AU2010273101B2 - Compounds as hypoxia mimetics, and compositions, and uses thereof - Google Patents
Compounds as hypoxia mimetics, and compositions, and uses thereof Download PDFInfo
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- AU2010273101B2 AU2010273101B2 AU2010273101A AU2010273101A AU2010273101B2 AU 2010273101 B2 AU2010273101 B2 AU 2010273101B2 AU 2010273101 A AU2010273101 A AU 2010273101A AU 2010273101 A AU2010273101 A AU 2010273101A AU 2010273101 B2 AU2010273101 B2 AU 2010273101B2
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- compound
- haloalkyl
- oxo
- hydroxy
- halogen
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 259
- 206010021143 Hypoxia Diseases 0.000 title abstract description 9
- 230000007954 hypoxia Effects 0.000 title abstract description 8
- 239000000203 mixture Substances 0.000 title description 19
- 238000000034 method Methods 0.000 claims abstract description 70
- 230000000694 effects Effects 0.000 claims abstract description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 154
- 125000001188 haloalkyl group Chemical group 0.000 claims description 117
- 150000003839 salts Chemical class 0.000 claims description 96
- 125000003545 alkoxy group Chemical group 0.000 claims description 95
- 229910052736 halogen Inorganic materials 0.000 claims description 83
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 79
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 69
- 150000002367 halogens Chemical class 0.000 claims description 64
- -1 methoxy, ethoxy Chemical group 0.000 claims description 53
- 125000001072 heteroaryl group Chemical group 0.000 claims description 51
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 201000010099 disease Diseases 0.000 claims description 37
- 208000035475 disorder Diseases 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
- 125000005843 halogen group Chemical group 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 12
- 208000007502 anemia Diseases 0.000 claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 10
- 208000028867 ischemia Diseases 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 10
- 206010020772 Hypertension Diseases 0.000 claims description 9
- 208000002903 Thalassemia Diseases 0.000 claims description 9
- 238000011316 allogeneic transplantation Methods 0.000 claims description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims description 9
- 208000027866 inflammatory disease Diseases 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 230000009885 systemic effect Effects 0.000 claims description 9
- 238000002054 transplantation Methods 0.000 claims description 9
- 230000029663 wound healing Effects 0.000 claims description 9
- 238000002689 xenotransplantation Methods 0.000 claims description 9
- 239000002671 adjuvant Substances 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 239000013522 chelant Substances 0.000 claims description 6
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- GQWSJBDFFCLFQM-UHFFFAOYSA-N 2-[(4-hydroxy-2-oxo-7-phenylchromene-3-carbonyl)amino]acetic acid Chemical compound C1=C2OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=C1C1=CC=CC=C1 GQWSJBDFFCLFQM-UHFFFAOYSA-N 0.000 claims description 2
- XWBVTPDNZPTHIF-UHFFFAOYSA-N 2-[(4-hydroxy-2-oxo-7-pyridin-3-ylchromene-3-carbonyl)amino]acetic acid Chemical compound C1=C2OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=C1C1=CC=CN=C1 XWBVTPDNZPTHIF-UHFFFAOYSA-N 0.000 claims description 2
- PNGRZARBGBCVQC-UHFFFAOYSA-N 2-[(4-hydroxy-2-oxo-7-pyridin-4-ylchromene-3-carbonyl)amino]acetic acid Chemical compound C1=C2OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=C1C1=CC=NC=C1 PNGRZARBGBCVQC-UHFFFAOYSA-N 0.000 claims description 2
- QJRMHRZSVIXIAM-UHFFFAOYSA-N 2-[[4-hydroxy-2-oxo-7-(3,4,5-trifluorophenyl)chromene-3-carbonyl]amino]acetic acid Chemical compound C1=C2OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=C1C1=CC(F)=C(F)C(F)=C1 QJRMHRZSVIXIAM-UHFFFAOYSA-N 0.000 claims description 2
- XZTYLGWJFOBYTJ-UHFFFAOYSA-N 2-[[4-hydroxy-2-oxo-7-[3-(trifluoromethyl)phenyl]chromene-3-carbonyl]amino]acetic acid Chemical compound C1=C2OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=C1C1=CC=CC(C(F)(F)F)=C1 XZTYLGWJFOBYTJ-UHFFFAOYSA-N 0.000 claims description 2
- PRVDWMUCVHSLOZ-UHFFFAOYSA-N 2-[[4-hydroxy-2-oxo-7-[4-(trifluoromethoxy)phenyl]chromene-3-carbonyl]amino]acetic acid Chemical compound C1=C2OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=C1C1=CC=C(OC(F)(F)F)C=C1 PRVDWMUCVHSLOZ-UHFFFAOYSA-N 0.000 claims description 2
- UAUBZCPCBQNYJZ-UHFFFAOYSA-N 2-[[4-hydroxy-2-oxo-8-[3-(trifluoromethoxy)phenyl]chromene-3-carbonyl]amino]acetic acid Chemical compound C=12OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=CC=1C1=CC=CC(OC(F)(F)F)=C1 UAUBZCPCBQNYJZ-UHFFFAOYSA-N 0.000 claims description 2
- BLXWBOGYYXGCHA-UHFFFAOYSA-N 2-[[4-hydroxy-2-oxo-8-[4-(trifluoromethoxy)phenyl]chromene-3-carbonyl]amino]acetic acid Chemical compound C=12OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=CC=1C1=CC=C(OC(F)(F)F)C=C1 BLXWBOGYYXGCHA-UHFFFAOYSA-N 0.000 claims description 2
- VKCWXFGQPZTWPB-UHFFFAOYSA-N 2-[[4-hydroxy-2-oxo-8-[4-(trifluoromethyl)phenyl]chromene-3-carbonyl]amino]acetic acid Chemical compound C=12OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=CC=1C1=CC=C(C(F)(F)F)C=C1 VKCWXFGQPZTWPB-UHFFFAOYSA-N 0.000 claims description 2
- SAKKIQANFNOMQE-UHFFFAOYSA-N 2-[[4-hydroxy-7-(3-methylphenyl)-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound CC1=CC=CC(C=2C=C3OC(=O)C(C(=O)NCC(O)=O)=C(O)C3=CC=2)=C1 SAKKIQANFNOMQE-UHFFFAOYSA-N 0.000 claims description 2
- IVGRAINASGPBHC-UHFFFAOYSA-N 2-[[4-hydroxy-7-(4-methoxyphenyl)-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound C1=CC(OC)=CC=C1C1=CC=C(C(O)=C(C(=O)NCC(O)=O)C(=O)O2)C2=C1 IVGRAINASGPBHC-UHFFFAOYSA-N 0.000 claims description 2
- KWWRZRSSDDWGLG-UHFFFAOYSA-N 2-[[4-hydroxy-7-(4-methylphenyl)-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound C1=CC(C)=CC=C1C1=CC=C(C(O)=C(C(=O)NCC(O)=O)C(=O)O2)C2=C1 KWWRZRSSDDWGLG-UHFFFAOYSA-N 0.000 claims description 2
- IWYFVVWNUKLMKY-UHFFFAOYSA-N 2-[[4-hydroxy-7-(6-methoxypyridin-3-yl)-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound C1=NC(OC)=CC=C1C1=CC=C(C(O)=C(C(=O)NCC(O)=O)C(=O)O2)C2=C1 IWYFVVWNUKLMKY-UHFFFAOYSA-N 0.000 claims description 2
- LXTBGJQEBUNWIZ-UHFFFAOYSA-N 2-[[4-hydroxy-8-(3-methoxyphenyl)-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound COC1=CC=CC(C=2C=3OC(=O)C(C(=O)NCC(O)=O)=C(O)C=3C=CC=2)=C1 LXTBGJQEBUNWIZ-UHFFFAOYSA-N 0.000 claims description 2
- YVKNNNVAKTWJPO-UHFFFAOYSA-N 2-[[4-hydroxy-8-(3-methylphenyl)-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound CC1=CC=CC(C=2C=3OC(=O)C(C(=O)NCC(O)=O)=C(O)C=3C=CC=2)=C1 YVKNNNVAKTWJPO-UHFFFAOYSA-N 0.000 claims description 2
- KAEYBTXGARFSES-UHFFFAOYSA-N 2-[[4-hydroxy-8-(4-methoxyphenyl)-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound C1=CC(OC)=CC=C1C1=CC=CC2=C1OC(=O)C(C(=O)NCC(O)=O)=C2O KAEYBTXGARFSES-UHFFFAOYSA-N 0.000 claims description 2
- HATJKDJVUKAARX-UHFFFAOYSA-N 2-[[4-hydroxy-8-(4-methylphenyl)-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound C1=CC(C)=CC=C1C1=CC=CC2=C1OC(=O)C(C(=O)NCC(O)=O)=C2O HATJKDJVUKAARX-UHFFFAOYSA-N 0.000 claims description 2
- VQDGZTSYLDTUJX-UHFFFAOYSA-N 2-[[7-(2-chlorophenyl)-4-hydroxy-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound C1=C2OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=C1C1=CC=CC=C1Cl VQDGZTSYLDTUJX-UHFFFAOYSA-N 0.000 claims description 2
- FSGOIFXKECYHML-UHFFFAOYSA-N 2-[[7-(3,4-dichlorophenyl)-4-hydroxy-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound C1=C2OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=C1C1=CC=C(Cl)C(Cl)=C1 FSGOIFXKECYHML-UHFFFAOYSA-N 0.000 claims description 2
- VMGTWIAOEZSBRU-UHFFFAOYSA-N 2-[[7-(3,4-difluorophenyl)-4-hydroxy-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound C1=C2OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=C1C1=CC=C(F)C(F)=C1 VMGTWIAOEZSBRU-UHFFFAOYSA-N 0.000 claims description 2
- DECCQHPOJXLRFO-UHFFFAOYSA-N 2-[[7-(3-chlorophenyl)-4-hydroxy-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound C1=C2OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=C1C1=CC=CC(Cl)=C1 DECCQHPOJXLRFO-UHFFFAOYSA-N 0.000 claims description 2
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- VZHKYSITSMSQIL-UHFFFAOYSA-N 2-[[8-(3,4-dichlorophenyl)-4-hydroxy-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound C=12OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=CC=1C1=CC=C(Cl)C(Cl)=C1 VZHKYSITSMSQIL-UHFFFAOYSA-N 0.000 claims description 2
- ZGMOHZCFBTUWCU-UHFFFAOYSA-N 2-[[8-(3,4-difluorophenyl)-4-hydroxy-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound C=12OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=CC=1C1=CC=C(F)C(F)=C1 ZGMOHZCFBTUWCU-UHFFFAOYSA-N 0.000 claims description 2
- PNMYKFPHOXOIMB-UHFFFAOYSA-N 2-[[8-(4-chlorophenyl)-4-hydroxy-2-oxochromene-3-carbonyl]amino]acetic acid Chemical compound C=12OC(=O)C(C(=O)NCC(=O)O)=C(O)C2=CC=CC=1C1=CC=C(Cl)C=C1 PNMYKFPHOXOIMB-UHFFFAOYSA-N 0.000 claims description 2
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/42—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/42—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4
- C07D311/56—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 without hydrogen atoms in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| CN200910089274.1 | 2009-07-15 | ||
| CN200910089274 | 2009-07-15 | ||
| PCT/CN2010/001057 WO2011006355A1 (en) | 2009-07-15 | 2010-07-14 | Compounds as hypoxia mimetics, and compositions, and uses thereof |
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| AU2010273101A2 AU2010273101A2 (en) | 2012-03-15 |
| AU2010273101B2 true AU2010273101B2 (en) | 2016-02-25 |
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| JP (1) | JP5847710B2 (enExample) |
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| WO (1) | WO2011006355A1 (enExample) |
| ZA (1) | ZA201200293B (enExample) |
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| KR102029951B1 (ko) | 2011-07-22 | 2019-11-08 | 베이징 베타 파머수티컬 컴퍼니 리미티드 | 프로릴 히드록실라제 억제제로서 화합물의 다형체형, 및 이의 용도 |
| JP2014523917A (ja) * | 2011-07-29 | 2014-09-18 | ベイジン ベータ ファーマシューティカルズ カンパニー， リミテッド | 低酸素模倣剤としての化合物の安定な多形体、およびその使用 |
| WO2016034108A1 (zh) | 2014-09-02 | 2016-03-10 | 广东东阳光药业有限公司 | 喹啉酮类化合物及其应用 |
| US20160193238A1 (en) * | 2015-01-05 | 2016-07-07 | National Cancer Center | HNF4-alpha ANTAGONIST AND USE THEREOF |
| CN108367017A (zh) * | 2015-08-13 | 2018-08-03 | 索马根尼科斯公司 | 用于伤口愈合的短小发夹rna与微rna的组合物以及方法 |
| CN113004271A (zh) | 2017-05-09 | 2021-06-22 | 杭州安道药业有限公司 | 吲哚嗪衍生物及其在医药上的应用 |
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| AU2003228348A1 (en) | 2002-03-20 | 2003-10-08 | John T. Fassett | Induction of hepatocyte proliferation in vitro by inhibition of cell cycle inhibitors |
| AU2006282888A1 (en) * | 2005-08-25 | 2007-03-01 | Emory University | HIF inhibitors |
| WO2007038571A2 (en) * | 2005-09-26 | 2007-04-05 | Smithkline Beecham Corporation | Prolyl hydroxylase antagonists |
| AU2006326662B2 (en) | 2005-12-09 | 2011-07-28 | Amgen Inc. | Quinolone based compounds exhibiting prolyl hydroxylase inhibitory activity, and compositions, and uses thereof |
| TW200808793A (en) * | 2006-03-07 | 2008-02-16 | Smithkline Beecham Corp | Prolyl hydroxylase inhibitors |
| RU2009139811A (ru) | 2007-03-29 | 2011-05-10 | Новартис АГ (CH) | Гетероциклические спиросоединения |
| US20110263642A1 (en) * | 2008-08-26 | 2011-10-27 | Fibrogen, Inc. | Methods for treatment of multiple sclerosis |
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- 2010-07-14 EP EP10799353.7A patent/EP2454249B1/en not_active Not-in-force
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2009100250A1 (en) * | 2008-02-05 | 2009-08-13 | Fibrogen, Inc. | Chromene derivatives and use thereof as hif hydroxylase activity inhibitors |
Non-Patent Citations (1)
| Title |
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| CAS RN 200063-28-1, STN Entry Date 21 January 1998 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2012532897A (ja) | 2012-12-20 |
| HK1161234A1 (en) | 2012-08-24 |
| CA2767911A1 (en) | 2011-01-20 |
| EP2454249A4 (en) | 2012-12-12 |
| AU2010273101A2 (en) | 2012-03-15 |
| IL217531A0 (en) | 2012-02-29 |
| AU2010273101A1 (en) | 2012-02-02 |
| CN102164905B (zh) | 2014-04-30 |
| KR20120065311A (ko) | 2012-06-20 |
| ZA201200293B (en) | 2012-09-26 |
| SG177598A1 (en) | 2012-02-28 |
| US20120172399A1 (en) | 2012-07-05 |
| EP2454249B1 (en) | 2018-09-19 |
| ES2702524T3 (es) | 2019-03-01 |
| CA2767911C (en) | 2016-03-29 |
| CN102164905A (zh) | 2011-08-24 |
| WO2011006355A1 (en) | 2011-01-20 |
| IN2012DN00549A (enExample) | 2015-06-12 |
| US8742138B2 (en) | 2014-06-03 |
| JP5847710B2 (ja) | 2016-01-27 |
| EP2454249A1 (en) | 2012-05-23 |
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