KR20150120380A - 황반 변성의 치료에서 신규한 트랩 - Google Patents
황반 변성의 치료에서 신규한 트랩 Download PDFInfo
- Publication number
- KR20150120380A KR20150120380A KR1020157022937A KR20157022937A KR20150120380A KR 20150120380 A KR20150120380 A KR 20150120380A KR 1020157022937 A KR1020157022937 A KR 1020157022937A KR 20157022937 A KR20157022937 A KR 20157022937A KR 20150120380 A KR20150120380 A KR 20150120380A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- cycloalkyl
- substituted
- pharmaceutically acceptable
- aryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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- 208000002780 macular degeneration Diseases 0.000 title claims abstract description 25
- 150000001875 compounds Chemical class 0.000 claims abstract description 122
- 238000000034 method Methods 0.000 claims abstract description 67
- 208000024891 symptom Diseases 0.000 claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- 239000000126 substance Substances 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims description 116
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 84
- 125000000217 alkyl group Chemical group 0.000 claims description 81
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 77
- 150000003839 salts Chemical class 0.000 claims description 52
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 44
- 125000003118 aryl group Chemical group 0.000 claims description 42
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 40
- 229910052799 carbon Inorganic materials 0.000 claims description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 208000017442 Retinal disease Diseases 0.000 claims description 22
- 150000001721 carbon Chemical group 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 238000009825 accumulation Methods 0.000 claims description 19
- 229910052801 chlorine Inorganic materials 0.000 claims description 19
- 229910052731 fluorine Inorganic materials 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 18
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 17
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 17
- 230000036542 oxidative stress Effects 0.000 claims description 17
- 230000002207 retinal effect Effects 0.000 claims description 17
- 230000011664 signaling Effects 0.000 claims description 17
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- 150000002367 halogens Chemical class 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
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- 230000002265 prevention Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
- 235000020945 retinal Nutrition 0.000 description 56
- 239000011604 retinal Substances 0.000 description 56
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- NCYCYZXNIZJOKI-OVSJKPMPSA-N Retinaldehyde Chemical compound O=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-OVSJKPMPSA-N 0.000 description 53
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 37
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 37
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 36
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 36
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 229910052786 argon Inorganic materials 0.000 description 18
- 208000011325 dry age related macular degeneration Diseases 0.000 description 17
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 14
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- 208000008069 Geographic Atrophy Diseases 0.000 description 13
- 206010064930 age-related macular degeneration Diseases 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 11
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
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- 229910002027 silica gel Inorganic materials 0.000 description 10
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- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 9
- 230000008859 change Effects 0.000 description 9
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- 229910004373 HOAc Inorganic materials 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 229920002472 Starch Polymers 0.000 description 8
- 235000011089 carbon dioxide Nutrition 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 239000000463 material Substances 0.000 description 8
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- 208000000208 Wet Macular Degeneration Diseases 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 238000007912 intraperitoneal administration Methods 0.000 description 7
- CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 108091008695 photoreceptors Proteins 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- LINGCICXOISULU-UHFFFAOYSA-N 4-chloro-3-cyclopropyl-1,2-benzoxazol-6-amine Chemical compound N=1OC2=CC(N)=CC(Cl)=C2C=1C1CC1 LINGCICXOISULU-UHFFFAOYSA-N 0.000 description 6
- DHXVGJBLRPWPCS-UHFFFAOYSA-N C1CCOCC1 Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 6
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- 229930002945 all-trans-retinaldehyde Natural products 0.000 description 6
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
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- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 6
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 6
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- QINZXTWXTGLAIP-UHFFFAOYSA-N 2-(6-amino-4-chloro-3-cyclopropyl-1,2-benzoxazol-5-yl)propan-2-ol Chemical compound C12=C(Cl)C(C(C)(O)C)=C(N)C=C2ON=C1C1CC1 QINZXTWXTGLAIP-UHFFFAOYSA-N 0.000 description 5
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- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 5
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- VQWVTUDKHQZFNL-UHFFFAOYSA-N ethyl 4-amino-5-hydroxy-2-nitrobenzoate Chemical compound CCOC(=O)C1=CC(O)=C(N)C=C1[N+]([O-])=O VQWVTUDKHQZFNL-UHFFFAOYSA-N 0.000 description 5
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- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 3
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- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
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- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
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| US20170298081A1 (en) * | 2014-08-08 | 2017-10-19 | Kasuma Partners Inc. | Condensed heterocyclic compound |
| CN118724806A (zh) * | 2015-08-21 | 2024-10-01 | 奥尔德拉医疗公司 | 氘化化合物和其用途 |
| KR20180116416A (ko) | 2016-02-28 | 2018-10-24 | 알데이라 테라퓨틱스, 아이엔씨. | 사이클로덱스트린으로의 알레르기성 안질환의 치료 |
| CN109152774A (zh) | 2016-05-09 | 2019-01-04 | 奥尔德拉医疗公司 | 眼部炎性病症和疾病的组合治疗 |
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| CN111356451A (zh) | 2017-10-10 | 2020-06-30 | 奥尔德拉医疗公司 | 炎性病症的治疗 |
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| WO2011071995A2 (en) | 2009-12-08 | 2011-06-16 | Case Western Reserve University | Compounds and methods of treating ocular disorders |
| CA2782015C (en) * | 2009-12-11 | 2020-08-25 | Neuron Systems, Inc. | Topical ophthalmic compositions and methods for the treatment of macular degeneration |
| MX346387B (es) | 2011-01-12 | 2017-03-02 | Ventirx Pharmaceuticals Inc | Benzoazepinas sustituidas como moduladores de receptores tipo toll. |
| US9302013B2 (en) | 2011-01-31 | 2016-04-05 | Termira Ab | Active principle for mitigating undesired medical conditions |
| KR20150118106A (ko) | 2012-12-20 | 2015-10-21 | 알데이라 테라퓨틱스, 아이엔씨. | 페리-카르비놀 |
| CN111135171B (zh) | 2013-01-23 | 2023-09-08 | 奥尔德拉医疗公司 | 与毒性醛相关的疾病和治疗 |
-
2014
- 2014-01-21 AU AU2014209585A patent/AU2014209585A1/en not_active Abandoned
- 2014-01-21 CA CA2898869A patent/CA2898869A1/en not_active Abandoned
- 2014-01-21 JP JP2015555214A patent/JP6266023B2/ja not_active Expired - Fee Related
- 2014-01-21 CN CN201480005973.2A patent/CN105228989A/zh active Pending
- 2014-01-21 KR KR1020157022937A patent/KR20150120380A/ko not_active Withdrawn
- 2014-01-21 HK HK16105524.6A patent/HK1217490A1/zh unknown
- 2014-01-21 RU RU2015126015A patent/RU2015126015A/ru not_active Application Discontinuation
- 2014-01-21 US US14/760,041 patent/US10111862B2/en active Active
- 2014-01-21 MX MX2015009444A patent/MX2015009444A/es unknown
- 2014-01-21 SG SG11201505599YA patent/SG11201505599YA/en unknown
- 2014-01-21 EP EP14743787.5A patent/EP2948436A4/en not_active Withdrawn
- 2014-01-21 WO PCT/US2014/012356 patent/WO2014116593A1/en not_active Ceased
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2015
- 2015-07-01 IL IL239736A patent/IL239736A0/en unknown
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2018
- 2018-10-23 US US16/168,309 patent/US20190125729A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA2898869A1 (en) | 2014-07-31 |
| US10111862B2 (en) | 2018-10-30 |
| RU2015126015A (ru) | 2017-03-03 |
| AU2014209585A1 (en) | 2015-07-23 |
| EP2948436A4 (en) | 2016-07-13 |
| MX2015009444A (es) | 2016-04-15 |
| HK1217490A1 (zh) | 2017-01-13 |
| US20190125729A1 (en) | 2019-05-02 |
| WO2014116593A1 (en) | 2014-07-31 |
| EP2948436A1 (en) | 2015-12-02 |
| JP6266023B2 (ja) | 2018-01-24 |
| US20150344447A1 (en) | 2015-12-03 |
| CN105228989A (zh) | 2016-01-06 |
| SG11201505599YA (en) | 2015-08-28 |
| JP2016505637A (ja) | 2016-02-25 |
| IL239736A0 (en) | 2015-08-31 |
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