ZA200603463B

ZA200603463B - Cytokine inhibitory druugs for treatment of macular degeneration

Cytokine inhibitory druugs for treatment of macular degeneration Download PDF

Info

Publication number: ZA200603463B
Authority: ZA; South Africa
Prior art keywords: carbon atoms; alkyl; substituted; amino; unsubstituted
Prior art date: 2003-10-30

Application number

ZA200603463A

Other languages

English (en)

Inventor

Jerome B Zeldis

Original Assignee

Celgene Corp

Priority date

2003-10-30

Filing date

2004-04-28

Publication date

2007-09-26

2004-04-28 Application filed by Celgene Corp filed Critical Celgene Corp

2007-09-26 Publication of ZA200603463B publication Critical patent/ZA200603463B/en

Links

230000002401 inhibitory effect Effects 0.000 title claims description 134
102000004127 Cytokines Human genes 0.000 title claims description 133
108090000695 Cytokines Proteins 0.000 title claims description 133
208000002780 macular degeneration Diseases 0.000 title claims description 114
238000011282 treatment Methods 0.000 title description 26
125000004432 carbon atom Chemical group C* 0.000 claims description 505
125000000217 alkyl group Chemical group 0.000 claims description 347
-1 carbethoxy, carbomethoxy, carbopropoxy, acetyl Chemical group 0.000 claims description 330
239000003814 drug Substances 0.000 claims description 171
125000003545 alkoxy group Chemical group 0.000 claims description 162
125000004093 cyano group Chemical group *C#N 0.000 claims description 148
229940079593 drug Drugs 0.000 claims description 143
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 128
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 126
125000005843 halogen group Chemical group 0.000 claims description 122
229910052739 hydrogen Inorganic materials 0.000 claims description 122
239000001257 hydrogen Substances 0.000 claims description 118
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 118
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 117
150000001875 compounds Chemical class 0.000 claims description 112
125000001424 substituent group Chemical group 0.000 claims description 92
150000002431 hydrogen Chemical group 0.000 claims description 68
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 65
150000003839 salts Chemical class 0.000 claims description 62
125000000753 cycloalkyl group Chemical group 0.000 claims description 59
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 58
239000012453 solvate Substances 0.000 claims description 50
238000000034 method Methods 0.000 claims description 44
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 34
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 34
125000003118 aryl group Chemical group 0.000 claims description 34
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 30
125000000623 heterocyclic group Chemical group 0.000 claims description 27
125000003282 alkyl amino group Chemical group 0.000 claims description 26
125000004076 pyridyl group Chemical group 0.000 claims description 25
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 24
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
229910052736 halogen Inorganic materials 0.000 claims description 21
238000002360 preparation method Methods 0.000 claims description 21
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 20
125000004122 cyclic group Chemical group 0.000 claims description 20
150000002367 halogens Chemical class 0.000 claims description 20
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 18
229930192474 thiophene Natural products 0.000 claims description 18
229910052799 carbon Inorganic materials 0.000 claims description 17
125000000000 cycloalkoxy group Chemical group 0.000 claims description 17
125000001624 naphthyl group Chemical group 0.000 claims description 17
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 16
XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 16
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 14
239000005977 Ethylene Substances 0.000 claims description 14
125000004442 acylamino group Chemical group 0.000 claims description 14
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 14
DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 14
125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 13
125000004663 dialkyl amino group Chemical group 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
229940080818 propionamide Drugs 0.000 claims description 11
239000002253 acid Substances 0.000 claims description 10
125000001118 alkylidene group Chemical group 0.000 claims description 10
150000001602 bicycloalkyls Chemical group 0.000 claims description 10
125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 9
FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 8
SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical compound C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 claims description 8
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 8
239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 8
125000005592 polycycloalkyl group Polymers 0.000 claims description 8
150000001721 carbon Chemical group 0.000 claims description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
125000002252 acyl group Chemical group 0.000 claims description 6
125000003277 amino group Chemical group 0.000 claims description 6
125000005605 benzo group Chemical group 0.000 claims description 6
229910052792 caesium Inorganic materials 0.000 claims description 6
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 6
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical group C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
125000000168 pyrrolyl group Chemical group 0.000 claims description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 4
125000004450 alkenylene group Chemical group 0.000 claims description 4
125000004702 alkoxy alkyl carbonyl group Chemical group 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 4
125000005293 bicycloalkoxy group Chemical group 0.000 claims description 4
125000001589 carboacyl group Chemical group 0.000 claims description 4
229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
125000005724 cycloalkenylene group Chemical group 0.000 claims description 4
125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 4
125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 4
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
150000003222 pyridines Chemical class 0.000 claims description 4
125000000547 substituted alkyl group Chemical group 0.000 claims description 4
NTWLARBDJFXJNZ-UHFFFAOYSA-N 2-[1-(3,4-dimethoxyphenyl)-3-hydroxypropyl]isoindole-1,3-dione Chemical compound C1=C(OC)C(OC)=CC=C1C(CCO)N1C(=O)C2=CC=CC=C2C1=O NTWLARBDJFXJNZ-UHFFFAOYSA-N 0.000 claims description 3
240000007594 Oryza sativa Species 0.000 claims description 3
RKUKMEJKLRORIR-UHFFFAOYSA-N [[3-(1,3-dioxoisoindol-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoyl]amino] propanoate Chemical compound C1=C(OC)C(OCC)=CC(C(CC(=O)NOC(=O)CC)N2C(C3=CC=CC=C3C2=O)=O)=C1 RKUKMEJKLRORIR-UHFFFAOYSA-N 0.000 claims description 3
125000002993 cycloalkylene group Chemical group 0.000 claims description 3
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical group C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 claims description 3
YENYTUWIKANDNM-UHFFFAOYSA-N n-[3-amino-3-(3,4-dimethoxyphenyl)propanoyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(N)CC(=O)NC(=O)C1=CC=CC=C1 YENYTUWIKANDNM-UHFFFAOYSA-N 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
FACSMBGYDORUJJ-SFHVURJKSA-N 2-(dimethylamino)-n-[2-[(1r)-1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound C1=C(OC)C(OCC)=CC([C@H](CS(C)(=O)=O)N2C(C3=C(NC(=O)CN(C)C)C=CC=C3C2=O)=O)=C1 FACSMBGYDORUJJ-SFHVURJKSA-N 0.000 claims description 2
GODXRDNLVMRFSG-UHFFFAOYSA-N 2-[1-(3,4-dimethoxyphenyl)propan-2-yl]isoindole-1,3-dione Chemical compound C1=C(OC)C(OC)=CC=C1CC(C)N1C(=O)C2=CC=CC=C2C1=O GODXRDNLVMRFSG-UHFFFAOYSA-N 0.000 claims description 2
HPNGOUOSHMENJP-UHFFFAOYSA-N 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-(1h-pyrrol-2-ylmethyl)isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(CC=4NC=CC=4)C=CC=C3C2=O)=O)=C1 HPNGOUOSHMENJP-UHFFFAOYSA-N 0.000 claims description 2
AUYSFUSWFJUKMJ-UHFFFAOYSA-N 2-[1-(3-ethoxy-4-methoxyphenyl)-3-oxobutyl]-4-(1h-pyrrol-2-yl)isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CC(C)=O)N2C(C3=C(C=4NC=CC=4)C=CC=C3C2=O)=O)=C1 AUYSFUSWFJUKMJ-UHFFFAOYSA-N 0.000 claims description 2
KVBKXXOHQDLRLG-UHFFFAOYSA-N 2-chloro-n-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(NC(=O)CCl)C=CC=C3C2=O)=O)=C1 KVBKXXOHQDLRLG-UHFFFAOYSA-N 0.000 claims description 2
DZMANEJEPAEVPF-UHFFFAOYSA-N 3,3-bis(3,4-dimethoxyphenyl)prop-2-enenitrile Chemical compound C1=C(OC)C(OC)=CC=C1C(=CC#N)C1=CC=C(OC)C(OC)=C1 DZMANEJEPAEVPF-UHFFFAOYSA-N 0.000 claims description 2
QKHSAVPFILQVGW-UHFFFAOYSA-N 4,5-diamino-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(N)C(N)=CC=C3C2=O)=O)=C1 QKHSAVPFILQVGW-UHFFFAOYSA-N 0.000 claims description 2
HEWRXBRDIAUSKW-UHFFFAOYSA-N 4-amino-2-[1-(3-ethoxy-4-methoxyphenyl)-3-oxobutyl]isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CC(C)=O)N2C(C3=C(N)C=CC=C3C2=O)=O)=C1 HEWRXBRDIAUSKW-UHFFFAOYSA-N 0.000 claims description 2
PAOZAMACNXMCIB-UHFFFAOYSA-N N-[2-[1-(3,4-dimethoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]cyclopropanecarboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C(CS(C)(=O)=O)N1C(=O)C2=C(NC(=O)C3CC3)C=CC=C2C1=O PAOZAMACNXMCIB-UHFFFAOYSA-N 0.000 claims description 2
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 2
125000001980 alanyl group Chemical group 0.000 claims description 2
150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
125000004849 alkoxymethyl group Chemical group 0.000 claims description 2
125000000304 alkynyl group Chemical group 0.000 claims description 2
125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 2
125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims description 2
125000002883 imidazolyl group Chemical group 0.000 claims description 2
125000001041 indolyl group Chemical group 0.000 claims description 2
125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 claims description 2
229950003188 isovaleryl diethylamide Drugs 0.000 claims description 2
125000001998 leucyl group Chemical group 0.000 claims description 2
125000001288 lysyl group Chemical group 0.000 claims description 2
125000002073 methionyl group Chemical group 0.000 claims description 2
MQRUNQYIJQXVLP-PQJIZZRHSA-N n-[2-[(1r)-1-(3-ethoxy-4-methoxyphenyl)-3-hydroxybutyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CC(C)O)N2C(C3=C(NC(C)=O)C=CC=C3C2=O)=O)=C1 MQRUNQYIJQXVLP-PQJIZZRHSA-N 0.000 claims description 2
HHSCRXUCPLPVQX-GOSISDBHSA-N n-[2-[(1r)-1-(3-ethoxy-4-methoxyphenyl)-3-oxobutyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CC(C)=O)N2C(C3=C(NC(C)=O)C=CC=C3C2=O)=O)=C1 HHSCRXUCPLPVQX-GOSISDBHSA-N 0.000 claims description 2
CZVNIGALSIBARE-GOSISDBHSA-N n-[2-[(1s)-1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]cyclopropanecarboxamide Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CS(C)(=O)=O)N2C(C3=C(NC(=O)C4CC4)C=CC=C3C2=O)=O)=C1 CZVNIGALSIBARE-GOSISDBHSA-N 0.000 claims description 2
JKJDMNWLHGJEDK-UHFFFAOYSA-N n-[2-[1-(3,4-dimethoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]-2-(dimethylamino)acetamide Chemical compound C1=C(OC)C(OC)=CC=C1C(CS(C)(=O)=O)N1C(=O)C2=C(NC(=O)CN(C)C)C=CC=C2C1=O JKJDMNWLHGJEDK-UHFFFAOYSA-N 0.000 claims description 2
HTMFPTFPZHDRKM-UHFFFAOYSA-N n-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]-2,2,2-trifluoroacetamide Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(NC(=O)C(F)(F)F)C=CC=C3C2=O)=O)=C1 HTMFPTFPZHDRKM-UHFFFAOYSA-N 0.000 claims description 2
HHSCRXUCPLPVQX-UHFFFAOYSA-N n-[2-[1-(3-ethoxy-4-methoxyphenyl)-3-oxobutyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound C1=C(OC)C(OCC)=CC(C(CC(C)=O)N2C(C3=C(NC(C)=O)C=CC=C3C2=O)=O)=C1 HHSCRXUCPLPVQX-UHFFFAOYSA-N 0.000 claims description 2
150000002790 naphthalenes Chemical class 0.000 claims description 2
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 2
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
230000005588 protonation Effects 0.000 claims description 2
150000003235 pyrrolidines Chemical class 0.000 claims description 2
125000005493 quinolyl group Chemical group 0.000 claims description 2
125000002072 seryl group Chemical group 0.000 claims description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
150000003577 thiophenes Chemical class 0.000 claims description 2
125000001239 threonyl group Chemical group 0.000 claims description 2
125000001425 triazolyl group Chemical group 0.000 claims description 2
125000002233 tyrosyl group Chemical group 0.000 claims description 2
125000002114 valyl group Chemical group 0.000 claims description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
229920002554 vinyl polymer Polymers 0.000 claims description 2
GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims 1
ZTBBGZCPPYWHIZ-LJQANCHMSA-N 2-(dimethylamino)-n-[2-[(1r)-1-(3-ethoxy-4-methoxyphenyl)-3-oxobutyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CC(C)=O)N2C(C3=C(NC(=O)CN(C)C)C=CC=C3C2=O)=O)=C1 ZTBBGZCPPYWHIZ-LJQANCHMSA-N 0.000 claims 1
FACSMBGYDORUJJ-GOSISDBHSA-N 2-(dimethylamino)-n-[2-[(1s)-1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CS(C)(=O)=O)N2C(C3=C(NC(=O)CN(C)C)C=CC=C3C2=O)=O)=C1 FACSMBGYDORUJJ-GOSISDBHSA-N 0.000 claims 1
RJNHBBSGPDOAND-UHFFFAOYSA-N 2-(dimethylamino)-n-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]propanamide Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(NC(=O)C(C)N(C)C)C=CC=C3C2=O)=O)=C1 RJNHBBSGPDOAND-UHFFFAOYSA-N 0.000 claims 1
ZTBBGZCPPYWHIZ-UHFFFAOYSA-N 2-(dimethylamino)-n-[2-[1-(3-ethoxy-4-methoxyphenyl)-3-oxobutyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound C1=C(OC)C(OCC)=CC(C(CC(C)=O)N2C(C3=C(NC(=O)CN(C)C)C=CC=C3C2=O)=O)=C1 ZTBBGZCPPYWHIZ-UHFFFAOYSA-N 0.000 claims 1
AUVWUWFCGQNERQ-UHFFFAOYSA-N 2-[1-(3,4-dimethoxyphenyl)-2-methylsulfonylethyl]-4-(1h-pyrrol-2-yl)isoindole-1,3-dione Chemical compound C1=C(OC)C(OC)=CC=C1C(CS(C)(=O)=O)N1C(=O)C2=C(C=3NC=CC=3)C=CC=C2C1=O AUVWUWFCGQNERQ-UHFFFAOYSA-N 0.000 claims 1
LKEVYMKDZMOTIM-UHFFFAOYSA-N 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=CC=CC=C3C2=O)=O)=C1 LKEVYMKDZMOTIM-UHFFFAOYSA-N 0.000 claims 1
FFOXNTUNASQTMG-UHFFFAOYSA-N 2-amino-n-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(NC(=O)CN)C=CC=C3C2=O)=O)=C1 FFOXNTUNASQTMG-UHFFFAOYSA-N 0.000 claims 1
RREPAJHHRAPCQP-UHFFFAOYSA-N 2-chloro-n-[2-[1-(3-ethoxy-4-methoxyphenyl)-3-oxobutyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound C1=C(OC)C(OCC)=CC(C(CC(C)=O)N2C(C3=C(NC(=O)CCl)C=CC=C3C2=O)=O)=C1 RREPAJHHRAPCQP-UHFFFAOYSA-N 0.000 claims 1
JSLPDEPKIWZVKP-UHFFFAOYSA-N 4-[3-[(dimethylamino)methyl]-1h-pyrrol-2-yl]-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(C4=C(C=CN4)CN(C)C)C=CC=C3C2=O)=O)=C1 JSLPDEPKIWZVKP-UHFFFAOYSA-N 0.000 claims 1
AUYSFUSWFJUKMJ-HXUWFJFHSA-N C(C)OC=1C=C(C=CC=1OC)[C@@H](CC(C)=O)N1C(C2=CC=CC(=C2C1=O)C=1NC=CC=1)=O Chemical compound C(C)OC=1C=C(C=CC=1OC)[C@@H](CC(C)=O)N1C(C2=CC=CC(=C2C1=O)C=1NC=CC=1)=O AUYSFUSWFJUKMJ-HXUWFJFHSA-N 0.000 claims 1
101150065749 Churc1 gene Proteins 0.000 claims 1
GFUVTYHCYYMDMO-UHFFFAOYSA-N N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]cyclopentanecarboxamide Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(NC(=O)C4CCCC4)C=CC=C3C2=O)=O)=C1 GFUVTYHCYYMDMO-UHFFFAOYSA-N 0.000 claims 1
102100038239 Protein Churchill Human genes 0.000 claims 1
OKTJSMMVPCPJKN-YPZZEJLDSA-N carbon-10 atom Chemical group [10C] OKTJSMMVPCPJKN-YPZZEJLDSA-N 0.000 claims 1
MQRUNQYIJQXVLP-UHFFFAOYSA-N n-[2-[1-(3-ethoxy-4-methoxyphenyl)-3-hydroxybutyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound C1=C(OC)C(OCC)=CC(C(CC(C)O)N2C(C3=C(NC(C)=O)C=CC=C3C2=O)=O)=C1 MQRUNQYIJQXVLP-UHFFFAOYSA-N 0.000 claims 1
239000013543 active substance Substances 0.000 description 65
239000002552 dosage form Substances 0.000 description 56
239000000203 mixture Substances 0.000 description 38
239000008194 pharmaceutical composition Substances 0.000 description 33
239000000651 prodrug Substances 0.000 description 32
229940002612 prodrug Drugs 0.000 description 32
239000000546 pharmaceutical excipient Substances 0.000 description 19
210000003583 retinal pigment epithelium Anatomy 0.000 description 14
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 12
230000000694 effects Effects 0.000 description 12
ZQFGRJWRSLZCSQ-ZSFNYQMMSA-N verteporfin Chemical compound C=1C([C@@]2([C@H](C(=O)OC)C(=CC=C22)C(=O)OC)C)=NC2=CC(C(=C2C=C)C)=NC2=CC(C(=C2CCC(O)=O)C)=NC2=CC2=NC=1C(C)=C2CCC(=O)OC ZQFGRJWRSLZCSQ-ZSFNYQMMSA-N 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
239000003795 chemical substances by application Substances 0.000 description 11
201000010099 disease Diseases 0.000 description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
238000011477 surgical intervention Methods 0.000 description 11
208000024891 symptom Diseases 0.000 description 11
229960003895 verteporfin Drugs 0.000 description 11
206010064930 age-related macular degeneration Diseases 0.000 description 10
150000003431 steroids Chemical class 0.000 description 10
239000003826 tablet Substances 0.000 description 10
238000013270 controlled release Methods 0.000 description 9
238000009472 formulation Methods 0.000 description 9
239000007924 injection Substances 0.000 description 9
238000002347 injection Methods 0.000 description 9
210000001525 retina Anatomy 0.000 description 9
238000002560 therapeutic procedure Methods 0.000 description 9
229920000168 Microcrystalline cellulose Polymers 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
239000007884 disintegrant Substances 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
229940016286 microcrystalline cellulose Drugs 0.000 description 8
235000019813 microcrystalline cellulose Nutrition 0.000 description 8
239000008108 microcrystalline cellulose Substances 0.000 description 8
239000006186 oral dosage form Substances 0.000 description 8
239000006201 parenteral dosage form Substances 0.000 description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
206010025421 Macule Diseases 0.000 description 7
229920002472 Starch Polymers 0.000 description 7
230000003527 anti-angiogenesis Effects 0.000 description 7
239000003963 antioxidant agent Substances 0.000 description 7
235000006708 antioxidants Nutrition 0.000 description 7
239000002585 base Substances 0.000 description 7
210000004204 blood vessel Anatomy 0.000 description 7
238000002647 laser therapy Methods 0.000 description 7
238000004519 manufacturing process Methods 0.000 description 7
230000000649 photocoagulation Effects 0.000 description 7
238000001126 phototherapy Methods 0.000 description 7
239000007787 solid Substances 0.000 description 7
235000019698 starch Nutrition 0.000 description 7
210000001519 tissue Anatomy 0.000 description 7
102000014150 Interferons Human genes 0.000 description 6
108010050904 Interferons Proteins 0.000 description 6
206010029113 Neovascularisation Diseases 0.000 description 6
239000003242 anti bacterial agent Substances 0.000 description 6
230000003110 anti-inflammatory effect Effects 0.000 description 6
239000011230 binding agent Substances 0.000 description 6
230000002354 daily effect Effects 0.000 description 6
235000019441 ethanol Nutrition 0.000 description 6
239000000122 growth hormone Substances 0.000 description 6
150000004677 hydrates Chemical class 0.000 description 6
102000006495 integrins Human genes 0.000 description 6
108010044426 integrins Proteins 0.000 description 6
239000000314 lubricant Substances 0.000 description 6
239000003075 phytoestrogen Substances 0.000 description 6
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 6
235000019260 propionic acid Nutrition 0.000 description 6
150000003180 prostaglandins Chemical class 0.000 description 6
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 6
239000003981 vehicle Substances 0.000 description 6
230000004393 visual impairment Effects 0.000 description 6
LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 5
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
102100040247 Tumor necrosis factor Human genes 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
239000002775 capsule Substances 0.000 description 5
ZQSIJRDFPHDXIC-UHFFFAOYSA-N daidzein Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(O)=CC=C2C1=O ZQSIJRDFPHDXIC-UHFFFAOYSA-N 0.000 description 5
239000000839 emulsion Substances 0.000 description 5
210000001508 eye Anatomy 0.000 description 5
150000003949 imides Chemical class 0.000 description 5
238000000338 in vitro Methods 0.000 description 5
239000007788 liquid Substances 0.000 description 5
IMOZEMNVLZVGJZ-UHFFFAOYSA-N n-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(NC(C)=O)C=CC=C3C2=O)=O)=C1 IMOZEMNVLZVGJZ-UHFFFAOYSA-N 0.000 description 5
238000002428 photodynamic therapy Methods 0.000 description 5
230000001225 therapeutic effect Effects 0.000 description 5
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 4
201000004569 Blindness Diseases 0.000 description 4
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
101150015280 Cel gene Proteins 0.000 description 4
206010060823 Choroidal neovascularisation Diseases 0.000 description 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
229920000881 Modified starch Polymers 0.000 description 4
239000008156 Ringer's lactate solution Substances 0.000 description 4
230000009471 action Effects 0.000 description 4
239000000443 aerosol Substances 0.000 description 4
235000010443 alginic acid Nutrition 0.000 description 4
229920000615 alginic acid Polymers 0.000 description 4
229920000180 alkyd Polymers 0.000 description 4
125000003368 amide group Chemical group 0.000 description 4
230000003078 antioxidant effect Effects 0.000 description 4
SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 4
239000007894 caplet Substances 0.000 description 4
238000011443 conventional therapy Methods 0.000 description 4
150000003950 cyclic amides Chemical class 0.000 description 4
239000000945 filler Substances 0.000 description 4
239000000499 gel Substances 0.000 description 4
ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 description 4
OZBAVEKZGSOMOJ-MIUGBVLSSA-N glycitin Chemical compound COC1=CC(C(C(C=2C=CC(O)=CC=2)=CO2)=O)=C2C=C1O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O OZBAVEKZGSOMOJ-MIUGBVLSSA-N 0.000 description 4
239000008187 granular material Substances 0.000 description 4
229960001375 lactose Drugs 0.000 description 4
239000008101 lactose Substances 0.000 description 4
238000002430 laser surgery Methods 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
239000003921 oil Substances 0.000 description 4
238000007911 parenteral administration Methods 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
239000000843 powder Substances 0.000 description 4
230000000069 prophylactic effect Effects 0.000 description 4
230000002207 retinal effect Effects 0.000 description 4
239000000243 solution Substances 0.000 description 4
238000003860 storage Methods 0.000 description 4
208000011580 syndromic disease Diseases 0.000 description 4
230000000699 topical effect Effects 0.000 description 4
DHKAFTYWTCIWJX-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-3-(3-oxo-1h-isoindol-2-yl)propanamide Chemical compound C1=C(OC)C(OC)=CC=C1C(CC(N)=O)N1C(=O)C2=CC=CC=C2C1 DHKAFTYWTCIWJX-UHFFFAOYSA-N 0.000 description 3
HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
206010003694 Atrophy Diseases 0.000 description 3
GMTUGPYJRUMVTC-UHFFFAOYSA-N Daidzin Natural products OC(COc1ccc2C(=O)C(=COc2c1)c3ccc(O)cc3)C(O)C(O)C(O)C=O GMTUGPYJRUMVTC-UHFFFAOYSA-N 0.000 description 3
KYQZWONCHDNPDP-UHFFFAOYSA-N Daidzoside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 KYQZWONCHDNPDP-UHFFFAOYSA-N 0.000 description 3
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
ZCOLJUOHXJRHDI-FZHKGVQDSA-N Genistein 7-O-glucoside Natural products O([C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1)c1cc(O)c2C(=O)C(c3ccc(O)cc3)=COc2c1 ZCOLJUOHXJRHDI-FZHKGVQDSA-N 0.000 description 3
CJPNHKPXZYYCME-UHFFFAOYSA-N Genistin Natural products OCC1OC(Oc2ccc(O)c3OC(=CC(=O)c23)c4ccc(O)cc4)C(O)C(O)C1O CJPNHKPXZYYCME-UHFFFAOYSA-N 0.000 description 3
102000018997 Growth Hormone Human genes 0.000 description 3
108010051696 Growth Hormone Proteins 0.000 description 3
150000007945 N-acyl ureas Chemical class 0.000 description 3
YCUNGEJJOMKCGZ-UHFFFAOYSA-N Pallidiflorin Natural products C1=CC(OC)=CC=C1C1=COC2=CC=CC(O)=C2C1=O YCUNGEJJOMKCGZ-UHFFFAOYSA-N 0.000 description 3
235000019483 Peanut oil Nutrition 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
230000002159 abnormal effect Effects 0.000 description 3
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
230000002411 adverse Effects 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
230000000964 angiostatic effect Effects 0.000 description 3
229940088710 antibiotic agent Drugs 0.000 description 3
230000037444 atrophy Effects 0.000 description 3
230000003115 biocidal effect Effects 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000008280 blood Substances 0.000 description 3
210000001775 bruch membrane Anatomy 0.000 description 3
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 3
239000000969 carrier Substances 0.000 description 3
230000015556 catabolic process Effects 0.000 description 3
239000001913 cellulose Substances 0.000 description 3
235000010980 cellulose Nutrition 0.000 description 3
229920002678 cellulose Polymers 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
235000012343 cottonseed oil Nutrition 0.000 description 3
239000002385 cottonseed oil Substances 0.000 description 3
230000001351 cycling effect Effects 0.000 description 3
KYQZWONCHDNPDP-QNDFHXLGSA-N daidzein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 KYQZWONCHDNPDP-QNDFHXLGSA-N 0.000 description 3
230000006378 damage Effects 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
238000006731 degradation reaction Methods 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 3
229940093471 ethyl oleate Drugs 0.000 description 3
VBQUDDWATQWCPP-UHFFFAOYSA-N ethylsulfonylbenzene Chemical class CCS(=O)(=O)C1=CC=CC=C1 VBQUDDWATQWCPP-UHFFFAOYSA-N 0.000 description 3
239000003889 eye drop Substances 0.000 description 3
229940012356 eye drops Drugs 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
229940079322 interferon Drugs 0.000 description 3
229940047124 interferons Drugs 0.000 description 3
239000008297 liquid dosage form Substances 0.000 description 3
238000007726 management method Methods 0.000 description 3
239000000463 material Substances 0.000 description 3
208000015122 neurodegenerative disease Diseases 0.000 description 3
210000002569 neuron Anatomy 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
238000004806 packaging method and process Methods 0.000 description 3
239000000312 peanut oil Substances 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
230000003389 potentiating effect Effects 0.000 description 3
231100000241 scar Toxicity 0.000 description 3
239000008159 sesame oil Substances 0.000 description 3
235000011803 sesame oil Nutrition 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
239000008107 starch Substances 0.000 description 3
229940032147 starch Drugs 0.000 description 3
239000000725 suspension Substances 0.000 description 3
229940124597 therapeutic agent Drugs 0.000 description 3
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
150000005072 1,3,4-oxadiazoles Chemical class 0.000 description 2
UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 2
XTNHNNYYNNRZIV-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-n-hydroxy-3-(3-oxo-1h-isoindol-2-yl)propanamide Chemical compound C1=C(OC)C(OC)=CC=C1C(CC(=O)NO)N1C(=O)C2=CC=CC=C2C1 XTNHNNYYNNRZIV-UHFFFAOYSA-N 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 2
108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
102000003974 Fibroblast growth factor 2 Human genes 0.000 description 2
108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
208000008069 Geographic Atrophy Diseases 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
XJTZHGNBKZYODI-UHFFFAOYSA-N Glycitin Natural products OCC1OC(Oc2ccc3OC=C(C(=O)c3c2CO)c4ccc(O)cc4)C(O)C(O)C1O XJTZHGNBKZYODI-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
102000013462 Interleukin-12 Human genes 0.000 description 2
108010065805 Interleukin-12 Proteins 0.000 description 2
206010024229 Leprosy Diseases 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 2
229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
208000027073 Stargardt disease Diseases 0.000 description 2
235000021355 Stearic acid Nutrition 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
230000005856 abnormality Effects 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000000654 additive Substances 0.000 description 2
235000010419 agar Nutrition 0.000 description 2
239000000783 alginic acid Substances 0.000 description 2
229960001126 alginic acid Drugs 0.000 description 2
150000004781 alginic acids Chemical class 0.000 description 2
239000008135 aqueous vehicle Substances 0.000 description 2
229960002903 benzyl benzoate Drugs 0.000 description 2
WUADCCWRTIWANL-UHFFFAOYSA-N biochanin A Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O WUADCCWRTIWANL-UHFFFAOYSA-N 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
229940077737 brain-derived neurotrophic factor Drugs 0.000 description 2
210000005252 bulbus oculi Anatomy 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910000019 calcium carbonate Inorganic materials 0.000 description 2
BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 2
BMLSTPRTEKLIPM-UHFFFAOYSA-I calcium;potassium;disodium;hydrogen carbonate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].OC([O-])=O BMLSTPRTEKLIPM-UHFFFAOYSA-I 0.000 description 2
150000004657 carbamic acid derivatives Chemical class 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
210000003161 choroid Anatomy 0.000 description 2
230000018109 developmental process Effects 0.000 description 2
239000008356 dextrose and sodium chloride injection Substances 0.000 description 2
239000008355 dextrose injection Substances 0.000 description 2
206010012601 diabetes mellitus Diseases 0.000 description 2
210000003038 endothelium Anatomy 0.000 description 2
FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 2
HKQYGTCOTHHOMP-UHFFFAOYSA-N formononetin Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(O)=CC=C2C1=O HKQYGTCOTHHOMP-UHFFFAOYSA-N 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical group OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
150000002334 glycols Chemical class 0.000 description 2
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
239000007943 implant Substances 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
238000001361 intraarterial administration Methods 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
229940074928 isopropyl myristate Drugs 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
125000005439 maleimidyl group Chemical class C1(C=CC(N1*)=O)=O 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
238000000465 moulding Methods 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
239000002687 nonaqueous vehicle Substances 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229940094443 oxytocics prostaglandins Drugs 0.000 description 2
229960001476 pentoxifylline Drugs 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 2
XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
229920001451 polypropylene glycol Polymers 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
230000002265 prevention Effects 0.000 description 2
102000004196 processed proteins & peptides Human genes 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
230000000750 progressive effect Effects 0.000 description 2
238000001959 radiotherapy Methods 0.000 description 2
229940061341 retisert Drugs 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
150000003335 secondary amines Chemical class 0.000 description 2
235000012239 silicon dioxide Nutrition 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
239000008117 stearic acid Substances 0.000 description 2
PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical group C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 2
150000003440 styrenes Chemical class 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
238000001356 surgical procedure Methods 0.000 description 2
230000002195 synergetic effect Effects 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
229960003433 thalidomide Drugs 0.000 description 2
230000005945 translocation Effects 0.000 description 2
238000002054 transplantation Methods 0.000 description 2
229960005294 triamcinolone Drugs 0.000 description 2
GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 2
239000008136 water-miscible vehicle Substances 0.000 description 2
BFESEYUXGQAUDS-LJQANCHMSA-N (3r)-3-(4-acetamido-3-oxo-1h-isoindol-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-n,n-dimethylpropanamide Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CC(=O)N(C)C)N2C(C3=C(NC(C)=O)C=CC=C3C2)=O)=C1 BFESEYUXGQAUDS-LJQANCHMSA-N 0.000 description 1
VAZPGDVTTOAULR-LJQANCHMSA-N (3r)-3-[4-[[2-(dimethylamino)acetyl]amino]-1,3-dioxoisoindol-2-yl]-3-(3-ethoxy-4-methoxyphenyl)-n,n-dimethylpropanamide Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CC(=O)N(C)C)N2C(C3=C(NC(=O)CN(C)C)C=CC=C3C2=O)=O)=C1 VAZPGDVTTOAULR-LJQANCHMSA-N 0.000 description 1
239000001124 (E)-prop-1-ene-1,2,3-tricarboxylic acid Substances 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
QDZOOXXOMWRVPD-UHFFFAOYSA-N 2-(3-ethoxy-4-methoxyphenyl)-n,n-dimethylpropanamide Chemical compound CCOC1=CC(C(C)C(=O)N(C)C)=CC=C1OC QDZOOXXOMWRVPD-UHFFFAOYSA-N 0.000 description 1
LHMYYQCQGPBDIH-UHFFFAOYSA-N 2-(3-oxo-1h-isoindol-2-yl)-3-phenylpropanamide Chemical compound C1C2=CC=CC=C2C(=O)N1C(C(=O)N)CC1=CC=CC=C1 LHMYYQCQGPBDIH-UHFFFAOYSA-N 0.000 description 1
FZEBPJBRDFXKIH-UHFFFAOYSA-N 2-(3-oxo-1h-isoindol-2-yl)-3-phenylpropanoic acid Chemical compound C1C2=CC=CC=C2C(=O)N1C(C(=O)O)CC1=CC=CC=C1 FZEBPJBRDFXKIH-UHFFFAOYSA-N 0.000 description 1
HHZHPBGFUBYKRN-UHFFFAOYSA-N 2-(dimethylamino)-n-[[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]methyl]acetamide Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(CNC(=O)CN(C)C)C=CC=C3C2=O)=O)=C1 HHZHPBGFUBYKRN-UHFFFAOYSA-N 0.000 description 1
ISPUPFYJUWLMEH-CAWMZFRYSA-N 2-[(1r)-1-(3-ethoxy-4-methoxyphenyl)-3-hydroxybutyl]-4-(1h-pyrrol-2-ylmethyl)isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CC(C)O)N2C(C3=C(CC=4NC=CC=4)C=CC=C3C2=O)=O)=C1 ISPUPFYJUWLMEH-CAWMZFRYSA-N 0.000 description 1
NAKSEFFBNWKUJH-OAQYLSRUSA-N 2-[(1r)-1-(3-ethoxy-4-methoxyphenyl)-3-oxobutyl]-4-(1h-pyrrol-2-ylmethyl)isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CC(C)=O)N2C(C3=C(CC=4NC=CC=4)C=CC=C3C2=O)=O)=C1 NAKSEFFBNWKUJH-OAQYLSRUSA-N 0.000 description 1
YEALSVAJNLBPLB-UHFFFAOYSA-N 2-[1-(3-cyclopentyloxy-4-methoxyphenyl)-2-(1,3,4-oxadiazol-2-yl)ethyl]-5-methylisoindole-1,3-dione Chemical compound COC1=CC=C(C(CC=2OC=NN=2)N2C(C3=CC(C)=CC=C3C2=O)=O)C=C1OC1CCCC1 YEALSVAJNLBPLB-UHFFFAOYSA-N 0.000 description 1
HGWJEAFEEZXCPG-UHFFFAOYSA-N 2-[1-(3-cyclopentyloxy-4-methoxyphenyl)-3-oxobutyl]-4-(1h-pyrrol-2-yl)isoindole-1,3-dione Chemical compound COC1=CC=C(C(CC(C)=O)N2C(C3=C(C=4NC=CC=4)C=CC=C3C2=O)=O)C=C1OC1CCCC1 HGWJEAFEEZXCPG-UHFFFAOYSA-N 0.000 description 1
OXYAFFHMEHZDGM-UHFFFAOYSA-N 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4,5-dinitroisoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(C(=CC=C3C2=O)[N+]([O-])=O)[N+]([O-])=O)=O)=C1 OXYAFFHMEHZDGM-UHFFFAOYSA-N 0.000 description 1
ZOMMYBFPBGWUAT-UHFFFAOYSA-N 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-(1h-imidazol-2-ylmethyl)isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(CC=4NC=CN=4)C=CC=C3C2=O)=O)=C1 ZOMMYBFPBGWUAT-UHFFFAOYSA-N 0.000 description 1
KYBGGKMHMYDTDS-UHFFFAOYSA-N 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-(5-methyl-1,3,4-oxadiazol-2-yl)isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(C=4OC(C)=NN=4)C=CC=C3C2=O)=O)=C1 KYBGGKMHMYDTDS-UHFFFAOYSA-N 0.000 description 1
GSCRRCMZMKJZFP-UHFFFAOYSA-N 3-(1,3-dioxoisoindol-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-n-phenylmethoxypropanamide Chemical compound C1=C(OC)C(OCC)=CC(C(CC(=O)NOCC=2C=CC=CC=2)N2C(C3=CC=CC=C3C2=O)=O)=C1 GSCRRCMZMKJZFP-UHFFFAOYSA-N 0.000 description 1
QONJXSUGPNCIKG-UHFFFAOYSA-N 3-(1,3-dioxoisoindol-2-yl)-n-hydroxy-3-(4-methoxy-3-propan-2-yloxyphenyl)propanamide Chemical compound C1=C(OC(C)C)C(OC)=CC=C1C(CC(=O)NO)N1C(=O)C2=CC=CC=C2C1=O QONJXSUGPNCIKG-UHFFFAOYSA-N 0.000 description 1
OQYFIVKWHLAOKT-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-3-(1,3-dioxoisoindol-2-yl)-n-hydroxypropanamide Chemical compound C1=C(OC)C(OC)=CC=C1C(CC(=O)NO)N1C(=O)C2=CC=CC=C2C1=O OQYFIVKWHLAOKT-UHFFFAOYSA-N 0.000 description 1
HHRBRFMDLUNNSX-UHFFFAOYSA-N 3-(3-butoxy-4-methoxyphenyl)-3-(3-oxo-1h-isoindol-2-yl)propanamide Chemical compound C1=C(OC)C(OCCCC)=CC(C(CC(N)=O)N2C(C3=CC=CC=C3C2)=O)=C1 HHRBRFMDLUNNSX-UHFFFAOYSA-N 0.000 description 1
DJGWCAKHYFQWHI-UHFFFAOYSA-N 3-(3-cyclopentyloxy-4-methoxyphenyl)-3-(1,3-dioxobenzo[f]isoindol-2-yl)propanamide Chemical compound COC1=CC=C(C(CC(N)=O)N2C(C3=CC4=CC=CC=C4C=C3C2=O)=O)C=C1OC1CCCC1 DJGWCAKHYFQWHI-UHFFFAOYSA-N 0.000 description 1
HHVLVKOMFOFNPK-UHFFFAOYSA-N 3-(3-cyclopentyloxy-4-methoxyphenyl)-3-(1,3-dioxoisoindol-2-yl)-n-hydroxypropanamide Chemical compound COC1=CC=C(C(CC(=O)NO)N2C(C3=CC=CC=C3C2=O)=O)C=C1OC1CCCC1 HHVLVKOMFOFNPK-UHFFFAOYSA-N 0.000 description 1
XHDUFCCOLBQWDW-UHFFFAOYSA-N 3-(3-cyclopentyloxy-4-methoxyphenyl)-n-hydroxy-3-(3-oxo-1h-isoindol-2-yl)propanamide Chemical compound COC1=CC=C(C(CC(=O)NO)N2C(C3=CC=CC=C3C2)=O)C=C1OC1CCCC1 XHDUFCCOLBQWDW-UHFFFAOYSA-N 0.000 description 1
FYNUUEVQBYCTHI-UHFFFAOYSA-N 3-(3-ethoxy-4-methoxyphenyl)-3-(3-oxo-1h-isoindol-2-yl)-n-phenylmethoxypropanamide Chemical compound C1=C(OC)C(OCC)=CC(C(CC(=O)NOCC=2C=CC=CC=2)N2C(C3=CC=CC=C3C2)=O)=C1 FYNUUEVQBYCTHI-UHFFFAOYSA-N 0.000 description 1
QYOSHOBNEQEKHZ-UHFFFAOYSA-N 3-(3-ethoxy-4-methoxyphenyl)-3-(3-oxo-1h-isoindol-2-yl)propanoic acid Chemical compound C1=C(OC)C(OCC)=CC(C(CC(O)=O)N2C(C3=CC=CC=C3C2)=O)=C1 QYOSHOBNEQEKHZ-UHFFFAOYSA-N 0.000 description 1
HRYCWEZIWMFEDD-UHFFFAOYSA-N 3-(3-ethoxy-4-methoxyphenyl)-3-(4-nitro-1,3-dioxoisoindol-2-yl)-n-phenylmethoxypropanamide Chemical compound C1=C(OC)C(OCC)=CC(C(CC(=O)NOCC=2C=CC=CC=2)N2C(C3=C(C=CC=C3C2=O)[N+]([O-])=O)=O)=C1 HRYCWEZIWMFEDD-UHFFFAOYSA-N 0.000 description 1
UWQLHYJEPXAAIF-UHFFFAOYSA-N 3-(3-ethoxy-4-methoxyphenyl)-n-hydroxy-3-(4-nitro-1,3-dioxoisoindol-2-yl)propanamide Chemical compound C1=C(OC)C(OCC)=CC(C(CC(=O)NO)N2C(C3=C(C=CC=C3C2=O)[N+]([O-])=O)=O)=C1 UWQLHYJEPXAAIF-UHFFFAOYSA-N 0.000 description 1
JBOBZXFXFVDGNO-UHFFFAOYSA-N 3-(3-ethoxy-4-methoxyphenyl)-n-methoxy-3-(3-oxo-1h-isoindol-2-yl)propanamide Chemical compound C1=C(OC)C(OCC)=CC(C(CC(=O)NOC)N2C(C3=CC=CC=C3C2)=O)=C1 JBOBZXFXFVDGNO-UHFFFAOYSA-N 0.000 description 1
CMBFWNFHRMUSLM-UHFFFAOYSA-N 3-(3-oxo-1h-isoindol-2-yl)-3-phenylpropanamide Chemical compound C1C2=CC=CC=C2C(=O)N1C(CC(=O)N)C1=CC=CC=C1 CMBFWNFHRMUSLM-UHFFFAOYSA-N 0.000 description 1
LVGHSBVWSORFEX-UHFFFAOYSA-N 3-(4-amino-1,3-dioxoisoindol-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-n-hydroxypropanamide Chemical compound C1=C(OC)C(OCC)=CC(C(CC(=O)NO)N2C(C3=C(N)C=CC=C3C2=O)=O)=C1 LVGHSBVWSORFEX-UHFFFAOYSA-N 0.000 description 1
XTEVFIVUZLSJHJ-UHFFFAOYSA-N 3-(4-methoxy-3-propoxyphenyl)-3-(3-oxo-1h-isoindol-2-yl)propanamide Chemical compound C1=C(OC)C(OCCC)=CC(C(CC(N)=O)N2C(C3=CC=CC=C3C2)=O)=C1 XTEVFIVUZLSJHJ-UHFFFAOYSA-N 0.000 description 1
ASXKYGLTYKLCLZ-UHFFFAOYSA-N 3-(5-amino-1,3-dioxoisoindol-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-n-hydroxypropanamide Chemical compound C1=C(OC)C(OCC)=CC(C(CC(=O)NO)N2C(C3=CC(N)=CC=C3C2=O)=O)=C1 ASXKYGLTYKLCLZ-UHFFFAOYSA-N 0.000 description 1
VEXOSRQHSWXFDL-UHFFFAOYSA-N 3-[1,3-dioxo-4-(1h-pyrrol-2-yl)isoindol-2-yl]-3-(3-ethoxy-4-methoxyphenyl)-n,n-dimethylpropanamide Chemical compound C1=C(OC)C(OCC)=CC(C(CC(=O)N(C)C)N2C(C3=C(C=4NC=CC=4)C=CC=C3C2=O)=O)=C1 VEXOSRQHSWXFDL-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
CEUCTMSNRQZUSX-UHFFFAOYSA-N 4-(aminomethyl)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(CN)C=CC=C3C2=O)=O)=C1 CEUCTMSNRQZUSX-UHFFFAOYSA-N 0.000 description 1
HEWRXBRDIAUSKW-MRXNPFEDSA-N 4-amino-2-[(1r)-1-(3-ethoxy-4-methoxyphenyl)-3-oxobutyl]isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CC(C)=O)N2C(C3=C(N)C=CC=C3C2=O)=O)=C1 HEWRXBRDIAUSKW-MRXNPFEDSA-N 0.000 description 1
NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
YUWPMEXLKGOSBF-GACAOOTBSA-N Anecortave acetate Chemical compound O=C1CC[C@]2(C)C3=CC[C@]4(C)[C@](C(=O)COC(=O)C)(O)CC[C@H]4[C@@H]3CCC2=C1 YUWPMEXLKGOSBF-GACAOOTBSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
239000004358 Butane-1, 3-diol Substances 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
QIEPWCSVQYUPIY-LEKSSAKUSA-N Delta(1)-progesterone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 QIEPWCSVQYUPIY-LEKSSAKUSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 description 1
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
102400001368 Epidermal growth factor Human genes 0.000 description 1
101800003838 Epidermal growth factor Proteins 0.000 description 1
239000001856 Ethyl cellulose Substances 0.000 description 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
108010073385 Fibrin Proteins 0.000 description 1
102000009123 Fibrin Human genes 0.000 description 1
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
241000206672 Gelidium Species 0.000 description 1
108010024636 Glutathione Proteins 0.000 description 1
229920002907 Guar gum Polymers 0.000 description 1
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 1
102000003810 Interleukin-18 Human genes 0.000 description 1
108090000171 Interleukin-18 Proteins 0.000 description 1
108010044467 Isoenzymes Proteins 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
102000004895 Lipoproteins Human genes 0.000 description 1
108090001030 Lipoproteins Proteins 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
206010025412 Macular dystrophy congenital Diseases 0.000 description 1
208000035719 Maculopathy Diseases 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
240000003183 Manihot esculenta Species 0.000 description 1
235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
239000004909 Moisturizer Substances 0.000 description 1
101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 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
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
229910003844 NSO2 Inorganic materials 0.000 description 1
108010025020 Nerve Growth Factor Proteins 0.000 description 1
102000007072 Nerve Growth Factors Human genes 0.000 description 1
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
102000001938 Plasminogen Activators Human genes 0.000 description 1
108010001014 Plasminogen Activators Proteins 0.000 description 1
101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 description 1
239000004721 Polyphenylene oxide Substances 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
229920000297 Rayon Polymers 0.000 description 1
229930189077 Rifamycin Natural products 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
235000019486 Sunflower oil Nutrition 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
239000004098 Tetracycline Substances 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
102000009618 Transforming Growth Factors Human genes 0.000 description 1
108010009583 Transforming Growth Factors Proteins 0.000 description 1
206010047139 Vasoconstriction Diseases 0.000 description 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
235000011054 acetic acid Nutrition 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
229940091181 aconitic acid Drugs 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
125000004945 acylaminoalkyl group Chemical group 0.000 description 1
125000005041 acyloxyalkyl group Chemical group 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
238000009098 adjuvant therapy Methods 0.000 description 1
239000008272 agar Substances 0.000 description 1
230000032683 aging Effects 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
125000004183 alkoxy alkyl group Chemical group 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
229960001232 anecortave Drugs 0.000 description 1
239000004037 angiogenesis inhibitor Substances 0.000 description 1
229960004977 anhydrous lactose Drugs 0.000 description 1
238000010171 animal model Methods 0.000 description 1
238000011122 anti-angiogenic therapy Methods 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000002260 anti-inflammatory agent Substances 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
125000004429 atom Chemical group 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
230000008901 benefit Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000036765 blood level Effects 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
239000000872 buffer Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
235000019437 butane-1,3-diol Nutrition 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229960003563 calcium carbonate Drugs 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
239000007910 chewable tablet Substances 0.000 description 1
VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
229960002023 chloroprocaine Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
GTZCVFVGUGFEME-IWQZZHSRSA-N cis-aconitic acid Chemical compound OC(=O)C\C(C(O)=O)=C\C(O)=O GTZCVFVGUGFEME-IWQZZHSRSA-N 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
230000035602 clotting Effects 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
238000013329 compounding Methods 0.000 description 1
239000007891 compressed tablet Substances 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
229960001681 croscarmellose sodium Drugs 0.000 description 1
229960000913 crospovidone Drugs 0.000 description 1
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
235000007240 daidzein Nutrition 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000000593 degrading effect Effects 0.000 description 1
239000003405 delayed action preparation Substances 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
229940096516 dextrates Drugs 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000007876 drug discovery Methods 0.000 description 1
229940088679 drug related substance Drugs 0.000 description 1
238000002651 drug therapy Methods 0.000 description 1
150000002066 eicosanoids Chemical class 0.000 description 1
230000003073 embolic effect Effects 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
229940116977 epidermal growth factor Drugs 0.000 description 1
210000000981 epithelium Anatomy 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
ISVXIZFUEUVXPG-UHFFFAOYSA-N etiopurpurin Chemical compound CC1C2(CC)C(C(=O)OCC)=CC(C3=NC(C(=C3C)CC)=C3)=C2N=C1C=C(N1)C(CC)=C(C)C1=CC1=C(CC)C(C)=C3N1 ISVXIZFUEUVXPG-UHFFFAOYSA-N 0.000 description 1
230000003203 everyday effect Effects 0.000 description 1
208000030533 eye disease Diseases 0.000 description 1
229950003499 fibrin Drugs 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000020375 flavoured syrup Nutrition 0.000 description 1
239000012530 fluid Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
239000011888 foil Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
RIKPNWPEMPODJD-UHFFFAOYSA-N formononetin Natural products C1=CC(OC)=CC=C1C1=COC2=CC=CC=C2C1=O RIKPNWPEMPODJD-UHFFFAOYSA-N 0.000 description 1
239000012634 fragment Substances 0.000 description 1
239000007897 gelcap Substances 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
229940045109 genistein Drugs 0.000 description 1
235000006539 genistein Nutrition 0.000 description 1
TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 1
229960003180 glutathione Drugs 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
NNUVCMKMNCKPKN-UHFFFAOYSA-N glycitein Natural products COc1c(O)ccc2OC=C(C(=O)c12)c3ccc(O)cc3 NNUVCMKMNCKPKN-UHFFFAOYSA-N 0.000 description 1
235000008466 glycitein Nutrition 0.000 description 1
DXYUAIFZCFRPTH-UHFFFAOYSA-N glycitein Chemical compound C1=C(O)C(OC)=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 DXYUAIFZCFRPTH-UHFFFAOYSA-N 0.000 description 1
239000003979 granulating agent Substances 0.000 description 1
235000010417 guar gum Nutrition 0.000 description 1
239000000665 guar gum Substances 0.000 description 1
229960002154 guar gum Drugs 0.000 description 1
235000015220 hamburgers Nutrition 0.000 description 1
125000001072 heteroaryl group Chemical group 0.000 description 1
125000000592 heterocycloalkyl group Chemical group 0.000 description 1
239000003906 humectant Substances 0.000 description 1
239000008172 hydrogenated vegetable oil Substances 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
230000002519 immonomodulatory effect Effects 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
208000014674 injury Diseases 0.000 description 1
230000037041 intracellular level Effects 0.000 description 1
XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
230000000366 juvenile effect Effects 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 description 1
229960001160 latanoprost Drugs 0.000 description 1
150000002617 leukotrienes Chemical class 0.000 description 1
229940059904 light mineral oil Drugs 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
239000002502 liposome Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
230000007774 longterm Effects 0.000 description 1
208000018769 loss of vision Diseases 0.000 description 1
231100000864 loss of vision Toxicity 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
239000003120 macrolide antibiotic agent Substances 0.000 description 1
229940041033 macrolides Drugs 0.000 description 1
229920002521 macromolecule Polymers 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
238000002483 medication Methods 0.000 description 1
210000004379 membrane Anatomy 0.000 description 1
239000012528 membrane Substances 0.000 description 1
108020004999 messenger RNA Proteins 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
BPBRDDCTMUGRTO-UHFFFAOYSA-N methyl 3-(3-butoxy-4-methoxyphenyl)-3-(3-oxo-1h-isoindol-2-yl)propanoate Chemical compound C1=C(OC)C(OCCCC)=CC(C(CC(=O)OC)N2C(C3=CC=CC=C3C2)=O)=C1 BPBRDDCTMUGRTO-UHFFFAOYSA-N 0.000 description 1
OWDLKUNGWLGJFD-UHFFFAOYSA-N methyl 3-(4-methoxy-3-propoxyphenyl)-3-(3-oxo-1h-isoindol-2-yl)propanoate Chemical compound C1=C(OC)C(OCCC)=CC(C(CC(=O)OC)N2C(C3=CC=CC=C3C2)=O)=C1 OWDLKUNGWLGJFD-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
PRLWVFYRDLQZBF-UHFFFAOYSA-N methyl n-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]carbamate Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(NC(=O)OC)C=CC=C3C2=O)=O)=C1 PRLWVFYRDLQZBF-UHFFFAOYSA-N 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
229960000282 metronidazole Drugs 0.000 description 1
VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
239000011859 microparticle Substances 0.000 description 1
239000004005 microsphere Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000001333 moisturizer Effects 0.000 description 1
239000007932 molded tablet Substances 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
WIQKYZYFTAEWBF-UHFFFAOYSA-L motexafin lutetium hydrate Chemical compound O.[Lu+3].CC([O-])=O.CC([O-])=O.C1=C([N-]2)C(CC)=C(CC)C2=CC(C(=C2C)CCCO)=NC2=CN=C2C=C(OCCOCCOCCOC)C(OCCOCCOCCOC)=CC2=NC=C2C(C)=C(CCCO)C1=N2 WIQKYZYFTAEWBF-UHFFFAOYSA-L 0.000 description 1
210000000214 mouth Anatomy 0.000 description 1
239000002324 mouth wash Substances 0.000 description 1
210000004400 mucous membrane Anatomy 0.000 description 1
ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 1
QDZOBXFRIVOQBR-IBGZPJMESA-N n-[2-[(1r)-1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-3-oxo-1h-isoindol-4-yl]cyclopropanecarboxamide Chemical compound C1=C(OC)C(OCC)=CC([C@H](CS(C)(=O)=O)N2C(C3=C(NC(=O)C4CC4)C=CC=C3C2)=O)=C1 QDZOBXFRIVOQBR-IBGZPJMESA-N 0.000 description 1
XCCGODHJXOPFSU-HXUWFJFHSA-N n-[2-[(1r)-3-(dimethylamino)-1-(3-ethoxy-4-methoxyphenyl)-3-oxopropyl]-3-oxo-1h-isoindol-4-yl]cyclopropanecarboxamide Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CC(=O)N(C)C)N2C(C3=C(NC(=O)C4CC4)C=CC=C3C2)=O)=C1 XCCGODHJXOPFSU-HXUWFJFHSA-N 0.000 description 1
QDZOBXFRIVOQBR-LJQANCHMSA-N n-[2-[(1s)-1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-3-oxo-1h-isoindol-4-yl]cyclopropanecarboxamide Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CS(C)(=O)=O)N2C(C3=C(NC(=O)C4CC4)C=CC=C3C2)=O)=C1 QDZOBXFRIVOQBR-LJQANCHMSA-N 0.000 description 1
REHJAEDOIKWMDG-UHFFFAOYSA-N n-[2-[1-(3,4-dimethoxyphenyl)-3-oxobutyl]-1,3-dioxoisoindol-4-yl]-n-methylsulfonylmethanesulfonamide Chemical compound C1=C(OC)C(OC)=CC=C1C(CC(C)=O)N1C(=O)C2=C(N(S(C)(=O)=O)S(C)(=O)=O)C=CC=C2C1=O REHJAEDOIKWMDG-UHFFFAOYSA-N 0.000 description 1
OSPVHMLBWYKLBB-UHFFFAOYSA-N n-[2-[1-(3-cyclopentyloxy-4-methoxyphenyl)-3-hydroxybutyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound COC1=CC=C(C(CC(C)O)N2C(C3=C(NC(C)=O)C=CC=C3C2=O)=O)C=C1OC1CCCC1 OSPVHMLBWYKLBB-UHFFFAOYSA-N 0.000 description 1
MVFSISZBKOLEKN-UHFFFAOYSA-N n-[2-[1-(3-cyclopentyloxy-4-methoxyphenyl)-3-oxobutyl]-1,3-dioxoisoindol-4-yl]acetamide Chemical compound COC1=CC=C(C(CC(C)=O)N2C(C3=C(NC(C)=O)C=CC=C3C2=O)=O)C=C1OC1CCCC1 MVFSISZBKOLEKN-UHFFFAOYSA-N 0.000 description 1
YERMOCFDEPTPGV-UHFFFAOYSA-N n-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]-n-methylsulfonylmethanesulfonamide Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(N(S(C)(=O)=O)S(C)(=O)=O)C=CC=C3C2=O)=O)=C1 YERMOCFDEPTPGV-UHFFFAOYSA-N 0.000 description 1
QDZOBXFRIVOQBR-UHFFFAOYSA-N n-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-3-oxo-1h-isoindol-4-yl]cyclopropanecarboxamide Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(NC(=O)C4CC4)C=CC=C3C2)=O)=C1 QDZOBXFRIVOQBR-UHFFFAOYSA-N 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
230000037125 natural defense Effects 0.000 description 1
239000003900 neurotrophic factor Substances 0.000 description 1
239000002547 new drug Substances 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
230000000474 nursing effect Effects 0.000 description 1
229920001542 oligosaccharide Polymers 0.000 description 1
150000002482 oligosaccharides Chemical class 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
239000006174 pH buffer Substances 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
229940055076 parasympathomimetics choline ester Drugs 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000003961 penetration enhancing agent Substances 0.000 description 1
210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000035699 permeability Effects 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
125000005633 phthalidyl group Chemical group 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
229940127126 plasminogen activator Drugs 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
229960000540 polacrilin potassium Drugs 0.000 description 1
229920000570 polyether Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
WVWZXTJUCNEUAE-UHFFFAOYSA-M potassium;1,2-bis(ethenyl)benzene;2-methylprop-2-enoate Chemical compound [K+].CC(=C)C([O-])=O.C=CC1=CC=CC=C1C=C WVWZXTJUCNEUAE-UHFFFAOYSA-M 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
229920003124 powdered cellulose Polymers 0.000 description 1
235000019814 powdered cellulose Nutrition 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
239000003805 procoagulant Substances 0.000 description 1
238000004393 prognosis Methods 0.000 description 1
239000001294 propane Substances 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000001698 pyrogenic effect Effects 0.000 description 1
150000003248 quinolines Chemical class 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000010410 reperfusion Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
229960003292 rifamycin Drugs 0.000 description 1
HJYYPODYNSCCOU-ODRIEIDWSA-N rifamycin SV Chemical compound OC1=C(C(O)=C2C)C3=C(O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O HJYYPODYNSCCOU-ODRIEIDWSA-N 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
238000007493 shaping process Methods 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
229940126586 small molecule drug Drugs 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000008354 sodium chloride injection Substances 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
239000007905 soft elastic gelatin capsule Substances 0.000 description 1
239000012439 solid excipient Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000011301 standard therapy Methods 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
239000002600 sunflower oil Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229940066765 systemic antihistamines substituted ethylene diamines Drugs 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229960002180 tetracycline Drugs 0.000 description 1
229930101283 tetracycline Natural products 0.000 description 1
235000019364 tetracycline Nutrition 0.000 description 1
150000003522 tetracyclines Chemical class 0.000 description 1
230000008719 thickening Effects 0.000 description 1
RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
GTZCVFVGUGFEME-UHFFFAOYSA-N trans-aconitic acid Natural products OC(=O)CC(C(O)=O)=CC(O)=O GTZCVFVGUGFEME-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000008733 trauma Effects 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
230000002792 vascular Effects 0.000 description 1
230000002227 vasoactive effect Effects 0.000 description 1
230000025033 vasoconstriction Effects 0.000 description 1
201000007790 vitelliform macular dystrophy Diseases 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1