BRPI0718459A2 - Derivados de pirazolo(1,5-a) (1,3,5) triazina e pirazolo(1,5-a) pirimidina úteis como inibidores de proteína quinase - Google Patents
Derivados de pirazolo(1,5-a) (1,3,5) triazina e pirazolo(1,5-a) pirimidina úteis como inibidores de proteína quinase Download PDFInfo
- Publication number
- BRPI0718459A2 BRPI0718459A2 BRPI0718459-0A BRPI0718459A BRPI0718459A2 BR PI0718459 A2 BRPI0718459 A2 BR PI0718459A2 BR PI0718459 A BRPI0718459 A BR PI0718459A BR PI0718459 A2 BRPI0718459 A2 BR PI0718459A2
- Authority
- BR
- Brazil
- Prior art keywords
- amino
- phenyl
- triazin
- diaza
- cyclotetradeca
- Prior art date
Links
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 title description 5
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title description 4
- 239000003909 protein kinase inhibitor Substances 0.000 title description 4
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 title description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 87
- -1 alkenyl alkynyl Chemical group 0.000 claims description 66
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 34
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 230000004663 cell proliferation Effects 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 208000031888 Mycoses Diseases 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 230000003612 virological effect Effects 0.000 claims description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 2
- IMHBYKMAHXWHRP-UHFFFAOYSA-N anilazine Chemical compound ClC1=CC=CC=C1NC1=NC(Cl)=NC(Cl)=N1 IMHBYKMAHXWHRP-UHFFFAOYSA-N 0.000 claims 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- SLPUTJFVMJPMKV-UHFFFAOYSA-N 1-methylpyrrolidin-3-one Chemical compound CN1CCC(=O)C1 SLPUTJFVMJPMKV-UHFFFAOYSA-N 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 230000004770 neurodegeneration Effects 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 28
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- 102000043139 CK2 family Human genes 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000012267 brine Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- RFFFKMOABOFIDF-UHFFFAOYSA-N Pentanenitrile Chemical compound CCCCC#N RFFFKMOABOFIDF-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000005711 Benzoic acid Substances 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 4
- LTJGCRSXJUTKSU-UHFFFAOYSA-N OC1=NC(S)=NC2=C(CCCCC#N)C=NN12 Chemical compound OC1=NC(S)=NC2=C(CCCCC#N)C=NN12 LTJGCRSXJUTKSU-UHFFFAOYSA-N 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 108060006633 protein kinase Proteins 0.000 description 4
- CFKCDYDPMUYNSL-UHFFFAOYSA-N 3-[[5-(3-aminoanilino)-3-(4-carboxybutyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino]benzoic acid Chemical compound NC1=CC=CC(NC2=NC3=C(CCCCC(O)=O)C=NN3C(NC=3C=C(C=CC=3)C(O)=O)=C2)=C1 CFKCDYDPMUYNSL-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 3
- LLEVMYXEJUDBTA-UHFFFAOYSA-N heptanedinitrile Chemical compound N#CCCCCCC#N LLEVMYXEJUDBTA-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- WZCQRUWWHSTZEM-UHFFFAOYSA-N 1,3-phenylenediamine Chemical compound NC1=CC=CC(N)=C1 WZCQRUWWHSTZEM-UHFFFAOYSA-N 0.000 description 2
- YVFLDZOAIRMBNV-UHFFFAOYSA-N 5-(5-amino-1h-pyrazol-4-yl)pentanenitrile Chemical compound NC=1NN=CC=1CCCCC#N YVFLDZOAIRMBNV-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 102000052052 Casein Kinase II Human genes 0.000 description 2
- 108010010919 Casein Kinase II Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- BDTDECDAHYOJRO-UHFFFAOYSA-N ethyl n-(sulfanylidenemethylidene)carbamate Chemical compound CCOC(=O)N=C=S BDTDECDAHYOJRO-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- GNWBLLYJQXKPIP-ZOGIJGBBSA-N (1s,3as,3bs,5ar,9ar,9bs,11as)-n,n-diethyl-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1h-indeno[5,4-f]quinoline-1-carboxamide Chemical compound CN([C@@H]1CC2)C(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)N(CC)CC)[C@@]2(C)CC1 GNWBLLYJQXKPIP-ZOGIJGBBSA-N 0.000 description 1
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 1
- MXUKTFBCWISLPC-UHFFFAOYSA-N 2-(3-aminoanilino)acetic acid Chemical compound NC1=CC=CC(NCC(O)=O)=C1 MXUKTFBCWISLPC-UHFFFAOYSA-N 0.000 description 1
- WIAAIYJUCDAKFY-UHFFFAOYSA-N 3-(4-methoxyphenyl)-9-(prop-2-ynylamino)pyrido[1,2]thieno[3,4-d]pyrimidin-4-one Chemical compound C1=CC(OC)=CC=C1N1C(=O)C(SC=2C3=C(NCC#C)C=CN=2)=C3N=C1 WIAAIYJUCDAKFY-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
- UUOFSRVHZJTWDE-UHFFFAOYSA-N 3-chloro-3-oxopropanoic acid Chemical compound OC(=O)CC(Cl)=O UUOFSRVHZJTWDE-UHFFFAOYSA-N 0.000 description 1
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
- XHSQDZXAVJRBMX-DDHJBXDOSA-N 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=CC(Cl)=C(Cl)C=C2N=C1 XHSQDZXAVJRBMX-DDHJBXDOSA-N 0.000 description 1
- GADZYJKFSRPXNO-UHFFFAOYSA-N 5-(2-benzylsulfanyl-4-chloropyrazolo[1,5-a][1,3,5]triazin-8-yl)pentanenitrile Chemical compound N=1C2=C(CCCCC#N)C=NN2C(Cl)=NC=1SCC1=CC=CC=C1 GADZYJKFSRPXNO-UHFFFAOYSA-N 0.000 description 1
- VXZOLMXCNOCEGB-UHFFFAOYSA-N 5-(5,7-dichloropyrazolo[1,5-a]pyrimidin-3-yl)pentanenitrile Chemical compound N1=C(Cl)C=C(Cl)N2N=CC(CCCCC#N)=C21 VXZOLMXCNOCEGB-UHFFFAOYSA-N 0.000 description 1
- IFNRUIJNTRYQPC-UHFFFAOYSA-N 5-(7-hydroxy-5-oxo-4H-pyrazolo[1,5-a]pyrimidin-3-yl)pentanenitrile Chemical compound N1=C(O)C=C(O)N2N=CC(CCCCC#N)=C21 IFNRUIJNTRYQPC-UHFFFAOYSA-N 0.000 description 1
- QTYQWILQKGANCI-UHFFFAOYSA-N 5-[2-benzylsulfonyl-4-(cyclopropylamino)pyrazolo[1,5-a][1,3,5]triazin-8-yl]pentanenitrile Chemical compound N1=C(NC2CC2)N2N=CC(CCCCC#N)=C2N=C1S(=O)(=O)CC1=CC=CC=C1 QTYQWILQKGANCI-UHFFFAOYSA-N 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- ZICRALLMHKILDG-UHFFFAOYSA-N 5-propan-2-yl-1h-pyrazole Chemical compound CC(C)C1=CC=NN1 ZICRALLMHKILDG-UHFFFAOYSA-N 0.000 description 1
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102100030011 Endoribonuclease Human genes 0.000 description 1
- 101710199605 Endoribonuclease Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- 101001128692 Mus musculus Neuroendocrine convertase 1 Proteins 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 101100133350 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) nhp-1 gene Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 101710113029 Serine/threonine-protein kinase Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Natural products C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 238000005574 benzylation reaction Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 125000000332 coumarinyl group Chemical class O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 238000006298 dechlorination reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- VASFLQKDXBAWEL-UHFFFAOYSA-N emodin Natural products OC1=C(OC2=C(C=CC(=C2C1=O)O)O)C1=CC=C(C=C1)O VASFLQKDXBAWEL-UHFFFAOYSA-N 0.000 description 1
- VVEKCQAFOLKNKB-UHFFFAOYSA-N emodine Natural products C1=CC=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1O VVEKCQAFOLKNKB-UHFFFAOYSA-N 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- MASIFJQPMIZOKN-UHFFFAOYSA-N ethyl 3-[[5-(3-aminoanilino)-3-(4-cyanobutyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino]benzoate Chemical compound CCOC(=O)C1=CC=CC(NC=2N3N=CC(CCCCC#N)=C3N=C(NC=3C=C(N)C=CC=3)C=2)=C1 MASIFJQPMIZOKN-UHFFFAOYSA-N 0.000 description 1
- KWFADUNOPOSMIJ-UHFFFAOYSA-N ethyl 3-chloro-3-oxopropanoate Chemical compound CCOC(=O)CC(Cl)=O KWFADUNOPOSMIJ-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- 150000002678 macrocyclic compounds Chemical class 0.000 description 1
- 238000005710 macrocyclization reaction Methods 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 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
- 230000036210 malignancy Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- CZGIEJXGCLWRPY-UHFFFAOYSA-N n,1-dimethylpyrrolidin-3-amine Chemical compound CNC1CCN(C)C1 CZGIEJXGCLWRPY-UHFFFAOYSA-N 0.000 description 1
- AVAWMINJNRAQFS-UHFFFAOYSA-N n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)C1CCNC1 AVAWMINJNRAQFS-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229930029653 phosphoenolpyruvate Natural products 0.000 description 1
- DTBNBXWJWCWCIK-UHFFFAOYSA-N phosphoenolpyruvic acid Chemical compound OC(=O)C(=C)OP(O)(O)=O DTBNBXWJWCWCIK-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- JUXWUYWPUDKPSD-UHFFFAOYSA-N pyrazolo[1,5-a][1,3,5]triazine Chemical compound N1=CN=CN2N=CC=C21 JUXWUYWPUDKPSD-UHFFFAOYSA-N 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 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 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- ZMCBYSBVJIMENC-UHFFFAOYSA-N tricaine Chemical compound CCOC(=O)C1=CC=CC(N)=C1 ZMCBYSBVJIMENC-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/16—Peri-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US84531406P | 2006-09-18 | 2006-09-18 | |
| US60/845,314 | 2006-09-18 | ||
| US11/856,476 US7517882B2 (en) | 2006-09-18 | 2007-09-17 | Protein kinase inhibitors |
| US11/856,476 | 2007-09-17 | ||
| PCT/US2007/020231 WO2008036277A1 (en) | 2006-09-18 | 2007-09-18 | Pyraz0l0(l,5-a) (1, 3, 5) triazine and pyrazolo (1, 5-a) pyrimidine derivatives useful as protein kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0718459A2 true BRPI0718459A2 (pt) | 2013-12-03 |
Family
ID=39052753
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0718459-0A BRPI0718459A2 (pt) | 2006-09-18 | 2007-09-18 | Derivados de pirazolo(1,5-a) (1,3,5) triazina e pirazolo(1,5-a) pirimidina úteis como inibidores de proteína quinase |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US7517882B2 (enExample) |
| EP (1) | EP2064214B1 (enExample) |
| JP (1) | JP5232786B2 (enExample) |
| KR (1) | KR101418619B1 (enExample) |
| CN (1) | CN101522683B (enExample) |
| AU (1) | AU2007297675B2 (enExample) |
| BR (1) | BRPI0718459A2 (enExample) |
| CA (1) | CA2663791C (enExample) |
| ES (1) | ES2400450T3 (enExample) |
| TW (1) | TWI472530B (enExample) |
| WO (1) | WO2008036277A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7517882B2 (en) * | 2006-09-18 | 2009-04-14 | Polaris Group | Protein kinase inhibitors |
| JP5214799B2 (ja) * | 2008-04-07 | 2013-06-19 | アイアールエム・リミテッド・ライアビリティ・カンパニー | キナーゼ阻害剤としての化合物および組成物 |
| MX347765B (es) * | 2011-09-30 | 2017-05-12 | Oncodesign Sa | Inhibidores macrociclicos de la quinasa flt3. |
| CA2906262A1 (en) * | 2013-03-15 | 2014-09-18 | Oncodesign S.A. | Macrocyclic salt-inducible kinase inhibitors |
| CN103570728B (zh) * | 2013-11-12 | 2015-12-30 | 山东大学 | 一种取代吡唑并[1,5-a]嘧啶类衍生物及其制备方法与应用 |
| EP3268000B1 (en) * | 2015-03-09 | 2021-08-04 | Aurigene Discovery Technologies Limited | Pyrazolo[1,5-a][1,3,5]triazine and pyrazolo[1,5-a]pyrimidine derivatives as cdk inhibitors |
| AU2017302019A1 (en) * | 2016-07-28 | 2019-02-07 | Turning Point Therapeutics, Inc. | Macrocycle kinase inhibitors |
| RS66346B1 (sr) | 2018-10-22 | 2025-01-31 | Alumis Inc | Inhibitori tyk2 i njihova upotreba |
| US20220177486A1 (en) * | 2019-03-11 | 2022-06-09 | Esker Therapeutics, Inc. | Tyk2 inhibitors and uses thereof |
| SG11202110523XA (en) * | 2019-03-26 | 2021-10-28 | Ventyx Biosciences Inc | Tyk2 pseudokinase ligands |
| IL301385A (en) | 2020-09-16 | 2023-05-01 | Alumis Inc | TYK2 inhibitors and their use |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10255343B4 (de) | 2002-11-27 | 2006-09-07 | Nad Ag | N,N-Verbrückte, Stickstoff-Substituierte Carbacyclische Indolocarbazole als Proteinkinase-Inhibitoren |
| ES2436524T3 (es) * | 2003-05-22 | 2014-01-02 | Nerviano Medical Sciences S.R.L. | Derivados de pirazolo-quinazolina, procedimiento para su preparación y su uso como inhibidores de cinasas |
| MEP8409A (en) * | 2004-06-02 | 2011-12-20 | Fused heterocyclic compound | |
| US7517882B2 (en) * | 2006-09-18 | 2009-04-14 | Polaris Group | Protein kinase inhibitors |
-
2007
- 2007-09-17 US US11/856,476 patent/US7517882B2/en not_active Expired - Fee Related
- 2007-09-18 WO PCT/US2007/020231 patent/WO2008036277A1/en not_active Ceased
- 2007-09-18 CA CA2663791A patent/CA2663791C/en not_active Expired - Fee Related
- 2007-09-18 KR KR1020097005501A patent/KR101418619B1/ko not_active Expired - Fee Related
- 2007-09-18 ES ES07838443T patent/ES2400450T3/es active Active
- 2007-09-18 BR BRPI0718459-0A patent/BRPI0718459A2/pt not_active Application Discontinuation
- 2007-09-18 CN CN2007800342168A patent/CN101522683B/zh active Active
- 2007-09-18 AU AU2007297675A patent/AU2007297675B2/en not_active Ceased
- 2007-09-18 JP JP2009528344A patent/JP5232786B2/ja not_active Expired - Fee Related
- 2007-09-18 EP EP07838443A patent/EP2064214B1/en not_active Not-in-force
- 2007-09-19 TW TW96134833A patent/TWI472530B/zh not_active IP Right Cessation
-
2009
- 2009-03-03 US US12/396,919 patent/US20090247501A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008036277A1 (en) | 2008-03-27 |
| ES2400450T3 (es) | 2013-04-10 |
| EP2064214A1 (en) | 2009-06-03 |
| US20090247501A1 (en) | 2009-10-01 |
| JP2010503690A (ja) | 2010-02-04 |
| EP2064214B1 (en) | 2013-01-30 |
| TW200837065A (en) | 2008-09-16 |
| CA2663791C (en) | 2015-11-03 |
| CN101522683A (zh) | 2009-09-02 |
| TWI472530B (zh) | 2015-02-11 |
| JP5232786B2 (ja) | 2013-07-10 |
| KR101418619B1 (ko) | 2014-07-14 |
| HK1135688A1 (en) | 2010-06-11 |
| CN101522683B (zh) | 2013-02-27 |
| AU2007297675B2 (en) | 2012-09-20 |
| AU2007297675A1 (en) | 2008-03-27 |
| US7517882B2 (en) | 2009-04-14 |
| US20080070893A1 (en) | 2008-03-20 |
| KR20090083889A (ko) | 2009-08-04 |
| CA2663791A1 (en) | 2008-03-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2400450T3 (es) | Derivados de pirazolo[1,5-a][1,3,5]triazina y pirazolo[1,5-a]pirimidina para uso como inhibidores de la proteina quinasa | |
| AU2007316417B2 (en) | Imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine derivatives and their use as protein kinase inhibitors | |
| AU2007332440B2 (en) | Quinoxaline derivative | |
| US9422297B2 (en) | Tricyclic compounds having cytostatic and/or cytotoxic activity and methods of use thereof | |
| CA2896711A1 (en) | 2,3-dihydro-isoindol-1-one derivatives and methods of use thereof as btk inhibitor | |
| EP2121634A1 (en) | Pyrimidine-2,4-diamine derivatives and their use as jak2 kinase inhibitors | |
| KR20210136995A (ko) | 브루톤 티로신 키나아제 억제제 | |
| CN109721600B (zh) | 一类含氮稠环化合物及其制备方法和用途 | |
| CA2604284A1 (en) | Protein kinase inhibitors | |
| JP2021506935A (ja) | ピリミジン誘導体系キナーゼ阻害剤類 | |
| EP4186902A1 (en) | Salt of dihydropyrido[2,3-d]pyrimidinone derivative, preparation method therefor, and use thereof | |
| EP3397640B1 (en) | Xanthine derivative inhibitors of bet proteins | |
| Akgül et al. | Unconventional amino acids in medicinal chemistry: First report on taurine merged within carbonic anhydrase inhibitors | |
| PL236355B1 (pl) | Pochodne 7-(morfolin-4-ylo)pirazolo[1,5-α]pirymidyny jako inhibitory kinazy PI3 | |
| EP3380476B1 (en) | Fused pyrimidines as isoform selective phosphoinositide-3-kinase-alpha inhibitors and process for preparation thereof | |
| Karaali et al. | Synthesis and urease inhibition study of some new quinazolinone derivatives bearing triazole, thiadiazole, and piperazine moiety | |
| BRPI0619955A2 (pt) | derivados tricìclicos da lactama, sua produção e seus usos como agentes farmacêuticos | |
| CN119285624B (zh) | 一种含噻吩的嘧啶类化合物及其制备方法与在制备具有抗癌作用的药物中的应用 | |
| HK1135688B (en) | Pyrazolo (1,5-a)(1,3,5) triazine and pyrazolo (1,5-a) pyrimidine derivatives useful as protein kinase inhibitors | |
| US10040803B2 (en) | 4-((2-acrylamidophenyl)amino)thieno[3,2-D]pyrimidine-7-carboxamide derivatives as protein kinase inhibitors | |
| WO2025149623A1 (en) | Wnk1 inhibitors | |
| KR20010086658A (ko) | 벤조디아제핀 유도체 및 이를 함유하는 싸이클린 의존키나아제 저해제 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B07D | Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette] |
Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. |
|
| B06F | Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette] | ||
| B07E | Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette] | ||
| B06U | Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette] | ||
| B11B | Dismissal acc. art. 36, par 1 of ipl - no reply within 90 days to fullfil the necessary requirements |