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound CCOC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 SXUKHUQRLXBBJH-UHFFFAOYSA-N 0.000 description 1
• MCOKCTAPEUYJLT-UHFFFAOYSA-N n-[1-[(4-butylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(CCCC)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 MCOKCTAPEUYJLT-UHFFFAOYSA-N 0.000 description 1
• CINLZTAGAYPKGA-UHFFFAOYSA-N n-[1-[(4-methoxyphenyl)methyl]piperidin-3-yl]isoquinolin-5-amine Chemical compound C1=CC(OC)=CC=C1CN1CC(NC=2C3=CC=NC=C3C=CC=2)CCC1 CINLZTAGAYPKGA-UHFFFAOYSA-N 0.000 description 1
• XOHJYOXUEUCFEV-UHFFFAOYSA-N n-[1-[(4-phenylphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1CCC(NC=2C=C3C=NNC3=CC=2)CN1CC(C=C1)=CC=C1C1=CC=CC=C1 XOHJYOXUEUCFEV-UHFFFAOYSA-N 0.000 description 1
• HIYQICVQFRZMAK-UHFFFAOYSA-N n-[1-[(4-propan-2-yloxyphenyl)methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(OC(C)C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 HIYQICVQFRZMAK-UHFFFAOYSA-N 0.000 description 1
• QUPJHUJXKHEQKC-UHFFFAOYSA-N n-[1-[[3-(4-chlorophenoxy)phenyl]methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(Cl)=CC=C1OC1=CC=CC(CN2CC(CCC2)NC=2C=C3C=NNC3=CC=2)=C1 QUPJHUJXKHEQKC-UHFFFAOYSA-N 0.000 description 1
• SSRBFIKGFONJBY-UHFFFAOYSA-N n-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrrolidin-3-yl]isoquinolin-5-amine Chemical compound FC(F)(F)C1=CC=CC(CN2CC(CC2)NC=2C3=CC=NC=C3C=CC=2)=C1 SSRBFIKGFONJBY-UHFFFAOYSA-N 0.000 description 1
• IISNQHYBSOMGPJ-UHFFFAOYSA-N n-[1-[[4-(dimethylamino)phenyl]methyl]piperidin-3-yl]-1h-indazol-5-amine Chemical compound C1=CC(N(C)C)=CC=C1CN1CC(NC=2C=C3C=NNC3=CC=2)CCC1 IISNQHYBSOMGPJ-UHFFFAOYSA-N 0.000 description 1
• JVACKTOSODNYNH-HXUWFJFHSA-N n-[3-[[(3r)-3-(isoquinolin-5-ylamino)piperidin-1-yl]methyl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(CN2C[C@@H](CCC2)NC=2C3=CC=NC=C3C=CC=2)=C1 JVACKTOSODNYNH-HXUWFJFHSA-N 0.000 description 1
• ZRMHZVWQKSOWAN-LJQANCHMSA-N n-[3-[[(3r)-3-(isoquinolin-5-ylamino)pyrrolidin-1-yl]methyl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(CN2C[C@@H](CC2)NC=2C3=CC=NC=C3C=CC=2)=C1 ZRMHZVWQKSOWAN-LJQANCHMSA-N 0.000 description 1
• CSDTZUBPSYWZDX-UHFFFAOYSA-N n-pentyl nitrite Chemical compound CCCCCON=O CSDTZUBPSYWZDX-UHFFFAOYSA-N 0.000 description 1
• GIRTZPHCSWNEBN-UHFFFAOYSA-N n-piperidin-3-ylpyridin-4-amine Chemical compound C1CCNCC1NC1=CC=NC=C1 GIRTZPHCSWNEBN-UHFFFAOYSA-N 0.000 description 1
• 230000017074 necrotic cell death Effects 0.000 description 1
• 238000011587 new zealand white rabbit Methods 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 230000004493 normal intraocular pressure Effects 0.000 description 1
• 229920002113 octoxynol Polymers 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000002357 osmotic agent Substances 0.000 description 1
• 230000008723 osmotic stress Effects 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-O oxonium Chemical compound [OH3+] XLYOFNOQVPJJNP-UHFFFAOYSA-O 0.000 description 1
• 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 239000002540 palm oil Substances 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000001991 pathophysiological effect Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 239000003209 petroleum derivative Substances 0.000 description 1
• 238000002733 pharmacodynamic assay Methods 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 238000002732 pharmacokinetic assay Methods 0.000 description 1
• 239000002831 pharmacologic agent Substances 0.000 description 1
• 229950000688 phenothiazine Drugs 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 125000001095 phosphatidyl group Chemical group 0.000 description 1
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
• 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 150000003020 phtalazines Chemical class 0.000 description 1
• 230000035479 physiological effects, processes and functions Effects 0.000 description 1
• 229920001983 poloxamer Polymers 0.000 description 1
• 229920000570 polyether Polymers 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
• 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 229940068977 polysorbate 20 Drugs 0.000 description 1
• 229940113124 polysorbate 60 Drugs 0.000 description 1
• 229940068968 polysorbate 80 Drugs 0.000 description 1
• 229920000053 polysorbate 80 Polymers 0.000 description 1
• 229940068965 polysorbates Drugs 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 239000001103 potassium chloride Substances 0.000 description 1
• 235000011164 potassium chloride Nutrition 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 229940069328 povidone Drugs 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 238000011533 pre-incubation Methods 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 150000003180 prostaglandins Chemical class 0.000 description 1
• 230000009979 protective mechanism Effects 0.000 description 1
• 239000003909 protein kinase inhibitor Substances 0.000 description 1
• CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
• 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000008521 reorganization Effects 0.000 description 1
• 230000001850 reproductive effect Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 230000002207 retinal effect Effects 0.000 description 1
• 230000004233 retinal vasculature Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 230000036573 scar formation Effects 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
• 230000004905 short-term response Effects 0.000 description 1
• 238000010898 silica gel chromatography Methods 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 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 1
• 210000002460 smooth muscle Anatomy 0.000 description 1
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
• 229940010747 sodium hyaluronate Drugs 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
• 238000000638 solvent extraction Methods 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 229910001220 stainless steel Inorganic materials 0.000 description 1
• 239000010935 stainless steel Substances 0.000 description 1
• 235000011150 stannous chloride Nutrition 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 210000003518 stress fiber Anatomy 0.000 description 1
• 125000005017 substituted alkenyl group Chemical group 0.000 description 1
• 125000004426 substituted alkynyl group Chemical group 0.000 description 1
• 150000003461 sulfonyl halides Chemical class 0.000 description 1
• RJVBVECTCMRNFG-ANKJNSLFSA-N swinholide a Chemical compound C1[C@H](OC)C[C@H](C)O[C@H]1CC[C@H](C)[C@H](O)[C@H](C)[C@@H]1[C@@H](C)[C@H](O)C[C@H](O)[C@H](C)[C@@H](OC)C[C@H](CC=C2)O[C@@H]2C[C@@H](O)C/C=C(\C)/C=C/C(=O)O[C@H]([C@@H](C)[C@@H](O)[C@@H](C)CC[C@@H]2O[C@@H](C)C[C@H](C2)OC)[C@@H](C)[C@H](O)C[C@H](O)[C@H](C)[C@@H](OC)C[C@H](CC=C2)O[C@@H]2C[C@@H](O)C/C=C(\C)/C=C/C(=O)O1 RJVBVECTCMRNFG-ANKJNSLFSA-N 0.000 description 1
• GDACDJNQZCXLNU-UHFFFAOYSA-N swinholide-A Natural products C1C(OC)CC(C)OC1CCC(C)C(O)C(C)C1C(C)C(O)CC(O)C(C)C(OC)CC(CC=C2)OC2CC(O)CC=C(C)C=CC(=O)O1 GDACDJNQZCXLNU-UHFFFAOYSA-N 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• AKQXKEBCONUWCL-QMMMGPOBSA-N tert-butyl (3s)-3-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H](N)C1 AKQXKEBCONUWCL-QMMMGPOBSA-N 0.000 description 1
• JOIBKJXPUBQJSB-UHFFFAOYSA-N tert-butyl 3-[4-(4-amino-1,2,5-oxadiazol-3-yl)anilino]piperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC1NC1=CC=C(C=2C(=NON=2)N)C=C1 JOIBKJXPUBQJSB-UHFFFAOYSA-N 0.000 description 1
• PMLBUVZPRKXMOX-UHFFFAOYSA-N tert-butyl 4-oxoazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(=O)CC1 PMLBUVZPRKXMOX-UHFFFAOYSA-N 0.000 description 1
• RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 1
• JGVWCANSWKRBCS-UHFFFAOYSA-N tetramethylrhodamine thiocyanate Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(SC#N)C=C1C(O)=O JGVWCANSWKRBCS-UHFFFAOYSA-N 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
• 229940033663 thimerosal Drugs 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
• 239000011732 tocopherol Substances 0.000 description 1
• 229930003799 tocopherol Natural products 0.000 description 1
• 235000019149 tocopherols Nutrition 0.000 description 1
• 239000012049 topical pharmaceutical composition Substances 0.000 description 1
• 230000002110 toxicologic effect Effects 0.000 description 1
• 231100000759 toxicological effect Toxicity 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• 150000008648 triflates Chemical class 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 230000002666 vasoprotective effect Effects 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000003871 white petrolatum Substances 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1