JP2010524942A - プロリルヒドロキシラーゼを阻害するキノロン及びアザキノロン - Google Patents
プロリルヒドロキシラーゼを阻害するキノロン及びアザキノロン Download PDFInfo
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- JP2010524942A JP2010524942A JP2010504084A JP2010504084A JP2010524942A JP 2010524942 A JP2010524942 A JP 2010524942A JP 2010504084 A JP2010504084 A JP 2010504084A JP 2010504084 A JP2010504084 A JP 2010504084A JP 2010524942 A JP2010524942 A JP 2010524942A
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- Prior art keywords
- methyl
- oxo
- hydroxy
- oxobutyric acid
- substituted
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- 108010043005 Prolyl Hydroxylases Proteins 0.000 title abstract description 14
- 102000004079 Prolyl Hydroxylases Human genes 0.000 title abstract description 14
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 292
- 238000000034 method Methods 0.000 claims description 93
- 239000000203 mixture Substances 0.000 claims description 88
- 125000000217 alkyl group Chemical group 0.000 claims description 76
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 60
- -1 perhaloalkyl Chemical group 0.000 claims description 56
- 125000001072 heteroaryl group Chemical group 0.000 claims description 46
- 238000002360 preparation method Methods 0.000 claims description 44
- 201000010099 disease Diseases 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 35
- 125000000623 heterocyclic group Chemical group 0.000 claims description 34
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 125000001188 haloalkyl group Chemical group 0.000 claims description 28
- 239000003814 drug Substances 0.000 claims description 27
- 230000000694 effects Effects 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 19
- 230000002401 inhibitory effect Effects 0.000 claims description 19
- 208000028867 ischemia Diseases 0.000 claims description 18
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 208000007502 anemia Diseases 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 230000033444 hydroxylation Effects 0.000 claims description 14
- 238000005805 hydroxylation reaction Methods 0.000 claims description 14
- 102000003951 Erythropoietin Human genes 0.000 claims description 13
- 108090000394 Erythropoietin Proteins 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 210000004369 blood Anatomy 0.000 claims description 13
- 239000008280 blood Substances 0.000 claims description 13
- 229940105423 erythropoietin Drugs 0.000 claims description 13
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 12
- 229910052740 iodine Inorganic materials 0.000 claims description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
- 208000002903 Thalassemia Diseases 0.000 claims description 11
- 206010012601 diabetes mellitus Diseases 0.000 claims description 11
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 208000027866 inflammatory disease Diseases 0.000 claims description 11
- 208000037905 systemic hypertension Diseases 0.000 claims description 11
- 230000029663 wound healing Effects 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 10
- 125000003107 substituted aryl group Chemical group 0.000 claims description 10
- 206010021143 Hypoxia Diseases 0.000 claims description 9
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 125000004450 alkenylene group Chemical group 0.000 claims description 8
- 125000004419 alkynylene group Chemical group 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 230000000087 stabilizing effect Effects 0.000 claims description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 230000007954 hypoxia Effects 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- FAWSLMNFZXXCSE-UHFFFAOYSA-N 4-(7,8-difluoro-4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound FC1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1F FAWSLMNFZXXCSE-UHFFFAOYSA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 6
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- YOPREHPEFDOGBH-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-6-phenyl-1,8-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C1=CC=CC=C1 YOPREHPEFDOGBH-UHFFFAOYSA-N 0.000 claims description 5
- PTIPDKFKGRYNBP-UHFFFAOYSA-N 4-(4-hydroxy-6-iodo-1-methyl-2-oxo-1,8-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=C(I)C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=N1 PTIPDKFKGRYNBP-UHFFFAOYSA-N 0.000 claims description 5
- VGDSPTSAQNTGDA-UHFFFAOYSA-N 4-(6-cyclohexyl-4-hydroxy-1-methyl-2-oxo-1,8-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C1CCCCC1 VGDSPTSAQNTGDA-UHFFFAOYSA-N 0.000 claims description 5
- MEVOFGCHWMIIFA-UHFFFAOYSA-N 4-[4-hydroxy-1-methyl-2-oxo-6-(trifluoromethyl)-1,8-naphthyridin-3-yl]-4-oxobutanoic acid Chemical compound C1=C(C(F)(F)F)C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=N1 MEVOFGCHWMIIFA-UHFFFAOYSA-N 0.000 claims description 5
- OVPREICYZRSPCE-UHFFFAOYSA-N 6-(3-carboxypropanoyl)-5-hydroxy-8-methyl-7-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=N1 OVPREICYZRSPCE-UHFFFAOYSA-N 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 4
- FCBGADAOCBIFSG-UHFFFAOYSA-N 3-(3-carboxypropanoyl)-4-hydroxy-1-methyl-2-oxo-1,7-naphthyridine-6-carboxylic acid Chemical compound N1=C(C(O)=O)C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 FCBGADAOCBIFSG-UHFFFAOYSA-N 0.000 claims description 3
- GBFBFKZVMZZMOO-UHFFFAOYSA-N 3-(3-carboxypropanoyl)-4-hydroxy-1-methyl-2-oxoquinoline-6-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 GBFBFKZVMZZMOO-UHFFFAOYSA-N 0.000 claims description 3
- SJZXVRXQWCLHRN-UHFFFAOYSA-N 3-(3-carboxypropanoyl)-4-hydroxy-1-methyl-2-oxoquinoline-7-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 SJZXVRXQWCLHRN-UHFFFAOYSA-N 0.000 claims description 3
- VONBKRUVLFOEAW-UHFFFAOYSA-N 3-(3-carboxypropanoyl)-7,8-difluoro-4-hydroxy-1-methyl-2-oxoquinoline-6-carboxylic acid Chemical compound FC1=C(C(O)=O)C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1F VONBKRUVLFOEAW-UHFFFAOYSA-N 0.000 claims description 3
- JHZDQKFXZSDGEJ-UHFFFAOYSA-N 4-(1-benzyl-4-hydroxy-2-oxo-1,8-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound O=C1C(C(=O)CCC(=O)O)=C(O)C2=CC=CN=C2N1CC1=CC=CC=C1 JHZDQKFXZSDGEJ-UHFFFAOYSA-N 0.000 claims description 3
- HTFCBCOEBHSEAY-UHFFFAOYSA-N 4-(1-benzyl-4-hydroxy-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound O=C1C(C(=O)CCC(=O)O)=C(O)C2=CC=CC=C2N1CC1=CC=CC=C1 HTFCBCOEBHSEAY-UHFFFAOYSA-N 0.000 claims description 3
- NGQMOMCWKBIGPS-UHFFFAOYSA-N 4-(1-benzyl-7,8-difluoro-4-hydroxy-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound O=C1C(C(=O)CCC(=O)O)=C(O)C2=CC=C(F)C(F)=C2N1CC1=CC=CC=C1 NGQMOMCWKBIGPS-UHFFFAOYSA-N 0.000 claims description 3
- APZBXINEKFBHMY-UHFFFAOYSA-N 4-(1-benzyl-7-bromo-4-hydroxy-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound O=C1C(C(=O)CCC(=O)O)=C(O)C2=CC=C(Br)C=C2N1CC1=CC=CC=C1 APZBXINEKFBHMY-UHFFFAOYSA-N 0.000 claims description 3
- ZDSHJJSUYHSJON-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-1,5-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=CN=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 ZDSHJJSUYHSJON-UHFFFAOYSA-N 0.000 claims description 3
- RETQKIVXWLHCTB-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-1,7-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound N1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 RETQKIVXWLHCTB-UHFFFAOYSA-N 0.000 claims description 3
- DZVKKDNRFVPAPW-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-1,8-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=N1 DZVKKDNRFVPAPW-UHFFFAOYSA-N 0.000 claims description 3
- VPMJBCORSOGLST-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-6-phenyl-1,7-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CN=C1C1=CC=CC=C1 VPMJBCORSOGLST-UHFFFAOYSA-N 0.000 claims description 3
- LPEQEFOPSJSTKP-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-6-phenylquinolin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=C1C1=CC=CC=C1 LPEQEFOPSJSTKP-UHFFFAOYSA-N 0.000 claims description 3
- MDAQYLRVTZKTHG-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-6-thiophen-2-yl-1,8-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C1=CC=CS1 MDAQYLRVTZKTHG-UHFFFAOYSA-N 0.000 claims description 3
- KEBLJXILKZQOQQ-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-7-phenylquinolin-3-yl)-4-oxobutanoic acid Chemical compound C=1C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=1C1=CC=CC=C1 KEBLJXILKZQOQQ-UHFFFAOYSA-N 0.000 claims description 3
- TUKIBJBFQBPBIT-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-7-thiophen-2-yl-1,5-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C=1N=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=1C1=CC=CS1 TUKIBJBFQBPBIT-UHFFFAOYSA-N 0.000 claims description 3
- VOIIANIAJYFQRM-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-7-thiophen-2-ylquinolin-3-yl)-4-oxobutanoic acid Chemical compound C=1C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=1C1=CC=CS1 VOIIANIAJYFQRM-UHFFFAOYSA-N 0.000 claims description 3
- PEHGRZOSSVYJIL-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-7-thiophen-3-yl-1,5-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C=1N=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=1C=1C=CSC=1 PEHGRZOSSVYJIL-UHFFFAOYSA-N 0.000 claims description 3
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- DCJKRKYLAIKIQM-UHFFFAOYSA-N 4-(5-bromo-4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound C1=CC(Br)=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 DCJKRKYLAIKIQM-UHFFFAOYSA-N 0.000 claims description 3
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- QMQPHLFJRRTUJR-UHFFFAOYSA-N 4-(6-cyclopentyl-4-hydroxy-1-methyl-2-oxo-1,8-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C1CCCC1 QMQPHLFJRRTUJR-UHFFFAOYSA-N 0.000 claims description 3
- FEKWXSVPTLHHCK-UHFFFAOYSA-N 4-(6-cyclopropyl-7,8-difluoro-4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C(F)C(F)=C1C1CC1 FEKWXSVPTLHHCK-UHFFFAOYSA-N 0.000 claims description 3
- QATCZKHAJFAEST-UHFFFAOYSA-N 4-(7,8-dichloro-4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound ClC1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1Cl QATCZKHAJFAEST-UHFFFAOYSA-N 0.000 claims description 3
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- GZQNECCMESWBBW-UHFFFAOYSA-N 4-(7-bromo-4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound BrC1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 GZQNECCMESWBBW-UHFFFAOYSA-N 0.000 claims description 3
- GRYVYFQDXHKMOA-UHFFFAOYSA-N 4-(8-bromo-4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound C1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1Br GRYVYFQDXHKMOA-UHFFFAOYSA-N 0.000 claims description 3
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D215/22—Oxygen atoms attached in position 2 or 4
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- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Nitrogen Condensed Heterocyclic Rings (AREA)
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| JP2013184893A (ja) * | 2012-03-06 | 2013-09-19 | Tokyo Univ Of Agriculture & Technology | トリフルオロメチルピリジノン化合物およびその製造方法 |
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| EP2111399A2 (en) * | 2006-12-18 | 2009-10-28 | Amgen Inc. | Naphthalenone compounds exhibiting prolyl hydroxylase inhibitory activity, compositions, and uses thereof |
| EP2142509B1 (en) * | 2007-04-18 | 2013-12-04 | Amgen, Inc | Quinolones and azaquinolones that inhibit prolyl hydroxylase |
| EP2252619B1 (en) | 2008-01-11 | 2013-10-09 | Fibrogen, Inc. | Isothiazole-pyridine derivatives as modulators of hif (hypoxia inducible factor) activity |
| US8324405B2 (en) | 2008-02-05 | 2012-12-04 | Fibrogen, Inc. | Chromene derivatives and use thereof as HIF hydroxylase activity inhibitors |
| US8759345B2 (en) | 2008-04-28 | 2014-06-24 | Janssen Pharmaceutica Nv | Benzoimidazoles as prolyl hydroxylase inhibitors |
| US8217043B2 (en) | 2008-08-20 | 2012-07-10 | Fibrogen, Inc. | Compounds and methods for their use |
| CN102272117B (zh) | 2008-11-14 | 2015-06-17 | 菲布罗根有限公司 | 作为hif羟化酶抑制剂的苯并噻喃衍生物 |
| PT2455381E (pt) * | 2009-07-17 | 2014-06-24 | Japan Tobacco Inc | Composto de triazolopiridina e sua acção como inibidor da prolil-hidroxilase e indutor da produção de eritropoietina |
| KR20130065728A (ko) | 2010-10-14 | 2013-06-19 | 임뮤나르 에이비 | Ahr 활성화제로서의 1,2-디히드로-4-히드록시-2-옥소-퀴놀린-3-카르복사닐리드 |
| CN103608346B (zh) | 2011-02-02 | 2016-06-15 | 菲布罗根有限公司 | 作为缺氧诱导因子(hif)羟化酶抑制剂的萘啶衍生物 |
| GB201102659D0 (en) | 2011-02-15 | 2011-03-30 | Isis Innovation | Assay |
| GB201113101D0 (en) | 2011-07-28 | 2011-09-14 | Isis Innovation | Assay |
| ES2818977T3 (es) | 2011-10-25 | 2021-04-14 | Janssen Pharmaceutica Nv | Método para obtener cristales de sal de meglumina de ácido 1-(5,6-dicloro-1H-benzo[d]imidazol-2-il)-1H-pirazol-4-carboxílico |
| US20140256767A1 (en) | 2011-10-31 | 2014-09-11 | The Broad Institute, Inc. | Direct inhibitors of keap1-nrf2 interaction as antioxidant inflammation modulators |
| US9145411B2 (en) | 2012-08-02 | 2015-09-29 | Asana Biosciences, Llc | Substituted amino-pyrimidine derivatives |
| FR2994184B1 (fr) | 2012-08-02 | 2017-12-08 | Biomerieux Sa | Procedes de fonctionalisation et reactifs utilises dans de tels procedes utilisant un anhydride aza-isatoique ou un de ses derives, molecules biologiques ainsi traitees et kits |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2013184893A (ja) * | 2012-03-06 | 2013-09-19 | Tokyo Univ Of Agriculture & Technology | トリフルオロメチルピリジノン化合物およびその製造方法 |
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| AU2008241483A1 (en) | 2008-10-30 |
| US8048894B2 (en) | 2011-11-01 |
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| US8349868B2 (en) | 2013-01-08 |
| CA2683956A1 (en) | 2008-10-30 |
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| CA2683956C (en) | 2012-12-18 |
| US20090156605A1 (en) | 2009-06-18 |
| WO2008130600A2 (en) | 2008-10-30 |
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