TW202313608A - ２，８—二氮雜螺［４．５］癸烷化合物 - Google Patents
２，８—二氮雜螺［４．５］癸烷化合物 Download PDFInfo
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- TW202313608A TW202313608A TW111120777A TW111120777A TW202313608A TW 202313608 A TW202313608 A TW 202313608A TW 111120777 A TW111120777 A TW 111120777A TW 111120777 A TW111120777 A TW 111120777A TW 202313608 A TW202313608 A TW 202313608A
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- alkyl
- compound
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- hydrogen
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- WYZZNMWIWHRXRM-UHFFFAOYSA-N 2,8-diazaspiro[4.5]decane Chemical class C1NCCC21CCNCC2 WYZZNMWIWHRXRM-UHFFFAOYSA-N 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 567
- 238000000034 method Methods 0.000 claims abstract description 114
- 239000000203 mixture Substances 0.000 claims abstract description 59
- 101001047642 Homo sapiens Serine/threonine-protein kinase LATS1 Proteins 0.000 claims abstract description 33
- 102100024031 Serine/threonine-protein kinase LATS1 Human genes 0.000 claims abstract description 33
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 642
- 229910052739 hydrogen Inorganic materials 0.000 claims description 383
- 239000001257 hydrogen Substances 0.000 claims description 383
- 125000001424 substituent group Chemical group 0.000 claims description 361
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 250
- -1 cyano, hydroxyl Chemical group 0.000 claims description 244
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 237
- 125000000623 heterocyclic group Chemical group 0.000 claims description 209
- 125000003118 aryl group Chemical group 0.000 claims description 179
- 150000003839 salts Chemical class 0.000 claims description 153
- 229910052736 halogen Inorganic materials 0.000 claims description 150
- 150000002367 halogens Chemical class 0.000 claims description 136
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 124
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 108
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 100
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 88
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 87
- 125000001072 heteroaryl group Chemical group 0.000 claims description 83
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 78
- 229910052757 nitrogen Inorganic materials 0.000 claims description 69
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 65
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 59
- 239000000460 chlorine Substances 0.000 claims description 53
- 239000001301 oxygen Substances 0.000 claims description 52
- 229910052760 oxygen Inorganic materials 0.000 claims description 52
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 51
- 229910052801 chlorine Inorganic materials 0.000 claims description 51
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 50
- 125000005842 heteroatom Chemical group 0.000 claims description 48
- 150000002431 hydrogen Chemical class 0.000 claims description 47
- 229910052731 fluorine Inorganic materials 0.000 claims description 45
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 44
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 44
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 44
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 43
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 40
- 229910052799 carbon Inorganic materials 0.000 claims description 40
- 201000010099 disease Diseases 0.000 claims description 39
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 39
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 35
- 229910052717 sulfur Chemical group 0.000 claims description 35
- 239000011593 sulfur Chemical group 0.000 claims description 35
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 33
- 239000011737 fluorine Substances 0.000 claims description 33
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 31
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 31
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 27
- 125000006239 protecting group Chemical group 0.000 claims description 26
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 23
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 21
- 229910052794 bromium Inorganic materials 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 21
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 20
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 20
- 229910052698 phosphorus Inorganic materials 0.000 claims description 20
- 229910052740 iodine Inorganic materials 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000001153 fluoro group Chemical group F* 0.000 claims description 17
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 16
- 125000004429 atom Chemical group 0.000 claims description 16
- 239000003638 chemical reducing agent Substances 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 16
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
- 125000002950 monocyclic group Chemical group 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 238000006467 substitution reaction Methods 0.000 claims description 11
- 125000006085 pyrrolopyridyl group Chemical group 0.000 claims description 10
- 125000004437 phosphorous atom Chemical group 0.000 claims description 9
- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 6
- 239000012190 activator Substances 0.000 claims description 6
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- 125000004501 isothiazol-5-yl group Chemical group S1N=CC=C1* 0.000 claims description 6
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
- 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 150000001924 cycloalkanes Chemical class 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims 1
- 150000001204 N-oxides Chemical class 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 14
- 239000003112 inhibitor Substances 0.000 abstract description 6
- JXOOWAHOIVVXTO-UHFFFAOYSA-N C1C2(CCNCC2)C(C2=CC=NC3=CN=CC=C23)NC1 Chemical class C1C2(CCNCC2)C(C2=CC=NC3=CN=CC=C23)NC1 JXOOWAHOIVVXTO-UHFFFAOYSA-N 0.000 abstract 1
- WQTPVGBGEZLEPX-UHFFFAOYSA-N C1C2(CCNCC2)C(C2=NC=CC3=CN=CC=C23)NC1 Chemical class C1C2(CCNCC2)C(C2=NC=CC3=CN=CC=C23)NC1 WQTPVGBGEZLEPX-UHFFFAOYSA-N 0.000 abstract 1
- OULOWGOQURYEIL-UHFFFAOYSA-N C1C2(CCNCC2)C(C2=NC=NC3=C2C=CN=C3)NC1 Chemical class C1C2(CCNCC2)C(C2=NC=NC3=C2C=CN=C3)NC1 OULOWGOQURYEIL-UHFFFAOYSA-N 0.000 abstract 1
- 235000002639 sodium chloride Nutrition 0.000 description 135
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 71
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 60
- 125000004432 carbon atom Chemical group C* 0.000 description 59
- 239000007787 solid Substances 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- 239000002585 base Substances 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 101001047637 Homo sapiens Serine/threonine-protein kinase LATS2 Proteins 0.000 description 30
- 102100024043 Serine/threonine-protein kinase LATS2 Human genes 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 29
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 125000005843 halogen group Chemical group 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- XLSMFKSTNGKWQX-UHFFFAOYSA-N hydroxyacetone Chemical compound CC(=O)CO XLSMFKSTNGKWQX-UHFFFAOYSA-N 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- 239000000651 prodrug Substances 0.000 description 19
- 229940002612 prodrug Drugs 0.000 description 19
- 239000002253 acid Substances 0.000 description 17
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- 239000002207 metabolite Substances 0.000 description 14
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 13
- 239000011574 phosphorus Chemical group 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- 230000017423 tissue regeneration Effects 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- LIMFPAAAIVQRRD-BCGVJQADSA-N N-[2-[(3S,4R)-3-fluoro-4-methoxypiperidin-1-yl]pyrimidin-4-yl]-8-[(2R,3S)-2-methyl-3-(methylsulfonylmethyl)azetidin-1-yl]-5-propan-2-ylisoquinolin-3-amine Chemical compound F[C@H]1CN(CC[C@H]1OC)C1=NC=CC(=N1)NC=1N=CC2=C(C=CC(=C2C=1)C(C)C)N1[C@@H]([C@H](C1)CS(=O)(=O)C)C LIMFPAAAIVQRRD-BCGVJQADSA-N 0.000 description 12
- 239000007832 Na2SO4 Substances 0.000 description 12
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 12
- 208000027418 Wounds and injury Diseases 0.000 description 12
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 12
- 125000002947 alkylene group Chemical group 0.000 description 12
- 125000001309 chloro group Chemical group Cl* 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 208000014674 injury Diseases 0.000 description 12
- 150000007530 organic bases Chemical class 0.000 description 12
- 125000004122 cyclic group Chemical group 0.000 description 11
- 125000000753 cycloalkyl group Chemical group 0.000 description 11
- 230000006378 damage Effects 0.000 description 11
- 150000007529 inorganic bases Chemical class 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 239000012453 solvate Substances 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- GJBAVSCFKIVOKU-UHFFFAOYSA-N CC1=NNC=C1C1=NC(C=NC(CN2N=CC(Cl)=C2)=C2)=C2C(N2CCC3(CN(C)CC3)CC2)=N1 Chemical compound CC1=NNC=C1C1=NC(C=NC(CN2N=CC(Cl)=C2)=C2)=C2C(N2CCC3(CN(C)CC3)CC2)=N1 GJBAVSCFKIVOKU-UHFFFAOYSA-N 0.000 description 10
- JMMSATQCDJFHAW-INIZCTEOSA-N OC[C@H](C1)NCC1(CC1)CCN1C1=NC(C2=CC=NC=C2)=NC2=C1C=CN=C2 Chemical compound OC[C@H](C1)NCC1(CC1)CCN1C1=NC(C2=CC=NC=C2)=NC2=C1C=CN=C2 JMMSATQCDJFHAW-INIZCTEOSA-N 0.000 description 10
- 230000008901 benefit Effects 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 230000001737 promoting effect Effects 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 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 9
- ZHGNHOOVYPHPNJ-UHFFFAOYSA-N Amigdalin Chemical compound FC(F)(F)C(=O)OCC1OC(OCC2OC(OC(C#N)C3=CC=CC=C3)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C2OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C1OC(=O)C(F)(F)F ZHGNHOOVYPHPNJ-UHFFFAOYSA-N 0.000 description 9
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 9
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 9
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 9
- PAQYIEZTLSDLQO-UHFFFAOYSA-N pyrido[3,4-d]pyrimidine Chemical compound N1=CN=C2C=NC=CC2=C1 PAQYIEZTLSDLQO-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- PQUSVJVVRXWKDG-UHFFFAOYSA-N methyl 2-bromo-2-methylpropanoate Chemical compound COC(=O)C(C)(C)Br PQUSVJVVRXWKDG-UHFFFAOYSA-N 0.000 description 8
- 238000004808 supercritical fluid chromatography Methods 0.000 description 8
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 7
- 108700038175 YAP-Signaling Proteins Proteins 0.000 description 7
- 235000011054 acetic acid Nutrition 0.000 description 7
- 125000003342 alkenyl group Chemical group 0.000 description 7
- 125000005907 alkyl ester group Chemical group 0.000 description 7
- 125000000304 alkynyl group Chemical group 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 235000019253 formic acid Nutrition 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 description 7
- 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 7
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 229920002554 vinyl polymer Polymers 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000012467 final product Substances 0.000 description 5
- 150000002430 hydrocarbons Chemical class 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 4
- PANBXEPRTUWMHA-UHFFFAOYSA-N C(CNC1)C1(CC1)CCN1C1=NC(C2=CC=NC=C2)=NC2=C1C=CN=C2 Chemical compound C(CNC1)C1(CC1)CCN1C1=NC(C2=CC=NC=C2)=NC2=C1C=CN=C2 PANBXEPRTUWMHA-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
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- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- 125000001793 isothiazol-3-yl group Chemical group [H]C1=C([H])C(*)=NS1 0.000 description 1
- 125000004500 isothiazol-4-yl group Chemical group S1N=CC(=C1)* 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 231100000515 lung injury Toxicity 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 235000012245 magnesium oxide Nutrition 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 229940017219 methyl propionate Drugs 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000003136 n-heptyl group Chemical class [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical class C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000008184 oral solid dosage form Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
- PXDVPPINZKNVNF-UHFFFAOYSA-N oxetane-3-carbonitrile Chemical compound N#CC1COC1 PXDVPPINZKNVNF-UHFFFAOYSA-N 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- JLPJFSCQKHRSQR-UHFFFAOYSA-N oxolan-3-one Chemical compound O=C1CCOC1 JLPJFSCQKHRSQR-UHFFFAOYSA-N 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- PENAXHPKEVTBLF-UHFFFAOYSA-L palladium(2+);prop-1-ene;dichloride Chemical compound [Pd+]Cl.[Pd+]Cl.[CH2-]C=C.[CH2-]C=C PENAXHPKEVTBLF-UHFFFAOYSA-L 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 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
- 210000000664 rectum Anatomy 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000004950 trifluoroalkyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—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
- 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
- C07D471/10—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Pens And Brushes (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2021098358 | 2021-06-04 | ||
| WOPCT/CN2021/098358 | 2021-06-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202313608A true TW202313608A (zh) | 2023-04-01 |
Family
ID=84322789
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW111120777A TW202313608A (zh) | 2021-06-04 | 2022-06-03 | ２，８—二氮雜螺［４．５］癸烷化合物 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20240174696A1 (https=) |
| EP (1) | EP4347594A4 (https=) |
| JP (1) | JP2024521929A (https=) |
| KR (1) | KR20240016977A (https=) |
| CN (1) | CN117425654A (https=) |
| AR (1) | AR126078A1 (https=) |
| AU (1) | AU2022284188A1 (https=) |
| BR (1) | BR112023025393A2 (https=) |
| CA (1) | CA3222054A1 (https=) |
| TW (1) | TW202313608A (https=) |
| WO (1) | WO2022253341A1 (https=) |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101679418A (zh) * | 2007-04-06 | 2010-03-24 | 诺瓦提斯公司 | 用作蛋白质激酶抑制剂的[2,6]萘啶类化合物 |
| JP2011529932A (ja) * | 2008-08-05 | 2011-12-15 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 置換ナフチリジン及び医薬としてのその使用 |
| WO2012167423A1 (en) * | 2011-06-08 | 2012-12-13 | Hutchison Medipharma Limited | Substituted pyridopyrazines as novel syk inhibitors |
| KR20140048216A (ko) * | 2011-06-29 | 2014-04-23 | 오츠카 세이야쿠 가부시키가이샤 | 치료 화합물로서의 퀴나졸린 및 관련된 사용 방법 |
| TWI675836B (zh) * | 2014-03-25 | 2019-11-01 | 美商伊格尼塔公司 | 非典型蛋白質激酶ｃ之氮雜喹唑啉抑制劑 |
| JOP20190257A1 (ar) * | 2017-04-28 | 2019-10-28 | Novartis Ag | مركبات أريل غير متجانسة ثنائية الحلقة مندمجة 6-6 واستخدامها كمثبطات lats |
| KR102328435B1 (ko) * | 2018-09-11 | 2021-11-18 | 재단법인 대구경북첨단의료산업진흥재단 | 신규 피리도-피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 단백질 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물 |
| WO2021050059A1 (en) * | 2019-09-11 | 2021-03-18 | Provincial Health Services Authority | Dna-pk inhibiting compounds |
-
2022
- 2022-06-03 JP JP2023574635A patent/JP2024521929A/ja active Pending
- 2022-06-03 AU AU2022284188A patent/AU2022284188A1/en active Pending
- 2022-06-03 CA CA3222054A patent/CA3222054A1/en active Pending
- 2022-06-03 BR BR112023025393A patent/BR112023025393A2/pt unknown
- 2022-06-03 AR ARP220101483A patent/AR126078A1/es not_active Application Discontinuation
- 2022-06-03 TW TW111120777A patent/TW202313608A/zh unknown
- 2022-06-03 WO PCT/CN2022/097025 patent/WO2022253341A1/en not_active Ceased
- 2022-06-03 EP EP22815380.5A patent/EP4347594A4/en active Pending
- 2022-06-03 KR KR1020237042291A patent/KR20240016977A/ko active Pending
- 2022-06-03 CN CN202280039813.4A patent/CN117425654A/zh active Pending
-
2023
- 2023-12-01 US US18/526,572 patent/US20240174696A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN117425654A (zh) | 2024-01-19 |
| AU2022284188A1 (en) | 2023-11-30 |
| WO2022253341A1 (en) | 2022-12-08 |
| AR126078A1 (es) | 2023-09-06 |
| EP4347594A1 (en) | 2024-04-10 |
| BR112023025393A2 (pt) | 2024-02-27 |
| KR20240016977A (ko) | 2024-02-06 |
| US20240174696A1 (en) | 2024-05-30 |
| JP2024521929A (ja) | 2024-06-04 |
| EP4347594A4 (en) | 2025-06-18 |
| CA3222054A1 (en) | 2022-12-08 |
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