ES2893452T3 - Derivados de pirimidina como moduladores del receptor de PGE2 - Google Patents
Derivados de pirimidina como moduladores del receptor de PGE2 Download PDFInfo
- Publication number
- ES2893452T3 ES2893452T3 ES18725222T ES18725222T ES2893452T3 ES 2893452 T3 ES2893452 T3 ES 2893452T3 ES 18725222 T ES18725222 T ES 18725222T ES 18725222 T ES18725222 T ES 18725222T ES 2893452 T3 ES2893452 T3 ES 2893452T3
- Authority
- ES
- Spain
- Prior art keywords
- phenyl
- pyrimidin
- ethylamino
- ethoxy
- bromo
- 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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- 150000003230 pyrimidines Chemical class 0.000 title description 13
- 102000008866 Prostaglandin E receptors Human genes 0.000 title description 5
- 108010088540 Prostaglandin E receptors Proteins 0.000 title description 5
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 5
- -1 cycloprop-1,1-diyl group Chemical group 0.000 claims abstract description 821
- 150000001875 compounds Chemical class 0.000 claims abstract description 313
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 170
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 142
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 142
- 239000001257 hydrogen Substances 0.000 claims abstract description 142
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 140
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 116
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 115
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 89
- 125000001424 substituent group Chemical group 0.000 claims abstract description 83
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 79
- 201000011510 cancer Diseases 0.000 claims abstract description 69
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 68
- 238000011282 treatment Methods 0.000 claims abstract description 65
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 59
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 58
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 54
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 36
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 36
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 36
- 150000002367 halogens Chemical class 0.000 claims abstract description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 32
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims abstract description 31
- 238000002512 chemotherapy Methods 0.000 claims abstract description 29
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 24
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 21
- 238000001959 radiotherapy Methods 0.000 claims abstract description 19
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 17
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 17
- 125000002993 cycloalkylene group Chemical group 0.000 claims abstract description 16
- 238000002626 targeted therapy Methods 0.000 claims abstract description 16
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 13
- 230000028993 immune response Effects 0.000 claims abstract description 10
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 10
- 239000001301 oxygen Substances 0.000 claims abstract description 10
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 9
- 210000000987 immune system Anatomy 0.000 claims abstract description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 7
- 150000001721 carbon Chemical group 0.000 claims abstract description 7
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims abstract description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 6
- 230000007420 reactivation Effects 0.000 claims abstract description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 5
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 5
- 125000006574 non-aromatic ring group Chemical group 0.000 claims abstract description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 28
- CTQPPUPWHLGKOB-UHFFFAOYSA-N 4h-oxadiazol-5-one Chemical compound O=C1CN=NO1 CTQPPUPWHLGKOB-UHFFFAOYSA-N 0.000 claims description 31
- 239000003814 drug Substances 0.000 claims description 24
- 125000001153 fluoro group Chemical group F* 0.000 claims description 24
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 20
- 230000002265 prevention Effects 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 14
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 12
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 10
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 8
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 201000001441 melanoma Diseases 0.000 claims description 8
- 206010005003 Bladder cancer Diseases 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
- 206010033128 Ovarian cancer Diseases 0.000 claims description 7
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 7
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 7
- 201000010881 cervical cancer Diseases 0.000 claims description 7
- 201000005202 lung cancer Diseases 0.000 claims description 7
- 208000020816 lung neoplasm Diseases 0.000 claims description 7
- 230000004770 neurodegeneration Effects 0.000 claims description 7
- 208000010061 Autosomal Dominant Polycystic Kidney Diseases 0.000 claims description 6
- 201000009273 Endometriosis Diseases 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 6
- 208000022185 autosomal dominant polycystic kidney disease Diseases 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 230000035558 fertility Effects 0.000 claims description 6
- 239000012634 fragment Substances 0.000 claims description 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
- 208000011580 syndromic disease Diseases 0.000 claims description 6
- 206010035664 Pneumonia Diseases 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 5
- 230000000302 ischemic effect Effects 0.000 claims description 5
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 4
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 4
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
- 230000003143 atherosclerotic effect Effects 0.000 claims description 4
- 201000003719 cervical neuroblastoma Diseases 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- QJGLOGMNORETMH-UHFFFAOYSA-N 3-[3-ethoxy-5-[6-[2-(2,4,6-trifluorophenyl)ethylamino]pyrimidin-4-yl]thiophen-2-yl]-4H-1,2,4-oxadiazol-5-one Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=C(C=C1F)F)F)C1=NOC(N1)=O QJGLOGMNORETMH-UHFFFAOYSA-N 0.000 claims description 3
- QBXRJYJOLLINKR-UHFFFAOYSA-N 3-[3-ethoxy-5-[6-[2-(2-ethoxy-4-fluorophenyl)ethylamino]pyrimidin-4-yl]thiophen-2-yl]-4H-1,2,4-oxadiazol-5-one Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=C(C=C1)F)OCC)C1=NOC(N1)=O QBXRJYJOLLINKR-UHFFFAOYSA-N 0.000 claims description 3
- XLDCYMRZFRLVNW-UHFFFAOYSA-N 3-[3-ethoxy-5-[6-[2-(2-ethyl-4-methoxyphenyl)ethylamino]pyrimidin-4-yl]thiophen-2-yl]-4H-1,2,4-oxadiazol-5-one Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=C(C=C1)OC)CC)C1=NOC(N1)=O XLDCYMRZFRLVNW-UHFFFAOYSA-N 0.000 claims description 3
- BWAJWJWTQHXEEH-UHFFFAOYSA-N 3-[3-ethoxy-5-[6-[2-(2-fluoro-4-methoxyphenyl)ethylamino]pyrimidin-4-yl]thiophen-2-yl]-4H-1,2,4-oxadiazol-5-one Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=C(C=C1)OC)F)C1=NOC(N1)=O BWAJWJWTQHXEEH-UHFFFAOYSA-N 0.000 claims description 3
- ZXFCHOFSTUKCOJ-UHFFFAOYSA-N 3-[3-ethoxy-5-[6-[2-[2-ethoxy-4-(trifluoromethyl)phenyl]ethylamino]pyrimidin-4-yl]thiophen-2-yl]-4H-1,2,4-oxadiazol-5-one Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=C(C=C1)C(F)(F)F)OCC)C1=NOC(N1)=O ZXFCHOFSTUKCOJ-UHFFFAOYSA-N 0.000 claims description 3
- VQJPXXKFYYMECV-UHFFFAOYSA-N 3-[3-ethoxy-5-[6-[2-[2-fluoro-4-(trifluoromethyl)phenyl]ethylamino]pyrimidin-4-yl]thiophen-2-yl]-4H-1,2,4-oxadiazol-5-one Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=C(C=C1)C(F)(F)F)F)C1=NOC(N1)=O VQJPXXKFYYMECV-UHFFFAOYSA-N 0.000 claims description 3
- ZMUBAEDFKODQDU-UHFFFAOYSA-N 5-[4-[6-[2-(4-bromo-2,6-difluorophenyl)ethylamino]pyrimidin-4-yl]-2-ethoxyphenyl]-1,2-oxazol-3-one Chemical compound BrC1=CC(=C(CCNC2=CC(=NC=N2)C2=CC(=C(C=C2)C2=CC(NO2)=O)OCC)C(=C1)F)F ZMUBAEDFKODQDU-UHFFFAOYSA-N 0.000 claims description 3
- KPCBRVFEMIFEJW-UHFFFAOYSA-N 5-[4-[6-[2-(4-bromo-2,6-difluorophenyl)ethylamino]pyrimidin-4-yl]-2-methoxyphenyl]-1,2-oxazol-3-one Chemical compound BrC1=CC(=C(C(=C1)F)CCNC1=CC(=NC=N1)C1=CC(=C(C=C1)C1=CC(=NO1)O)OC)F KPCBRVFEMIFEJW-UHFFFAOYSA-N 0.000 claims description 3
- ABTIJEQHHVCFBA-UHFFFAOYSA-N BrC1=CC(=C(C(=C1)F)CCNC1=CC(=NC(=N1)C)C1=CC(=C(S1)C1=NOC(N1)=O)OCC)F Chemical compound BrC1=CC(=C(C(=C1)F)CCNC1=CC(=NC(=N1)C)C1=CC(=C(S1)C1=NOC(N1)=O)OCC)F ABTIJEQHHVCFBA-UHFFFAOYSA-N 0.000 claims description 3
- YLSUGACLIOXGSH-UHFFFAOYSA-N BrC1=CC=C(C=C1)CCNC1=CC(=NC=N1)C1=CC(=C(C=C1)C1=NOC(N1)=O)OCC Chemical compound BrC1=CC=C(C=C1)CCNC1=CC(=NC=N1)C1=CC(=C(C=C1)C1=NOC(N1)=O)OCC YLSUGACLIOXGSH-UHFFFAOYSA-N 0.000 claims description 3
- UETKRCWPGASLTL-UHFFFAOYSA-N C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC=C1)OCC)C1=NOC(N1)=O Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=C(C=CC=C1)OCC)C1=NOC(N1)=O UETKRCWPGASLTL-UHFFFAOYSA-N 0.000 claims description 3
- DMRVMUKPEWYJIE-UHFFFAOYSA-N C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=CC(=C(C=C1)OC)O)C1=NOC(N1)=O Chemical compound C(C)OC1=C(SC(=C1)C1=NC=NC(=C1)NCCC1=CC(=C(C=C1)OC)O)C1=NOC(N1)=O DMRVMUKPEWYJIE-UHFFFAOYSA-N 0.000 claims description 3
- GOBGCXSMLFKIOV-UHFFFAOYSA-N C(C)OC=1C=C(SC=1C1=NOC(N1)=O)C1=CC(=NC=N1)NCCC1=C(C#N)C=C(C=C1)F Chemical compound C(C)OC=1C=C(SC=1C1=NOC(N1)=O)C1=CC(=NC=N1)NCCC1=C(C#N)C=C(C=C1)F GOBGCXSMLFKIOV-UHFFFAOYSA-N 0.000 claims description 3
- RJMNOJSFWLQMDK-UHFFFAOYSA-N CCOc1cc(sc1-c1nc(=O)o[nH]1)-c1cc(NCCc2ccc(C)c(C)c2)ncn1 Chemical compound CCOc1cc(sc1-c1nc(=O)o[nH]1)-c1cc(NCCc2ccc(C)c(C)c2)ncn1 RJMNOJSFWLQMDK-UHFFFAOYSA-N 0.000 claims description 3
- ZLEWETBNRXECTR-UHFFFAOYSA-N CCOc1cc(sc1-c1nc(=O)o[nH]1)-c1cc(NCCc2cccc(OC)c2OC)ncn1 Chemical compound CCOc1cc(sc1-c1nc(=O)o[nH]1)-c1cc(NCCc2cccc(OC)c2OC)ncn1 ZLEWETBNRXECTR-UHFFFAOYSA-N 0.000 claims description 3
- PBFGJYQMRPZKEH-UHFFFAOYSA-N Cc1cc(sc1-c1nc(=O)o[nH]1)-c1cc(NCCc2c(F)cc(Br)cc2F)ncn1 Chemical compound Cc1cc(sc1-c1nc(=O)o[nH]1)-c1cc(NCCc2c(F)cc(Br)cc2F)ncn1 PBFGJYQMRPZKEH-UHFFFAOYSA-N 0.000 claims description 3
- BSZWDEJEHIKFIJ-UHFFFAOYSA-N Fc1cc(Br)cc(F)c1CCNc1cc(ncn1)-c1cc(c(s1)-c1nc(=O)o[nH]1)C(F)(F)F Chemical compound Fc1cc(Br)cc(F)c1CCNc1cc(ncn1)-c1cc(c(s1)-c1nc(=O)o[nH]1)C(F)(F)F BSZWDEJEHIKFIJ-UHFFFAOYSA-N 0.000 claims description 3
- UPOSDIJZIPMWJK-UHFFFAOYSA-N 2-[2-ethoxy-4-[6-[2-[2-ethoxy-4-(trifluoromethyl)phenyl]ethylamino]pyrimidin-4-yl]phenyl]acetic acid Chemical compound C(C)OC1=C(C=CC(=C1)C1=NC=NC(=C1)NCCC1=C(C=C(C=C1)C(F)(F)F)OCC)CC(=O)O UPOSDIJZIPMWJK-UHFFFAOYSA-N 0.000 claims description 2
- UNYZZEYKJJLGQR-UHFFFAOYSA-N 2-[4-[6-[2-(4-bromo-2,6-difluorophenyl)ethylamino]pyrimidin-4-yl]-2-chloro-6-ethylphenyl]acetic acid Chemical compound BrC1=CC(=C(C(=C1)F)CCNC1=CC(=NC=N1)C1=CC(=C(C(=C1)CC)CC(=O)O)Cl)F UNYZZEYKJJLGQR-UHFFFAOYSA-N 0.000 claims description 2
- DFFMMMFVYYAYQJ-UHFFFAOYSA-N 2-[4-[6-[2-(4-bromo-2,6-difluorophenyl)ethylamino]pyrimidin-4-yl]-2-ethoxyanilino]-2-oxoacetic acid Chemical compound BrC1=CC(=C(C(=C1)F)CCNC1=CC(=NC=N1)C1=CC(=C(C=C1)NC(C(=O)O)=O)OCC)F DFFMMMFVYYAYQJ-UHFFFAOYSA-N 0.000 claims description 2
- TZBQHKVYDSXDFF-UHFFFAOYSA-N 2-[4-[6-[2-(4-bromo-2,6-difluorophenyl)ethylamino]pyrimidin-4-yl]-2-ethoxyphenyl]acetic acid Chemical compound BrC1=CC(=C(C(=C1)F)CCNC1=CC(=NC=N1)C1=CC(=C(C=C1)CC(=O)O)OCC)F TZBQHKVYDSXDFF-UHFFFAOYSA-N 0.000 claims description 2
- AOONYWBXRCJZBL-UHFFFAOYSA-N 2-[5-[6-[2-(4-bromo-2,6-difluorophenyl)ethylamino]pyrimidin-4-yl]-3-(difluoromethoxy)thiophen-2-yl]acetic acid Chemical compound BrC1=CC(=C(C(=C1)F)CCNC1=CC(=NC=N1)C1=CC(=C(S1)CC(=O)O)OC(F)F)F AOONYWBXRCJZBL-UHFFFAOYSA-N 0.000 claims description 2
- LFGFVQLYJJQWIM-UHFFFAOYSA-N 2-[5-[6-[2-(4-bromo-2,6-difluorophenyl)ethylamino]pyrimidin-4-yl]-3-ethoxythiophen-2-yl]acetic acid Chemical compound BrC1=CC(=C(C(=C1)F)CCNC1=CC(=NC=N1)C1=CC(=C(S1)CC(=O)O)OCC)F LFGFVQLYJJQWIM-UHFFFAOYSA-N 0.000 claims description 2
- POOYSDGCTPSSCB-UHFFFAOYSA-N 2-[5-[6-[2-(4-bromo-2,6-difluorophenyl)ethylamino]pyrimidin-4-yl]-3-ethylthiophen-2-yl]acetic acid Chemical compound BrC1=CC(=C(C(=C1)F)CCNC1=CC(=NC=N1)C1=CC(=C(S1)CC(=O)O)CC)F POOYSDGCTPSSCB-UHFFFAOYSA-N 0.000 claims description 2
- ZWMXGOGMAHSYRL-UHFFFAOYSA-N 2-[5-[6-[2-(4-bromo-2,6-difluorophenyl)ethylamino]pyrimidin-4-yl]-3-propylthiophen-2-yl]acetic acid Chemical compound BrC1=CC(=C(C(=C1)F)CCNC1=CC(=NC=N1)C1=CC(=C(S1)CC(=O)O)CCC)F ZWMXGOGMAHSYRL-UHFFFAOYSA-N 0.000 claims description 2
- KGPPXZXCVUCFRH-UHFFFAOYSA-N 2-[6-[2-(4-bromo-2,6-difluorophenyl)ethylamino]pyrimidin-4-yl]-4-ethoxy-1,3-thiazole-5-carboxylic acid Chemical compound BrC1=CC(=C(C(=C1)F)CCNC1=CC(=NC=N1)C=1SC(=C(N=1)OCC)C(=O)O)F KGPPXZXCVUCFRH-UHFFFAOYSA-N 0.000 claims description 2
- BHKVCAWNQKTRTO-UHFFFAOYSA-N 2-[6-[2-(4-bromo-2,6-difluorophenyl)ethylamino]pyrimidin-4-yl]-4-ethyl-1,3-thiazole-5-carboxylic acid Chemical compound BrC1=CC(=C(C(=C1)F)CCNC1=CC(=NC=N1)C=1SC(=C(N=1)CC)C(=O)O)F BHKVCAWNQKTRTO-UHFFFAOYSA-N 0.000 claims description 2
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- TWCNGWQGTHPZFV-UHFFFAOYSA-N 2-cyclobutyloxy-4-[6-[2-(2-methoxy-4,5-dimethylphenyl)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=C(C(=C1)C)C)OC TWCNGWQGTHPZFV-UHFFFAOYSA-N 0.000 claims description 2
- YZMQSSRDJFHVIQ-UHFFFAOYSA-N 2-cyclobutyloxy-4-[6-[2-[4-(difluoromethyl)-5-fluoro-2-methoxyphenyl]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=C(C(=C1)F)C(F)F)OC YZMQSSRDJFHVIQ-UHFFFAOYSA-N 0.000 claims description 2
- JJIDHZWJDQKVTE-UHFFFAOYSA-N 2-ethoxy-4-[6-[2-(2-methoxy-4,5-dimethylphenyl)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=C(C(=C1)C)C)OC JJIDHZWJDQKVTE-UHFFFAOYSA-N 0.000 claims description 2
- DLHNDNVYCFGEKN-UHFFFAOYSA-N 2-ethoxy-4-[6-[2-[2-ethoxy-4-(trifluoromethyl)phenyl]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=C(C=C1)C(F)(F)F)OCC DLHNDNVYCFGEKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
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- FJWLUPNOVVHNEP-UHFFFAOYSA-N 3-[4-[6-[2-(4-bromo-2,6-difluorophenyl)ethylamino]pyrimidin-4-yl]-2-ethoxyphenyl]-4H-1,2,4-oxadiazol-5-one Chemical compound BrC1=CC(=C(C(=C1)F)CCNC1=CC(=NC=N1)C1=CC(=C(C=C1)C1=NOC(N1)=O)OCC)F FJWLUPNOVVHNEP-UHFFFAOYSA-N 0.000 claims description 2
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- MHNHYTDAOYJUEZ-UHFFFAOYSA-N triphenylphosphane Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 MHNHYTDAOYJUEZ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
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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
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- A—HUMAN NECESSITIES
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- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Electrochromic Elements, Electrophoresis, Or Variable Reflection Or Absorption Elements (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
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| Application Number | Priority Date | Filing Date | Title |
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| EP2017062031 | 2017-05-18 | ||
| PCT/EP2018/062862 WO2018210994A1 (en) | 2017-05-18 | 2018-05-17 | Phenyl derivatives as pge2 receptor modulators |
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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 |
| CN110621671A (zh) | 2017-05-18 | 2019-12-27 | 爱杜西亚药品有限公司 | 作为pge2受体调节剂的苯并呋喃及苯并噻吩衍生物 |
| CN110621667A (zh) | 2017-05-18 | 2019-12-27 | 爱杜西亚药品有限公司 | 嘧啶衍生物 |
| PL3625228T3 (pl) | 2017-05-18 | 2021-12-20 | Idorsia Pharmaceuticals Ltd | Pochodne pirymidyny jako modulatory receptora pge2 |
| WO2019136320A1 (en) | 2018-01-05 | 2019-07-11 | Icahn School Of Medicine At Mount Sinai | Method of increasing proliferation of pancreatic beta cells, treatment method, and composition |
| JP2021518413A (ja) | 2018-03-20 | 2021-08-02 | アイカーン スクール オブ メディシン アット マウント サイナイ | キナーゼ阻害剤化合物及び組成物ならびに使用方法 |
| EP3906028A4 (en) * | 2018-12-31 | 2022-10-12 | Icahn School of Medicine at Mount Sinai | KINA INHIBITOR COMPOUNDS AND COMPOSITIONS AND METHODS OF USE |
| US20230390303A1 (en) | 2020-11-13 | 2023-12-07 | Ono Pharmaceutical Co., Ltd. | Cancer treatment by combination of ep4 antagonist and immune checkpoint inhibitor |
| WO2022272062A1 (en) | 2021-06-24 | 2022-12-29 | Reservoir Neuroscience, Inc. | Ep2 antagonist compounds |
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Family Cites Families (88)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5948786A (en) | 1996-04-12 | 1999-09-07 | Sumitomo Pharmaceuticals Company, Limited | Piperidinylpyrimidine derivatives |
| AU3445100A (en) | 2000-03-24 | 2001-10-08 | Pharmagene Lab Ltd | Use of prostanoid ep4 receptor antagonists for the treatment of headache and assays for such antagonists |
| HN2001000224A (es) | 2000-10-19 | 2002-06-13 | Pfizer | Compuestos de imidazol condensado con arilo o heteroarilo como agentes anti - inflamatorios y analgesicos. |
| GB0031302D0 (en) | 2000-12-21 | 2001-01-31 | Glaxo Group Ltd | Napthalene derivatives |
| GB0031295D0 (en) | 2000-12-21 | 2001-01-31 | Glaxo Group Ltd | Naphthalene derivatives |
| GB0103269D0 (en) | 2001-02-09 | 2001-03-28 | Glaxo Group Ltd | Napthalene derivatives |
| WO2003086390A1 (en) | 2002-04-12 | 2003-10-23 | Pfizer Japan Inc. | Imidazole compounds as anti-inflammatory and analgesic agents |
| WO2003087061A1 (en) | 2002-04-12 | 2003-10-23 | Pfizer Japan Inc. | Pyrazole compounds as anti-inflammatory and analgesic agents |
| JP2006506327A (ja) | 2002-05-23 | 2006-02-23 | セラテクノロジーズ インコーポレイティド | プロスタグランジンｅ２の受容体サブタイプｅｐ４のアンタゴニスト・ポリペプチド |
| ES2308139T3 (es) | 2003-01-29 | 2008-12-01 | Asterand Uk Limited | Antagonista de receptos ep4. |
| CA2536887C (en) | 2003-08-26 | 2012-03-06 | Teijin Pharma Limited | Pyrrolopyrimidinone derivatives |
| CN1867551B (zh) | 2003-09-03 | 2013-09-11 | 拉夸里亚创药株式会社 | 作为前列腺素e2拮抗剂的苯基或吡啶基酰胺化合物 |
| WO2005026129A1 (en) | 2003-09-15 | 2005-03-24 | Gpc Biotech Ag | Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases |
| GB0324269D0 (en) | 2003-10-16 | 2003-11-19 | Pharmagene Lab Ltd | EP4 receptor antagonists |
| AP2006003769A0 (en) | 2004-05-04 | 2006-10-31 | Pfizer | Ortho substituted aryl or heteroaryl amide compounds |
| CN1950333A (zh) | 2004-05-04 | 2007-04-18 | 辉瑞大药厂 | 取代的甲基芳基或杂芳基酰胺化合物 |
| HN2005000795A (es) | 2004-10-15 | 2010-08-19 | Aventis Pharma Inc | Pirimidinas como antagonistas del receptor de prostaglandina d2 |
| US8013159B2 (en) | 2005-05-19 | 2011-09-06 | Merck Canada Inc. | Quinoline derivatives as EP4 antagonists |
| WO2006128129A2 (en) | 2005-05-26 | 2006-11-30 | Synta Pharmaceuticals Corp. | Method for treating cancer |
| DOP2007000068A (es) | 2006-04-12 | 2007-10-31 | Sanofi Aventis Us Llc | Compuestos de amino-pirimidina 2,6-sustituidos-4-monosustituidos como antagonistas del receptor de prostaglandina d2 |
| EP2013169B1 (en) | 2006-04-24 | 2012-08-22 | Merck Canada Inc. | Indole amide derivatives as ep4 receptor antagonists |
| EP2035376B1 (en) | 2006-06-12 | 2014-08-27 | Merck Canada Inc. | Indoline amide derivatives as ep4 receptor ligands |
| US20080280891A1 (en) | 2006-06-27 | 2008-11-13 | Locus Pharmaceuticals, Inc. | Anti-cancer agents and uses thereof |
| WO2008008059A1 (en) | 2006-07-12 | 2008-01-17 | Locus Pharmaceuticals, Inc. | Anti-cancer agents ans uses thereof |
| BRPI0714409A2 (pt) | 2006-07-14 | 2013-03-12 | Novartis Ag | derivados de pirimidina como inibidores de alk-5 |
| EP2054401B1 (en) | 2006-08-11 | 2013-05-01 | Merck Canada Inc. | Thiophenecarboxamide derivatives as ep4 receptor ligands |
| WO2008039882A1 (en) | 2006-09-30 | 2008-04-03 | Sanofi-Aventis U.S. Llc | A combination of niacin and a prostaglandin d2 receptor antagonist |
| JP5301469B2 (ja) | 2007-02-26 | 2013-09-25 | メルク カナダ インコーポレイテッド | Ｅｐ４受容体アンタゴニストとしてのインドール及びインドリンシクロプロピルアミド誘導体 |
| JPWO2008123207A1 (ja) | 2007-03-26 | 2010-07-15 | アステラス製薬株式会社 | オルニチン誘導体 |
| US8003661B2 (en) | 2007-03-26 | 2011-08-23 | Merck Canada Inc. | Naphthalene and quinoline sulfonylurea derivatives as EP4 receptor antagonists |
| EP2014657A1 (de) | 2007-06-21 | 2009-01-14 | Bayer Schering Pharma Aktiengesellschaft | Diaminopyrimidine als Modulatoren des EP2-Rezeptors |
| JP5408434B2 (ja) | 2007-07-03 | 2014-02-05 | アステラス製薬株式会社 | アミド化合物 |
| AU2008309517B2 (en) | 2007-10-12 | 2013-03-14 | Astrazeneca Ab | Inhibitors of protein kinases |
| CA2714743C (en) | 2008-02-19 | 2017-01-17 | Janssen Pharmaceutica N.V. | Aryl-hydroxyethylamino-pyrimidines and triazines as modulators of fatty acid amide hydrolase |
| EP2565191B1 (en) | 2008-05-14 | 2014-10-08 | Astellas Pharma Inc. | 4-(Indol-7-ylcarbonylaminomethyl)cyclohexanecarboxylic acid derivatives as EP4 receptor antagonists useful for the treatment of chronic renal failure or diabetic nephropathy |
| US20130225528A1 (en) | 2008-05-21 | 2013-08-29 | Ariad Pharmaceuticals, Inc. | Phosphorus Derivatives as Kinase Inhibitors |
| WO2010019796A1 (en) | 2008-08-14 | 2010-02-18 | Chemietek, Llc | Heterocyclic amide derivatives as ep4 receptor antagonists |
| CN102164942B (zh) | 2008-09-19 | 2017-02-15 | 生物科技研究有限公司 | 三萜系化合物及其使用的方法 |
| CA2737618A1 (en) | 2008-09-25 | 2010-04-01 | Merck Frosst Canada Ltd. | Beta-carboline sulphonylurea derivatives as ep4 receptor antagonists |
| US8906914B2 (en) | 2009-08-18 | 2014-12-09 | Janssen Pharmaceutica Nv | Ethylene diamine modulators of fatty acid hydrolase |
| WO2011063181A1 (en) | 2009-11-23 | 2011-05-26 | Lexicon Pharmaceuticals, Inc. | Methods and assays for the treatment of irritable bowel syndrome |
| US8927547B2 (en) | 2010-05-21 | 2015-01-06 | Noviga Research Ab | Pyrimidine derivatives |
| CA2806121C (en) | 2010-09-21 | 2018-10-09 | Eisai R&D Management Co., Ltd. | Pharmaceutical composition |
| JP5273689B2 (ja) | 2010-09-29 | 2013-08-28 | 株式会社エヌビィー健康研究所 | ヒトプロスタグランジンｅ２受容体ｅｐ４に対する抗体 |
| WO2012066065A1 (en) | 2010-11-17 | 2012-05-24 | Novartis Ag | Phenyl-heteroaryl amine compounds and their uses |
| JP2013542967A (ja) | 2010-11-17 | 2013-11-28 | ノバルティス アーゲー | ３−（アミノアリール）−ピリジン化合物 |
| WO2012076063A1 (en) | 2010-12-10 | 2012-06-14 | Rottapharm S.P.A. | Pyridine amide derivatives as ep4 receptor antagonists |
| WO2012103071A2 (en) | 2011-01-25 | 2012-08-02 | Eisai R&D Management Co., Ltd. | Compounds and compositions |
| DK2688883T3 (en) | 2011-03-24 | 2016-09-05 | Noviga Res Ab | pyrimidine |
| WO2012149528A1 (en) | 2011-04-29 | 2012-11-01 | Exelixis, Inc. | Inhibitors of inducible form of 6-phosphofructose-2-kinase |
| WO2012177618A1 (en) | 2011-06-20 | 2012-12-27 | Emory University | Prostaglandin receptor ep2 antagonists, derivatives, compositions, and uses related thereto |
| EP2729445B1 (en) | 2011-07-04 | 2015-10-21 | Rottapharm Biotech S.r.l. | Cyclic amine derivatives as ep4 receptor antagonists |
| EP2554662A1 (en) | 2011-08-05 | 2013-02-06 | M Maria Pia Cosma | Methods of treatment of retinal degeneration diseases |
| US20150004175A1 (en) | 2011-12-13 | 2015-01-01 | Yale University | Compositions and Methods for Reducing CTL Exhaustion |
| JP6378171B2 (ja) * | 2012-04-24 | 2018-08-22 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ｄｎａ−ｐｋ阻害剤 |
| AR091429A1 (es) | 2012-06-29 | 2015-02-04 | Lilly Co Eli | Compuestos de fenoxietil piperidina |
| TWI572597B (zh) | 2012-06-29 | 2017-03-01 | 美國禮來大藥廠 | 二甲基－苯甲酸化合物 |
| EP2711364A1 (en) | 2012-09-21 | 2014-03-26 | Chemilia AB | 4-(Indolyl or benzimidazolyl)amino-2-(2-(indol-3-yl)ethyl)aminopyrimidines useful for the treatment of cancer |
| US9604937B2 (en) | 2012-11-27 | 2017-03-28 | Thomas Helledays Stiftelse For Medicinsk Forskning | Pyrimidine-2,4-diamine derivatives for treatment of cancer |
| UA115576C2 (uk) | 2012-12-06 | 2017-11-27 | Байєр Фарма Акцієнгезелльшафт | Похідні бензимідазолу як антагоністи ер4 |
| EP2765128A1 (en) | 2013-02-07 | 2014-08-13 | Almirall, S.A. | Substituted benzamides with activity towards EP4 receptors |
| TW201443004A (zh) | 2013-02-15 | 2014-11-16 | Lilly Co Eli | 苯氧基乙氧基化合物 |
| TWI636046B (zh) | 2013-05-17 | 2018-09-21 | 美國禮來大藥廠 | 苯氧基乙基二氫－１ｈ－異喹啉化合物 |
| EA028604B1 (ru) | 2013-05-30 | 2017-12-29 | Идорсиа Фармасьютиклз Лтд. | Модуляторы рецептора cxcr7 |
| HRP20180703T1 (hr) | 2013-06-12 | 2018-06-15 | Kaken Pharmaceutical Co., Ltd. | Derivat 4-alkinil imidazola i lijek koji kao aktivni sastojak sadrži isti |
| JP6417419B2 (ja) | 2013-09-04 | 2018-11-07 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 免疫調節剤として有用な化合物 |
| HRP20181052T1 (hr) | 2013-09-06 | 2018-09-07 | Aurigene Discovery Technologies Limited | Derivati 1,2,4-oksadiazola kao imunomodulatori |
| WO2015044900A1 (en) | 2013-09-27 | 2015-04-02 | Aurigene Discovery Technologies Limited | Therapeutic immunomodulating compounds |
| RU2675270C2 (ru) | 2013-10-17 | 2018-12-18 | Вертекс Фармасьютикалз Инкорпорейтед | Сокристаллы и содержащие их фармацевтические композиции |
| PT3057959T (pt) * | 2013-10-17 | 2018-06-04 | Vertex Pharma | Inibidores de adn-pk |
| CN105793236B (zh) | 2013-12-17 | 2017-10-10 | 伊莱利利公司 | 二甲基苯甲酸化合物 |
| ME02896B (me) | 2013-12-17 | 2018-04-20 | Lilly Co Eli | Fenoksietilni derivati prstenastog amina i njihova aktivnost kao modulatora receptora ep4 |
| TW201607943A (zh) | 2013-12-19 | 2016-03-01 | 拜耳製藥公司 | 作為ｅｐ４配體之新穎苯并咪唑衍生物 |
| TW201623277A (zh) | 2014-03-26 | 2016-07-01 | 安斯泰來製藥股份有限公司 | 醯胺化合物 |
| WO2015167825A1 (en) | 2014-04-29 | 2015-11-05 | Emory University | Prostaglandin receptor ep2 antagonists, derivatives, compositions, and uses related thereto |
| KR102535283B1 (ko) | 2014-05-23 | 2023-05-22 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 암의 치료를 위한 조합 요법 |
| CN106794181A (zh) | 2014-06-04 | 2017-05-31 | 托马斯·黑勒戴药物研究基金会 | 用于治疗炎性和自身免疫性病况的mth1抑制剂 |
| CN110526912B (zh) | 2014-06-19 | 2023-02-14 | 武田药品工业株式会社 | 用于激酶抑制的杂芳基化合物 |
| WO2016021742A1 (en) | 2014-08-07 | 2016-02-11 | Takeda Pharmaceutical Company Limited | Heterocyclic compounds as ep4 receptor antagonists |
| NZ733575A (en) | 2015-01-09 | 2022-10-28 | Ono Pharmaceutical Co | Tricyclic spiro compound |
| EP3325490B1 (en) | 2015-07-23 | 2019-12-18 | Takeda Pharmaceutical Company Limited | 1-substituted 1,2,3,4-tetrahydro-1,7-naphthyridin-8-amine derivatives and their use as ep4 receptor antagonists |
| BR112018007664B1 (pt) | 2015-10-16 | 2023-12-19 | Eisai R&D Management Co., Ltd | Compostos antagonistas de ep4, composição compreendendo o composto e uso dos mesmos para tratar câncer |
| CR20180323A (es) | 2015-11-20 | 2018-08-06 | Idorsia Pharmaceuticals Ltd | Derivados de indol n-sustituídos como moduladores de los receptores de pge2 |
| EP3484870B1 (en) | 2016-07-13 | 2022-11-16 | Vertex Pharmaceuticals Incorporated | Methods, compositions and kits for increasing genome editing efficiency |
| CN110621667A (zh) | 2017-05-18 | 2019-12-27 | 爱杜西亚药品有限公司 | 嘧啶衍生物 |
| CN110621671A (zh) | 2017-05-18 | 2019-12-27 | 爱杜西亚药品有限公司 | 作为pge2受体调节剂的苯并呋喃及苯并噻吩衍生物 |
| PL3625228T3 (pl) | 2017-05-18 | 2021-12-20 | Idorsia Pharmaceuticals Ltd | Pochodne pirymidyny jako modulatory receptora pge2 |
| EP3625224B1 (en) | 2017-05-18 | 2021-08-04 | Idorsia Pharmaceuticals Ltd | N-substituted indole derivatives |
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