ES2639293T3 - Derivados de oxazolina terapéuticamente activos - Google Patents
Derivados de oxazolina terapéuticamente activos Download PDFInfo
- Publication number
- ES2639293T3 ES2639293T3 ES13776992.3T ES13776992T ES2639293T3 ES 2639293 T3 ES2639293 T3 ES 2639293T3 ES 13776992 T ES13776992 T ES 13776992T ES 2639293 T3 ES2639293 T3 ES 2639293T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- amino
- heteroaryl
- aryl
- optionally substituted
- 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.)
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- 125000003504 2-oxazolinyl group Chemical class O1C(=NCC1)* 0.000 title 1
- -1 hydroxy, hydroxy Chemical group 0.000 claims abstract description 305
- 150000001875 compounds Chemical class 0.000 claims abstract description 152
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 114
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 111
- 239000001257 hydrogen Substances 0.000 claims abstract description 111
- 125000001424 substituent group Chemical group 0.000 claims abstract description 103
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 77
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 72
- 125000003118 aryl group Chemical group 0.000 claims abstract description 62
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 49
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 39
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 33
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 31
- 150000002367 halogens Chemical class 0.000 claims abstract description 31
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 22
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 22
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims abstract description 19
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 19
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 18
- 239000012453 solvate Substances 0.000 claims abstract description 18
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims abstract description 17
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 17
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims abstract description 16
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 16
- 125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims abstract description 15
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 15
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 14
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims abstract description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 14
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 13
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 13
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims abstract description 12
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims abstract description 12
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims abstract description 12
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 12
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 11
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 9
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 9
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 8
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 6
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims abstract description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 5
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims abstract description 5
- 125000005530 alkylenedioxy group Chemical group 0.000 claims abstract description 5
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims abstract description 5
- 125000005647 linker group Chemical group 0.000 claims abstract description 5
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 5
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 4
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims abstract description 4
- 125000004171 alkoxy aryl group Chemical group 0.000 claims abstract description 3
- 125000001769 aryl amino group Chemical group 0.000 claims abstract description 3
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims abstract description 3
- 125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims abstract description 3
- 125000004996 haloaryloxy group Chemical group 0.000 claims abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims abstract 2
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims abstract 2
- 150000002431 hydrogen Chemical group 0.000 claims abstract 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 35
- 210000000056 organ Anatomy 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 11
- 208000023275 Autoimmune disease Diseases 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- IVXQBCUBSIPQGU-UHFFFAOYSA-N piperazine-1-carboxamide Chemical compound NC(=O)N1CCNCC1 IVXQBCUBSIPQGU-UHFFFAOYSA-N 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 230000002757 inflammatory effect Effects 0.000 claims description 5
- 230000003612 virological effect Effects 0.000 claims description 5
- 125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims description 4
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 claims 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 1
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 abstract description 3
- 239000002904 solvent Substances 0.000 description 60
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 54
- 239000000543 intermediate Substances 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 43
- 238000000034 method Methods 0.000 description 43
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 30
- 230000008569 process Effects 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 23
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- 239000002585 base Substances 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- 238000007429 general method Methods 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 230000014759 maintenance of location Effects 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 10
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 8
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 125000001544 thienyl group Chemical group 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 7
- 125000003386 piperidinyl group Chemical group 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000007822 coupling agent Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 150000007530 organic bases Chemical class 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 125000003944 tolyl group Chemical group 0.000 description 6
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 230000001363 autoimmune Effects 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 5
- 230000002140 halogenating effect Effects 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 125000003282 alkyl amino group Chemical group 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 125000001041 indolyl group Chemical group 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 4
- 125000002757 morpholinyl group Chemical group 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
- 125000003107 substituted aryl group Chemical group 0.000 description 4
- 125000001984 thiazolidinyl group Chemical group 0.000 description 4
- 125000000335 thiazolyl group Chemical group 0.000 description 4
- DDWBRNXDKNIQDY-UHFFFAOYSA-N thieno[2,3-d]pyrimidine Chemical compound N1=CN=C2SC=CC2=C1 DDWBRNXDKNIQDY-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- DMTPHHCZCSWKLM-UHFFFAOYSA-N 2-amino-4-[4-[(4-methoxy-2-methylphenyl)carbamoyl]piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylic acid Chemical compound COc1ccc(NC(=O)N2CCN(CC2)c2nc(N)nc3scc(C(O)=O)c23)c(C)c1 DMTPHHCZCSWKLM-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000709661 Enterovirus Species 0.000 description 3
- 241000531123 GB virus C Species 0.000 description 3
- 241000282414 Homo sapiens Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 3
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 3
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
- 150000002918 oxazolines Chemical class 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 125000004344 phenylpropyl group Chemical group 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000003373 pyrazinyl group Chemical group 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 125000006513 pyridinyl methyl group Chemical group 0.000 description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 3
- 238000005245 sintering Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
- HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical compound CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/424—Oxazoles condensed with heterocyclic ring systems, e.g. clavulanic acid
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| GBGB1217704.4A GB201217704D0 (en) | 2012-10-03 | 2012-10-03 | Therapeutic agents |
| GB201217704 | 2012-10-03 | ||
| PCT/EP2013/070600 WO2014053581A1 (en) | 2012-10-03 | 2013-10-02 | Therapeutically active oxazoline derivatives |
Publications (1)
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| ES2639293T3 true ES2639293T3 (es) | 2017-10-26 |
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| ES13776992.3T Active ES2639293T3 (es) | 2012-10-03 | 2013-10-02 | Derivados de oxazolina terapéuticamente activos |
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| EP (1) | EP2903990B1 (enExample) |
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| IN (1) | IN2015DN03751A (enExample) |
| RU (1) | RU2656209C2 (enExample) |
| WO (1) | WO2014053581A1 (enExample) |
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| US10526341B2 (en) | 2014-11-19 | 2020-01-07 | Memorial Sloan-Kettering Cancer Center | Thienopyrimidines and uses thereof |
| TWI703150B (zh) * | 2015-06-04 | 2020-09-01 | 美商庫拉腫瘤技術股份有限公司 | 用於抑制ｍｅｎｉｎ及ｍｌｌ蛋白之交互作用的方法及組合物 |
| GB201517263D0 (en) | 2015-09-30 | 2015-11-11 | Ucb Biopharma Sprl And Katholieke Universiteit Leuven | Therapeutic agents |
| GB201521767D0 (en) | 2015-12-10 | 2016-01-27 | Ucb Biopharma Sprl And Katholieke Universiteit Leuven K U Leuven R&D | Therapeutic agents |
| EP3429591B1 (en) | 2016-03-16 | 2023-03-15 | Kura Oncology, Inc. | Substituted thieno[2,3-d]pyrimidine derivatives as inhibitors of menin-mll and methods of use |
| US11944627B2 (en) | 2017-03-24 | 2024-04-02 | Kura Oncology, Inc. | Methods for treating hematological malignancies and Ewing's sarcoma |
| US11542248B2 (en) | 2017-06-08 | 2023-01-03 | Kura Oncology, Inc. | Methods and compositions for inhibiting the interaction of menin with MLL proteins |
| TW201920170A (zh) | 2017-09-20 | 2019-06-01 | 美商庫拉腫瘤技術股份有限公司 | 經取代之menin-mll 抑制劑及使用方法 |
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| EP1274708A1 (en) * | 2000-04-17 | 2003-01-15 | Basf Aktiengesellschaft | Herbicidal 3-heterocyclic substituted benzisothiazole and benzisoxazole compounds |
| EP1675861B1 (en) * | 2003-08-29 | 2015-12-23 | Vernalis (R&D) Ltd. | Pyrimidothiophene compounds |
| US20080200475A1 (en) * | 2005-03-28 | 2008-08-21 | Pfizer Inc. | 4-Piperazinothieno[2,3-D] Pyrimidine Compounds As Platelet Aggregation Inhibitors |
| AU2009291783A1 (en) * | 2008-09-10 | 2010-03-18 | Alcon Research, Ltd | Aminopyrimidine inhibitors of histamine receptors for the treatment of disease |
| CA2754890C (en) * | 2009-03-13 | 2018-01-16 | Piet Herdewijn | Bicyclic heterocycles |
| CA2773131C (en) * | 2009-09-04 | 2015-07-14 | The Regents Of The University Of Michigan | Compositions and methods for treatment of leukemia |
| GB201012889D0 (en) | 2010-08-02 | 2010-09-15 | Univ Leuven Kath | Antiviral activity of novel bicyclic heterocycles |
| GB201015411D0 (en) | 2010-09-15 | 2010-10-27 | Univ Leuven Kath | Anti-cancer activity of novel bicyclic heterocycles |
| GB201114212D0 (en) * | 2011-08-18 | 2011-10-05 | Ucb Pharma Sa | Therapeutic agents |
| GB201119401D0 (en) * | 2011-11-10 | 2011-12-21 | Ucb Pharma Sa | Therapeutic agents |
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2013
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| CA2886265A1 (en) | 2014-04-10 |
| US9382263B2 (en) | 2016-07-05 |
| RU2015116643A (ru) | 2016-11-27 |
| CN104936962A (zh) | 2015-09-23 |
| GB201217704D0 (en) | 2012-11-14 |
| RU2656209C2 (ru) | 2018-06-01 |
| BR112015007503A2 (pt) | 2017-07-04 |
| EP2903990A1 (en) | 2015-08-12 |
| JP2015531388A (ja) | 2015-11-02 |
| CN104936962B (zh) | 2017-02-22 |
| JP6184501B2 (ja) | 2017-08-23 |
| EP2903990B1 (en) | 2017-06-14 |
| WO2014053581A1 (en) | 2014-04-10 |
| IN2015DN03751A (enExample) | 2015-10-02 |
| US20150274748A1 (en) | 2015-10-01 |
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