TW201900180A - 嘧啶衍生物 - Google Patents
嘧啶衍生物 Download PDFInfo
- Publication number
- TW201900180A TW201900180A TW107116760A TW107116760A TW201900180A TW 201900180 A TW201900180 A TW 201900180A TW 107116760 A TW107116760 A TW 107116760A TW 107116760 A TW107116760 A TW 107116760A TW 201900180 A TW201900180 A TW 201900180A
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- TW
- Taiwan
- Prior art keywords
- pyrimidin
- ethoxy
- ethylamino
- alkyl
- methoxy
- Prior art date
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- 150000003230 pyrimidines Chemical class 0.000 title abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 354
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 117
- 201000011510 cancer Diseases 0.000 claims abstract description 71
- 238000011282 treatment Methods 0.000 claims abstract description 47
- 150000003839 salts Chemical class 0.000 claims abstract description 43
- 239000003814 drug Substances 0.000 claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 230000028993 immune response Effects 0.000 claims abstract description 10
- 210000000987 immune system Anatomy 0.000 claims abstract description 10
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 230000007420 reactivation Effects 0.000 claims abstract description 5
- -1 cyclopropyl-1,1-diyl Chemical group 0.000 claims description 939
- 125000000217 alkyl group Chemical group 0.000 claims description 253
- 238000000034 method Methods 0.000 claims description 150
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 149
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 123
- 229910052739 hydrogen Inorganic materials 0.000 claims description 117
- 239000001257 hydrogen Substances 0.000 claims description 117
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 94
- 125000001424 substituent group Chemical group 0.000 claims description 85
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 73
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 65
- 125000004429 atom Chemical group 0.000 claims description 62
- 125000002947 alkylene group Chemical group 0.000 claims description 61
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 59
- 239000004593 Epoxy Substances 0.000 claims description 58
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 57
- 125000003545 alkoxy group Chemical group 0.000 claims description 51
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 50
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 39
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 38
- 125000003118 aryl group Chemical group 0.000 claims description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 33
- 150000002367 halogens Chemical class 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 239000000460 chlorine Substances 0.000 claims description 25
- 239000012634 fragment Substances 0.000 claims description 25
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- 239000011737 fluorine Substances 0.000 claims description 22
- 229910052731 fluorine Inorganic materials 0.000 claims description 22
- 238000001959 radiotherapy Methods 0.000 claims description 22
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 239000001301 oxygen Substances 0.000 claims description 20
- 150000001412 amines Chemical class 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 17
- 125000001544 thienyl group Chemical group 0.000 claims description 17
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 16
- 239000004480 active ingredient Substances 0.000 claims description 16
- 238000002626 targeted therapy Methods 0.000 claims description 15
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 14
- 125000002619 bicyclic group Chemical group 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 125000001041 indolyl group Chemical group 0.000 claims description 14
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 14
- 229920006395 saturated elastomer Polymers 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 13
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 12
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 11
- 239000002246 antineoplastic agent Substances 0.000 claims description 11
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 10
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 9
- 206010005003 Bladder cancer Diseases 0.000 claims description 9
- 206010029260 Neuroblastoma Diseases 0.000 claims description 9
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 9
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 8
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 8
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 229940127089 cytotoxic agent Drugs 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 201000005202 lung cancer Diseases 0.000 claims description 8
- 208000020816 lung neoplasm Diseases 0.000 claims description 8
- 201000001441 melanoma Diseases 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 230000004770 neurodegeneration Effects 0.000 claims description 8
- 230000002265 prevention Effects 0.000 claims description 8
- 229910052717 sulfur Chemical group 0.000 claims description 8
- CTQPPUPWHLGKOB-UHFFFAOYSA-N 4h-oxadiazol-5-one Chemical compound O=C1CN=NO1 CTQPPUPWHLGKOB-UHFFFAOYSA-N 0.000 claims description 7
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 7
- 206010014733 Endometrial cancer Diseases 0.000 claims description 7
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 7
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 7
- 206010033128 Ovarian cancer Diseases 0.000 claims description 7
- 208000002193 Pain Diseases 0.000 claims description 7
- 206010038389 Renal cancer Diseases 0.000 claims description 7
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 7
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 7
- 201000010881 cervical cancer Diseases 0.000 claims description 7
- 201000010982 kidney cancer Diseases 0.000 claims description 7
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
- 208000011580 syndromic disease Diseases 0.000 claims description 7
- 201000009273 Endometriosis Diseases 0.000 claims description 6
- 206010035664 Pneumonia Diseases 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
- 230000000302 ischemic effect Effects 0.000 claims description 6
- 208000030761 polycystic kidney disease Diseases 0.000 claims description 6
- 230000000392 somatic effect Effects 0.000 claims description 6
- 239000011593 sulfur Chemical group 0.000 claims description 6
- 230000035558 fertility Effects 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- 125000005605 benzo group Chemical group 0.000 claims description 4
- 229960004365 benzoic acid Drugs 0.000 claims description 4
- 239000012829 chemotherapy agent Substances 0.000 claims description 4
- 150000003553 thiiranes Chemical group 0.000 claims description 4
- VUEONTPMDHNVHR-UHFFFAOYSA-N C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C2C=CNC2=CC=C1)C1=NOC(N1)=O Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C2C=CNC2=CC=C1)C1=NOC(N1)=O VUEONTPMDHNVHR-UHFFFAOYSA-N 0.000 claims description 3
- BKLHWNXTURQKNF-UHFFFAOYSA-N C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC=1C=CC=C2C=CC=NC=12)C1=NOC(N1)=O Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC=1C=CC=C2C=CC=NC=12)C1=NOC(N1)=O BKLHWNXTURQKNF-UHFFFAOYSA-N 0.000 claims description 3
- YZZPXLJBWJDUCV-UHFFFAOYSA-N N1C=CC2=CC=CC(=C12)CCNC1=CC(=NC=N1)C1=CC(=C(S1)C1=NOC(=N1)O)OCC Chemical compound N1C=CC2=CC=CC(=C12)CCNC1=CC(=NC=N1)C1=CC(=C(S1)C1=NOC(=N1)O)OCC YZZPXLJBWJDUCV-UHFFFAOYSA-N 0.000 claims description 3
- BOWYQHCFTNADQJ-UHFFFAOYSA-N OC1=CN=NO1 Chemical compound OC1=CN=NO1 BOWYQHCFTNADQJ-UHFFFAOYSA-N 0.000 claims description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- YELLUWAGQVKCEQ-ZHACJKMWSA-N (E)-3-[3-ethoxy-5-[6-[2-(2-methoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]thiophen-2-yl]prop-2-enoic acid Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OC)/C=C/C(=O)O YELLUWAGQVKCEQ-ZHACJKMWSA-N 0.000 claims description 2
- PDQRQJVPEFGVRK-UHFFFAOYSA-N 2,1,3-benzothiadiazole Chemical compound C1=CC=CC2=NSN=C21 PDQRQJVPEFGVRK-UHFFFAOYSA-N 0.000 claims description 2
- LGPAAAVNLKVZLA-UHFFFAOYSA-N 2-(2-hydroxyethoxy)-4-[6-[2-(2-methoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound OCCOC1=C(C(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OC LGPAAAVNLKVZLA-UHFFFAOYSA-N 0.000 claims description 2
- MSOOEGZULITGAO-UHFFFAOYSA-N 2-[2-ethoxy-4-[6-[2-(5-fluoronaphthalen-1-yl)ethylamino]pyrimidin-4-yl]phenyl]acetic acid Chemical compound C(C)OC1=C(C=CC(=C1)C1=NC=NC(=C1)NCCC1=CC=CC2=C(C=CC=C12)F)CC(=O)O MSOOEGZULITGAO-UHFFFAOYSA-N 0.000 claims description 2
- GEKANDQYTKFKRR-UHFFFAOYSA-N 2-[2-ethoxy-4-[6-[2-(5-methylnaphthalen-1-yl)ethylamino]pyrimidin-4-yl]phenyl]acetic acid Chemical compound C(C)OC1=C(C=CC(=C1)C1=NC=NC(=C1)NCCC1=CC=CC2=C(C=CC=C12)C)CC(=O)O GEKANDQYTKFKRR-UHFFFAOYSA-N 0.000 claims description 2
- AGTHGFJXPNXZFV-UHFFFAOYSA-N 2-[3-ethoxy-5-[6-[2-(2-methoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]thiophen-2-yl]acetic acid Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OC)CC(=O)O AGTHGFJXPNXZFV-UHFFFAOYSA-N 0.000 claims description 2
- BCMUZUWYJVPNHI-UHFFFAOYSA-N 2-butoxy-4-[6-[2-(2-methoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound C(CCC)OC1=C(C(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OC BCMUZUWYJVPNHI-UHFFFAOYSA-N 0.000 claims description 2
- FJSYNQADNPNRDP-UHFFFAOYSA-N 2-butoxy-6-fluoro-4-[6-[2-(2-methoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound C(CCC)OC1=C(C(=O)O)C(=CC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OC)F FJSYNQADNPNRDP-UHFFFAOYSA-N 0.000 claims description 2
- HLCCSAMCKPNYDS-UHFFFAOYSA-N 2-cyclobutyloxy-4-[6-[2-(1-methylindol-4-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound C1(CCC1)OC1=C(C(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=C2C=CN(C2=CC=C1)C HLCCSAMCKPNYDS-UHFFFAOYSA-N 0.000 claims description 2
- RNQHJLHFYFKDHR-UHFFFAOYSA-N 2-cyclobutyloxy-4-[6-[2-(2-ethoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound C1(CCC1)OC1=C(C(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OCC RNQHJLHFYFKDHR-UHFFFAOYSA-N 0.000 claims description 2
- HONGSMWWUADXNX-UHFFFAOYSA-N 2-cyclobutyloxy-4-[6-[2-(2-methoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound C1(CCC1)OC1=C(C(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OC HONGSMWWUADXNX-UHFFFAOYSA-N 0.000 claims description 2
- MNBJSMFQNPTKBK-UHFFFAOYSA-N 2-ethoxy-4-[6-[2-(2-ethoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound C(C)OC1=C(C(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OCC MNBJSMFQNPTKBK-UHFFFAOYSA-N 0.000 claims description 2
- PNXLIMSFSSKCDO-UHFFFAOYSA-N 2-ethoxy-4-[6-[2-(2-fluoronaphthalen-1-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound C(C)OC1=C(C(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)F PNXLIMSFSSKCDO-UHFFFAOYSA-N 0.000 claims description 2
- DUVRDYGFJRKPBT-UHFFFAOYSA-N 2-ethoxy-4-[6-[2-(2-methoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound C(C)OC1=C(C(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OC DUVRDYGFJRKPBT-UHFFFAOYSA-N 0.000 claims description 2
- FUPVSZQXWQQSMJ-UHFFFAOYSA-N 2-ethoxy-4-[6-[2-(5-fluoronaphthalen-1-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound C(C)OC1=C(C(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=CC=CC2=C(C=CC=C12)F FUPVSZQXWQQSMJ-UHFFFAOYSA-N 0.000 claims description 2
- DFURTOXHJRTLLB-UHFFFAOYSA-N 2-ethoxy-4-[6-[2-(5-methoxy-1-benzothiophen-4-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound C(C)OC1=C(C(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC=2SC=CC=21)OC DFURTOXHJRTLLB-UHFFFAOYSA-N 0.000 claims description 2
- GHKDPVZDNVYMIO-UHFFFAOYSA-N 2-ethoxy-4-[6-[2-(5-methoxy-1-methylindol-4-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound C(C)OC1=C(C(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=C2C=CN(C2=CC=C1OC)C GHKDPVZDNVYMIO-UHFFFAOYSA-N 0.000 claims description 2
- LUQYWVDQSWLMKV-UHFFFAOYSA-N 2-ethoxy-4-[6-[2-(5-methylnaphthalen-1-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound C(C)OC1=C(C(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=CC=CC2=C(C=CC=C12)C LUQYWVDQSWLMKV-UHFFFAOYSA-N 0.000 claims description 2
- HYWOJAFGCKEDNG-UHFFFAOYSA-N 2-ethylsulfanyl-4-[6-[2-(4-methylnaphthalen-1-yl)ethylamino]pyrimidin-4-yl]benzoic acid Chemical compound C(C)SC1=C(C(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=CC=C(C2=CC=CC=C12)C HYWOJAFGCKEDNG-UHFFFAOYSA-N 0.000 claims description 2
- YGTPBBJTFZKRQW-UHFFFAOYSA-N 2-fluoro-4-[6-[2-(2-methoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]-6-propylbenzoic acid Chemical compound FC1=C(C(=O)O)C(=CC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OC)CCC YGTPBBJTFZKRQW-UHFFFAOYSA-N 0.000 claims description 2
- BIGWXAGEQONZGD-UHFFFAOYSA-N 2h-oxadiazol-5-one Chemical compound O=C1C=NNO1 BIGWXAGEQONZGD-UHFFFAOYSA-N 0.000 claims description 2
- SILSNVVREOXZHF-UHFFFAOYSA-N 3-(2-hydroxyethoxy)-5-[6-[2-(2-methoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]thiophene-2-carboxylic acid Chemical compound OCCOC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OC)C(=O)O SILSNVVREOXZHF-UHFFFAOYSA-N 0.000 claims description 2
- RCAFKJJOITZWSR-UHFFFAOYSA-N 3-[2-ethoxy-4-[6-[2-(2-methoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]phenoxy]propanoic acid Chemical compound C(C)OC1=C(OCCC(=O)O)C=CC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OC RCAFKJJOITZWSR-UHFFFAOYSA-N 0.000 claims description 2
- ZUQABPPYELXLDD-UHFFFAOYSA-N 3-ethoxy-5-[6-(2-naphthalen-1-ylethylamino)pyrimidin-4-yl]thiophene-2-carboxylic acid Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=CC=CC2=CC=CC=C12)C(=O)O ZUQABPPYELXLDD-UHFFFAOYSA-N 0.000 claims description 2
- IQNHIKGMXFLXSO-UHFFFAOYSA-N 3-ethoxy-5-[6-[2-(1-methylindol-7-yl)ethylamino]pyrimidin-4-yl]thiophene-2-carboxylic acid Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC=1C=CC=C2C=CN(C=12)C)C(=O)O IQNHIKGMXFLXSO-UHFFFAOYSA-N 0.000 claims description 2
- SGRMZVRSGGTJLE-UHFFFAOYSA-N 3-ethoxy-5-[6-[2-(1H-indol-7-yl)ethylamino]pyrimidin-4-yl]thiophene-2-carboxylic acid Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC=1C=CC=C2C=CNC=12)C(=O)O SGRMZVRSGGTJLE-UHFFFAOYSA-N 0.000 claims description 2
- NQKZSEZXQCGBRT-UHFFFAOYSA-N 3-ethoxy-5-[6-[2-(2-ethoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]thiophene-2-carboxylic acid Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OCC)C(=O)O NQKZSEZXQCGBRT-UHFFFAOYSA-N 0.000 claims description 2
- VMSHRTRYIKWZHJ-UHFFFAOYSA-N 3-ethoxy-5-[6-[2-(2-fluoronaphthalen-1-yl)ethylamino]pyrimidin-4-yl]thiophene-2-carboxylic acid Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)F)C(=O)O VMSHRTRYIKWZHJ-UHFFFAOYSA-N 0.000 claims description 2
- CLZFKCUEKMVYPW-UHFFFAOYSA-N 3-ethoxy-5-[6-[2-(2-methoxynaphthalen-1-yl)ethylamino]pyrimidin-4-yl]-N-methylsulfonylthiophene-2-carboxamide Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)OC)C(=O)NS(=O)(=O)C CLZFKCUEKMVYPW-UHFFFAOYSA-N 0.000 claims description 2
- CLGNJZIJDCXZBQ-UHFFFAOYSA-N 3-ethoxy-5-[6-[2-(2-methylnaphthalen-1-yl)ethylamino]pyrimidin-4-yl]thiophene-2-carboxylic acid Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=CC=CC=C12)C)C(=O)O CLGNJZIJDCXZBQ-UHFFFAOYSA-N 0.000 claims description 2
- PUXGNSONFSSFQA-UHFFFAOYSA-N 3-ethoxy-5-[6-[2-(4-methylnaphthalen-1-yl)ethylamino]pyrimidin-4-yl]thiophene-2-carboxylic acid Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=CC=C(C2=CC=CC=C12)C)C(=O)O PUXGNSONFSSFQA-UHFFFAOYSA-N 0.000 claims description 2
- SYYCBQUXFHSPNO-UHFFFAOYSA-N 3-ethoxy-5-[6-[2-(5-methoxy-2,3-dihydro-1-benzofuran-4-yl)ethylamino]pyrimidin-4-yl]thiophene-2-carboxylic acid Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC2=C1CCO2)OC)C(=O)O SYYCBQUXFHSPNO-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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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
- A61K31/495—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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| EP2017062022 | 2017-05-18 | ||
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| TW107116760A TW201900180A (zh) | 2017-05-18 | 2018-05-17 | 嘧啶衍生物 |
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| EP (1) | EP3625223B1 (enExample) |
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| CA (1) | CA3063788A1 (enExample) |
| ES (1) | ES2896476T3 (enExample) |
| TW (1) | TW201900180A (enExample) |
| WO (1) | WO2018210992A1 (enExample) |
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| CR20180323A (es) | 2015-11-20 | 2018-08-06 | Idorsia Pharmaceuticals Ltd | Derivados de indol n-sustituídos como moduladores de los receptores de pge2 |
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- 2018-05-17 TW TW107116760A patent/TW201900180A/zh unknown
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| WO2018210992A1 (en) | 2018-11-22 |
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| EP3625223A1 (en) | 2020-03-25 |
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| CN110621667A (zh) | 2019-12-27 |
| KR102612140B1 (ko) | 2023-12-08 |
| US11446298B2 (en) | 2022-09-20 |
| US20200108068A1 (en) | 2020-04-09 |
| ES2896476T3 (es) | 2022-02-24 |
| KR20200007049A (ko) | 2020-01-21 |
| CA3063788A1 (en) | 2018-11-22 |
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