TW202216143A - 作為眼疾病的治療藥之trpv4抑制藥 - Google Patents
作為眼疾病的治療藥之trpv4抑制藥 Download PDFInfo
- Publication number
- TW202216143A TW202216143A TW110126328A TW110126328A TW202216143A TW 202216143 A TW202216143 A TW 202216143A TW 110126328 A TW110126328 A TW 110126328A TW 110126328 A TW110126328 A TW 110126328A TW 202216143 A TW202216143 A TW 202216143A
- Authority
- TW
- Taiwan
- Prior art keywords
- phenyl
- cyclopropyl
- hexahydro
- pyrimido
- alkyl
- Prior art date
Links
- 101150098315 TRPV4 gene Proteins 0.000 title claims abstract description 48
- 239000003112 inhibitor Substances 0.000 title description 44
- 208000030533 eye disease Diseases 0.000 title description 5
- 229940126585 therapeutic drug Drugs 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 237
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 126
- 238000000034 method Methods 0.000 claims abstract description 114
- 208000017442 Retinal disease Diseases 0.000 claims abstract description 102
- 201000010099 disease Diseases 0.000 claims abstract description 51
- 150000003839 salts Chemical class 0.000 claims abstract description 48
- 239000003814 drug Substances 0.000 claims abstract description 39
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 39
- 230000001413 cellular effect Effects 0.000 claims abstract description 26
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 239000003550 marker Substances 0.000 claims abstract description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 238000012216 screening Methods 0.000 claims abstract description 19
- 241000282414 Homo sapiens Species 0.000 claims abstract description 17
- 238000004519 manufacturing process Methods 0.000 claims abstract description 16
- 241001465754 Metazoa Species 0.000 claims abstract description 15
- 230000002265 prevention Effects 0.000 claims abstract description 12
- 102000003567 TRPV4 Human genes 0.000 claims abstract 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 198
- GLZXFITXXAMCRJ-UHFFFAOYSA-N azepin-4-one Chemical compound O=C1C=CC=NC=C1 GLZXFITXXAMCRJ-UHFFFAOYSA-N 0.000 claims description 174
- -1 nitro, hydroxyl Chemical group 0.000 claims description 144
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 137
- 125000000217 alkyl group Chemical group 0.000 claims description 126
- 239000000126 substance Substances 0.000 claims description 124
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 93
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 92
- 208000035475 disorder Diseases 0.000 claims description 72
- 238000012360 testing method Methods 0.000 claims description 64
- 208000004644 retinal vein occlusion Diseases 0.000 claims description 62
- 230000017531 blood circulation Effects 0.000 claims description 58
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 52
- 239000001257 hydrogen Substances 0.000 claims description 51
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 50
- 125000003545 alkoxy group Chemical group 0.000 claims description 49
- 230000014509 gene expression Effects 0.000 claims description 49
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 48
- 235000010290 biphenyl Nutrition 0.000 claims description 48
- 125000001424 substituent group Chemical group 0.000 claims description 45
- 230000008569 process Effects 0.000 claims description 44
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 43
- 125000003118 aryl group Chemical group 0.000 claims description 41
- 229910052736 halogen Inorganic materials 0.000 claims description 41
- 125000001072 heteroaryl group Chemical group 0.000 claims description 40
- 150000002367 halogens Chemical class 0.000 claims description 39
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 38
- 229910052757 nitrogen Inorganic materials 0.000 claims description 35
- 125000000623 heterocyclic group Chemical group 0.000 claims description 31
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 29
- 239000003446 ligand Substances 0.000 claims description 27
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 26
- 108090000623 proteins and genes Proteins 0.000 claims description 25
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 206010038848 Retinal detachment Diseases 0.000 claims description 21
- 230000004264 retinal detachment Effects 0.000 claims description 21
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
- 239000001301 oxygen Substances 0.000 claims description 20
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 19
- 102000004169 proteins and genes Human genes 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 18
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 17
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 17
- 208000002780 macular degeneration Diseases 0.000 claims description 17
- 239000000523 sample Substances 0.000 claims description 17
- NCZYSQOTAYFTNM-UHFFFAOYSA-N 2-methyl-1-(3-morpholin-4-ylpropyl)-5-phenyl-n-[3-(trifluoromethyl)phenyl]pyrrole-3-carboxamide Chemical compound C1COCCN1CCCN1C(C)=C(C(=O)NC=2C=C(C=CC=2)C(F)(F)F)C=C1C1=CC=CC=C1 NCZYSQOTAYFTNM-UHFFFAOYSA-N 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 201000004569 Blindness Diseases 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
- 239000011593 sulfur Substances 0.000 claims description 14
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 13
- 125000001188 haloalkyl group Chemical group 0.000 claims description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 238000005259 measurement Methods 0.000 claims description 12
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 11
- 229940124597 therapeutic agent Drugs 0.000 claims description 11
- 241000282412 Homo Species 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 239000000463 material Substances 0.000 claims description 10
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 9
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- URCMKDJBULWNAI-DQEYMECFSA-N 3-[[(5s,7s)-3-[5-(2-hydroxypropan-2-yl)pyrazin-2-yl]-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC(C(C)(O)C)=CN=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 URCMKDJBULWNAI-DQEYMECFSA-N 0.000 claims description 9
- UIVOZBSCHXCGPS-UHFFFAOYSA-N 7-bromo-n-(1-phenylcyclopropyl)-3-[(4-piperidin-1-ylpiperidin-1-yl)methyl]-2-[3-(trifluoromethyl)phenyl]quinoline-4-carboxamide Chemical compound FC(F)(F)C1=CC=CC(C=2C(=C(C(=O)NC3(CC3)C=3C=CC=CC=3)C3=CC=C(Br)C=C3N=2)CN2CCC(CC2)N2CCCCC2)=C1 UIVOZBSCHXCGPS-UHFFFAOYSA-N 0.000 claims description 9
- 208000010412 Glaucoma Diseases 0.000 claims description 9
- 108020004459 Small interfering RNA Proteins 0.000 claims description 9
- 201000005667 central retinal vein occlusion Diseases 0.000 claims description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
- XGQARGJNRMNFJU-UIOOFZCWSA-N 3-[[(5s,7s)-3-[5-(2-hydroxypropan-2-yl)pyridin-2-yl]-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound N1=CC(C(C)(O)C)=CC=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 XGQARGJNRMNFJU-UIOOFZCWSA-N 0.000 claims description 8
- HJOFAWLMCOBZFZ-GDLZYMKVSA-N 6-[(2R)-2-[3-(1-benzofuran-2-yl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC(C=CC=C3)=C3O2)=CC=C1 HJOFAWLMCOBZFZ-GDLZYMKVSA-N 0.000 claims description 8
- NQCQLXARDFPQDK-OAQYLSRUSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC(C(F)(F)F)=CC=C4)O)=O)=C3C2=O)=C1 NQCQLXARDFPQDK-OAQYLSRUSA-N 0.000 claims description 8
- 125000002757 morpholinyl group Chemical group 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 108091033319 polynucleotide Proteins 0.000 claims description 8
- 102000040430 polynucleotide Human genes 0.000 claims description 8
- 239000002157 polynucleotide Substances 0.000 claims description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
- VLHCWBMCBLUFBN-HXUWFJFHSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 VLHCWBMCBLUFBN-HXUWFJFHSA-N 0.000 claims description 7
- 201000007527 Retinal artery occlusion Diseases 0.000 claims description 7
- 206010038926 Retinopathy hypertensive Diseases 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 7
- 239000013543 active substance Substances 0.000 claims description 7
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 7
- 206010001902 amaurosis Diseases 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 238000001514 detection method Methods 0.000 claims description 7
- 201000001948 hypertensive retinopathy Diseases 0.000 claims description 7
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 206010070957 Choroidal haemangioma Diseases 0.000 claims description 6
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 6
- 230000000295 complement effect Effects 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 230000001394 metastastic effect Effects 0.000 claims description 6
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 5
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 5
- RAYCYIKGBWRQBC-RBUKOAKNSA-N 2-[(3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-5-(trifluoromethyl)benzonitrile Chemical compound C(#N)C1=C(C=CC(=C1)C(F)(F)F)S(=O)(=O)N1C[C@@H]([C@@](C1)(CO)O)OC1=CC(=C(C#N)C=C1)F RAYCYIKGBWRQBC-RBUKOAKNSA-N 0.000 claims description 5
- SEFCMBALQOAGOY-HXUWFJFHSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 SEFCMBALQOAGOY-HXUWFJFHSA-N 0.000 claims description 5
- KMEBPJJCIGVJLK-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-[3-(3-chlorophenyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC=CC(C2=CC(Cl)=CC=C2)=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O KMEBPJJCIGVJLK-UHFFFAOYSA-N 0.000 claims description 5
- RYSFWVYIDNEFJE-GOSISDBHSA-N 2-[1-(4-bromothiophen-2-yl)cyclopropyl]-6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Br)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 RYSFWVYIDNEFJE-GOSISDBHSA-N 0.000 claims description 5
- BJISKLSCGVLOBA-HXUWFJFHSA-N 2-[1-(4-chlorophenyl)cyclopropyl]-6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC=C1Cl)NC2=O)=O)C1=CC(Cl)=CC=C1 BJISKLSCGVLOBA-HXUWFJFHSA-N 0.000 claims description 5
- MBTAGZVBGASURJ-GDLZYMKVSA-N 2-[1-[3-(1-benzofuran-3-yl)phenyl]cyclopropyl]-6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=COC4=C3C=CC=C4)=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 MBTAGZVBGASURJ-GDLZYMKVSA-N 0.000 claims description 5
- KORKKQLDGMHNKO-UHFFFAOYSA-N 2-nitro-N-[4-(4-propan-2-ylpiperazin-1-yl)sulfonylphenyl]-4-(trifluoromethyl)benzamide Chemical compound CC(C)N1CCN(CC1)S(=O)(=O)c1ccc(NC(=O)c2ccc(cc2[N+]([O-])=O)C(F)(F)F)cc1 KORKKQLDGMHNKO-UHFFFAOYSA-N 0.000 claims description 5
- YECPQQNZCNAUSU-HXUWFJFHSA-N 6-[(2R)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=CC=C1F)=C1F YECPQQNZCNAUSU-HXUWFJFHSA-N 0.000 claims description 5
- ZSQBQRMOFWVALR-OAQYLSRUSA-N 6-[(2R)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=CC=C1F)=C1F ZSQBQRMOFWVALR-OAQYLSRUSA-N 0.000 claims description 5
- STMKJKYCEZWKKI-MUUNZHRXSA-N 6-[(2R)-2-[3-(1-benzofuran-2-yl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC(C=CC=C3)=C3O2)=CC=C1 STMKJKYCEZWKKI-MUUNZHRXSA-N 0.000 claims description 5
- CXKXKINYEXGYAS-HHHXNRCGSA-N 6-[(2R)-2-[3-(3-chlorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(Cl)=CC=C2)=C1 CXKXKINYEXGYAS-HHHXNRCGSA-N 0.000 claims description 5
- CZHMNOORLQRJTL-GDLZYMKVSA-N 6-[(2R)-2-hydroxy-2-(3-quinolin-3-ylphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC3=CC=CC=C3N=C2)=CC=C1 CZHMNOORLQRJTL-GDLZYMKVSA-N 0.000 claims description 5
- ZVFDKSTYVBZBQV-HXUWFJFHSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 ZVFDKSTYVBZBQV-HXUWFJFHSA-N 0.000 claims description 5
- CTTAVDITUXVCMM-XMMPIXPASA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(C(F)(F)F)=CC=C4)O)=O)=C3C2=O)=C1 CTTAVDITUXVCMM-XMMPIXPASA-N 0.000 claims description 5
- SBVYFBNMMXNACJ-HSZRJFAPSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(5-propan-2-ylpyridin-3-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CN=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(C(F)(F)F)=CC=C4)O)=O)=C3C2=O)=C1 SBVYFBNMMXNACJ-HSZRJFAPSA-N 0.000 claims description 5
- RFPONOCDAFZOFJ-SSEXGKCCSA-N 6-[(2R)-2-hydroxy-2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC=CC(C5=CC(C(F)(F)F)=CC=C5)=C4)O)=O)=C3C2=O)=C1 RFPONOCDAFZOFJ-SSEXGKCCSA-N 0.000 claims description 5
- GIIMCKMWIWZEFY-RUZDIDTESA-N 6-[(2R)-2-hydroxy-2-[3-[6-(trifluoromethyl)pyridin-2-yl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=NC(C(F)(F)F)=CC=C2)=CC=C1 GIIMCKMWIWZEFY-RUZDIDTESA-N 0.000 claims description 5
- WDDWYPDZWONBAK-UHFFFAOYSA-N 6-[2,2-difluoro-2-[3-[3-(trifluoromethoxy)phenyl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(C(C1=CC=CC(C2=CC(OC(F)(F)F)=CC=C2)=C1)(F)F)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O WDDWYPDZWONBAK-UHFFFAOYSA-N 0.000 claims description 5
- OCFKMOVBTRZPFW-UHFFFAOYSA-N 6-[2-[3-(4-chlorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC=C2Cl)=C1 OCFKMOVBTRZPFW-UHFFFAOYSA-N 0.000 claims description 5
- 108091023037 Aptamer Proteins 0.000 claims description 5
- 208000016623 Choroid neoplasm Diseases 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 208000010038 Ischemic Optic Neuropathy Diseases 0.000 claims description 5
- 108091034117 Oligonucleotide Proteins 0.000 claims description 5
- 206010030924 Optic ischaemic neuropathy Diseases 0.000 claims description 5
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 5
- 125000005103 alkyl silyl group Chemical group 0.000 claims description 5
- 201000007058 anterior ischemic optic neuropathy Diseases 0.000 claims description 5
- 201000002588 choroid cancer Diseases 0.000 claims description 5
- 208000014188 hereditary optic neuropathy Diseases 0.000 claims description 5
- 201000001441 melanoma Diseases 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- 230000003449 preventive effect Effects 0.000 claims description 5
- 230000000069 prophylactic effect Effects 0.000 claims description 5
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 4
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000006771 (C1-C6) haloalkylthio group Chemical group 0.000 claims description 4
- YLGFCBPUEFFPIV-UHFFFAOYSA-N 2-(1-phenylcyclopropyl)-6-[2-(2-phenylmethoxyphenyl)acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC(C=CC=C1)=C1OCC1=CC=CC=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O YLGFCBPUEFFPIV-UHFFFAOYSA-N 0.000 claims description 4
- MOWVKVRJDNCJSF-UHFFFAOYSA-N 2-(1-phenylcyclopropyl)-6-[2-(3-phenylmethoxyphenyl)acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC(OCC2=CC=CC=C2)=CC=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O MOWVKVRJDNCJSF-UHFFFAOYSA-N 0.000 claims description 4
- JOSZTOREWPGZKA-OAQYLSRUSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 JOSZTOREWPGZKA-OAQYLSRUSA-N 0.000 claims description 4
- BTHSHBBGAPSHMR-AREMUKBSSA-N 2-[1-(5-cyclohexylpyridin-3-yl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCCC3)=CN=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 BTHSHBBGAPSHMR-AREMUKBSSA-N 0.000 claims description 4
- QBQOSDHCOLDKBS-HHHXNRCGSA-N 5-[3-[1-[6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-4-oxo-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-2-yl]cyclopropyl]phenyl]pyridine-3-carbonitrile Chemical compound N#CC1=CN=CC(C2=CC(C3(CC3)C(N3)=NC(CCCN(C4)C([C@@H](C5=CC(C(F)(F)F)=CC=C5)O)=O)=C4C3=O)=CC=C2)=C1 QBQOSDHCOLDKBS-HHHXNRCGSA-N 0.000 claims description 4
- KMGHLAZNAOBHIN-OAQYLSRUSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 KMGHLAZNAOBHIN-OAQYLSRUSA-N 0.000 claims description 4
- GKGCWVLNVIEFOV-GOSISDBHSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 GKGCWVLNVIEFOV-GOSISDBHSA-N 0.000 claims description 4
- NEWNAJYUHJYSNQ-HXUWFJFHSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(3-fluorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 NEWNAJYUHJYSNQ-HXUWFJFHSA-N 0.000 claims description 4
- JNEVSAYJVYYWEL-XMMPIXPASA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-phenylthiophen-2-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CC=C3)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 JNEVSAYJVYYWEL-XMMPIXPASA-N 0.000 claims description 4
- LTEWNOPUYSHHIK-JOCHJYFZSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(Cl)=CC=C4)O)=O)=C3C2=O)=C1 LTEWNOPUYSHHIK-JOCHJYFZSA-N 0.000 claims description 4
- KCCSZFWJFLRJCT-UUWRZZSWSA-N 6-[(2R)-2-[3-(3-tert-butylphenyl)phenyl]-2-hydroxyacetyl]-2-[1-(4-phenylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)(C)C1=CC=CC(C2=CC([C@H](C(N(CCC3)CC4=C3N=C(C3(CC3)C3=CC(C5=CC=CC=C5)=CS3)NC4=O)=O)O)=CC=C2)=C1 KCCSZFWJFLRJCT-UUWRZZSWSA-N 0.000 claims description 4
- VHTRFHDWEFAVLI-WJOKGBTCSA-N 6-[(2R)-2-[3-(3-tert-butylphenyl)phenyl]-2-hydroxyacetyl]-2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC=CC(C5=CC(C(C)(C)C)=CC=C5)=C4)O)=O)=C3C2=O)=C1 VHTRFHDWEFAVLI-WJOKGBTCSA-N 0.000 claims description 4
- VUFYQLRJKQCYTN-JOCHJYFZSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(C(F)(F)F)=CC=C4)O)=O)=C3C2=O)=C1 VUFYQLRJKQCYTN-JOCHJYFZSA-N 0.000 claims description 4
- ADZAIQHBWAWNLQ-AREMUKBSSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(5-phenylpyridin-3-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CC=C3)=CN=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 ADZAIQHBWAWNLQ-AREMUKBSSA-N 0.000 claims description 4
- SLDGIRZIDJHKDH-AREMUKBSSA-N 6-[(2R)-2-hydroxy-2-[3-[6-(trifluoromethyl)pyridin-2-yl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=NC(C(F)(F)F)=CC=C2)=CC=C1 SLDGIRZIDJHKDH-AREMUKBSSA-N 0.000 claims description 4
- CWDOAKKAHZFWMZ-UHFFFAOYSA-N 6-[2,2-difluoro-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(5-phenylpyridin-3-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(C(C1=CC(C(F)(F)F)=CC=C1)(F)F)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CC=C3)=CN=C1)NC2=O CWDOAKKAHZFWMZ-UHFFFAOYSA-N 0.000 claims description 4
- BFXWGFYETMHNDU-UHFFFAOYSA-N 6-[2-(3-chloro-2-fluorophenyl)-2-hydroxyacetyl]-2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCCN(C3)C(C(C(C=CC=C4Cl)=C4F)O)=O)=C3C2=O)=C1 BFXWGFYETMHNDU-UHFFFAOYSA-N 0.000 claims description 4
- RPHSFYHMWNTDKT-UHFFFAOYSA-N 6-[2-[3-(3-chloro-5-fluorophenyl)phenyl]acetyl]-2-[1-(3-chlorophenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC=CC(C2=CC(Cl)=CC(F)=C2)=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O RPHSFYHMWNTDKT-UHFFFAOYSA-N 0.000 claims description 4
- IZYFIKQNSHAFDR-UHFFFAOYSA-N 6-[2-[3-(3-chlorophenyl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC=CC(C2=CC(Cl)=CC=C2)=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O IZYFIKQNSHAFDR-UHFFFAOYSA-N 0.000 claims description 4
- IMRNIYDMYSXIRR-UHFFFAOYSA-N 6-[2-[3-(3-chlorophenyl)phenyl]acetyl]-2-[1-(5-phenylpyridin-3-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC=CC(C2=CC(Cl)=CC=C2)=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CC=C3)=CN=C1)NC2=O IMRNIYDMYSXIRR-UHFFFAOYSA-N 0.000 claims description 4
- FZWHDZBGNNNEDO-UHFFFAOYSA-N 6-[2-[3-(3-cyclopropylphenyl)phenyl]-2,2-difluoroacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(C(C1=CC=CC(C2=CC(C3CC3)=CC=C2)=C1)(F)F)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O FZWHDZBGNNNEDO-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
- 239000012634 fragment Substances 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 3
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 3
- 206010038923 Retinopathy Diseases 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 239000002773 nucleotide Substances 0.000 claims description 3
- 125000003729 nucleotide group Chemical group 0.000 claims description 3
- 125000003566 oxetanyl group Chemical group 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000003943 azolyl group Chemical group 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 230000036961 partial effect Effects 0.000 claims description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 229920002521 macromolecule Polymers 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 23
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 229940127557 pharmaceutical product Drugs 0.000 abstract 1
- 208000019553 vascular disease Diseases 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 69
- 210000001525 retina Anatomy 0.000 description 65
- 239000002585 base Substances 0.000 description 49
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 42
- 230000002207 retinal effect Effects 0.000 description 41
- 210000001508 eye Anatomy 0.000 description 32
- 210000004204 blood vessel Anatomy 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 229940126062 Compound A Drugs 0.000 description 23
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 23
- 241000699666 Mus <mouse, genus> Species 0.000 description 23
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 20
- 238000003786 synthesis reaction Methods 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 19
- 230000005764 inhibitory process Effects 0.000 description 19
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 18
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 18
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 18
- 210000001328 optic nerve Anatomy 0.000 description 18
- 235000018102 proteins Nutrition 0.000 description 17
- 239000002904 solvent Substances 0.000 description 16
- 208000024891 symptom Diseases 0.000 description 16
- 239000003981 vehicle Substances 0.000 description 16
- 210000003462 vein Anatomy 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000004305 biphenyl Substances 0.000 description 15
- 239000003889 eye drop Substances 0.000 description 15
- 241000699670 Mus sp. Species 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 210000003161 choroid Anatomy 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 230000004393 visual impairment Effects 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 239000007983 Tris buffer Substances 0.000 description 12
- 238000006880 cross-coupling reaction Methods 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 11
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 11
- 210000005252 bulbus oculi Anatomy 0.000 description 11
- 239000003826 tablet Substances 0.000 description 11
- 238000000692 Student's t-test Methods 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 230000007423 decrease Effects 0.000 description 10
- 206010012689 Diabetic retinopathy Diseases 0.000 description 9
- 208000032843 Hemorrhage Diseases 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 206010061218 Inflammation Diseases 0.000 description 9
- 201000010183 Papilledema Diseases 0.000 description 9
- 239000004698 Polyethylene Substances 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 206010038886 Retinal oedema Diseases 0.000 description 9
- 150000001409 amidines Chemical class 0.000 description 9
- 229940012356 eye drops Drugs 0.000 description 9
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 9
- 230000004054 inflammatory process Effects 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 229920000573 polyethylene Polymers 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 201000011195 retinal edema Diseases 0.000 description 9
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 9
- 206010025421 Macule Diseases 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- 108700008625 Reporter Genes Proteins 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 206010053648 Vascular occlusion Diseases 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000000654 additive Substances 0.000 description 8
- 239000000556 agonist Substances 0.000 description 8
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 238000011156 evaluation Methods 0.000 description 8
- 239000012530 fluid Substances 0.000 description 8
- 230000006872 improvement Effects 0.000 description 8
- 230000000302 ischemic effect Effects 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
- 230000002792 vascular Effects 0.000 description 8
- 208000021331 vascular occlusion disease Diseases 0.000 description 8
- 230000008728 vascular permeability Effects 0.000 description 8
- 108091006146 Channels Proteins 0.000 description 7
- 208000001344 Macular Edema Diseases 0.000 description 7
- 206010025415 Macular oedema Diseases 0.000 description 7
- 206010030113 Oedema Diseases 0.000 description 7
- 206010047571 Visual impairment Diseases 0.000 description 7
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 7
- 239000000306 component Substances 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 230000004438 eyesight Effects 0.000 description 7
- 201000010230 macular retinal edema Diseases 0.000 description 7
- 210000000608 photoreceptor cell Anatomy 0.000 description 7
- DAUYIKBTMNZABP-UHFFFAOYSA-N thiophene-3-carboxamide Chemical compound NC(=O)C=1C=CSC=1 DAUYIKBTMNZABP-UHFFFAOYSA-N 0.000 description 7
- 230000001052 transient effect Effects 0.000 description 7
- 208000029257 vision disease Diseases 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 210000001367 artery Anatomy 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 239000012442 inert solvent Substances 0.000 description 6
- 230000004410 intraocular pressure Effects 0.000 description 6
- 210000004379 membrane Anatomy 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 108020004707 nucleic acids Proteins 0.000 description 6
- 102000039446 nucleic acids Human genes 0.000 description 6
- 150000007523 nucleic acids Chemical class 0.000 description 6
- 230000010412 perfusion Effects 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 210000001957 retinal vein Anatomy 0.000 description 6
- 230000002889 sympathetic effect Effects 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 5
- 206010020772 Hypertension Diseases 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 230000033115 angiogenesis Effects 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000006184 cosolvent Substances 0.000 description 5
- 239000011888 foil Substances 0.000 description 5
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 5
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 229920002307 Dextran Polymers 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 208000002367 Retinal Perforations Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 108010081667 aflibercept Proteins 0.000 description 4
- 150000001413 amino acids Chemical group 0.000 description 4
- 229940114079 arachidonic acid Drugs 0.000 description 4
- 235000021342 arachidonic acid Nutrition 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 210000004925 microvascular endothelial cell Anatomy 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 4
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 4
- 230000035699 permeability Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 4
- 210000003994 retinal ganglion cell Anatomy 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 238000007910 systemic administration Methods 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- 210000003556 vascular endothelial cell Anatomy 0.000 description 4
- 230000004382 visual function Effects 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 238000001061 Dunnett's test Methods 0.000 description 3
- IVYQPSHHYIAUFO-VXKWHMMOSA-N GSK1016790A Chemical compound N([C@@H](CO)C(=O)N1CCN(CC1)C(=O)[C@@H](NC(=O)C=1SC2=CC=CC=C2C=1)CC(C)C)S(=O)(=O)C1=CC=C(Cl)C=C1Cl IVYQPSHHYIAUFO-VXKWHMMOSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 206010038934 Retinopathy proliferative Diseases 0.000 description 3
- 208000034698 Vitreous haemorrhage Diseases 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 125000004414 alkyl thio group Chemical group 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 239000000074 antisense oligonucleotide Substances 0.000 description 3
- 238000012230 antisense oligonucleotides Methods 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- IANQTJSKSUMEQM-UHFFFAOYSA-N benzofuran Natural products C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 3
- 239000002876 beta blocker Substances 0.000 description 3
- 229940097320 beta blocking agent Drugs 0.000 description 3
- 229960000397 bevacizumab Drugs 0.000 description 3
- 239000012503 blood component Substances 0.000 description 3
- 230000036770 blood supply Effects 0.000 description 3
- 150000001642 boronic acid derivatives Chemical class 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000012611 container material Substances 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000003885 eye ointment Substances 0.000 description 3
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
- 230000005714 functional activity Effects 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 230000001678 irradiating effect Effects 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 3
- 229920001684 low density polyethylene Polymers 0.000 description 3
- 239000004702 low-density polyethylene Substances 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229960004063 propylene glycol Drugs 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 208000032253 retinal ischemia Diseases 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000021 stimulant Substances 0.000 description 3
- 229940124530 sulfonamide Drugs 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- 230000004304 visual acuity Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- HGERHERQHBJWIY-UIOOFZCWSA-N 3-[[(5s,7s)-3-(6-ethoxy-4-methylpyridin-3-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC(OCC)=CC(C)=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 HGERHERQHBJWIY-UIOOFZCWSA-N 0.000 description 2
- TURDIGXLIVIFRO-UIOOFZCWSA-N 3-[[(5s,7s)-3-[(5-ethoxypyridin-2-yl)methyl]-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound N1=CC(OCC)=CC=C1CN1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 TURDIGXLIVIFRO-UIOOFZCWSA-N 0.000 description 2
- 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 2
- DWOZNANUEDYIOF-UHFFFAOYSA-L 4-ditert-butylphosphanyl-n,n-dimethylaniline;dichloropalladium Chemical compound Cl[Pd]Cl.CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1.CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1 DWOZNANUEDYIOF-UHFFFAOYSA-L 0.000 description 2
- SQVKTYPDFXSZIC-UHFFFAOYSA-N 6-[2-(3,5-difluorophenyl)-2-hydroxyacetyl]-2-[1-(3-fluorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C1=CC(F)=CC(F)=C1 SQVKTYPDFXSZIC-UHFFFAOYSA-N 0.000 description 2
- MTDYZLHEMUOHTH-UHFFFAOYSA-N 6-[2-hydroxy-2-(3-propan-2-ylphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=C1 MTDYZLHEMUOHTH-UHFFFAOYSA-N 0.000 description 2
- WLCZTRVUXYALDD-IBGZPJMESA-N 7-[[(2s)-2,6-bis(2-methoxyethoxycarbonylamino)hexanoyl]amino]heptoxy-methylphosphinic acid Chemical compound COCCOC(=O)NCCCC[C@H](NC(=O)OCCOC)C(=O)NCCCCCCCOP(C)(O)=O WLCZTRVUXYALDD-IBGZPJMESA-N 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 206010048554 Endothelial dysfunction Diseases 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 101000633097 Homo sapiens Transient receptor potential cation channel subfamily V member 4 Proteins 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- FAIIFDPAEUKBEP-UHFFFAOYSA-N Nilvadipine Chemical compound COC(=O)C1=C(C#N)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 FAIIFDPAEUKBEP-UHFFFAOYSA-N 0.000 description 2
- 208000022873 Ocular disease Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 102100026918 Phospholipase A2 Human genes 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 208000037111 Retinal Hemorrhage Diseases 0.000 description 2
- 206010038897 Retinal tear Diseases 0.000 description 2
- 208000014139 Retinal vascular disease Diseases 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
- BGDKAVGWHJFAGW-UHFFFAOYSA-N Tropicamide Chemical compound C=1C=CC=CC=1C(CO)C(=O)N(CC)CC1=CC=NC=C1 BGDKAVGWHJFAGW-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 206010047555 Visual field defect Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 150000001266 acyl halides Chemical class 0.000 description 2
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 2
- 229960002833 aflibercept Drugs 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N aminomethyl benzene Natural products NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 210000001742 aqueous humor Anatomy 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
- 239000000605 aspartame Substances 0.000 description 2
- 235000010357 aspartame Nutrition 0.000 description 2
- 229960003438 aspartame Drugs 0.000 description 2
- GMHPWGYTSXHHPI-UHFFFAOYSA-N azepan-4-one Chemical compound O=C1CCCNCC1 GMHPWGYTSXHHPI-UHFFFAOYSA-N 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229920002988 biodegradable polymer Polymers 0.000 description 2
- 239000004621 biodegradable polymer Substances 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- 239000001273 butane Substances 0.000 description 2
- 230000009460 calcium influx Effects 0.000 description 2
- 229930003827 cannabinoid Natural products 0.000 description 2
- 239000003557 cannabinoid Substances 0.000 description 2
- 229940065144 cannabinoids Drugs 0.000 description 2
- 210000001043 capillary endothelial cell Anatomy 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 239000006274 endogenous ligand Substances 0.000 description 2
- 230000008694 endothelial dysfunction Effects 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000010101 extrusion blow moulding Methods 0.000 description 2
- 238000003682 fluorination reaction Methods 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 229920001903 high density polyethylene Polymers 0.000 description 2
- 239000004700 high-density polyethylene Substances 0.000 description 2
- 230000036732 histological change Effects 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 125000005945 imidazopyridyl group Chemical group 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000010102 injection blow moulding Methods 0.000 description 2
- 230000031146 intracellular signal transduction Effects 0.000 description 2
- 230000000622 irritating effect Effects 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229960001160 latanoprost Drugs 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229920001179 medium density polyethylene Polymers 0.000 description 2
- 239000004701 medium-density polyethylene Substances 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical group CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 201000003142 neovascular glaucoma Diseases 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 2
- 229960001597 nifedipine Drugs 0.000 description 2
- 229960005366 nilvadipine Drugs 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 238000012014 optical coherence tomography Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000002357 osmotic agent Substances 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 229940124641 pain reliever Drugs 0.000 description 2
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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.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 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 2
- 229960001802 phenylephrine Drugs 0.000 description 2
- 230000000649 photocoagulation Effects 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- MMCIXNVRVDTQSG-UHFFFAOYSA-N quinoline-7-carboxamide Chemical compound C1=CC=NC2=CC(C(=O)N)=CC=C21 MMCIXNVRVDTQSG-UHFFFAOYSA-N 0.000 description 2
- 150000003248 quinolines Chemical class 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 229960003876 ranibizumab Drugs 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000001927 retinal artery Anatomy 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 210000003786 sclera Anatomy 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 239000004055 small Interfering RNA Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 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 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 239000013076 target substance Substances 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- 229960004791 tropicamide Drugs 0.000 description 2
- 210000004127 vitreous body Anatomy 0.000 description 2
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- SSJXIUAHEKJCMH-WDSKDSINSA-N (1s,2s)-cyclohexane-1,2-diamine Chemical compound N[C@H]1CCCC[C@@H]1N SSJXIUAHEKJCMH-WDSKDSINSA-N 0.000 description 1
- YLXIPWWIOISBDD-NDAAPVSOSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;4-[(1r)-1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.CNC[C@H](O)C1=CC=C(O)C(O)=C1 YLXIPWWIOISBDD-NDAAPVSOSA-N 0.000 description 1
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- 125000006717 (C3-C10) cycloalkenyl group Chemical group 0.000 description 1
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 1
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
- WLRMANUAADYWEA-NWASOUNVSA-N (S)-timolol maleate Chemical compound OC(=O)\C=C/C(O)=O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 WLRMANUAADYWEA-NWASOUNVSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RWNNRGBCWXOVAC-UHFFFAOYSA-N 1,4-bis[bis(aziridin-1-yl)phosphoryl]piperazine Chemical compound C1CN1P(N1CCN(CC1)P(=O)(N1CC1)N1CC1)(=O)N1CC1 RWNNRGBCWXOVAC-UHFFFAOYSA-N 0.000 description 1
- RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- UTHYMAQILGSBNH-UHFFFAOYSA-N 1-[[3-[(5-chloro-1-benzothiophen-3-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]indole-6-carbonitrile Chemical compound C1=CC2=CC=C(C#N)C=C2N1CC(C1)CCCC1(OC1=O)CN1CC1=CSC2=CC=C(Cl)C=C21 UTHYMAQILGSBNH-UHFFFAOYSA-N 0.000 description 1
- JQSAYKKFZOSZGJ-UHFFFAOYSA-N 1-[bis(4-fluorophenyl)methyl]-4-[(2,3,4-trimethoxyphenyl)methyl]piperazine Chemical compound COC1=C(OC)C(OC)=CC=C1CN1CCN(C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 JQSAYKKFZOSZGJ-UHFFFAOYSA-N 0.000 description 1
- QDXQAOGNBCOEQX-UHFFFAOYSA-N 1-methylcyclohexa-1,4-diene Chemical compound CC1=CCC=CC1 QDXQAOGNBCOEQX-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- XTNOEYFQXCQKLC-UHFFFAOYSA-N 18-(oxiren-2-yl)octadeca-15,17-dienoic acid Chemical compound C1=C(C=CC=CCCCCCCCCCCCCCC(=O)O)O1 XTNOEYFQXCQKLC-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- LSIXBBPOJBJQHN-UHFFFAOYSA-N 2,3-Dimethylbicyclo[2.2.1]hept-2-ene Chemical compound C1CC2C(C)=C(C)C1C2 LSIXBBPOJBJQHN-UHFFFAOYSA-N 0.000 description 1
- LFVYDQYRKRRLNP-QGZVFWFLSA-N 2-(1-phenylcyclopropyl)-6-[(2R)-2-phenylpropanoyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound C[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC=C1 LFVYDQYRKRRLNP-QGZVFWFLSA-N 0.000 description 1
- KASOEMBJDMOCBN-UHFFFAOYSA-N 2-(1-phenylcyclopropyl)-6-[2-(3-phenylphenyl)acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC1=CC=CC(C2=CC=CC=C2)=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O KASOEMBJDMOCBN-UHFFFAOYSA-N 0.000 description 1
- PYXGOVFPVDWDTA-UHFFFAOYSA-N 2-(1-phenylcyclopropyl)-6-[2-(4-propan-2-ylphenyl)acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CC=C(CC(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)C=C1 PYXGOVFPVDWDTA-UHFFFAOYSA-N 0.000 description 1
- YGMHEEXCYKVNET-UHFFFAOYSA-N 2-(1-phenylcyclopropyl)-6-[2-(4-pyridin-2-ylphenyl)acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC(C=C1)=CC=C1C1=NC=CC=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O YGMHEEXCYKVNET-UHFFFAOYSA-N 0.000 description 1
- RXQMWPLKBUVSCR-UHFFFAOYSA-N 2-(1-phenylcyclopropyl)-6-[2-[3-(trifluoromethoxy)phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC1=CC(OC(F)(F)F)=CC=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O RXQMWPLKBUVSCR-UHFFFAOYSA-N 0.000 description 1
- VWGYNJLUUOZPHR-UHFFFAOYSA-N 2-(1-phenylcyclopropyl)-6-[2-[3-(trifluoromethyl)phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC1=CC(C(F)(F)F)=CC=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O VWGYNJLUUOZPHR-UHFFFAOYSA-N 0.000 description 1
- IXYVKNUYQQQFJL-UHFFFAOYSA-N 2-(1-phenylcyclopropyl)-6-[2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC(C(F)(F)F)=CC=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O IXYVKNUYQQQFJL-UHFFFAOYSA-N 0.000 description 1
- AQUCJPCZDSRMPR-UHFFFAOYSA-N 2-(1-phenylcyclopropyl)-6-[2-[3-[3-(trifluoromethoxy)phenyl]phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC=CC(C2=CC(OC(F)(F)F)=CC=C2)=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O AQUCJPCZDSRMPR-UHFFFAOYSA-N 0.000 description 1
- RKEINICOJISGJY-UHFFFAOYSA-N 2-(1-phenylcyclopropyl)-6-[2-[4-(trifluoromethyl)phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC1=CC=C(C(F)(F)F)C=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O RKEINICOJISGJY-UHFFFAOYSA-N 0.000 description 1
- WLKQGISHMQEZFC-UHFFFAOYSA-N 2-(1-phenylcyclopropyl)-6-[2-[4-(trifluoromethyl)phenyl]propanoyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=C(C(F)(F)F)C=C1 WLKQGISHMQEZFC-UHFFFAOYSA-N 0.000 description 1
- HGKLFEWLHSELFC-UHFFFAOYSA-N 2-(1-phenylcyclopropyl)-6-[6-(trifluoromethyl)-1H-benzimidazole-2-carbonyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(C1=NC(C=C(C(F)(F)F)C=C2)=C2N1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O HGKLFEWLHSELFC-UHFFFAOYSA-N 0.000 description 1
- GTTMIRCZJXZBPN-UHFFFAOYSA-N 2-(3-bromophenyl)-6-methylsulfonyl-N-(1-phenylcyclopropyl)-3-[(4-pyrrolidin-1-ylpiperidin-1-yl)methyl]quinoline-4-carboxamide Chemical compound CS(=O)(=O)c1ccc2nc(c(CN3CCC(CC3)N3CCCC3)c(C(=O)NC3(CC3)c3ccccc3)c2c1)-c1cccc(Br)c1 GTTMIRCZJXZBPN-UHFFFAOYSA-N 0.000 description 1
- LCLYSRWVRIXEFS-UHFFFAOYSA-N 2-(4-methoxyphenyl)-6-methylsulfonyl-N-(1-phenylcyclopropyl)-3-[(4-pyrrolidin-1-ylpiperidin-1-yl)methyl]quinoline-4-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC=C(S(C)(=O)=O)C=C2C(C(=O)NC2(CC2)C=2C=CC=CC=2)=C1CN1CCC(N2CCCC2)CC1 LCLYSRWVRIXEFS-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- FPYYUVTVBPDKRH-HXUWFJFHSA-N 2-[1-(3,4-difluorophenyl)cyclopropyl]-6-[(2R)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC(F)=C1F)NC2=O)=O)C(C=CC=C1F)=C1F FPYYUVTVBPDKRH-HXUWFJFHSA-N 0.000 description 1
- VGSWYOIRMXTTSZ-HXUWFJFHSA-N 2-[1-(3,5-difluorophenyl)cyclopropyl]-6-[(2R)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC(F)=C1)NC2=O)=O)C(C=CC=C1F)=C1F VGSWYOIRMXTTSZ-HXUWFJFHSA-N 0.000 description 1
- ZAUFEBRWQJWNRU-HXUWFJFHSA-N 2-[1-(3-bromophenyl)cyclopropyl]-6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Br)=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 ZAUFEBRWQJWNRU-HXUWFJFHSA-N 0.000 description 1
- WTHXGCCPDFVJRI-QGZVFWFLSA-N 2-[1-(3-bromothiophen-2-yl)cyclopropyl]-6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C(SC=C1)=C1Br)NC2=O)=O)C1=CC(Cl)=CC=C1 WTHXGCCPDFVJRI-QGZVFWFLSA-N 0.000 description 1
- AAPDFDCLHWMGKA-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-(2-naphthalen-1-ylacetyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC=CC2=CC=CC=C12)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O AAPDFDCLHWMGKA-UHFFFAOYSA-N 0.000 description 1
- UKLIMAUOVRERMO-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-(3-phenylbenzoyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(C1=CC=CC(C2=CC=CC=C2)=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O UKLIMAUOVRERMO-UHFFFAOYSA-N 0.000 description 1
- BYBLZLFBPKCNSI-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-(4-phenylbenzoyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(C(C=C1)=CC=C1C1=CC=CC=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O BYBLZLFBPKCNSI-UHFFFAOYSA-N 0.000 description 1
- XGQHWODJMCDQPS-HXUWFJFHSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C(C=CC=C1F)=C1F XGQHWODJMCDQPS-HXUWFJFHSA-N 0.000 description 1
- NJTRZJHRETYRIA-OAQYLSRUSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C(C=CC=C1F)=C1F NJTRZJHRETYRIA-OAQYLSRUSA-N 0.000 description 1
- FBLPFOAVSDBKBY-OAQYLSRUSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 FBLPFOAVSDBKBY-OAQYLSRUSA-N 0.000 description 1
- NJDZYFFQNSLISP-AREMUKBSSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-[3-(3-chlorophenyl)phenyl]-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(Cl)=CC=C2)=C1 NJDZYFFQNSLISP-AREMUKBSSA-N 0.000 description 1
- VCTIJOPXJKFFJP-SSEXGKCCSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-[3-(3-cyclopropylphenyl)phenyl]-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(C3CC3)=CC=C2)=C1 VCTIJOPXJKFFJP-SSEXGKCCSA-N 0.000 description 1
- INUJSXZGAIMWEY-HHHXNRCGSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-[3-(4-chlorophenyl)phenyl]-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC=C2Cl)=C1 INUJSXZGAIMWEY-HHHXNRCGSA-N 0.000 description 1
- ULEZILGXXDAQHB-HHHXNRCGSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-[3-[3-chloro-5-(trifluoromethoxy)phenyl]phenyl]-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(Cl)=CC(OC(F)(F)F)=C2)=C1 ULEZILGXXDAQHB-HHHXNRCGSA-N 0.000 description 1
- OZMBSEBDXXZBSN-AREMUKBSSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-[3-[3-chloro-5-(trifluoromethyl)phenyl]phenyl]-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(Cl)=CC(C(F)(F)F)=C2)=C1 OZMBSEBDXXZBSN-AREMUKBSSA-N 0.000 description 1
- GBPJQFUSOARMML-SSEXGKCCSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(3-propan-2-ylphenyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CC=CC(C2=CC([C@H](C(N(CCC3)CC4=C3N=C(C3(CC3)C3=CC(Cl)=CC=C3)NC4=O)=O)O)=CC=C2)=C1 GBPJQFUSOARMML-SSEXGKCCSA-N 0.000 description 1
- XPAXGXFGMFKGEJ-HXUWFJFHSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 XPAXGXFGMFKGEJ-HXUWFJFHSA-N 0.000 description 1
- MHPVJSICIQSBKM-AREMUKBSSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-[2-(trifluoromethyl)pyridin-4-yl]phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(C2=CC(C(F)(F)F)=NC=C2)=CC=C1 MHPVJSICIQSBKM-AREMUKBSSA-N 0.000 description 1
- PNPWQKPAUGWDAM-HHHXNRCGSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-[3-(trifluoromethoxy)phenyl]phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(OC(F)(F)F)=CC=C2)=C1 PNPWQKPAUGWDAM-HHHXNRCGSA-N 0.000 description 1
- CYNHXFGXWMXNJC-AREMUKBSSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(C(F)(F)F)=CC=C2)=C1 CYNHXFGXWMXNJC-AREMUKBSSA-N 0.000 description 1
- YLACUOPJBZILCK-RUZDIDTESA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-[6-(trifluoromethyl)pyridin-2-yl]phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(C2=NC(C(F)(F)F)=CC=C2)=CC=C1 YLACUOPJBZILCK-RUZDIDTESA-N 0.000 description 1
- XGQHWODJMCDQPS-FQEVSTJZSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2S)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C(C=CC=C1F)=C1F XGQHWODJMCDQPS-FQEVSTJZSA-N 0.000 description 1
- JOSZTOREWPGZKA-NRFANRHFSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[(2S)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 JOSZTOREWPGZKA-NRFANRHFSA-N 0.000 description 1
- YJMQPIUXRRXKOC-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2,2-difluoro-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(C(C1=CC(C(F)(F)F)=CC=C1)(F)F)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O YJMQPIUXRRXKOC-UHFFFAOYSA-N 0.000 description 1
- UWBLISFWIQOCJU-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-(3-chlorophenyl)-2,2-difluoroacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(C(C1=CC(Cl)=CC=C1)(F)F)N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O UWBLISFWIQOCJU-UHFFFAOYSA-N 0.000 description 1
- NODDUIZJXSJVCN-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-(3-chlorophenyl)-2,2-difluoroacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(C(C1=CC(Cl)=CC=C1)(F)F)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O NODDUIZJXSJVCN-UHFFFAOYSA-N 0.000 description 1
- QMMTVMFRVXZVLD-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-(3-cyclopropylphenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(C2CC2)=CC=C1 QMMTVMFRVXZVLD-UHFFFAOYSA-N 0.000 description 1
- WOZUEPHEBQKYTN-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-(3-cyclopropylphenyl)-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(C2CC2)=CC=C1 WOZUEPHEBQKYTN-UHFFFAOYSA-N 0.000 description 1
- XJLNVRVJFLTWEE-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-(3-cyclopropylphenyl)acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC(C2CC2)=CC=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O XJLNVRVJFLTWEE-UHFFFAOYSA-N 0.000 description 1
- NQACHEZCKPCFSD-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-(3-phenoxyphenyl)acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC(OC2=CC=CC=C2)=CC=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O NQACHEZCKPCFSD-UHFFFAOYSA-N 0.000 description 1
- CLHOAGBGEJGWGA-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-(4-phenylmethoxyphenyl)acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC(C=C1)=CC=C1OCC1=CC=CC=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O CLHOAGBGEJGWGA-UHFFFAOYSA-N 0.000 description 1
- LZBYYBPWLLTMCC-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-[3-(3-fluorophenyl)phenyl]-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(F)=CC=C2)=C1 LZBYYBPWLLTMCC-UHFFFAOYSA-N 0.000 description 1
- PLTBBINRNZXNIS-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-[3-(4-chlorophenyl)phenyl]-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC=C2Cl)=C1 PLTBBINRNZXNIS-UHFFFAOYSA-N 0.000 description 1
- LAYFOVLUZRJUIW-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-[3-(4-chlorophenyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC=CC(C(C=C2)=CC=C2Cl)=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O LAYFOVLUZRJUIW-UHFFFAOYSA-N 0.000 description 1
- RJJSYENEPQHVGL-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-[3-(trifluoromethoxy)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC(OC(F)(F)F)=CC=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O RJJSYENEPQHVGL-UHFFFAOYSA-N 0.000 description 1
- LAOFXCHGZHPUTD-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC(C(F)(F)F)=CC=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O LAOFXCHGZHPUTD-UHFFFAOYSA-N 0.000 description 1
- YWXXFHUSALFGQC-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-[3-[3-(trifluoromethoxy)phenyl]phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC1=CC=CC(C2=CC(OC(F)(F)F)=CC=C2)=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O YWXXFHUSALFGQC-UHFFFAOYSA-N 0.000 description 1
- WYLXRSGJQSUHSH-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-[3-[4-(trifluoromethoxy)phenyl]phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC=CC(C(C=C2)=CC=C2OC(F)(F)F)=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O WYLXRSGJQSUHSH-UHFFFAOYSA-N 0.000 description 1
- UYEVWBVAEJKMQS-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-hydroxy-2-(3-phenoxyphenyl)acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(OC2=CC=CC=C2)=CC=C1 UYEVWBVAEJKMQS-UHFFFAOYSA-N 0.000 description 1
- KOSNADVUBBMIEY-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-hydroxy-2-(3-phenoxyphenyl)acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(OC2=CC=CC=C2)=CC=C1 KOSNADVUBBMIEY-UHFFFAOYSA-N 0.000 description 1
- KNXUAVLSQLJGIX-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-hydroxy-2-(3-phenylmethoxyphenyl)acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(OCC2=CC=CC=C2)=CC=C1 KNXUAVLSQLJGIX-UHFFFAOYSA-N 0.000 description 1
- XIOPNTQRFSDDQZ-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-hydroxy-2-(3-propan-2-ylphenyl)acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC(Cl)=CC=C2)NC3=O)=O)O)=C1 XIOPNTQRFSDDQZ-UHFFFAOYSA-N 0.000 description 1
- HPHYKMQUGOBORN-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-hydroxy-2-(3-quinolin-3-ylphenyl)acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(C2=CC3=CC=CC=C3N=C2)=CC=C1 HPHYKMQUGOBORN-UHFFFAOYSA-N 0.000 description 1
- REMXZAPDQJRQNC-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-hydroxy-2-[3-(2,2,2-trifluoroethoxy)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(OCC(F)(F)F)=CC=C1 REMXZAPDQJRQNC-UHFFFAOYSA-N 0.000 description 1
- UVZOKJAYGKHWAC-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-hydroxy-2-[3-(trifluoromethylsulfanyl)phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(SC(F)(F)F)=CC=C1 UVZOKJAYGKHWAC-UHFFFAOYSA-N 0.000 description 1
- PCEORHOZQKWOSD-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-hydroxy-2-[3-[3-(trifluoromethyl)phenoxy]phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC(OC2=CC(C(F)(F)F)=CC=C2)=CC=C1 PCEORHOZQKWOSD-UHFFFAOYSA-N 0.000 description 1
- DYMCZBWMXHBHPF-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[2-hydroxy-2-[4-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC=C(C(F)(F)F)C=C1 DYMCZBWMXHBHPF-UHFFFAOYSA-N 0.000 description 1
- NOZZQRCOEYYIKX-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)cyclopropyl]-6-[3-[3-(trifluoromethyl)phenyl]propanoyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CCC1=CC(C(F)(F)F)=CC=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O NOZZQRCOEYYIKX-UHFFFAOYSA-N 0.000 description 1
- OORNKWZKZKKMGC-MGBGTMOVSA-N 2-[1-(3-cyclohexylphenyl)cyclopropyl]-6-[(2R)-2-[3-(3-fluorophenyl)phenyl]-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCCC3)=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(F)=CC=C2)=C1 OORNKWZKZKKMGC-MGBGTMOVSA-N 0.000 description 1
- XWAFZLLVZGYYPM-UHFFFAOYSA-N 2-[1-(3-cyclohexylphenyl)cyclopropyl]-6-[2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC1=CC=CC(C2=CC(C(F)(F)F)=CC=C2)=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCCC3)=CC=C1)NC2=O XWAFZLLVZGYYPM-UHFFFAOYSA-N 0.000 description 1
- NSKOKAIUNCGPRA-AREMUKBSSA-N 2-[1-(3-cyclopentylphenyl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCC3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 NSKOKAIUNCGPRA-AREMUKBSSA-N 0.000 description 1
- SWKPJDIVHDIMGF-HXUWFJFHSA-N 2-[1-(3-fluorophenyl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 SWKPJDIVHDIMGF-HXUWFJFHSA-N 0.000 description 1
- OKJGMYNZQUJIFL-UHFFFAOYSA-N 2-[1-(3-fluorophenyl)cyclopropyl]-6-[2-[3-(3-fluorophenyl)phenyl]-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(F)=CC=C2)=C1 OKJGMYNZQUJIFL-UHFFFAOYSA-N 0.000 description 1
- AEROENTYWRRBBA-UHFFFAOYSA-N 2-[1-(3-fluorophenyl)cyclopropyl]-6-[2-[3-(3-fluorophenyl)phenyl]-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(F)=CC=C2)=C1 AEROENTYWRRBBA-UHFFFAOYSA-N 0.000 description 1
- KUKAIFLTSWBCPY-UHFFFAOYSA-N 2-[1-(3-fluorophenyl)cyclopropyl]-6-[2-[3-(trifluoromethyl)phenyl]propanoyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 KUKAIFLTSWBCPY-UHFFFAOYSA-N 0.000 description 1
- JOESZKKRMQKNKP-UHFFFAOYSA-N 2-[1-(3-fluorophenyl)cyclopropyl]-6-[2-hydroxy-2-(3-propan-2-ylphenyl)acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC(F)=CC=C2)NC3=O)=O)O)=C1 JOESZKKRMQKNKP-UHFFFAOYSA-N 0.000 description 1
- ZFNYIFINSDNESK-UHFFFAOYSA-N 2-[1-(3-fluorophenyl)cyclopropyl]-6-[2-hydroxy-2-[3-(trifluoromethylsulfanyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C1=CC(SC(F)(F)F)=CC=C1 ZFNYIFINSDNESK-UHFFFAOYSA-N 0.000 description 1
- CUIIJHGGONWFMB-UHFFFAOYSA-N 2-[1-(3-fluorophenyl)cyclopropyl]-6-[2-hydroxy-2-[3-[3-(trifluoromethoxy)phenyl]phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(OC(F)(F)F)=CC=C2)=C1 CUIIJHGGONWFMB-UHFFFAOYSA-N 0.000 description 1
- PVWKYQNBPDUPIX-HXUWFJFHSA-N 2-[1-(4-bromophenyl)cyclopropyl]-6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC=C1Br)NC2=O)=O)C1=CC(Cl)=CC=C1 PVWKYQNBPDUPIX-HXUWFJFHSA-N 0.000 description 1
- YQCSLYIEBOBXTH-LJQANCHMSA-N 2-[1-(4-bromothiophen-2-yl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Br)=CS1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 YQCSLYIEBOBXTH-LJQANCHMSA-N 0.000 description 1
- WBXLSZQULANJAL-HXUWFJFHSA-N 2-[1-(4-chlorophenyl)cyclopropyl]-6-[(2R)-2-(2-chlorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC=C1Cl)NC2=O)=O)C(C=CC=C1)=C1Cl WBXLSZQULANJAL-HXUWFJFHSA-N 0.000 description 1
- VUDBYAKRPQYUTB-LJQANCHMSA-N 2-[1-(4-chlorophenyl)cyclopropyl]-6-[(2R)-2-[4-(2-methylpropyl)phenyl]propanoyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)CC1=CC=C([C@@H](C)C(N(CC2)CC3=C2N=C(C2(CC2)C(C=C2)=CC=C2Cl)NC3=O)=O)C=C1 VUDBYAKRPQYUTB-LJQANCHMSA-N 0.000 description 1
- AVHZGEQISDGBFH-UHFFFAOYSA-N 2-[1-(4-chlorophenyl)cyclopropyl]-6-[2-(2,3-difluorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC=C1Cl)NC2=O)=O)C(C=CC=C1F)=C1F AVHZGEQISDGBFH-UHFFFAOYSA-N 0.000 description 1
- SNSYKFRMQSEYSK-UHFFFAOYSA-N 2-[1-(4-chlorophenyl)cyclopropyl]-6-[2-(3,5-difluorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC=C1Cl)NC2=O)=O)C1=CC(F)=CC(F)=C1 SNSYKFRMQSEYSK-UHFFFAOYSA-N 0.000 description 1
- HNOGJYMRIQZDAO-RUZDIDTESA-N 2-[1-(4-cycloheptylthiophen-2-yl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCCCC3)=CS1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 HNOGJYMRIQZDAO-RUZDIDTESA-N 0.000 description 1
- LDFCUIIMPZHYKM-WJOKGBTCSA-N 2-[1-(4-cyclohexylthiophen-2-yl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-[3-(trifluoromethoxy)phenyl]phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCCC3)=CS1)NC2=O)=O)C1=CC=CC(C2=CC(OC(F)(F)F)=CC=C2)=C1 LDFCUIIMPZHYKM-WJOKGBTCSA-N 0.000 description 1
- VHPXBGMNQCNMIP-HSZRJFAPSA-N 2-[1-(4-cyclopentylthiophen-2-yl)cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCC3)=CS1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 VHPXBGMNQCNMIP-HSZRJFAPSA-N 0.000 description 1
- CPCOIEIOXNOLNY-UHFFFAOYSA-N 2-[1-(4-fluorophenyl)cyclopropyl]-6-[2-(3-fluorophenyl)-2-hydroxyacetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC=C1F)NC2=O)=O)C1=CC(F)=CC=C1 CPCOIEIOXNOLNY-UHFFFAOYSA-N 0.000 description 1
- AEJURAKYLOELPK-UHFFFAOYSA-N 2-[1-(4-fluorophenyl)cyclopropyl]-6-[2-hydroxy-2-(3-methylphenyl)acetyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC1=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C(C=C2)=CC=C2F)NC3=O)=O)O)=CC=C1 AEJURAKYLOELPK-UHFFFAOYSA-N 0.000 description 1
- QANRZYNMEANWPK-UHFFFAOYSA-N 2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-6-[2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCCN(C3)C(CC4=CC=CC(C5=CC(C(F)(F)F)=CC=C5)=C4)=O)=C3C2=O)=C1 QANRZYNMEANWPK-UHFFFAOYSA-N 0.000 description 1
- LFTVOIFAGMHXRA-UHFFFAOYSA-N 2-[1-(5-phenylpyridin-3-yl)cyclopropyl]-6-[2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC=CC(C2=CC(C(F)(F)F)=CC=C2)=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CC=C3)=CN=C1)NC2=O LFTVOIFAGMHXRA-UHFFFAOYSA-N 0.000 description 1
- NCJIUWMHAIVXFG-HHHXNRCGSA-N 2-[1-[3-(1,3-benzothiazol-2-yl)phenyl]cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=NC(C=CC=C4)=C4S3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 NCJIUWMHAIVXFG-HHHXNRCGSA-N 0.000 description 1
- BVMVJRPDZQPSRE-GDLZYMKVSA-N 2-[1-[3-(1-benzofuran-2-yl)phenyl]cyclopropyl]-6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC(C=CC=C4)=C4O3)=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 BVMVJRPDZQPSRE-GDLZYMKVSA-N 0.000 description 1
- DKTGIXZQCOGVTK-GDLZYMKVSA-N 2-[1-[3-(1-benzothiophen-2-yl)phenyl]cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC(C=CC=C4)=C4S3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 DKTGIXZQCOGVTK-GDLZYMKVSA-N 0.000 description 1
- HLMFWAHVRGFCLX-GDLZYMKVSA-N 2-[1-[3-(1-benzothiophen-3-yl)phenyl]cyclopropyl]-6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CSC4=C3C=CC=C4)=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 HLMFWAHVRGFCLX-GDLZYMKVSA-N 0.000 description 1
- BEIOYZWNLKZGPX-PGUFJCEWSA-N 2-[1-[3-(1-benzothiophen-3-yl)phenyl]cyclopropyl]-6-[(2R)-2-[3-(3-chloro-5-fluorophenyl)phenyl]-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CSC4=C3C=CC=C4)=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(Cl)=CC(F)=C2)=C1 BEIOYZWNLKZGPX-PGUFJCEWSA-N 0.000 description 1
- WQSZZVCGRAQDBY-PGUFJCEWSA-N 2-[1-[3-(1-benzothiophen-3-yl)phenyl]cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CSC4=C3C=CC=C4)=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(C(F)(F)F)=CC=C2)=C1 WQSZZVCGRAQDBY-PGUFJCEWSA-N 0.000 description 1
- OJEUEFNQOVSLLJ-UHFFFAOYSA-N 2-[1-[3-(1-benzothiophen-3-yl)phenyl]cyclopropyl]-6-[2,2-difluoro-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(C(C1=CC(C(F)(F)F)=CC=C1)(F)F)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CSC4=C3C=CC=C4)=CC=C1)NC2=O OJEUEFNQOVSLLJ-UHFFFAOYSA-N 0.000 description 1
- OUEPQOFSJUBWRG-HHHXNRCGSA-N 2-[1-[3-(2-fluorophenyl)phenyl]cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC(C(C=CC=C3)=C3F)=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 OUEPQOFSJUBWRG-HHHXNRCGSA-N 0.000 description 1
- ROGQYGYFNWTAFC-HHHXNRCGSA-N 2-[1-[3-(3,4-difluorophenyl)phenyl]cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC(C(C=C3)=CC(F)=C3F)=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 ROGQYGYFNWTAFC-HHHXNRCGSA-N 0.000 description 1
- IPDLUJGIRIBPSS-HHHXNRCGSA-N 2-[1-[3-(3-fluorophenyl)phenyl]cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC(C3=CC(F)=CC=C3)=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 IPDLUJGIRIBPSS-HHHXNRCGSA-N 0.000 description 1
- JZSJJZISXIABCG-SSEXGKCCSA-N 2-[1-[3-(4-tert-butylphenyl)phenyl]cyclopropyl]-6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)(C)C(C=C1)=CC=C1C1=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(Cl)=CC=C4)O)=O)=C3C2=O)=CC=C1 JZSJJZISXIABCG-SSEXGKCCSA-N 0.000 description 1
- UNTKZSDCVIMZCG-UHFFFAOYSA-N 2-[1-[3-(cyclohexen-1-yl)phenyl]cyclopropyl]-6-[2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC=CC(C2=CC(C(F)(F)F)=CC=C2)=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC(C3=CCCCC3)=C1)NC2=O UNTKZSDCVIMZCG-UHFFFAOYSA-N 0.000 description 1
- HPKAZNSGYRDSLH-JOCHJYFZSA-N 2-[1-[3-(hydroxymethyl)phenyl]cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OCC1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(C(F)(F)F)=CC=C4)O)=O)=C3C2=O)=C1 HPKAZNSGYRDSLH-JOCHJYFZSA-N 0.000 description 1
- FHIMYKZTODHUAD-WJOKGBTCSA-N 2-[1-[3-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl]cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)(C)CC(N(CC1)CCC1C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(C(F)(F)F)=CC=C4)O)=O)=C3C2=O)=C1)=O FHIMYKZTODHUAD-WJOKGBTCSA-N 0.000 description 1
- FDCIIXAKNGIOBS-JGCGQSQUSA-N 2-[1-[3-[1-(4-fluorophenyl)sulfonyl-3,6-dihydro-2H-pyridin-4-yl]phenyl]cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C(CC3)=CCN3S(C(C=C3)=CC=C3F)(=O)=O)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 FDCIIXAKNGIOBS-JGCGQSQUSA-N 0.000 description 1
- MRFJSSGEMGSLLY-SSEXGKCCSA-N 2-[1-[3-[3-[(dimethylamino)methyl]phenyl]phenyl]cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CN(C)CC1=CC=CC(C2=CC(C3(CC3)C(N3)=NC(CCCN(C4)C([C@@H](C5=CC(C(F)(F)F)=CC=C5)O)=O)=C4C3=O)=CC=C2)=C1 MRFJSSGEMGSLLY-SSEXGKCCSA-N 0.000 description 1
- QFASKSWIQMRQRK-WJOKGBTCSA-N 2-[1-[3-[4-(4-hydroxyoxan-4-yl)phenyl]phenyl]cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC(C3=CC=C(C4(CCOCC4)O)C=C3)=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 QFASKSWIQMRQRK-WJOKGBTCSA-N 0.000 description 1
- GRZWESKVWRHXFV-XMMPIXPASA-N 2-[1-[4-(4,4-difluorocyclohexyl)thiophen-2-yl]cyclopropyl]-6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C(CC3)CCC3(F)F)=CS1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 GRZWESKVWRHXFV-XMMPIXPASA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 1
- HMXKFQFKELSJFO-UHFFFAOYSA-N 2-methyl-1-(3-morpholin-4-ylpropyl)-5-phenyl-n-[3-(trifluoromethoxy)phenyl]pyrrole-3-carboxamide Chemical compound C1COCCN1CCCN1C(C)=C(C(=O)NC=2C=C(OC(F)(F)F)C=CC=2)C=C1C1=CC=CC=C1 HMXKFQFKELSJFO-UHFFFAOYSA-N 0.000 description 1
- IXFHNKMMVCHKQH-UHFFFAOYSA-N 2-methyl-1-(3-morpholin-4-ylpropyl)-n-[3-(trifluoromethyl)phenyl]indole-3-carboxamide Chemical compound C12=CC=CC=C2N(CCCN2CCOCC2)C(C)=C1C(=O)NC1=CC=CC(C(F)(F)F)=C1 IXFHNKMMVCHKQH-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- DTBDAFLSBDGPEA-UHFFFAOYSA-N 3-Methylquinoline Natural products C1=CC=CC2=CC(C)=CN=C21 DTBDAFLSBDGPEA-UHFFFAOYSA-N 0.000 description 1
- AUURQCXJBYKRQX-MUUNZHRXSA-N 3-[3-[1-[6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-4-oxo-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-2-yl]cyclopropyl]phenyl]benzonitrile Chemical compound N#CC1=CC=CC(C2=CC(C3(CC3)C(N3)=NC(CCCN(C4)C([C@@H](C5=CC(Cl)=CC=C5)O)=O)=C4C3=O)=CC=C2)=C1 AUURQCXJBYKRQX-MUUNZHRXSA-N 0.000 description 1
- WDLJLRYXOGGANF-GDLZYMKVSA-N 3-[3-[1-[6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-4-oxo-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-2-yl]cyclopropyl]phenyl]-N,N-dimethylbenzamide Chemical compound CN(C)C(C1=CC=CC(C2=CC(C3(CC3)C(N3)=NC(CCCN(C4)C([C@@H](C5=CC(C(F)(F)F)=CC=C5)O)=O)=C4C3=O)=CC=C2)=C1)=O WDLJLRYXOGGANF-GDLZYMKVSA-N 0.000 description 1
- VLRYMFWRLJLDIY-MUUNZHRXSA-N 3-[3-[1-[6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-4-oxo-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-2-yl]cyclopropyl]phenyl]benzonitrile Chemical compound N#CC1=CC=CC(C2=CC(C3(CC3)C(N3)=NC(CCCN(C4)C([C@@H](C5=CC(C(F)(F)F)=CC=C5)O)=O)=C4C3=O)=CC=C2)=C1 VLRYMFWRLJLDIY-MUUNZHRXSA-N 0.000 description 1
- KTFUKHNUUGSLQI-RRPNLBNLSA-N 3-[[(5r,7s)-7-methyl-2-oxo-3-[(1-phenyltriazol-4-yl)methyl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1CC(N=N1)=CN1C1=CC=CC=C1 KTFUKHNUUGSLQI-RRPNLBNLSA-N 0.000 description 1
- LOPOSCTYKDPUCB-DFBJGRDBSA-N 3-[[(5s,7s)-2-oxo-3-(6-propan-2-ylpyridin-3-yl)-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC(C(C)C)=CC=C1N1C(=O)O[C@@]2(C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 LOPOSCTYKDPUCB-DFBJGRDBSA-N 0.000 description 1
- UYHVLESCFJXBNJ-BVZFJXPGSA-N 3-[[(5s,7s)-2-oxo-3-(thieno[2,3-b]pyridin-3-ylmethyl)-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC2=CC=C(C#N)C=C2N1C[C@H](C1)CCC[C@]11OC(=O)N(CC=2C3=CC=CN=C3SC=2)C1 UYHVLESCFJXBNJ-BVZFJXPGSA-N 0.000 description 1
- BSPGOMROZRVZLE-FNZWTVRRSA-N 3-[[(5s,7s)-2-oxo-3-[(1-phenyltriazol-4-yl)methyl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(OC2=O)C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC1)N2CC(N=N1)=CN1C1=CC=CC=C1 BSPGOMROZRVZLE-FNZWTVRRSA-N 0.000 description 1
- FOGCMRDDKOPYNG-OOJDHBDPSA-N 3-[[(5s,7s)-2-oxo-3-[(1-pyridin-2-ylpyrrolidin-3-yl)methyl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(OC2=O)C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC1)N2CC(C1)CCN1C1=CC=CC=N1 FOGCMRDDKOPYNG-OOJDHBDPSA-N 0.000 description 1
- RZGVISXWEANAMQ-DCFHFQCYSA-N 3-[[(5s,7s)-2-oxo-3-[(3-phenyl-1,2-oxazol-5-yl)methyl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(OC2=O)C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC1)N2CC(ON=1)=CC=1C1=CC=CC=C1 RZGVISXWEANAMQ-DCFHFQCYSA-N 0.000 description 1
- FTTXJXMCEDWXRE-DCFHFQCYSA-N 3-[[(5s,7s)-2-oxo-3-[(4-phenyl-1,3-thiazol-2-yl)methyl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(OC2=O)C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC1)N2CC(SC=1)=NC=1C1=CC=CC=C1 FTTXJXMCEDWXRE-DCFHFQCYSA-N 0.000 description 1
- UAGTZGZDHNEWNI-XLGQKKSSSA-N 3-[[(5s,7s)-2-oxo-3-[(5-phenylpyridin-3-yl)methyl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@]1(OC2=O)C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC1)N2CC(C=1)=CN=CC=1C1=CC=CC=C1 UAGTZGZDHNEWNI-XLGQKKSSSA-N 0.000 description 1
- QGDOIUKOAGUFDG-ZTOMLWHTSA-N 3-[[(5s,7s)-2-oxo-3-[(6-phenylpyridin-2-yl)methyl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(OC2=O)C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC1)N2CC(N=1)=CC=CC=1C1=CC=CC=C1 QGDOIUKOAGUFDG-ZTOMLWHTSA-N 0.000 description 1
- DNMKAIHNGOJDPZ-SIBVEZHUSA-N 3-[[(5s,7s)-2-oxo-3-[[1-[4-(trifluoromethyl)phenyl]triazol-4-yl]methyl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=CC(C(F)(F)F)=CC=C1N1N=NC(CN2C(O[C@@]3(C[C@@H](CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=C1 DNMKAIHNGOJDPZ-SIBVEZHUSA-N 0.000 description 1
- UEIQVXPZVSHVMS-BVZFJXPGSA-N 3-[[(5s,7s)-2-oxo-3-[[1-[5-(trifluoromethyl)pyridin-3-yl]triazol-4-yl]methyl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound FC(F)(F)C1=CN=CC(N2N=NC(CN3C(O[C@@]4(C[C@@H](CN5C6=CC(=CC=C6N=C5)C#N)CCC4)C3)=O)=C2)=C1 UEIQVXPZVSHVMS-BVZFJXPGSA-N 0.000 description 1
- QTFSYDKDMPJZLJ-ZEQRLZLVSA-N 3-[[(5s,7s)-3-(1-ethyl-5-methylpyrazol-4-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CCN1N=CC(N2C(O[C@@]3(C[C@@](C)(CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=C1C QTFSYDKDMPJZLJ-ZEQRLZLVSA-N 0.000 description 1
- AFRKSXHUNUAWNX-DQEYMECFSA-N 3-[[(5s,7s)-3-(1-tert-butylpyrazol-4-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NN(C(C)(C)C)C=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 AFRKSXHUNUAWNX-DQEYMECFSA-N 0.000 description 1
- XEPGYSHKQBIYCM-ZEQRLZLVSA-N 3-[[(5s,7s)-3-(1-tert-butyltriazol-4-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound N1=NN(C(C)(C)C)C=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 XEPGYSHKQBIYCM-ZEQRLZLVSA-N 0.000 description 1
- WKVMXLVJYFNQMV-DQEYMECFSA-N 3-[[(5s,7s)-3-(2,6-dimethoxypyridin-3-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound COC1=NC(OC)=CC=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 WKVMXLVJYFNQMV-DQEYMECFSA-N 0.000 description 1
- KMUQTHRYROLLBY-ZEQRLZLVSA-N 3-[[(5s,7s)-3-(2-ethoxypyrimidin-5-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC(OCC)=NC=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 KMUQTHRYROLLBY-ZEQRLZLVSA-N 0.000 description 1
- MUAYDAHNXYQCMH-DQEYMECFSA-N 3-[[(5s,7s)-3-(2-methoxy-6-methylpyridin-3-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound COC1=NC(C)=CC=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 MUAYDAHNXYQCMH-DQEYMECFSA-N 0.000 description 1
- IDFKVGOOMSLDRI-BVZFJXPGSA-N 3-[[(5s,7s)-3-(2-tert-butylpyrimidin-5-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC(C(C)(C)C)=NC=C1N1C(=O)O[C@@]2(C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 IDFKVGOOMSLDRI-BVZFJXPGSA-N 0.000 description 1
- RJVYNJUTWUJKFM-ZEQRLZLVSA-N 3-[[(5s,7s)-3-(2-tert-butyltriazol-4-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CC(C)(C)N1N=CC(N2C(O[C@@]3(C[C@@](C)(CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=N1 RJVYNJUTWUJKFM-ZEQRLZLVSA-N 0.000 description 1
- UZEJABJVATVUNJ-GOTSBHOMSA-N 3-[[(5s,7s)-3-(3,4-dimethyl-1,2-oxazol-5-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CC1=NOC(N2C(O[C@@]3(C[C@@](C)(CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=C1C UZEJABJVATVUNJ-GOTSBHOMSA-N 0.000 description 1
- PQINISHGALMEBS-ZEQRLZLVSA-N 3-[[(5s,7s)-3-(3-chloro-5-methylpyridin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound ClC1=CC(C)=CN=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 PQINISHGALMEBS-ZEQRLZLVSA-N 0.000 description 1
- BKKHFQXUEPUWLP-GOTSBHOMSA-N 3-[[(5s,7s)-3-(3-chloropyridin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1C1=NC=CC=C1Cl BKKHFQXUEPUWLP-GOTSBHOMSA-N 0.000 description 1
- ILSRHLRSLJOTFB-DQEYMECFSA-N 3-[[(5s,7s)-3-(3-cyclobutyl-1,2-oxazol-5-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1C(ON=1)=CC=1C1CCC1 ILSRHLRSLJOTFB-DQEYMECFSA-N 0.000 description 1
- RJLSCTNIKNNESU-ZEQRLZLVSA-N 3-[[(5s,7s)-3-(3-cyclopropyl-1,2-oxazol-5-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1C(ON=1)=CC=1C1CC1 RJLSCTNIKNNESU-ZEQRLZLVSA-N 0.000 description 1
- UQOKNVDJMMZPFW-GOTSBHOMSA-N 3-[[(5s,7s)-3-(3-ethyl-1,2-oxazol-5-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1N=C(CC)C=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 UQOKNVDJMMZPFW-GOTSBHOMSA-N 0.000 description 1
- PKEIHQONCNVCQG-DQEYMECFSA-N 3-[[(5s,7s)-3-(3-ethylpyridin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CCC1=CC=CN=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 PKEIHQONCNVCQG-DQEYMECFSA-N 0.000 description 1
- BTTHQJFBAUMHQO-DQEYMECFSA-N 3-[[(5s,7s)-3-(3-methoxy-5-methylpyridin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound COC1=CC(C)=CN=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 BTTHQJFBAUMHQO-DQEYMECFSA-N 0.000 description 1
- PXMRWNDUICPMGO-ZEQRLZLVSA-N 3-[[(5s,7s)-3-(3-methoxypyridin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound COC1=CC=CN=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 PXMRWNDUICPMGO-ZEQRLZLVSA-N 0.000 description 1
- KOSAUXVCQPCSBE-DQEYMECFSA-N 3-[[(5s,7s)-3-(3-tert-butyl-1,2-oxazol-5-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1N=C(C(C)(C)C)C=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 KOSAUXVCQPCSBE-DQEYMECFSA-N 0.000 description 1
- GNHGHFSLUZWPOD-DQEYMECFSA-N 3-[[(5s,7s)-3-(3-tert-butyl-4-fluoro-1,2-oxazol-5-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CC(C)(C)C1=NOC(N2C(O[C@@]3(C[C@@](C)(CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=C1F GNHGHFSLUZWPOD-DQEYMECFSA-N 0.000 description 1
- MNYHTZIFZHVNQE-BVZFJXPGSA-N 3-[[(5s,7s)-3-(3-tert-butyl-4-methyl-1,2-oxazol-5-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1N=C(C(C)(C)C)C(C)=C1N1C(=O)O[C@@]2(C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 MNYHTZIFZHVNQE-BVZFJXPGSA-N 0.000 description 1
- KHIDUNPTKCZCLM-UIOOFZCWSA-N 3-[[(5s,7s)-3-(3-tert-butyl-4-methyl-1,2-oxazol-5-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1N=C(C(C)(C)C)C(C)=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 KHIDUNPTKCZCLM-UIOOFZCWSA-N 0.000 description 1
- PGWJASHLWFNOMU-XDHUDOTRSA-N 3-[[(5s,7s)-3-(4,6-dimethoxypyridin-3-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC(OC)=CC(OC)=C1N1C(=O)O[C@@]2(C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 PGWJASHLWFNOMU-XDHUDOTRSA-N 0.000 description 1
- HDJNDWKCQJVNMR-DQEYMECFSA-N 3-[[(5s,7s)-3-(4,6-dimethoxypyridin-3-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical group C1=NC(OC)=CC(OC)=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 HDJNDWKCQJVNMR-DQEYMECFSA-N 0.000 description 1
- MMNWTNHTOKUOIK-DQEYMECFSA-N 3-[[(5s,7s)-3-(4-bromo-3-tert-butyl-1,2-oxazol-5-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CC(C)(C)C1=NOC(N2C(O[C@@]3(C[C@@](C)(CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=C1Br MMNWTNHTOKUOIK-DQEYMECFSA-N 0.000 description 1
- TTYLJVUXIBQLAY-ZEQRLZLVSA-N 3-[[(5s,7s)-3-(4-methoxypyridin-3-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound COC1=CC=NC=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 TTYLJVUXIBQLAY-ZEQRLZLVSA-N 0.000 description 1
- OMLCUXNUUKPVCQ-DQEYMECFSA-N 3-[[(5s,7s)-3-(4-tert-butyl-1,3-oxazol-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CC(C)(C)C1=COC(N2C(O[C@@]3(C[C@@](C)(CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=N1 OMLCUXNUUKPVCQ-DQEYMECFSA-N 0.000 description 1
- VOQLGLLJDSTAPS-GOTSBHOMSA-N 3-[[(5s,7s)-3-(5-chloro-3-fluoropyridin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1C1=NC=C(Cl)C=C1F VOQLGLLJDSTAPS-GOTSBHOMSA-N 0.000 description 1
- DNUHPRVPHFULLB-ZEQRLZLVSA-N 3-[[(5s,7s)-3-(5-chloro-3-methylpyridin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CC1=CC(Cl)=CN=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 DNUHPRVPHFULLB-ZEQRLZLVSA-N 0.000 description 1
- ORNUGTMIWCFKMK-ZEQRLZLVSA-N 3-[[(5s,7s)-3-(5-methoxypyridin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound N1=CC(OC)=CC=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 ORNUGTMIWCFKMK-ZEQRLZLVSA-N 0.000 description 1
- SPAGPOAKCTZASZ-DQEYMECFSA-N 3-[[(5s,7s)-3-(5-tert-butyl-1,2-oxazol-3-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(C(C)(C)C)=CC(N2C(O[C@@]3(C[C@@](C)(CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=N1 SPAGPOAKCTZASZ-DQEYMECFSA-N 0.000 description 1
- IDFKXMRIMYXRPU-UIOOFZCWSA-N 3-[[(5s,7s)-3-(5-tert-butyl-2-methylpyrazol-3-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CN1N=C(C(C)(C)C)C=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 IDFKXMRIMYXRPU-UIOOFZCWSA-N 0.000 description 1
- UMEIYOSGBFNYLK-UIOOFZCWSA-N 3-[[(5s,7s)-3-(5-tert-butylpyrimidin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound N1=CC(C(C)(C)C)=CN=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 UMEIYOSGBFNYLK-UIOOFZCWSA-N 0.000 description 1
- QOCJWCNVDNWDOV-ZEQRLZLVSA-N 3-[[(5s,7s)-3-(6-chloro-4-methoxypyridin-3-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound COC1=CC(Cl)=NC=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 QOCJWCNVDNWDOV-ZEQRLZLVSA-N 0.000 description 1
- ZQOKGXLFIDIUNS-SBUREZEXSA-N 3-[[(5s,7s)-3-(6-chloro-4-methylpyridin-3-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CC1=CC(Cl)=NC=C1N1C(=O)O[C@@]2(C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 ZQOKGXLFIDIUNS-SBUREZEXSA-N 0.000 description 1
- ZYEGXBHPOTXFBP-ZEQRLZLVSA-N 3-[[(5s,7s)-3-(6-chloro-4-methylpyridin-3-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CC1=CC(Cl)=NC=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 ZYEGXBHPOTXFBP-ZEQRLZLVSA-N 0.000 description 1
- NCFFWDVQINNFPS-GKVSMKOHSA-N 3-[[(5s,7s)-3-(6-ethoxy-4-methylpyridin-3-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]-6-fluorobenzimidazole-5-carbonitrile Chemical compound C1=NC(OCC)=CC(C)=C1N1C(=O)O[C@@]2(C[C@@H](CN3C4=CC(=C(F)C=C4N=C3)C#N)CCC2)C1 NCFFWDVQINNFPS-GKVSMKOHSA-N 0.000 description 1
- GSTRVOSEYQRBME-DFBJGRDBSA-N 3-[[(5s,7s)-3-(6-ethoxy-4-methylpyridin-3-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical group C1=NC(OCC)=CC(C)=C1N1C(=O)O[C@@]2(C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 GSTRVOSEYQRBME-DFBJGRDBSA-N 0.000 description 1
- PNGJCXNXYWKYLW-UUOWRZLLSA-N 3-[[(5s,7s)-3-(6-methoxy-4-methylpyridin-3-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC(OC)=CC(C)=C1N1C(=O)O[C@@]2(C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 PNGJCXNXYWKYLW-UUOWRZLLSA-N 0.000 description 1
- RCIWZIZEVMHRQP-ZEQRLZLVSA-N 3-[[(5s,7s)-3-(6-methoxypyridin-3-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC(OC)=CC=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 RCIWZIZEVMHRQP-ZEQRLZLVSA-N 0.000 description 1
- LKXXGHUZOGZRQH-KMRXNPHXSA-N 3-[[(5s,7s)-3-[(1-methyl-5-phenylpyrazol-3-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CN1N=C(CN2C(O[C@@]3(C[C@@H](CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)C=C1C1=CC=CC=C1 LKXXGHUZOGZRQH-KMRXNPHXSA-N 0.000 description 1
- BFYYHHZINQDGMT-GKVSMKOHSA-N 3-[[(5s,7s)-3-[(3-bromothieno[2,3-b]pyridin-2-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound S1C2=NC=CC=C2C(Br)=C1CN1C(=O)O[C@@]2(C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 BFYYHHZINQDGMT-GKVSMKOHSA-N 0.000 description 1
- HFGXFDCAGFUJEL-RMBDDCHCSA-N 3-[[(5s,7s)-3-[(3-methyl-1-pyrimidin-2-ylpyrrolidin-3-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1C(C)(CN2C(O[C@@]3(C[C@@H](CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)CCN1C1=NC=CC=N1 HFGXFDCAGFUJEL-RMBDDCHCSA-N 0.000 description 1
- KAQVMVWKPXGSEP-UIOOFZCWSA-N 3-[[(5s,7s)-3-[(4-ethoxypyridin-2-yl)methyl]-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CCOC1=CC=NC(CN2C(O[C@@]3(C[C@@](C)(CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=C1 KAQVMVWKPXGSEP-UIOOFZCWSA-N 0.000 description 1
- NWDPWRQAMSGNMT-ZEQRLZLVSA-N 3-[[(5s,7s)-3-[(4-fluoropyridin-2-yl)methyl]-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1CC1=CC(F)=CC=N1 NWDPWRQAMSGNMT-ZEQRLZLVSA-N 0.000 description 1
- PTEOBTYDUZICJQ-QYBDOPJKSA-N 3-[[(5s,7s)-3-[(5-chloro-1-benzothiophen-3-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC2=CC=C(C#N)C=C2N1C[C@H](C1)CCC[C@@]1(OC1=O)CN1CC1=CSC2=CC=C(Cl)C=C21 PTEOBTYDUZICJQ-QYBDOPJKSA-N 0.000 description 1
- QQWOGSKUINIHMG-ZEQRLZLVSA-N 3-[[(5s,7s)-3-[(5-fluoropyridin-2-yl)methyl]-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1CC1=CC=C(F)C=N1 QQWOGSKUINIHMG-ZEQRLZLVSA-N 0.000 description 1
- XWFLVGMRDVJINT-DQEYMECFSA-N 3-[[(5s,7s)-3-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC(C(C)(O)C)=NC=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 XWFLVGMRDVJINT-DQEYMECFSA-N 0.000 description 1
- JNXBRKBEYULTBB-MMTVBGGISA-N 3-[[(5s,7s)-3-[2-(3-cyclopentyl-1,2,4-oxadiazol-5-yl)-2-methylpropyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1)C1)C(=O)N1CC(C)(C)C(ON=1)=NC=1C1CCCC1 JNXBRKBEYULTBB-MMTVBGGISA-N 0.000 description 1
- VDROKRSZXARPEI-BVZFJXPGSA-N 3-[[(5s,7s)-3-[2-(3-ethyl-1,2,4-oxadiazol-5-yl)-2-methylpropyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CCC1=NOC(C(C)(C)CN2C(O[C@@]3(C[C@@H](CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=N1 VDROKRSZXARPEI-BVZFJXPGSA-N 0.000 description 1
- MEMLJXRSCHXKLF-PPHZAIPVSA-N 3-[[(5s,7s)-3-[2-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-2-methylpropyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CC(C)(C)C1=NOC(C(C)(C)CN2C(O[C@@]3(C[C@@H](CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=N1 MEMLJXRSCHXKLF-PPHZAIPVSA-N 0.000 description 1
- DLGLTVSFTYBQGD-BTRDEYTCSA-N 3-[[(5s,7s)-3-[2-[3-(1-ethoxyethyl)-1,2,4-oxadiazol-5-yl]-2-methylpropyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CCOC(C)C1=NOC(C(C)(C)CN2C(O[C@@]3(C[C@@H](CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=N1 DLGLTVSFTYBQGD-BTRDEYTCSA-N 0.000 description 1
- JKFYAOMKWIYBTD-XSQNJVOOSA-N 3-[[(5s,7s)-3-[2-[3-(1-methoxyethyl)-1,2,4-oxadiazol-5-yl]-2-methylpropyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound COC(C)C1=NOC(C(C)(C)CN2C(O[C@@]3(C[C@@H](CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=N1 JKFYAOMKWIYBTD-XSQNJVOOSA-N 0.000 description 1
- TWRHLUBNNGBBOU-BVZFJXPGSA-N 3-[[(5s,7s)-3-[2-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]-2-methylpropyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound COCC1=NOC(C(C)(C)CN2C(O[C@@]3(C[C@@H](CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=N1 TWRHLUBNNGBBOU-BVZFJXPGSA-N 0.000 description 1
- SZYBRYJCHHALBT-UUOWRZLLSA-N 3-[[(5s,7s)-3-[2-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)propyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CC1=NOC(C(C)(C)CN2C(O[C@@]3(C[C@@H](CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=N1 SZYBRYJCHHALBT-UUOWRZLLSA-N 0.000 description 1
- UBZADUKSIXWOAW-LGGPFLRQSA-N 3-[[(5s,7s)-3-[2-methyl-2-(3-phenyl-1,2,4-oxadiazol-5-yl)propyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1)C1)C(=O)N1CC(C)(C)C(ON=1)=NC=1C1=CC=CC=C1 UBZADUKSIXWOAW-LGGPFLRQSA-N 0.000 description 1
- KODCLHXKXZXIET-PPHZAIPVSA-N 3-[[(5s,7s)-3-[2-methyl-2-(3-pyrimidin-5-yl-1,2,4-oxadiazol-5-yl)propyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1)C1)C(=O)N1CC(C)(C)C(ON=1)=NC=1C1=CN=CN=C1 KODCLHXKXZXIET-PPHZAIPVSA-N 0.000 description 1
- PDZSNKDNEDXRBK-LGGPFLRQSA-N 3-[[(5s,7s)-3-[2-methyl-2-(5-phenyl-1,3,4-oxadiazol-2-yl)propyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1)C1)C(=O)N1CC(C)(C)C(O1)=NN=C1C1=CC=CC=C1 PDZSNKDNEDXRBK-LGGPFLRQSA-N 0.000 description 1
- ZIJDHCDFIWYFMB-DCFHFQCYSA-N 3-[[(5s,7s)-3-[2-methyl-2-[3-(2-methylpropyl)-1,2,4-oxadiazol-5-yl]propyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CC(C)CC1=NOC(C(C)(C)CN2C(O[C@@]3(C[C@@H](CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=N1 ZIJDHCDFIWYFMB-DCFHFQCYSA-N 0.000 description 1
- RTIARAJDTFZQDX-GMAHTHKFSA-N 3-[[(5s,7s)-3-[3-(1,1-difluoroethyl)-1,2-oxazol-5-yl]-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1N=C(C(F)(F)C)C=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 RTIARAJDTFZQDX-GMAHTHKFSA-N 0.000 description 1
- ANWXFJFNERCHLR-SVBPBHIXSA-N 3-[[(5s,7s)-3-[6-(2-cyanopropan-2-yl)pyridin-3-yl]-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC(C(C)(C#N)C)=CC=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 ANWXFJFNERCHLR-SVBPBHIXSA-N 0.000 description 1
- UMFMYMJLDOHSCL-DQEYMECFSA-N 3-[[(5s,7s)-3-[6-(dimethylamino)pyridin-3-yl]-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC(N(C)C)=CC=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 UMFMYMJLDOHSCL-DQEYMECFSA-N 0.000 description 1
- IQGKTSDYEAKCJR-QYBDOPJKSA-N 3-[[(5s,7s)-3-[[1-(3,5-difluorophenyl)triazol-4-yl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound FC1=CC(F)=CC(N2N=NC(CN3C(O[C@@]4(C[C@@H](CN5C6=CC(=CC=C6N=C5)C#N)CCC4)C3)=O)=C2)=C1 IQGKTSDYEAKCJR-QYBDOPJKSA-N 0.000 description 1
- VEQUFJQVNXQSSC-PPHZAIPVSA-N 3-[[(5s,7s)-3-[[1-(3-chloro-5-cyanophenyl)triazol-4-yl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound ClC1=CC(C#N)=CC(N2N=NC(CN3C(O[C@@]4(C[C@@H](CN5C6=CC(=CC=C6N=C5)C#N)CCC4)C3)=O)=C2)=C1 VEQUFJQVNXQSSC-PPHZAIPVSA-N 0.000 description 1
- KZSACMUDZZDILE-SIBVEZHUSA-N 3-[[(5s,7s)-3-[[1-(3-chlorophenyl)triazol-4-yl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound ClC1=CC=CC(N2N=NC(CN3C(O[C@@]4(C[C@@H](CN5C6=CC(=CC=C6N=C5)C#N)CCC4)C3)=O)=C2)=C1 KZSACMUDZZDILE-SIBVEZHUSA-N 0.000 description 1
- HCTYFDLOVKVHSK-IDISGSTGSA-N 3-[[(5s,7s)-3-[[1-(3-cyanophenyl)triazol-4-yl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(OC2=O)C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC1)N2CC(N=N1)=CN1C1=CC=CC(C#N)=C1 HCTYFDLOVKVHSK-IDISGSTGSA-N 0.000 description 1
- WMUOEIURPANJRT-SIBVEZHUSA-N 3-[[(5s,7s)-3-[[1-(3-fluorophenyl)triazol-4-yl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound FC1=CC=CC(N2N=NC(CN3C(O[C@@]4(C[C@@H](CN5C6=CC(=CC=C6N=C5)C#N)CCC4)C3)=O)=C2)=C1 WMUOEIURPANJRT-SIBVEZHUSA-N 0.000 description 1
- CQKXQKLAULLWND-IDISGSTGSA-N 3-[[(5s,7s)-3-[[1-(3-methylphenyl)triazol-4-yl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CC1=CC=CC(N2N=NC(CN3C(O[C@@]4(C[C@@H](CN5C6=CC(=CC=C6N=C5)C#N)CCC4)C3)=O)=C2)=C1 CQKXQKLAULLWND-IDISGSTGSA-N 0.000 description 1
- MVXFGELRKKKCLN-IDISGSTGSA-N 3-[[(5s,7s)-3-[[1-(4-cyanophenyl)triazol-4-yl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(OC2=O)C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC1)N2CC(N=N1)=CN1C1=CC=C(C#N)C=C1 MVXFGELRKKKCLN-IDISGSTGSA-N 0.000 description 1
- GDXHRDONGTVEQX-IDISGSTGSA-N 3-[[(5s,7s)-3-[[1-(4-methylphenyl)triazol-4-yl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=CC(C)=CC=C1N1N=NC(CN2C(O[C@@]3(C[C@@H](CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=C1 GDXHRDONGTVEQX-IDISGSTGSA-N 0.000 description 1
- URERBFWHKBXPGE-BVZFJXPGSA-N 3-[[(5s,7s)-3-[[1-(5-chloropyridin-3-yl)triazol-4-yl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound ClC1=CN=CC(N2N=NC(CN3C(O[C@@]4(C[C@@H](CN5C6=CC(=CC=C6N=C5)C#N)CCC4)C3)=O)=C2)=C1 URERBFWHKBXPGE-BVZFJXPGSA-N 0.000 description 1
- AVGAOELALDXVRL-PPHZAIPVSA-N 3-[[(5s,7s)-3-[[3-(4-chlorophenyl)-1,2-oxazol-5-yl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=CC(Cl)=CC=C1C1=NOC(CN2C(O[C@@]3(C[C@@H](CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=C1 AVGAOELALDXVRL-PPHZAIPVSA-N 0.000 description 1
- STLHKAFHEAPIBY-LGGPFLRQSA-N 3-[[(5s,7s)-3-[[4-(4-methoxy-3-methylphenyl)-1,3-thiazol-2-yl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=C(C)C(OC)=CC=C1C1=CSC(CN2C(O[C@@]3(C[C@@H](CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=N1 STLHKAFHEAPIBY-LGGPFLRQSA-N 0.000 description 1
- JFDKAWITNHVOIK-SVBPBHIXSA-N 3-[[(5s,7s)-7-methyl-2-oxo-3-(3-phenyl-1,2-oxazol-5-yl)-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1C(ON=1)=CC=1C1=CC=CC=C1 JFDKAWITNHVOIK-SVBPBHIXSA-N 0.000 description 1
- BGWFPGSXVMEKMM-ZEQRLZLVSA-N 3-[[(5s,7s)-7-methyl-2-oxo-3-(3-prop-1-en-2-yl-1,2-oxazol-5-yl)-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1N=C(C(=C)C)C=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 BGWFPGSXVMEKMM-ZEQRLZLVSA-N 0.000 description 1
- QMDFYZGWKSODQN-ZEQRLZLVSA-N 3-[[(5s,7s)-7-methyl-2-oxo-3-(3-propan-2-yl-1,2-oxazol-5-yl)-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1N=C(C(C)C)C=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 QMDFYZGWKSODQN-ZEQRLZLVSA-N 0.000 description 1
- NULTZQPYYBAWCL-ZEQRLZLVSA-N 3-[[(5s,7s)-7-methyl-2-oxo-3-(pyridin-2-ylmethyl)-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1CC1=CC=CC=N1 NULTZQPYYBAWCL-ZEQRLZLVSA-N 0.000 description 1
- KTFUKHNUUGSLQI-SVBPBHIXSA-N 3-[[(5s,7s)-7-methyl-2-oxo-3-[(1-phenyltriazol-4-yl)methyl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1CC(N=N1)=CN1C1=CC=CC=C1 KTFUKHNUUGSLQI-SVBPBHIXSA-N 0.000 description 1
- UFOCGGVVMXEIIA-ZEQRLZLVSA-N 3-[[(5s,7s)-7-methyl-2-oxo-3-[(1-propan-2-yltriazol-4-yl)methyl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound N1=NN(C(C)C)C=C1CN1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 UFOCGGVVMXEIIA-ZEQRLZLVSA-N 0.000 description 1
- RESSSLMKEVWIMK-VXKWHMMOSA-N 3-[[(5s,7s)-7-methyl-2-oxo-3-[2-(trifluoromethyl)pyrimidin-5-yl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1C1=CN=C(C(F)(F)F)N=C1 RESSSLMKEVWIMK-VXKWHMMOSA-N 0.000 description 1
- DOSUZTMWMNSIEQ-GOTSBHOMSA-N 3-[[(5s,7s)-7-methyl-2-oxo-3-[4-(trifluoromethyl)pyridin-3-yl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1C1=CN=CC=C1C(F)(F)F DOSUZTMWMNSIEQ-GOTSBHOMSA-N 0.000 description 1
- ASYSUKWBKPTZDB-GOTSBHOMSA-N 3-[[(5s,7s)-7-methyl-2-oxo-3-[5-(trifluoromethyl)pyridin-2-yl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1C1=CC=C(C(F)(F)F)C=N1 ASYSUKWBKPTZDB-GOTSBHOMSA-N 0.000 description 1
- JTYZHTYUGPXOFR-GOTSBHOMSA-N 3-[[(5s,7s)-7-methyl-2-oxo-3-[6-(trifluoromethyl)pyridin-3-yl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1C1=CC=C(C(F)(F)F)N=C1 JTYZHTYUGPXOFR-GOTSBHOMSA-N 0.000 description 1
- SDYNLZSJQOFZJY-NSOVKSMOSA-N 3-[[(5s,7s)-7-methyl-3-(4-methyl-6-morpholin-4-ylpyridin-3-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound N=1C=C(N2C(O[C@@]3(C[C@@](C)(CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)C(C)=CC=1N1CCOCC1 SDYNLZSJQOFZJY-NSOVKSMOSA-N 0.000 description 1
- FBTIVMZAGQIVQP-ZEQRLZLVSA-N 3-[[(5s,7s)-7-methyl-3-(5-methylpyridin-2-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound N1=CC(C)=CC=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 FBTIVMZAGQIVQP-ZEQRLZLVSA-N 0.000 description 1
- AZBQCBPFJAYZSQ-DQEYMECFSA-N 3-[[(5s,7s)-7-methyl-3-[3-(2-methylpropyl)-1,2-oxazol-5-yl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1N=C(CC(C)C)C=C1N1C(=O)O[C@@]2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 AZBQCBPFJAYZSQ-DQEYMECFSA-N 0.000 description 1
- DRYQLZOXIAJDGV-NSOVKSMOSA-N 3-[[(5s,7s)-7-methyl-3-[[4-(1-methylpyrazol-4-yl)pyridin-2-yl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NN(C)C=C1C1=CC=NC(CN2C(O[C@@]3(C[C@@](C)(CN4C5=CC(=CC=C5N=C4)C#N)CCC3)C2)=O)=C1 DRYQLZOXIAJDGV-NSOVKSMOSA-N 0.000 description 1
- TURZMLRKHPVQOJ-NQCNTLBGSA-N 3-[[(7s)-3-(3,5-dichloropyridin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@](C1)(CN2C3=CC(=CC=C3N=C2)C#N)C)CCC1(OC1=O)CN1C1=NC=C(Cl)C=C1Cl TURZMLRKHPVQOJ-NQCNTLBGSA-N 0.000 description 1
- HONJYVRVDOBGME-UXMRNZNESA-N 3-[[(7s)-7-methyl-3-(6-methylpyridin-3-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC(C)=CC=C1N1C(=O)OC2(C[C@@](C)(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 HONJYVRVDOBGME-UXMRNZNESA-N 0.000 description 1
- VJCPTFGQFDRGBM-UHFFFAOYSA-N 3-[[3-[(5-chloro-1-benzothiophen-3-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]-2-(trifluoromethyl)benzimidazole-5-carbonitrile Chemical compound C1=C(Cl)C=C2C(CN3CC4(CCCC(C4)CN4C5=CC(=CC=C5N=C4C(F)(F)F)C#N)OC3=O)=CSC2=C1 VJCPTFGQFDRGBM-UHFFFAOYSA-N 0.000 description 1
- PTEOBTYDUZICJQ-UHFFFAOYSA-N 3-[[3-[(5-chloro-1-benzothiophen-3-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=NC2=CC=C(C#N)C=C2N1CC(C1)CCCC1(OC1=O)CN1CC1=CSC2=CC=C(Cl)C=C21 PTEOBTYDUZICJQ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ULNDQUSFQNAHAI-UHFFFAOYSA-N 3-chloro-5-[3-[2-[2-[1-(3-chlorophenyl)cyclopropyl]-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]-2-oxoethyl]phenyl]benzonitrile Chemical compound N#CC1=CC(Cl)=CC(C2=CC(CC(N(CC3)CC4=C3N=C(C3(CC3)C3=CC(Cl)=CC=C3)NC4=O)=O)=CC=C2)=C1 ULNDQUSFQNAHAI-UHFFFAOYSA-N 0.000 description 1
- ODRDHZDHXYIXEC-UHFFFAOYSA-N 3-chloro-5-[3-[2-oxo-2-[4-oxo-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-6-yl]ethyl]phenyl]benzonitrile Chemical compound N#CC1=CC(Cl)=CC(C2=CC(CC(N(CCC3)CC4=C3N=C(C3(CC3)C3=CC=CC=C3)NC4=O)=O)=CC=C2)=C1 ODRDHZDHXYIXEC-UHFFFAOYSA-N 0.000 description 1
- NYFXQIUHGAINAB-MUUNZHRXSA-N 3-fluoro-5-[3-[1-[6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-4-oxo-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-2-yl]cyclopropyl]phenyl]benzonitrile Chemical compound N#CC1=CC(F)=CC(C2=CC(C3(CC3)C(N3)=NC(CCCN(C4)C([C@@H](C5=CC(C(F)(F)F)=CC=C5)O)=O)=C4C3=O)=CC=C2)=C1 NYFXQIUHGAINAB-MUUNZHRXSA-N 0.000 description 1
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- JNRLEMMIVRBKJE-UHFFFAOYSA-N 4,4'-Methylenebis(N,N-dimethylaniline) Chemical compound C1=CC(N(C)C)=CC=C1CC1=CC=C(N(C)C)C=C1 JNRLEMMIVRBKJE-UHFFFAOYSA-N 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- FAZWLIABDNVRDW-UHFFFAOYSA-N 4-[1-[6-[2-(2,3-difluorophenyl)-2-hydroxyacetyl]-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl]cyclopropyl]benzonitrile Chemical compound N#CC1=CC=C(C2(CC2)C(N2)=NC(CCN(C3)C(C(C(C=CC=C4F)=C4F)O)=O)=C3C2=O)C=C1 FAZWLIABDNVRDW-UHFFFAOYSA-N 0.000 description 1
- LDSMAQJQNVBOKE-UHFFFAOYSA-N 4-[3-[2-[2-[1-(3-chlorophenyl)cyclopropyl]-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]-2-oxoethyl]phenyl]benzonitrile Chemical compound N#CC(C=C1)=CC=C1C1=CC(CC(N(CC2)CC3=C2N=C(C2(CC2)C2=CC(Cl)=CC=C2)NC3=O)=O)=CC=C1 LDSMAQJQNVBOKE-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KCBZFDVGFZBARE-LJQANCHMSA-N 5-[1-[6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl]cyclopropyl]thiophene-3-carbonitrile Chemical compound N#CC1=CSC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC(Cl)=CC=C4)O)=O)=C3C2=O)=C1 KCBZFDVGFZBARE-LJQANCHMSA-N 0.000 description 1
- LXFHOOCZOVJUKX-UHFFFAOYSA-N 6,6-dichlorohexyl-(2-phenylphenyl)phosphane Chemical group ClC(Cl)CCCCCPC1=CC=CC=C1C1=CC=CC=C1 LXFHOOCZOVJUKX-UHFFFAOYSA-N 0.000 description 1
- WTFJDPGIVAGNDM-UHFFFAOYSA-N 6,7-dimethoxy-3-[(4-morpholin-4-ylpiperidin-1-yl)methyl]-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]quinoline-4-carboxamide Chemical compound C1CC1(C=1C=CC=CC=1)NC(=O)C1=C2C=C(OC)C(OC)=CC2=NC(C=2C=C(C=CC=2)C(F)(F)F)=C1CN(CC1)CCC1N1CCOCC1 WTFJDPGIVAGNDM-UHFFFAOYSA-N 0.000 description 1
- FUXXURDUHQCLGQ-UHFFFAOYSA-N 6-(1H-benzimidazole-2-carbonyl)-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(C1=NC(C=CC=C2)=C2N1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O FUXXURDUHQCLGQ-UHFFFAOYSA-N 0.000 description 1
- UGBHTCKEUMWNIX-UHFFFAOYSA-N 6-(1H-benzimidazole-2-carbonyl)-2-[1-(3-chlorophenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(C1=NC(C=CC=C2)=C2N1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O UGBHTCKEUMWNIX-UHFFFAOYSA-N 0.000 description 1
- JKAMKYBMKIUSDA-UHFFFAOYSA-N 6-(2-fluoro-2-phenylacetyl)-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(C(C1=CC=CC=C1)F)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O JKAMKYBMKIUSDA-UHFFFAOYSA-N 0.000 description 1
- AHIFBPZWHFKKIV-UHFFFAOYSA-N 6-(3-indol-1-ylpropanoyl)-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CCN1C2=CC=CC=C2C=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O AHIFBPZWHFKKIV-UHFFFAOYSA-N 0.000 description 1
- HMXQUCNPWFVKQP-UHFFFAOYSA-N 6-(4-hydroxynaphthalene-2-carbonyl)-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC1=CC(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)=CC2=CC=CC=C12 HMXQUCNPWFVKQP-UHFFFAOYSA-N 0.000 description 1
- VGWWONCYEJYYPB-UHFFFAOYSA-N 6-(5,6-difluoro-1H-benzimidazole-2-carbonyl)-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(C1=NC(C=C(C(F)=C2)F)=C2N1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O VGWWONCYEJYYPB-UHFFFAOYSA-N 0.000 description 1
- YEPUJGJHOPKZIW-UHFFFAOYSA-N 6-(5,6-difluoro-1H-benzimidazole-2-carbonyl)-2-(2-phenylpropan-2-yl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)(C1=CC=CC=C1)C(N1)=NC(CCN(C2)C(C3=NC(C=C(C(F)=C4)F)=C4N3)=O)=C2C1=O YEPUJGJHOPKZIW-UHFFFAOYSA-N 0.000 description 1
- HXTANQQCFZYKPI-UHFFFAOYSA-N 6-(6-chloro-1H-indole-2-carbonyl)-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(C(NC1=C2)=CC1=CC=C2Cl)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O HXTANQQCFZYKPI-UHFFFAOYSA-N 0.000 description 1
- JVWQQPFMTCSKSD-GOSISDBHSA-N 6-[(2R)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C(C=CC=C1F)=C1F JVWQQPFMTCSKSD-GOSISDBHSA-N 0.000 description 1
- HKRXBRRQKFIELI-LJQANCHMSA-N 6-[(2R)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C(C=CC=C1F)=C1F HKRXBRRQKFIELI-LJQANCHMSA-N 0.000 description 1
- PLLDWZCGGLDOMN-QGZVFWFLSA-N 6-[(2R)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-[1-(1,3-thiazol-4-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CSC=N1)NC2=O)=O)C(C=CC=C1F)=C1F PLLDWZCGGLDOMN-QGZVFWFLSA-N 0.000 description 1
- HUSVNFCPCMADJQ-OAQYLSRUSA-N 6-[(2R)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-[1-(3-fluorophenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C(C=CC=C1F)=C1F HUSVNFCPCMADJQ-OAQYLSRUSA-N 0.000 description 1
- OHHDPJVZHMMHLG-HXUWFJFHSA-N 6-[(2R)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-[1-(4-fluorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC=C1F)NC2=O)=O)C(C=CC=C1F)=C1F OHHDPJVZHMMHLG-HXUWFJFHSA-N 0.000 description 1
- YHXMNPAMSHFEFK-OAQYLSRUSA-N 6-[(2R)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-[1-(4-methylphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC1=CC=C(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C(C=CC=C4F)=C4F)O)=O)=C3C2=O)C=C1 YHXMNPAMSHFEFK-OAQYLSRUSA-N 0.000 description 1
- NLBOWSGFBQKIRF-OAQYLSRUSA-N 6-[(2R)-2-(2-chlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclobutyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CCC1)C1=CC=CC=C1)NC2=O)=O)C(C=CC=C1)=C1Cl NLBOWSGFBQKIRF-OAQYLSRUSA-N 0.000 description 1
- OZTHTRMMCCVTFO-HXUWFJFHSA-N 6-[(2R)-2-(2-chlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=CC=C1)=C1Cl OZTHTRMMCCVTFO-HXUWFJFHSA-N 0.000 description 1
- FWBFMZSAYWQHPL-LJQANCHMSA-N 6-[(2R)-2-(2-chlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7-dihydro-3H-pyrrolo[3,4-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(C1)CC(N=C(C2(CC2)C2=CC=CC=C2)N2)=C1C2=O)=O)C(C=CC=C1)=C1Cl FWBFMZSAYWQHPL-LJQANCHMSA-N 0.000 description 1
- WABWULKYHCTJCS-GOSISDBHSA-N 6-[(2R)-2-(2-chlorophenyl)-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C(C=CC=C1)=C1Cl WABWULKYHCTJCS-GOSISDBHSA-N 0.000 description 1
- TYFOLEZBUDLQSB-HXUWFJFHSA-N 6-[(2R)-2-(2-chlorophenyl)-2-hydroxyacetyl]-2-(2-phenylpropan-2-yl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)(C1=CC=CC=C1)C(N1)=NC(CCN(C2)C([C@@H](C(C=CC=C3)=C3Cl)O)=O)=C2C1=O TYFOLEZBUDLQSB-HXUWFJFHSA-N 0.000 description 1
- JCNRYNGVGMHRGJ-HXUWFJFHSA-N 6-[(2R)-2-(2-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-fluorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC=C1F)NC2=O)=O)C(C=CC=C1)=C1Cl JCNRYNGVGMHRGJ-HXUWFJFHSA-N 0.000 description 1
- JOXOFLXMIGJCGK-HXUWFJFHSA-N 6-[(2R)-2-(3-bromophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(Br)=CC=C1 JOXOFLXMIGJCGK-HXUWFJFHSA-N 0.000 description 1
- SPFUZULENYYUQL-XMMPIXPASA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-(1-naphthalen-1-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC3=CC=CC=C13)NC2=O)=O)C1=CC(Cl)=CC=C1 SPFUZULENYYUQL-XMMPIXPASA-N 0.000 description 1
- SMQSMBQSQPPNHM-OAQYLSRUSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclobutyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CCC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 SMQSMBQSQPPNHM-OAQYLSRUSA-N 0.000 description 1
- OEXONZWFCIZDHW-LJQANCHMSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-(1-pyridin-3-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CN=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 OEXONZWFCIZDHW-LJQANCHMSA-N 0.000 description 1
- CKZARZDZZBLQCH-LJQANCHMSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 CKZARZDZZBLQCH-LJQANCHMSA-N 0.000 description 1
- PEKFPPORJOWSOS-GOSISDBHSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-(1-thiophen-3-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CSC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 PEKFPPORJOWSOS-GOSISDBHSA-N 0.000 description 1
- DNYYXNCIMQWPLV-HXUWFJFHSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-(2-phenylpropan-2-yl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)(C1=CC=CC=C1)C(N1)=NC(CCN(C2)C([C@@H](C3=CC(Cl)=CC=C3)O)=O)=C2C1=O DNYYXNCIMQWPLV-HXUWFJFHSA-N 0.000 description 1
- NHQUUTIEMXSTJF-HXUWFJFHSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(3,4-difluorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC(F)=C1F)NC2=O)=O)C1=CC(Cl)=CC=C1 NHQUUTIEMXSTJF-HXUWFJFHSA-N 0.000 description 1
- NVGMPTKKQLVKQX-HXUWFJFHSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(3,5-difluorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC(F)=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 NVGMPTKKQLVKQX-HXUWFJFHSA-N 0.000 description 1
- NUHQGDHCOZJHJF-AREMUKBSSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(3-cyclohexylphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCCC3)=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 NUHQGDHCOZJHJF-AREMUKBSSA-N 0.000 description 1
- YGCVLRQHEVQMDH-OAQYLSRUSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(3-fluorophenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 YGCVLRQHEVQMDH-OAQYLSRUSA-N 0.000 description 1
- CNNCPWFIQCXGDQ-AREMUKBSSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(3-phenylphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC(C3=CC=CC=C3)=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 CNNCPWFIQCXGDQ-AREMUKBSSA-N 0.000 description 1
- OETVMGJOGQCXRE-HSZRJFAPSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC(Cl)=CC=C4)O)=O)=C3C2=O)=C1 OETVMGJOGQCXRE-HSZRJFAPSA-N 0.000 description 1
- ZXXVJNWZGJGJGT-XMMPIXPASA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(Cl)=CC=C4)O)=O)=C3C2=O)=C1 ZXXVJNWZGJGJGT-XMMPIXPASA-N 0.000 description 1
- XCXPJCICTHQSHZ-AREMUKBSSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(3-pyridin-3-ylphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CN=C3)=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 XCXPJCICTHQSHZ-AREMUKBSSA-N 0.000 description 1
- GUPGMWAXAOOBPK-GOSISDBHSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-chlorothiophen-2-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 GUPGMWAXAOOBPK-GOSISDBHSA-N 0.000 description 1
- PMVUXOROTZPTSH-XMMPIXPASA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-cyclohexylthiophen-2-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCCC3)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 PMVUXOROTZPTSH-XMMPIXPASA-N 0.000 description 1
- DDQBGRMTWLITQX-RUZDIDTESA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-cyclohexylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCCC3)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 DDQBGRMTWLITQX-RUZDIDTESA-N 0.000 description 1
- FWKMCINFUVGYDN-HSZRJFAPSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-cyclopentylthiophen-2-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCC3)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 FWKMCINFUVGYDN-HSZRJFAPSA-N 0.000 description 1
- FXZNUXSZLTZUOZ-QGZVFWFLSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-methyl-1,3-thiazol-2-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC1=CSC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC(Cl)=CC=C4)O)=O)=C3C2=O)=N1 FXZNUXSZLTZUOZ-QGZVFWFLSA-N 0.000 description 1
- VANYCTSXJQRMGW-LJQANCHMSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-methylthiophen-2-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC1=CSC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC(Cl)=CC=C4)O)=O)=C3C2=O)=C1 VANYCTSXJQRMGW-LJQANCHMSA-N 0.000 description 1
- WJSDOZQUIKDPNV-HHHXNRCGSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-phenylmethoxyphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC=C1OCC1=CC=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 WJSDOZQUIKDPNV-HHHXNRCGSA-N 0.000 description 1
- SKLSVCVKSQQLTG-RUZDIDTESA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-phenylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CC=C3)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 SKLSVCVKSQQLTG-RUZDIDTESA-N 0.000 description 1
- HDVHPEOUTKWXDR-OAQYLSRUSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC(Cl)=CC=C4)O)=O)=C3C2=O)=C1 HDVHPEOUTKWXDR-OAQYLSRUSA-N 0.000 description 1
- PRFAPTBARCKWFW-XMMPIXPASA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-pyridin-3-ylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CN=C3)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 PRFAPTBARCKWFW-XMMPIXPASA-N 0.000 description 1
- NJGHZBBWERAFGK-HSZRJFAPSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(4-pyridin-4-ylthiophen-2-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=NC=C3)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 NJGHZBBWERAFGK-HSZRJFAPSA-N 0.000 description 1
- UBBWFXCODSCYEP-GOSISDBHSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(5-chlorothiophen-2-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C(S1)=CC=C1Cl)NC2=O)=O)C1=CC(Cl)=CC=C1 UBBWFXCODSCYEP-GOSISDBHSA-N 0.000 description 1
- ODTWNBMNKZYNBK-RUZDIDTESA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(5-cyclohexylpyridin-3-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCCC3)=CN=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 ODTWNBMNKZYNBK-RUZDIDTESA-N 0.000 description 1
- TVFCPYVCEPEPOY-LJQANCHMSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-(5-methylthiophen-2-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC1=CC=C(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC(Cl)=CC=C4)O)=O)=C3C2=O)S1 TVFCPYVCEPEPOY-LJQANCHMSA-N 0.000 description 1
- GFFDYFVNLDUBCH-HSZRJFAPSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-[3-(1,2-thiazol-4-yl)phenyl]cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CSN=C3)=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 GFFDYFVNLDUBCH-HSZRJFAPSA-N 0.000 description 1
- WGDAFRWEKYDGMN-GDLZYMKVSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-[3-(1-methylindazol-4-yl)phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CN(C1=CC=C2)N=CC1=C2C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(Cl)=CC=C4)O)=O)=C3C2=O)=C1 WGDAFRWEKYDGMN-GDLZYMKVSA-N 0.000 description 1
- MPRKZOYFTWSCQO-GDLZYMKVSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-[3-(1-methylindazol-5-yl)phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CN1N=CC2=CC(C3=CC=CC(C4(CC4)C(N4)=NC(CCCN(C5)C([C@@H](C6=CC(Cl)=CC=C6)O)=O)=C5C4=O)=C3)=CC=C12 MPRKZOYFTWSCQO-GDLZYMKVSA-N 0.000 description 1
- OCHMBONSCOFSJF-HHHXNRCGSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-[3-(3-chlorophenyl)phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC(C3=CC(Cl)=CC=C3)=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 OCHMBONSCOFSJF-HHHXNRCGSA-N 0.000 description 1
- JMLUUSVVUHQQSZ-HHHXNRCGSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-[3-(cyclohexen-1-yl)phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC(C3=CCCCC3)=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 JMLUUSVVUHQQSZ-HHHXNRCGSA-N 0.000 description 1
- LYQNDCNJWGIBDU-OAQYLSRUSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-[4-(1,3-thiazol-5-yl)thiophen-2-yl]cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CN=CS3)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 LYQNDCNJWGIBDU-OAQYLSRUSA-N 0.000 description 1
- WRTIPKLORPRRKZ-OAQYLSRUSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-[4-(1H-pyrazol-4-yl)thiophen-2-yl]cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CNN=C3)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 WRTIPKLORPRRKZ-OAQYLSRUSA-N 0.000 description 1
- HVBZLAJDMMOPRB-HSZRJFAPSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-[4-(4,4-difluorocyclohexyl)thiophen-2-yl]cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C(CC3)CCC3(F)F)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 HVBZLAJDMMOPRB-HSZRJFAPSA-N 0.000 description 1
- XPXFNJLNONJJOU-HSZRJFAPSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-[4-(oxan-4-yl)thiophen-2-yl]cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCOCC3)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 XPXFNJLNONJJOU-HSZRJFAPSA-N 0.000 description 1
- AKSYIBRLACZZKX-XMMPIXPASA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-[4-(oxan-4-yl)thiophen-2-yl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCOCC3)=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 AKSYIBRLACZZKX-XMMPIXPASA-N 0.000 description 1
- IABGOABPURASDW-HSZRJFAPSA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-[5-(1,2-thiazol-4-yl)pyridin-3-yl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CSN=C3)=CN=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 IABGOABPURASDW-HSZRJFAPSA-N 0.000 description 1
- ZMWSDZOMWBHRMW-XMMPIXPASA-N 6-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-[1-[5-(4,4-difluorocyclohexyl)pyridin-3-yl]cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C(CC3)CCC3(F)F)=CN=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 ZMWSDZOMWBHRMW-XMMPIXPASA-N 0.000 description 1
- UGAUFSIYUUDYDK-MUUNZHRXSA-N 6-[(2R)-2-[3-(1-benzofuran-3-yl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=COC3=C2C=CC=C3)=CC=C1 UGAUFSIYUUDYDK-MUUNZHRXSA-N 0.000 description 1
- BRQBOFHOJBZMKB-AREMUKBSSA-N 6-[(2R)-2-[3-(2,2-difluoro-1,3-benzodioxol-5-yl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C(C=C2)=CC(O3)=C2OC3(F)F)=CC=C1 BRQBOFHOJBZMKB-AREMUKBSSA-N 0.000 description 1
- XYLUNYCARJOFNX-AREMUKBSSA-N 6-[(2R)-2-[3-(2,5-dichlorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C(C=C2)Cl)=C2Cl)=C1 XYLUNYCARJOFNX-AREMUKBSSA-N 0.000 description 1
- BXULJFINLOZARH-AREMUKBSSA-N 6-[(2R)-2-[3-(3,4-dichlorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC(Cl)=C2Cl)=C1 BXULJFINLOZARH-AREMUKBSSA-N 0.000 description 1
- AKCHNLIMRGKITO-HHHXNRCGSA-N 6-[(2R)-2-[3-(3,4-dichlorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC(Cl)=C2Cl)=C1 AKCHNLIMRGKITO-HHHXNRCGSA-N 0.000 description 1
- QZYPOJPAZNXZEN-AREMUKBSSA-N 6-[(2R)-2-[3-(3,5-dichlorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(Cl)=CC(Cl)=C2)=C1 QZYPOJPAZNXZEN-AREMUKBSSA-N 0.000 description 1
- DYDRIGXLFCCXEQ-AREMUKBSSA-N 6-[(2R)-2-[3-(3-chloro-4-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC(Cl)=C2F)=C1 DYDRIGXLFCCXEQ-AREMUKBSSA-N 0.000 description 1
- FEMXIVYSIGGMIQ-HHHXNRCGSA-N 6-[(2R)-2-[3-(3-chloro-4-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC(Cl)=C2F)=C1 FEMXIVYSIGGMIQ-HHHXNRCGSA-N 0.000 description 1
- RNURULLBARJKHL-HHHXNRCGSA-N 6-[(2R)-2-[3-(3-chloro-4-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-[1-(3-chlorophenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC(Cl)=C2F)=C1 RNURULLBARJKHL-HHHXNRCGSA-N 0.000 description 1
- QRWGJCRXGMWPDD-HHHXNRCGSA-N 6-[(2R)-2-[3-(3-chloro-5-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(Cl)=CC(F)=C2)=C1 QRWGJCRXGMWPDD-HHHXNRCGSA-N 0.000 description 1
- MZBQXRQTQPPWSV-HHHXNRCGSA-N 6-[(2R)-2-[3-(3-chloro-5-methylphenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC1=CC(C2=CC([C@H](C(N(CC3)CC4=C3N=C(C3(CC3)C3=CC=CC=C3)NC4=O)=O)O)=CC=C2)=CC(Cl)=C1 MZBQXRQTQPPWSV-HHHXNRCGSA-N 0.000 description 1
- DOTAXXPQMNDGGR-MUUNZHRXSA-N 6-[(2R)-2-[3-(3-chloro-5-methylphenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC1=CC(C2=CC([C@H](C(N(CCC3)CC4=C3N=C(C3(CC3)C3=CC=CC=C3)NC4=O)=O)O)=CC=C2)=CC(Cl)=C1 DOTAXXPQMNDGGR-MUUNZHRXSA-N 0.000 description 1
- DBVAMJXPNSLPGH-AREMUKBSSA-N 6-[(2R)-2-[3-(3-chlorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(Cl)=CC=C2)=C1 DBVAMJXPNSLPGH-AREMUKBSSA-N 0.000 description 1
- HQKZLZNBDBJEJP-GDLZYMKVSA-N 6-[(2R)-2-[3-(3-chlorophenyl)phenyl]-2-hydroxyacetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC=CC(C5=CC(Cl)=CC=C5)=C4)O)=O)=C3C2=O)=C1 HQKZLZNBDBJEJP-GDLZYMKVSA-N 0.000 description 1
- ZWBIRCWXDXXWGR-SSEXGKCCSA-N 6-[(2R)-2-[3-(3-chlorophenyl)phenyl]-2-hydroxyacetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC=CC(C5=CC(Cl)=CC=C5)=C4)O)=O)=C3C2=O)=C1 ZWBIRCWXDXXWGR-SSEXGKCCSA-N 0.000 description 1
- FYZBBTIALHKKFY-WJOKGBTCSA-N 6-[(2R)-2-[3-(3-chlorophenyl)phenyl]-2-hydroxyacetyl]-2-[1-(4-phenylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CC=C3)=CS1)NC2=O)=O)C1=CC=CC(C2=CC(Cl)=CC=C2)=C1 FYZBBTIALHKKFY-WJOKGBTCSA-N 0.000 description 1
- FLIPQQVVZZRWPT-GDLZYMKVSA-N 6-[(2R)-2-[3-(3-chlorophenyl)phenyl]-2-hydroxyacetyl]-2-[1-(5-propan-2-ylpyridin-3-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CN=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC=CC(C5=CC(Cl)=CC=C5)=C4)O)=O)=C3C2=O)=C1 FLIPQQVVZZRWPT-GDLZYMKVSA-N 0.000 description 1
- MPNBDFPNKRFLJB-GDLZYMKVSA-N 6-[(2R)-2-[3-(3-cyclopropylphenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(C3CC3)=CC=C2)=C1 MPNBDFPNKRFLJB-GDLZYMKVSA-N 0.000 description 1
- STOJVKNGMVTQLT-SSEXGKCCSA-N 6-[(2R)-2-[3-(3-cyclopropylphenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(C3CC3)=CC=C2)=C1 STOJVKNGMVTQLT-SSEXGKCCSA-N 0.000 description 1
- HBUHVNMUDYWCQH-RUZDIDTESA-N 6-[(2R)-2-[3-(3-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C1=CC=CC(C2=CC(F)=CC=C2)=C1 HBUHVNMUDYWCQH-RUZDIDTESA-N 0.000 description 1
- ABVPIOIODMCZNA-GDLZYMKVSA-N 6-[(2R)-2-[3-(3-tert-butylphenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)(C)C1=CC=CC(C2=CC([C@H](C(N(CC3)CC4=C3N=C(C3(CC3)C3=CC=CC=C3)NC4=O)=O)O)=CC=C2)=C1 ABVPIOIODMCZNA-GDLZYMKVSA-N 0.000 description 1
- KZJCEBDSUUWQED-MUUNZHRXSA-N 6-[(2R)-2-[3-(3-tert-butylphenyl)phenyl]-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)(C)C1=CC=CC(C2=CC([C@H](C(N(CCC3)CC4=C3N=C(C3(CC3)C3=CC=CS3)NC4=O)=O)O)=CC=C2)=C1 KZJCEBDSUUWQED-MUUNZHRXSA-N 0.000 description 1
- GCHFERMLJDNYOU-GDLZYMKVSA-N 6-[(2R)-2-[3-(3-tert-butylphenyl)phenyl]-2-hydroxyacetyl]-2-[1-(3-chlorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)(C)C1=CC=CC(C2=CC([C@H](C(N(CC3)CC4=C3N=C(C3(CC3)C3=CC(Cl)=CC=C3)NC4=O)=O)O)=CC=C2)=C1 GCHFERMLJDNYOU-GDLZYMKVSA-N 0.000 description 1
- SQJOVCUAGAUXMQ-SSEXGKCCSA-N 6-[(2R)-2-[3-(3-tert-butylphenyl)phenyl]-2-hydroxyacetyl]-2-[1-(3-chlorophenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)(C)C1=CC=CC(C2=CC([C@H](C(N(CCC3)CC4=C3N=C(C3(CC3)C3=CC(Cl)=CC=C3)NC4=O)=O)O)=CC=C2)=C1 SQJOVCUAGAUXMQ-SSEXGKCCSA-N 0.000 description 1
- CJRSIDRBSMFQNO-JGCGQSQUSA-N 6-[(2R)-2-[3-(3-tert-butylphenyl)phenyl]-2-hydroxyacetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC=CC(C5=CC(C(C)(C)C)=CC=C5)=C4)O)=O)=C3C2=O)=C1 CJRSIDRBSMFQNO-JGCGQSQUSA-N 0.000 description 1
- ZDDAGNXTCFKMJV-MUUNZHRXSA-N 6-[(2R)-2-[3-(4-chloro-3-methylphenyl)phenyl]-2-hydroxyacetyl]-2-[1-(3-chlorophenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C=C(C=C1)C2=CC([C@H](C(N(CCC3)CC4=C3N=C(C3(CC3)C3=CC(Cl)=CC=C3)NC4=O)=O)O)=CC=C2)=C1Cl ZDDAGNXTCFKMJV-MUUNZHRXSA-N 0.000 description 1
- OCFKMOVBTRZPFW-AREMUKBSSA-N 6-[(2R)-2-[3-(4-chlorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC=C2Cl)=C1 OCFKMOVBTRZPFW-AREMUKBSSA-N 0.000 description 1
- XMSXAXAILLXHEG-MUUNZHRXSA-N 6-[(2R)-2-[3-(4-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-[1-(5-propan-2-ylpyridin-3-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CN=CC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC=CC(C(C=C5)=CC=C5F)=C4)O)=O)=C3C2=O)=C1 XMSXAXAILLXHEG-MUUNZHRXSA-N 0.000 description 1
- XDQXVXWSJVYUNE-GDLZYMKVSA-N 6-[(2R)-2-[3-(cyclopenten-1-yl)phenyl]-2-hydroxyacetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(C5=CCCC5)=CC=C4)O)=O)=C3C2=O)=C1 XDQXVXWSJVYUNE-GDLZYMKVSA-N 0.000 description 1
- FALWWMUCHSSCBU-HHHXNRCGSA-N 6-[(2R)-2-[3-[2-chloro-5-(trifluoromethyl)phenyl]phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C(C(F)(F)F)C=C2)=C2Cl)=C1 FALWWMUCHSSCBU-HHHXNRCGSA-N 0.000 description 1
- OQOAKLGMWCMNOH-AREMUKBSSA-N 6-[(2R)-2-[3-[4-chloro-3-(trifluoromethyl)phenyl]phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC(C(F)(F)F)=C2Cl)=C1 OQOAKLGMWCMNOH-AREMUKBSSA-N 0.000 description 1
- VEYQSTAXWJVYTN-HXUWFJFHSA-N 6-[(2R)-2-[4-(2-methylpropyl)phenyl]propanoyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)CC1=CC=C([C@@H](C)C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)C=C1 VEYQSTAXWJVYTN-HXUWFJFHSA-N 0.000 description 1
- FIMHNIMHWPIZTH-RUZDIDTESA-N 6-[(2R)-2-hydroxy-2-(3-pyridin-3-ylphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC=CN=C2)=CC=C1 FIMHNIMHWPIZTH-RUZDIDTESA-N 0.000 description 1
- SXUYTFXXDLIRKX-OAQYLSRUSA-N 6-[(2R)-2-hydroxy-2-(4-methylphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC1=CC=C([C@H](C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)C=C1 SXUYTFXXDLIRKX-OAQYLSRUSA-N 0.000 description 1
- CVMMPLWROKBEMT-MGBGTMOVSA-N 6-[(2R)-2-hydroxy-2-[3-(2-phenylmethoxyphenyl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=CC=C2)=C2OCC2=CC=CC=C2)=C1 CVMMPLWROKBEMT-MGBGTMOVSA-N 0.000 description 1
- GAUSAZSQFMNWNU-MGBGTMOVSA-N 6-[(2R)-2-hydroxy-2-[3-(3-phenylmethoxyphenyl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(OCC3=CC=CC=C3)=CC=C2)=C1 GAUSAZSQFMNWNU-MGBGTMOVSA-N 0.000 description 1
- YGVHTKOIBJMEKQ-OAQYLSRUSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 YGVHTKOIBJMEKQ-OAQYLSRUSA-N 0.000 description 1
- JRSPCQVULLGETO-GOSISDBHSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-(1-thiophen-2-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 JRSPCQVULLGETO-GOSISDBHSA-N 0.000 description 1
- IBEFVNWGQATJHK-WJOKGBTCSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(3-naphthalen-2-ylphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC4=CC=CC=C4C=C3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 IBEFVNWGQATJHK-WJOKGBTCSA-N 0.000 description 1
- KBHPEYUQQAKBKA-MUUNZHRXSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(3-phenylmethoxyphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(OCC3=CC=CC=C3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 KBHPEYUQQAKBKA-MUUNZHRXSA-N 0.000 description 1
- SQDAYKCPYNCAFN-AREMUKBSSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(3-phenylphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC(C3=CC=CC=C3)=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 SQDAYKCPYNCAFN-AREMUKBSSA-N 0.000 description 1
- YKNIEGNDGJSOJN-HSZRJFAPSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC(C(F)(F)F)=CC=C4)O)=O)=C3C2=O)=C1 YKNIEGNDGJSOJN-HSZRJFAPSA-N 0.000 description 1
- VYXTWOQDHSNHRB-AREMUKBSSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(3-pyridin-3-ylphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CN=C3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 VYXTWOQDHSNHRB-AREMUKBSSA-N 0.000 description 1
- YSAGNQZIVLRLGR-AREMUKBSSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(3-pyridin-4-ylphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=NC=C3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 YSAGNQZIVLRLGR-AREMUKBSSA-N 0.000 description 1
- NTYAKABTCMCRJZ-XMMPIXPASA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(4-piperidin-4-ylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCNCC3)=CS1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 NTYAKABTCMCRJZ-XMMPIXPASA-N 0.000 description 1
- NLWFUMUCKWAZSS-HSZRJFAPSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(4-pyridin-3-ylthiophen-2-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CN=C3)=CS1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 NLWFUMUCKWAZSS-HSZRJFAPSA-N 0.000 description 1
- KFUMYXQIDVWMSS-JOCHJYFZSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(5-propan-2-ylpyridin-3-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CN=CC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC(C(F)(F)F)=CC=C4)O)=O)=C3C2=O)=C1 KFUMYXQIDVWMSS-JOCHJYFZSA-N 0.000 description 1
- HMJIVODEQNCVSC-XMMPIXPASA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(5-pyridin-3-ylpyridin-3-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CN=CC(C3=CC=CN=C3)=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 HMJIVODEQNCVSC-XMMPIXPASA-N 0.000 description 1
- UNJNXDQOFPVKEH-HSZRJFAPSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(6-propan-2-ylpyridin-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(C(F)(F)F)=CC=C4)O)=O)=C3C2=O)=N1 UNJNXDQOFPVKEH-HSZRJFAPSA-N 0.000 description 1
- YEFMTXBYTXBXIA-XMMPIXPASA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-(1,2-thiazol-4-yl)phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CSN=C3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 YEFMTXBYTXBXIA-XMMPIXPASA-N 0.000 description 1
- VWRPJRKYDAAGNL-XMMPIXPASA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-(1,3-oxazol-5-yl)phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CN=CO3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 VWRPJRKYDAAGNL-XMMPIXPASA-N 0.000 description 1
- VWWGXGDCWVWTDC-XMMPIXPASA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-(1,3-thiazol-5-yl)phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CN=CS3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 VWWGXGDCWVWTDC-XMMPIXPASA-N 0.000 description 1
- PBDJJCDMXDRMNC-RUZDIDTESA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-(2-methylpropyl)phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)CC1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(C(F)(F)F)=CC=C4)O)=O)=C3C2=O)=C1 PBDJJCDMXDRMNC-RUZDIDTESA-N 0.000 description 1
- ANYNAUPNOXBTBC-GDLZYMKVSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-(2-phenyl-1,3-oxazol-5-yl)phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CN=C(C4=CC=CC=C4)O3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 ANYNAUPNOXBTBC-GDLZYMKVSA-N 0.000 description 1
- NKDSLCMRJNTKIC-MUUNZHRXSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-(3-methylphenyl)phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC1=CC=CC(C2=CC(C3(CC3)C(N3)=NC(CCCN(C4)C([C@@H](C5=CC(C(F)(F)F)=CC=C5)O)=O)=C4C3=O)=CC=C2)=C1 NKDSLCMRJNTKIC-MUUNZHRXSA-N 0.000 description 1
- WOLFGASIGSBOEO-GDLZYMKVSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-(5-phenyl-1,3-thiazol-2-yl)phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=NC=C(C4=CC=CC=C4)S3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 WOLFGASIGSBOEO-GDLZYMKVSA-N 0.000 description 1
- MKNLDKHSYSNTNJ-SSEXGKCCSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-(6-pyrrolidin-1-ylpyridin-3-yl)phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=C(N4CCCC4)N=C3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 MKNLDKHSYSNTNJ-SSEXGKCCSA-N 0.000 description 1
- AQZTVWQVNRUTHV-OAQYLSRUSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-(trifluoromethyl)phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C(F)(F)F)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 AQZTVWQVNRUTHV-OAQYLSRUSA-N 0.000 description 1
- GAMPYOVVGIPQMP-PGUFJCEWSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-[1-(3-phenylpropanoyl)piperidin-4-yl]phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C(CC3)CCN3C(CCC3=CC=CC=C3)=O)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 GAMPYOVVGIPQMP-PGUFJCEWSA-N 0.000 description 1
- CENSNKYUYVDXLH-AREMUKBSSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-[2-(trifluoromethyl)pyridin-4-yl]phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC(C(F)(F)F)=NC=C3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 CENSNKYUYVDXLH-AREMUKBSSA-N 0.000 description 1
- ADEKUWOVWSGCEW-SSEXGKCCSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-[3-(2-methoxyethoxy)phenyl]phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound COCCOC1=CC=CC(C2=CC(C3(CC3)C(N3)=NC(CCCN(C4)C([C@@H](C5=CC(C(F)(F)F)=CC=C5)O)=O)=C4C3=O)=CC=C2)=C1 ADEKUWOVWSGCEW-SSEXGKCCSA-N 0.000 description 1
- NXOVLFOKHJVWMR-JGCGQSQUSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-[3-(piperidine-1-carbonyl)phenyl]phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC(C3=CC(C(N4CCCCC4)=O)=CC=C3)=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 NXOVLFOKHJVWMR-JGCGQSQUSA-N 0.000 description 1
- NNULVRPXGIGCNN-MGBGTMOVSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-[4-(pyridin-2-ylmethoxy)phenyl]phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC(C(C=C3)=CC=C3OCC3=NC=CC=C3)=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 NNULVRPXGIGCNN-MGBGTMOVSA-N 0.000 description 1
- TVPLKJOCOWBKPF-RRHRGVEJSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-[4-[(4-phenylmethoxypiperidin-1-yl)methyl]phenyl]phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC(C3=CC=C(CN(CC4)CCC4OCC4=CC=CC=C4)C=C3)=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 TVPLKJOCOWBKPF-RRHRGVEJSA-N 0.000 description 1
- KXPNJJNLJNVSIL-AREMUKBSSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[3-[6-(trifluoromethyl)pyridin-3-yl]phenyl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=C(C(F)(F)F)N=C3)=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 KXPNJJNLJNVSIL-AREMUKBSSA-N 0.000 description 1
- SDXBKONRQSHSNW-RUZDIDTESA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[4-(1-methylpiperidin-4-yl)thiophen-2-yl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CN(CC1)CCC1C1=CSC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(C(F)(F)F)=CC=C4)O)=O)=C3C2=O)=C1 SDXBKONRQSHSNW-RUZDIDTESA-N 0.000 description 1
- YEADKVPCEALRRM-HHHXNRCGSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[4-(2-phenylethyl)thiophen-2-yl]cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(CCC3=CC=CC=C3)=CS1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 YEADKVPCEALRRM-HHHXNRCGSA-N 0.000 description 1
- HPHFNIVMIFHSTB-HSZRJFAPSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[4-(oxan-4-yl)thiophen-2-yl]cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCOCC3)=CS1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 HPHFNIVMIFHSTB-HSZRJFAPSA-N 0.000 description 1
- CEXYVVVBVMYEDK-JOCHJYFZSA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[5-(1,2-thiazol-4-yl)pyridin-3-yl]cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CSN=C3)=CN=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 CEXYVVVBVMYEDK-JOCHJYFZSA-N 0.000 description 1
- LPGANCRASMFVAC-XMMPIXPASA-N 6-[(2R)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-[5-(oxan-4-yl)pyridin-3-yl]cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCOCC3)=CN=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 LPGANCRASMFVAC-XMMPIXPASA-N 0.000 description 1
- ZJOYQEPCEZOXDY-MUUNZHRXSA-N 6-[(2R)-2-hydroxy-2-[3-[2-(trifluoromethyl)pyridin-4-yl]phenyl]acetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC(C5=CC(C(F)(F)F)=NC=C5)=CC=C4)O)=O)=C3C2=O)=C1 ZJOYQEPCEZOXDY-MUUNZHRXSA-N 0.000 description 1
- LCAIINGNKDQBIT-HHHXNRCGSA-N 6-[(2R)-2-hydroxy-2-[3-[2-(trifluoromethyl)pyridin-4-yl]phenyl]acetyl]-2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(C5=CC(C(F)(F)F)=NC=C5)=CC=C4)O)=O)=C3C2=O)=C1 LCAIINGNKDQBIT-HHHXNRCGSA-N 0.000 description 1
- CBXJOJWXFWROAD-MUUNZHRXSA-N 6-[(2R)-2-hydroxy-2-[3-[2-(trifluoromethyl)pyridin-4-yl]phenyl]acetyl]-2-[1-(5-propan-2-ylpyridin-3-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CN=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(C5=CC(C(F)(F)F)=NC=C5)=CC=C4)O)=O)=C3C2=O)=C1 CBXJOJWXFWROAD-MUUNZHRXSA-N 0.000 description 1
- NVMQEWNHDKBLBQ-AREMUKBSSA-N 6-[(2R)-2-hydroxy-2-[3-[3-(trifluoromethoxy)phenyl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(OC(F)(F)F)=CC=C2)=C1 NVMQEWNHDKBLBQ-AREMUKBSSA-N 0.000 description 1
- MDZCHWGWONFGCA-GDLZYMKVSA-N 6-[(2R)-2-hydroxy-2-[3-[3-(trifluoromethoxy)phenyl]phenyl]acetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC=CC(C5=CC(OC(F)(F)F)=CC=C5)=C4)O)=O)=C3C2=O)=C1 MDZCHWGWONFGCA-GDLZYMKVSA-N 0.000 description 1
- AVYITAWFNMIOSB-RUZDIDTESA-N 6-[(2R)-2-hydroxy-2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-2-(1-thiophen-2-ylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C1=CC=CC(C2=CC(C(F)(F)F)=CC=C2)=C1 AVYITAWFNMIOSB-RUZDIDTESA-N 0.000 description 1
- SLTNMVXSYNVTGK-JGCGQSQUSA-N 6-[(2R)-2-hydroxy-2-[3-[4-(pyridin-2-ylmethoxy)phenyl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC=C2OCC2=NC=CC=C2)=C1 SLTNMVXSYNVTGK-JGCGQSQUSA-N 0.000 description 1
- AXMIKYSVXVWIMJ-HHHXNRCGSA-N 6-[(2R)-2-hydroxy-2-[3-[4-(trifluoromethoxy)phenyl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC=C2OC(F)(F)F)=C1 AXMIKYSVXVWIMJ-HHHXNRCGSA-N 0.000 description 1
- AOJXPBWIXUBVLI-MUUNZHRXSA-N 6-[(2R)-2-hydroxy-2-[3-[4-(trifluoromethoxy)phenyl]phenyl]acetyl]-2-[1-(5-propan-2-ylpyridin-3-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CN=CC(C2(CC2)C(N2)=NC(CCN(C3)C([C@@H](C4=CC=CC(C(C=C5)=CC=C5OC(F)(F)F)=C4)O)=O)=C3C2=O)=C1 AOJXPBWIXUBVLI-MUUNZHRXSA-N 0.000 description 1
- NEJFTLSWQFODBV-AREMUKBSSA-N 6-[(2R)-2-hydroxy-2-[3-[5-(trifluoromethyl)pyridin-3-yl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC(C(F)(F)F)=CN=C2)=CC=C1 NEJFTLSWQFODBV-AREMUKBSSA-N 0.000 description 1
- WFSRDMKOMKJCBZ-OAQYLSRUSA-N 6-[(2R)-2-hydroxy-3-phenylpropanoyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@H](CC1=CC=CC=C1)C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O WFSRDMKOMKJCBZ-OAQYLSRUSA-N 0.000 description 1
- YECPQQNZCNAUSU-FQEVSTJZSA-N 6-[(2S)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=CC=C1F)=C1F YECPQQNZCNAUSU-FQEVSTJZSA-N 0.000 description 1
- IFLRGOZMZOYUCZ-FQEVSTJZSA-N 6-[(2S)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-[1-(3-fluorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C(C=CC=C1F)=C1F IFLRGOZMZOYUCZ-FQEVSTJZSA-N 0.000 description 1
- OHHDPJVZHMMHLG-FQEVSTJZSA-N 6-[(2S)-2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-[1-(4-fluorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@H](C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC=C1F)NC2=O)=O)C(C=CC=C1F)=C1F OHHDPJVZHMMHLG-FQEVSTJZSA-N 0.000 description 1
- OZTHTRMMCCVTFO-FQEVSTJZSA-N 6-[(2S)-2-(2-chlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=CC=C1)=C1Cl OZTHTRMMCCVTFO-FQEVSTJZSA-N 0.000 description 1
- ZTACWODXHGVOBN-MHZLTWQESA-N 6-[(2S)-2-[3-(3-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(F)=CC=C2)=C1 ZTACWODXHGVOBN-MHZLTWQESA-N 0.000 description 1
- ZVFDKSTYVBZBQV-FQEVSTJZSA-N 6-[(2S)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 ZVFDKSTYVBZBQV-FQEVSTJZSA-N 0.000 description 1
- ILUVXSFVPKPVQP-VWLOTQADSA-N 6-[(2S)-2-hydroxy-2-[3-[2-(trifluoromethyl)pyridin-4-yl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC(C(F)(F)F)=NC=C2)=CC=C1 ILUVXSFVPKPVQP-VWLOTQADSA-N 0.000 description 1
- VBSRLACFWZTAJD-SANMLTNESA-N 6-[(2S)-2-hydroxy-2-[3-[2-(trifluoromethyl)pyridin-4-yl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC(C(F)(F)F)=NC=C2)=CC=C1 VBSRLACFWZTAJD-SANMLTNESA-N 0.000 description 1
- ICLDEHXMBIJEML-MHZLTWQESA-N 6-[(2S)-2-hydroxy-2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O[C@H](C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(C(F)(F)F)=CC=C2)=C1 ICLDEHXMBIJEML-MHZLTWQESA-N 0.000 description 1
- AHEHEEVZWWNLIC-FQEVSTJZSA-N 6-[(2S)-2-hydroxy-2-phenylacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@H](C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC=C1 AHEHEEVZWWNLIC-FQEVSTJZSA-N 0.000 description 1
- CMBWVUQOCSHRMQ-OAQYLSRUSA-N 6-[(3R)-3-hydroxy-3-phenylpropanoyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O[C@H](CC(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC=C1 CMBWVUQOCSHRMQ-OAQYLSRUSA-N 0.000 description 1
- YFEFTFSRDSJWQT-UHFFFAOYSA-N 6-[2,2-difluoro-2-[3-(trifluoromethyl)phenyl]acetyl]-2-(1-thiophen-2-ylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(C(C1=CC(C(F)(F)F)=CC=C1)(F)F)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O YFEFTFSRDSJWQT-UHFFFAOYSA-N 0.000 description 1
- FGWGIGICHWEKGQ-UHFFFAOYSA-N 6-[2,2-difluoro-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(3-fluorophenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(C(C1=CC(C(F)(F)F)=CC=C1)(F)F)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O FGWGIGICHWEKGQ-UHFFFAOYSA-N 0.000 description 1
- GEFFOAASPGCZGV-UHFFFAOYSA-N 6-[2,2-difluoro-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C(C(C4=CC(C(F)(F)F)=CC=C4)(F)F)=O)=C3C2=O)=C1 GEFFOAASPGCZGV-UHFFFAOYSA-N 0.000 description 1
- BCXMTHSXBOSYAE-UHFFFAOYSA-N 6-[2,2-difluoro-2-[3-(trifluoromethyl)phenyl]acetyl]-2-[1-(5-phenylpyridin-3-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(C(C1=CC(C(F)(F)F)=CC=C1)(F)F)N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CC=C3)=CN=C1)NC2=O BCXMTHSXBOSYAE-UHFFFAOYSA-N 0.000 description 1
- SZWNLRGYPDEWBF-UHFFFAOYSA-N 6-[2-(1,2-benzoxazol-3-yl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC1=NOC2=C1C=CC=C2)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O SZWNLRGYPDEWBF-UHFFFAOYSA-N 0.000 description 1
- XOVXWJVVYSHYLC-UHFFFAOYSA-N 6-[2-(2,3-dichlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=CC=C1Cl)=C1Cl XOVXWJVVYSHYLC-UHFFFAOYSA-N 0.000 description 1
- BNDOZJQJQOXEOF-UHFFFAOYSA-N 6-[2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-(1-pyridin-3-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CN=C1)NC2=O)=O)C(C=CC=C1F)=C1F BNDOZJQJQOXEOF-UHFFFAOYSA-N 0.000 description 1
- JVWQQPFMTCSKSD-UHFFFAOYSA-N 6-[2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C(C=CC=C1F)=C1F JVWQQPFMTCSKSD-UHFFFAOYSA-N 0.000 description 1
- IFLRGOZMZOYUCZ-UHFFFAOYSA-N 6-[2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-[1-(3-fluorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C(C=CC=C1F)=C1F IFLRGOZMZOYUCZ-UHFFFAOYSA-N 0.000 description 1
- FFGSWFZSWFQETC-UHFFFAOYSA-N 6-[2-(2,3-dihydro-1-benzofuran-7-yl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC2=C1OCC2 FFGSWFZSWFQETC-UHFFFAOYSA-N 0.000 description 1
- PDMGAKDPDWKYCM-UHFFFAOYSA-N 6-[2-(2,5-dichlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=C(C=C1)Cl)=C1Cl PDMGAKDPDWKYCM-UHFFFAOYSA-N 0.000 description 1
- DUDHZHTYPABFOB-UHFFFAOYSA-N 6-[2-(2,5-difluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=C(C=C1)F)=C1F DUDHZHTYPABFOB-UHFFFAOYSA-N 0.000 description 1
- JVUKEEYBRSGWFZ-UHFFFAOYSA-N 6-[2-(2,6-difluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C(F)=CC=C1)=C1F JVUKEEYBRSGWFZ-UHFFFAOYSA-N 0.000 description 1
- FMEVDBTXTJNSRE-UHFFFAOYSA-N 6-[2-(2-chloro-3-fluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=CC=C1F)=C1Cl FMEVDBTXTJNSRE-UHFFFAOYSA-N 0.000 description 1
- AFZXFXHYDHKYHX-UHFFFAOYSA-N 6-[2-(2-chlorophenoxy)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(COC(C=CC=C1)=C1Cl)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O AFZXFXHYDHKYHX-UHFFFAOYSA-N 0.000 description 1
- SODPGMHALIRGMH-UHFFFAOYSA-N 6-[2-(2-chlorophenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC(C=CC=C1)=C1Cl)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O SODPGMHALIRGMH-UHFFFAOYSA-N 0.000 description 1
- VXFUAMARBPDYLW-UHFFFAOYSA-N 6-[2-(2-hydroxyphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC1=C(CC(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)C=CC=C1 VXFUAMARBPDYLW-UHFFFAOYSA-N 0.000 description 1
- RCKLCLFAXBMWKT-UHFFFAOYSA-N 6-[2-(2-methoxyphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound COC1=C(CC(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)C=CC=C1 RCKLCLFAXBMWKT-UHFFFAOYSA-N 0.000 description 1
- LPEMSHPYVFNMGY-UHFFFAOYSA-N 6-[2-(3,4-dichlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=C1)=CC(Cl)=C1Cl LPEMSHPYVFNMGY-UHFFFAOYSA-N 0.000 description 1
- MADXUYWSKRYRMZ-UHFFFAOYSA-N 6-[2-(3,4-difluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=C1)=CC(F)=C1F MADXUYWSKRYRMZ-UHFFFAOYSA-N 0.000 description 1
- QENPKPSVUTUJKX-UHFFFAOYSA-N 6-[2-(3,5-dichlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(Cl)=CC(Cl)=C1 QENPKPSVUTUJKX-UHFFFAOYSA-N 0.000 description 1
- HYLWRQJCHWMYPH-UHFFFAOYSA-N 6-[2-(3,5-difluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(F)=CC(F)=C1 HYLWRQJCHWMYPH-UHFFFAOYSA-N 0.000 description 1
- FHEFVGQPLBSHHW-UHFFFAOYSA-N 6-[2-(3,5-difluorophenyl)-2-hydroxyacetyl]-2-(2-phenylpropan-2-yl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)(C1=CC=CC=C1)C(N1)=NC(CCN(C2)C(C(C3=CC(F)=CC(F)=C3)O)=O)=C2C1=O FHEFVGQPLBSHHW-UHFFFAOYSA-N 0.000 description 1
- CTALAPYMWIKQIJ-UHFFFAOYSA-N 6-[2-(3,5-difluorophenyl)-2-hydroxyacetyl]-2-[1-(4-fluorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC=C1F)NC2=O)=O)C1=CC(F)=CC(F)=C1 CTALAPYMWIKQIJ-UHFFFAOYSA-N 0.000 description 1
- AQGKWLGJIBOGMY-UHFFFAOYSA-N 6-[2-(3,5-difluorophenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC1=CC(F)=CC(F)=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O AQGKWLGJIBOGMY-UHFFFAOYSA-N 0.000 description 1
- ZQSXGLBDOXJRNP-UHFFFAOYSA-N 6-[2-(3,5-difluorophenyl)propanoyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(F)=CC(F)=C1 ZQSXGLBDOXJRNP-UHFFFAOYSA-N 0.000 description 1
- WJZDRWTYGGXIRG-UHFFFAOYSA-N 6-[2-(3,5-difluorophenyl)propanoyl]-2-[1-(4-fluorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C(N(CC1)CC2=C1N=C(C1(CC1)C(C=C1)=CC=C1F)NC2=O)=O)C1=CC(F)=CC(F)=C1 WJZDRWTYGGXIRG-UHFFFAOYSA-N 0.000 description 1
- QNPOCXKDLMIDFZ-UHFFFAOYSA-N 6-[2-(3-acetylphenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=C1)=O QNPOCXKDLMIDFZ-UHFFFAOYSA-N 0.000 description 1
- BVZWONRIASSZHX-UHFFFAOYSA-N 6-[2-(3-bromophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(Br)=CC=C1 BVZWONRIASSZHX-UHFFFAOYSA-N 0.000 description 1
- NXIRJDFPKJVFTM-UHFFFAOYSA-N 6-[2-(3-chloro-2,4-difluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=CC(F)=C1Cl)=C1F NXIRJDFPKJVFTM-UHFFFAOYSA-N 0.000 description 1
- IPYJBLZYKPOIPQ-UHFFFAOYSA-N 6-[2-(3-chloro-2-fluorophenyl)-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C(C=CC=C1Cl)=C1F IPYJBLZYKPOIPQ-UHFFFAOYSA-N 0.000 description 1
- JKTXPIDTSHRBIW-UHFFFAOYSA-N 6-[2-(3-chloro-2-fluorophenyl)-2-hydroxyacetyl]-2-[1-(3-chlorophenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O)=O)C(C=CC=C1Cl)=C1F JKTXPIDTSHRBIW-UHFFFAOYSA-N 0.000 description 1
- VUEPIPKFLILTNW-UHFFFAOYSA-N 6-[2-(3-chloro-2-fluorophenyl)-2-hydroxyacetyl]-2-[1-(3-phenoxyphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(OC3=CC=CC=C3)=CC=C1)NC2=O)=O)C(C=CC=C1Cl)=C1F VUEPIPKFLILTNW-UHFFFAOYSA-N 0.000 description 1
- KAQNBGUBNSCGAA-UHFFFAOYSA-N 6-[2-(3-chloro-2-fluorophenyl)-2-hydroxyacetyl]-2-[1-(5-propan-2-ylpyridin-3-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CN=CC(C2(CC2)C(N2)=NC(CCCN(C3)C(C(C(C=CC=C4Cl)=C4F)O)=O)=C3C2=O)=C1 KAQNBGUBNSCGAA-UHFFFAOYSA-N 0.000 description 1
- HYMAHZRLDAXNNC-UHFFFAOYSA-N 6-[2-(3-chloro-2-methoxyphenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound COC1=C(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)C=CC=C1Cl HYMAHZRLDAXNNC-UHFFFAOYSA-N 0.000 description 1
- AOSKWENMOWGFES-UHFFFAOYSA-N 6-[2-(3-chloro-2-methylphenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC1=C(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)C=CC=C1Cl AOSKWENMOWGFES-UHFFFAOYSA-N 0.000 description 1
- VFVUAGQMSZOCNO-UHFFFAOYSA-N 6-[2-(3-chloro-4-fluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=C1)=CC(Cl)=C1F VFVUAGQMSZOCNO-UHFFFAOYSA-N 0.000 description 1
- XDHSAKCPNRNVKU-UHFFFAOYSA-N 6-[2-(3-chloro-5-fluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(Cl)=CC(F)=C1 XDHSAKCPNRNVKU-UHFFFAOYSA-N 0.000 description 1
- XXWYBNRENIQISR-UHFFFAOYSA-N 6-[2-(3-chlorophenoxy)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(COC1=CC(Cl)=CC=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O XXWYBNRENIQISR-UHFFFAOYSA-N 0.000 description 1
- FBSNNRUKLTTWSC-UHFFFAOYSA-N 6-[2-(3-chlorophenyl)-2,2-difluoroacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(C(C1=CC(Cl)=CC=C1)(F)F)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O FBSNNRUKLTTWSC-UHFFFAOYSA-N 0.000 description 1
- SZOQIOTUIODOOM-UHFFFAOYSA-N 6-[2-(3-chlorophenyl)-2,2-difluoroacetyl]-2-(1-thiophen-2-ylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(C(C1=CC(Cl)=CC=C1)(F)F)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O SZOQIOTUIODOOM-UHFFFAOYSA-N 0.000 description 1
- UHMBXNUMWIBZAG-UHFFFAOYSA-N 6-[2-(3-chlorophenyl)-2,2-difluoroacetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCN(C3)C(C(C4=CC(Cl)=CC=C4)(F)F)=O)=C3C2=O)=C1 UHMBXNUMWIBZAG-UHFFFAOYSA-N 0.000 description 1
- IFGZOTOMGYQODH-UHFFFAOYSA-N 6-[2-(3-chlorophenyl)-2,2-difluoroacetyl]-2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCCN(C3)C(C(C4=CC(Cl)=CC=C4)(F)F)=O)=C3C2=O)=C1 IFGZOTOMGYQODH-UHFFFAOYSA-N 0.000 description 1
- MMQDHMSDDWFINV-UHFFFAOYSA-N 6-[2-(3-chlorophenyl)-2,2-difluoroacetyl]-2-[1-(5-phenylpyridin-3-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(C(C1=CC(Cl)=CC=C1)(F)F)N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CC=C3)=CN=C1)NC2=O MMQDHMSDDWFINV-UHFFFAOYSA-N 0.000 description 1
- AAUZXFBYFHBACG-UHFFFAOYSA-N 6-[2-(3-chlorophenyl)-2,2-difluoroacetyl]-2-[1-(5-phenylpyridin-3-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(C(C1=CC(Cl)=CC=C1)(F)F)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CC=C3)=CN=C1)NC2=O AAUZXFBYFHBACG-UHFFFAOYSA-N 0.000 description 1
- YUUYXOIWWWNTBT-UHFFFAOYSA-N 6-[2-(3-chlorophenyl)-2,2-difluoroacetyl]-2-[1-(5-propan-2-ylpyridin-3-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CN=CC(C2(CC2)C(N2)=NC(CCN(C3)C(C(C4=CC(Cl)=CC=C4)(F)F)=O)=C3C2=O)=C1 YUUYXOIWWWNTBT-UHFFFAOYSA-N 0.000 description 1
- VLHCWBMCBLUFBN-UHFFFAOYSA-N 6-[2-(3-chlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(Cl)=CC=C1 VLHCWBMCBLUFBN-UHFFFAOYSA-N 0.000 description 1
- QHJZEAUIIJVVGQ-UHFFFAOYSA-N 6-[2-(3-cyclopentyloxyphenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(OC2CCCC2)=CC=C1 QHJZEAUIIJVVGQ-UHFFFAOYSA-N 0.000 description 1
- YXANKWGZMXGYAB-UHFFFAOYSA-N 6-[2-(3-cyclopropylphenyl)-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C1=CC(C2CC2)=CC=C1 YXANKWGZMXGYAB-UHFFFAOYSA-N 0.000 description 1
- YOYJZWNXFYFXOS-UHFFFAOYSA-N 6-[2-(3-cyclopropylphenyl)-2-hydroxyacetyl]-2-[1-(3-fluorophenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C1=CC(C2CC2)=CC=C1 YOYJZWNXFYFXOS-UHFFFAOYSA-N 0.000 description 1
- HTRLJWNRTKUHOU-UHFFFAOYSA-N 6-[2-(3-cyclopropylphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC1=CC(C2CC2)=CC=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O HTRLJWNRTKUHOU-UHFFFAOYSA-N 0.000 description 1
- OKXGLUDIHIJSFT-UHFFFAOYSA-N 6-[2-(3-ethylphenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CCC1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=C1 OKXGLUDIHIJSFT-UHFFFAOYSA-N 0.000 description 1
- AEORXGYSODAUSM-UHFFFAOYSA-N 6-[2-(3-tert-butylphenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)(C)C1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=C1 AEORXGYSODAUSM-UHFFFAOYSA-N 0.000 description 1
- JSTAJCHFCFHJDH-UHFFFAOYSA-N 6-[2-(3-tert-butylphenyl)-2-hydroxyacetyl]-2-[1-(3-fluorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)(C)C1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC(F)=CC=C2)NC3=O)=O)O)=C1 JSTAJCHFCFHJDH-UHFFFAOYSA-N 0.000 description 1
- OVFQFUZDBHYAMI-UHFFFAOYSA-N 6-[2-(3-tert-butylphenyl)-2-hydroxyacetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCN(C3)C(C(C4=CC(C(C)(C)C)=CC=C4)O)=O)=C3C2=O)=C1 OVFQFUZDBHYAMI-UHFFFAOYSA-N 0.000 description 1
- ZMHUYKMXPVPPPB-UHFFFAOYSA-N 6-[2-(3-tert-butylphenyl)-2-hydroxyacetyl]-2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCN(C3)C(C(C4=CC(C(C)(C)C)=CC=C4)O)=O)=C3C2=O)=C1 ZMHUYKMXPVPPPB-UHFFFAOYSA-N 0.000 description 1
- JZVOIYUYTULHQR-UHFFFAOYSA-N 6-[2-(3-tert-butylphenyl)-2-hydroxyacetyl]-2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCCN(C3)C(C(C4=CC(C(C)(C)C)=CC=C4)O)=O)=C3C2=O)=C1 JZVOIYUYTULHQR-UHFFFAOYSA-N 0.000 description 1
- HVRSMZKYXNJLPF-UHFFFAOYSA-N 6-[2-(3-tert-butylphenyl)-2-hydroxyacetyl]-2-[1-(5-phenylpyridin-3-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)(C)C1=CC=CC(C(C(N(CCC2)CC3=C2N=C(C2(CC2)C2=CC(C4=CC=CC=C4)=CN=C2)NC3=O)=O)O)=C1 HVRSMZKYXNJLPF-UHFFFAOYSA-N 0.000 description 1
- HXCVLTXXTWOBOA-UHFFFAOYSA-N 6-[2-(3-tert-butylphenyl)-2-hydroxyacetyl]-2-[1-(5-propan-2-ylpyridin-3-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CN=CC(C2(CC2)C(N2)=NC(CCCN(C3)C(C(C4=CC(C(C)(C)C)=CC=C4)O)=O)=C3C2=O)=C1 HXCVLTXXTWOBOA-UHFFFAOYSA-N 0.000 description 1
- MQQYBOIKJNGORC-UHFFFAOYSA-N 6-[2-(3-tert-butylphenyl)acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)(C)C1=CC=CC(CC(N(CCC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)=C1 MQQYBOIKJNGORC-UHFFFAOYSA-N 0.000 description 1
- NOHCUUSRPMURIY-UHFFFAOYSA-N 6-[2-(4-chloro-2-fluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=CC(Cl)=C1)=C1F NOHCUUSRPMURIY-UHFFFAOYSA-N 0.000 description 1
- KWQQIKGRHRBBJG-UHFFFAOYSA-N 6-[2-(4-chloro-3-fluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=C1)=CC(F)=C1Cl KWQQIKGRHRBBJG-UHFFFAOYSA-N 0.000 description 1
- FAIXINUNQSOXNY-UHFFFAOYSA-N 6-[2-(4-chlorophenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC(C=C1)=CC=C1Cl)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O FAIXINUNQSOXNY-UHFFFAOYSA-N 0.000 description 1
- HJCWFYUAPZGHQB-UHFFFAOYSA-N 6-[2-(4-chlorophenyl)propanoyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=C1)=CC=C1Cl HJCWFYUAPZGHQB-UHFFFAOYSA-N 0.000 description 1
- USHVEBJVFKVIIF-UHFFFAOYSA-N 6-[2-(4-cyclopropylphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC1=CC=C(C2CC2)C=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O USHVEBJVFKVIIF-UHFFFAOYSA-N 0.000 description 1
- MBLZYHNHZAVIPL-UHFFFAOYSA-N 6-[2-(4-fluorophenyl)propanoyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=C1)=CC=C1F MBLZYHNHZAVIPL-UHFFFAOYSA-N 0.000 description 1
- IQITXQXZZIBHEP-UHFFFAOYSA-N 6-[2-(4-phenoxyphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC(C=C1)=CC=C1OC1=CC=CC=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O IQITXQXZZIBHEP-UHFFFAOYSA-N 0.000 description 1
- WTKBVLWVGAYCIW-UHFFFAOYSA-N 6-[2-(5-chloro-2-fluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=C(C=C1)Cl)=C1F WTKBVLWVGAYCIW-UHFFFAOYSA-N 0.000 description 1
- ZRYLXJXVLOHWEC-UHFFFAOYSA-N 6-[2-(5-chlorothiophen-2-yl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(S1)=CC=C1Cl ZRYLXJXVLOHWEC-UHFFFAOYSA-N 0.000 description 1
- CKMNCLDZOBJCTQ-UHFFFAOYSA-N 6-[2-(5-fluoro-1H-indol-3-yl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC(C1=C2)=CNC1=CC=C2F)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O CKMNCLDZOBJCTQ-UHFFFAOYSA-N 0.000 description 1
- NCFQEIXHOLFNDV-UHFFFAOYSA-N 6-[2-(6-chloro-1H-benzimidazol-2-yl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC1=NC(C=C(C=C2)Cl)=C2N1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O NCFQEIXHOLFNDV-UHFFFAOYSA-N 0.000 description 1
- LGDUZGDAXUEURA-UHFFFAOYSA-N 6-[2-(6-chloropyridin-2-yl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=NC(Cl)=CC=C1 LGDUZGDAXUEURA-UHFFFAOYSA-N 0.000 description 1
- RVFPUYAHNQWAAP-UHFFFAOYSA-N 6-[2-[2-(azepan-1-yl)pyridin-4-yl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(N2CCCCCC2)=NC=C1 RVFPUYAHNQWAAP-UHFFFAOYSA-N 0.000 description 1
- IUKKSZZZOCTUQZ-UHFFFAOYSA-N 6-[2-[2-chloro-3-(trifluoromethyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=CC=C1C(F)(F)F)=C1Cl IUKKSZZZOCTUQZ-UHFFFAOYSA-N 0.000 description 1
- ZKGWZJDQLQJJNS-UHFFFAOYSA-N 6-[2-[2-fluoro-3-(trifluoromethyl)phenyl]-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C(C=CC=C1C(F)(F)F)=C1F ZKGWZJDQLQJJNS-UHFFFAOYSA-N 0.000 description 1
- WXSMNNHUGPNXSY-UHFFFAOYSA-N 6-[2-[2-fluoro-3-(trifluoromethyl)phenyl]-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C(C=CC=C1C(F)(F)F)=C1F WXSMNNHUGPNXSY-UHFFFAOYSA-N 0.000 description 1
- AEHHQTNCTJJZTC-UHFFFAOYSA-N 6-[2-[2-fluoro-3-(trifluoromethyl)phenyl]-2-hydroxyacetyl]-2-[1-(5-phenylpyridin-3-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CC=C3)=CN=C1)NC2=O)=O)C(C=CC=C1C(F)(F)F)=C1F AEHHQTNCTJJZTC-UHFFFAOYSA-N 0.000 description 1
- UETKMJNNXYUNHZ-UHFFFAOYSA-N 6-[2-[2-fluoro-3-[2-(trifluoromethyl)pyridin-4-yl]phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=CC=C1C2=CC(C(F)(F)F)=NC=C2)=C1F UETKMJNNXYUNHZ-UHFFFAOYSA-N 0.000 description 1
- LVRJKNDHIZKGTQ-UHFFFAOYSA-N 6-[2-[3-(1-benzofuran-3-yl)phenyl]acetyl]-2-[1-(3-chlorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC1=CC(C2=COC3=C2C=CC=C3)=CC=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC(Cl)=CC=C1)NC2=O LVRJKNDHIZKGTQ-UHFFFAOYSA-N 0.000 description 1
- IHICOSLQBNKBJW-UHFFFAOYSA-N 6-[2-[3-(1-benzothiophen-3-yl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CSC3=C2C=CC=C3)=CC=C1 IHICOSLQBNKBJW-UHFFFAOYSA-N 0.000 description 1
- VDOKYIOQQMYCFE-UHFFFAOYSA-N 6-[2-[3-(1-cyclopropylpyrazol-4-yl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CN(C3CC3)N=C2)=CC=C1 VDOKYIOQQMYCFE-UHFFFAOYSA-N 0.000 description 1
- QBBIYTKTCCYJHX-UHFFFAOYSA-N 6-[2-[3-(2,3-difluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=CC=C2F)=C2F)=C1 QBBIYTKTCCYJHX-UHFFFAOYSA-N 0.000 description 1
- VVARKCKFXAKRSF-UHFFFAOYSA-N 6-[2-[3-(2,4-difluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=CC(F)=C2)=C2F)=C1 VVARKCKFXAKRSF-UHFFFAOYSA-N 0.000 description 1
- LXVVJEVLYAWDRE-UHFFFAOYSA-N 6-[2-[3-(2-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=CC=C2)=C2F)=C1 LXVVJEVLYAWDRE-UHFFFAOYSA-N 0.000 description 1
- DYDRIGXLFCCXEQ-UHFFFAOYSA-N 6-[2-[3-(3-chloro-4-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC(Cl)=C2F)=C1 DYDRIGXLFCCXEQ-UHFFFAOYSA-N 0.000 description 1
- DANMNUBWJJOWSJ-UHFFFAOYSA-N 6-[2-[3-(3-chloro-4-methylphenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C=CC(C1=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=CC=C1)=C1)=C1Cl DANMNUBWJJOWSJ-UHFFFAOYSA-N 0.000 description 1
- YWGNSYXCGDKURI-UHFFFAOYSA-N 6-[2-[3-(3-chloro-5-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(Cl)=CC(F)=C2)=C1 YWGNSYXCGDKURI-UHFFFAOYSA-N 0.000 description 1
- CXKXKINYEXGYAS-UHFFFAOYSA-N 6-[2-[3-(3-chlorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(Cl)=CC=C2)=C1 CXKXKINYEXGYAS-UHFFFAOYSA-N 0.000 description 1
- QZDJCPGIZBMFDI-UHFFFAOYSA-N 6-[2-[3-(3-chlorophenyl)phenyl]acetyl]-2-[1-(3-cyclohexylphenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CC1=CC=CC(C2=CC(Cl)=CC=C2)=C1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCCC3)=CC=C1)NC2=O QZDJCPGIZBMFDI-UHFFFAOYSA-N 0.000 description 1
- ROKUKUQFFNHLHA-UHFFFAOYSA-N 6-[2-[3-(3-chlorophenyl)phenyl]acetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C(CC4=CC=CC(C5=CC(Cl)=CC=C5)=C4)=O)=C3C2=O)=C1 ROKUKUQFFNHLHA-UHFFFAOYSA-N 0.000 description 1
- VOMHTJBTEREDOP-UHFFFAOYSA-N 6-[2-[3-(3-chlorophenyl)phenyl]acetyl]-2-[1-(4-phenylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC=CC(C2=CC(Cl)=CC=C2)=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3=CC=CC=C3)=CS1)NC2=O VOMHTJBTEREDOP-UHFFFAOYSA-N 0.000 description 1
- HVHKMHGZWOILHV-UHFFFAOYSA-N 6-[2-[3-(3-chlorophenyl)phenyl]acetyl]-2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCCN(C3)C(CC4=CC=CC(C5=CC(Cl)=CC=C5)=C4)=O)=C3C2=O)=C1 HVHKMHGZWOILHV-UHFFFAOYSA-N 0.000 description 1
- JTAVNWAYLNNURH-UHFFFAOYSA-N 6-[2-[3-(3-fluoro-4-methylphenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C=CC(C1=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=CC=C1)=C1)=C1F JTAVNWAYLNNURH-UHFFFAOYSA-N 0.000 description 1
- VOMTYKMELDYRPU-UHFFFAOYSA-N 6-[2-[3-(3-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(F)=CC=C2)=C1 VOMTYKMELDYRPU-UHFFFAOYSA-N 0.000 description 1
- LFMAPSKIPOXQEJ-UHFFFAOYSA-N 6-[2-[3-(3-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C1=CC=CC(C2=CC(F)=CC=C2)=C1 LFMAPSKIPOXQEJ-UHFFFAOYSA-N 0.000 description 1
- WZYHBMQUVRFSBB-UHFFFAOYSA-N 6-[2-[3-(3-tert-butylphenyl)phenyl]-2,2-difluoroacetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)(C)C1=CC=CC(C2=CC(C(C(N(CCC3)CC4=C3N=C(C3(CC3)C3=CC=CC=C3)NC4=O)=O)(F)F)=CC=C2)=C1 WZYHBMQUVRFSBB-UHFFFAOYSA-N 0.000 description 1
- ABVPIOIODMCZNA-UHFFFAOYSA-N 6-[2-[3-(3-tert-butylphenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)(C)C1=CC=CC(C2=CC(C(C(N(CC3)CC4=C3N=C(C3(CC3)C3=CC=CC=C3)NC4=O)=O)O)=CC=C2)=C1 ABVPIOIODMCZNA-UHFFFAOYSA-N 0.000 description 1
- RHKFAFZOEZXHTN-UHFFFAOYSA-N 6-[2-[3-(3-tert-butylphenyl)phenyl]-2-hydroxyacetyl]-2-[1-(5-phenylpyridin-3-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)(C)C1=CC=CC(C2=CC(C(C(N(CCC3)CC4=C3N=C(C3(CC3)C3=CC(C5=CC=CC=C5)=CN=C3)NC4=O)=O)O)=CC=C2)=C1 RHKFAFZOEZXHTN-UHFFFAOYSA-N 0.000 description 1
- YXAPOFSAOSFKMZ-UHFFFAOYSA-N 6-[2-[3-(3-tert-butylphenyl)phenyl]acetyl]-2-[1-(3-chlorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)(C)C1=CC=CC(C2=CC(CC(N(CC3)CC4=C3N=C(C3(CC3)C3=CC(Cl)=CC=C3)NC4=O)=O)=CC=C2)=C1 YXAPOFSAOSFKMZ-UHFFFAOYSA-N 0.000 description 1
- OTMDANONWOLHOW-UHFFFAOYSA-N 6-[2-[3-(4-chloro-3-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC(F)=C2Cl)=C1 OTMDANONWOLHOW-UHFFFAOYSA-N 0.000 description 1
- DJBVNNHTNXAYFP-UHFFFAOYSA-N 6-[2-[3-(4-chlorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC=C2Cl)=C1 DJBVNNHTNXAYFP-UHFFFAOYSA-N 0.000 description 1
- SQUBJWAQDZVUFD-UHFFFAOYSA-N 6-[2-[3-(4-chlorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-thiophen-2-ylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC=C2Cl)=C1 SQUBJWAQDZVUFD-UHFFFAOYSA-N 0.000 description 1
- GQLQLMMHVCVJNB-UHFFFAOYSA-N 6-[2-[3-(4-chlorophenyl)phenyl]-2-hydroxyacetyl]-2-[1-(3-fluorophenyl)cyclopropyl]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC(F)=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC=C2Cl)=C1 GQLQLMMHVCVJNB-UHFFFAOYSA-N 0.000 description 1
- PLDYXQJCCZKTDH-UHFFFAOYSA-N 6-[2-[3-(4-chlorophenyl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound O=C(CC1=CC=CC(C(C=C2)=CC=C2Cl)=C1)N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O PLDYXQJCCZKTDH-UHFFFAOYSA-N 0.000 description 1
- FFVZPEZOEGJCIJ-UHFFFAOYSA-N 6-[2-[3-(4-fluorophenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC=C2F)=C1 FFVZPEZOEGJCIJ-UHFFFAOYSA-N 0.000 description 1
- UDHLXGLZFZSRQW-UHFFFAOYSA-N 6-[2-[3-(4-tert-butylphenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)(C)C(C=C1)=CC=C1C1=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=CC=C1 UDHLXGLZFZSRQW-UHFFFAOYSA-N 0.000 description 1
- OKKIJLGBTIAUKY-UHFFFAOYSA-N 6-[2-[3-(4-tert-butylphenyl)phenyl]acetyl]-2-[1-(3-chlorophenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)(C)C(C=C1)=CC=C1C1=CC(CC(N(CCC2)CC3=C2N=C(C2(CC2)C2=CC(Cl)=CC=C2)NC3=O)=O)=CC=C1 OKKIJLGBTIAUKY-UHFFFAOYSA-N 0.000 description 1
- NGEBABAWBHFWCS-UHFFFAOYSA-N 6-[2-[3-(5-chlorothiophen-3-yl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CSC(Cl)=C2)=CC=C1 NGEBABAWBHFWCS-UHFFFAOYSA-N 0.000 description 1
- LSZKBCUVFITXFI-UHFFFAOYSA-N 6-[2-[3-(5-fluoro-2-methylphenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C=CC(F)=C1)=C1C1=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=CC=C1 LSZKBCUVFITXFI-UHFFFAOYSA-N 0.000 description 1
- NWAVPUPTZVDHOD-UHFFFAOYSA-N 6-[2-[3-(difluoromethyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C(F)F)=CC=C1 NWAVPUPTZVDHOD-UHFFFAOYSA-N 0.000 description 1
- GYBODTFHSUUWNZ-UHFFFAOYSA-N 6-[2-[3-[2-chloro-3-(trifluoromethyl)phenyl]phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=CC=C2C(F)(F)F)=C2Cl)=C1 GYBODTFHSUUWNZ-UHFFFAOYSA-N 0.000 description 1
- NFAIOJATQVCOMA-UHFFFAOYSA-N 6-[2-[3-[2-chloro-5-(trifluoromethyl)phenyl]phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C(C(F)(F)F)C=C2)=C2Cl)=C1 NFAIOJATQVCOMA-UHFFFAOYSA-N 0.000 description 1
- INQOKNFHKUCRBR-UHFFFAOYSA-N 6-[2-[3-[3-[(dimethylamino)methyl]phenyl]phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CN(C)CC1=CC=CC(C2=CC(C(C(N(CC3)CC4=C3N=C(C3(CC3)C3=CC=CC=C3)NC4=O)=O)O)=CC=C2)=C1 INQOKNFHKUCRBR-UHFFFAOYSA-N 0.000 description 1
- PSKYJPOLFXXCOQ-UHFFFAOYSA-N 6-[2-[3-[4-(4-chlorophenyl)phenyl]phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC=C2C(C=C2)=CC=C2Cl)=C1 PSKYJPOLFXXCOQ-UHFFFAOYSA-N 0.000 description 1
- OQOAKLGMWCMNOH-UHFFFAOYSA-N 6-[2-[3-[4-chloro-3-(trifluoromethyl)phenyl]phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC(C(F)(F)F)=C2Cl)=C1 OQOAKLGMWCMNOH-UHFFFAOYSA-N 0.000 description 1
- OBHPFTCXGXLAGL-UHFFFAOYSA-N 6-[2-[5-(3-chlorophenyl)pyridin-3-yl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC(Cl)=CC=C2)=CN=C1 OBHPFTCXGXLAGL-UHFFFAOYSA-N 0.000 description 1
- CLEULBVCJOGHEK-UHFFFAOYSA-N 6-[2-[5-(3-fluorophenyl)pyridin-3-yl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC(F)=CC=C2)=CN=C1 CLEULBVCJOGHEK-UHFFFAOYSA-N 0.000 description 1
- NYOUNNWFYPBBFU-UHFFFAOYSA-N 6-[2-[6-(3-cyclopropylphenyl)pyridin-2-yl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=NC(C2=CC(C3CC3)=CC=C2)=CC=C1 NYOUNNWFYPBBFU-UHFFFAOYSA-N 0.000 description 1
- WXWIBHPPSTWAIP-UHFFFAOYSA-N 6-[2-[6-(3-fluorophenyl)pyridin-2-yl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=NC(C2=CC(F)=CC=C2)=CC=C1 WXWIBHPPSTWAIP-UHFFFAOYSA-N 0.000 description 1
- OYQZFIPNQJCOOI-UHFFFAOYSA-N 6-[2-[6-(3-tert-butylphenyl)pyridin-2-yl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)(C)C1=CC=CC(C2=CC=CC(C(C(N(CC3)CC4=C3N=C(C3(CC3)C3=CC=CC=C3)NC4=O)=O)O)=N2)=C1 OYQZFIPNQJCOOI-UHFFFAOYSA-N 0.000 description 1
- LXRFMMKMRJBMOC-UHFFFAOYSA-N 6-[2-amino-2-[3-(trifluoromethyl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound NC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=CC=C1 LXRFMMKMRJBMOC-UHFFFAOYSA-N 0.000 description 1
- VEAMMMJEHPBVEC-UHFFFAOYSA-N 6-[2-hydroxy-2-(1-methylindol-3-yl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CN1C2=CC=CC=C2C(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=C1 VEAMMMJEHPBVEC-UHFFFAOYSA-N 0.000 description 1
- LOSLTSVRAMHTOQ-UHFFFAOYSA-N 6-[2-hydroxy-2-(2-phenoxyphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C(C=CC=C1)=C1OC1=CC=CC=C1 LOSLTSVRAMHTOQ-UHFFFAOYSA-N 0.000 description 1
- FAMSNVZPDBVAPB-UHFFFAOYSA-N 6-[2-hydroxy-2-(2-phenylpyridin-4-yl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC=CC=C2)=NC=C1 FAMSNVZPDBVAPB-UHFFFAOYSA-N 0.000 description 1
- VIQFKWIEWVIEPF-UHFFFAOYSA-N 6-[2-hydroxy-2-(2-piperidin-1-ylpyridin-4-yl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(N2CCCCC2)=NC=C1 VIQFKWIEWVIEPF-UHFFFAOYSA-N 0.000 description 1
- FWMMUGLNGOTGIW-UHFFFAOYSA-N 6-[2-hydroxy-2-(3-hydroxyphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(O)=CC=C1 FWMMUGLNGOTGIW-UHFFFAOYSA-N 0.000 description 1
- RFKVKFOMGIZNAL-UHFFFAOYSA-N 6-[2-hydroxy-2-(3-methoxyphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound COC1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=C1 RFKVKFOMGIZNAL-UHFFFAOYSA-N 0.000 description 1
- RDGPKDXMWIUPEC-UHFFFAOYSA-N 6-[2-hydroxy-2-(3-methylphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC1=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=CC=C1 RDGPKDXMWIUPEC-UHFFFAOYSA-N 0.000 description 1
- IWZDBOUWTACSOZ-UHFFFAOYSA-N 6-[2-hydroxy-2-(3-phenoxyphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(OC2=CC=CC=C2)=CC=C1 IWZDBOUWTACSOZ-UHFFFAOYSA-N 0.000 description 1
- QOECENWIRHNFAA-UHFFFAOYSA-N 6-[2-hydroxy-2-(3-phenylmethoxyphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(OCC2=CC=CC=C2)=CC=C1 QOECENWIRHNFAA-UHFFFAOYSA-N 0.000 description 1
- DKSYFSUVBLQSFK-UHFFFAOYSA-N 6-[2-hydroxy-2-(3-phenylphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC=CC=C2)=C1 DKSYFSUVBLQSFK-UHFFFAOYSA-N 0.000 description 1
- UHTQERFGZAPHOM-UHFFFAOYSA-N 6-[2-hydroxy-2-(3-propan-2-ylphenyl)acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CC=CC(C(C(N(CCC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=C1 UHTQERFGZAPHOM-UHFFFAOYSA-N 0.000 description 1
- JGSNECJNDWYJDT-UHFFFAOYSA-N 6-[2-hydroxy-2-(3-propan-2-ylphenyl)acetyl]-2-(1-thiophen-2-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(C)C1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CS2)NC3=O)=O)O)=C1 JGSNECJNDWYJDT-UHFFFAOYSA-N 0.000 description 1
- DFFBFOGDNWOJTA-UHFFFAOYSA-N 6-[2-hydroxy-2-(3-pyrimidin-5-ylphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CN=CN=C2)=CC=C1 DFFBFOGDNWOJTA-UHFFFAOYSA-N 0.000 description 1
- CZHMNOORLQRJTL-UHFFFAOYSA-N 6-[2-hydroxy-2-(3-quinolin-3-ylphenyl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC3=CC=CC=C3N=C2)=CC=C1 CZHMNOORLQRJTL-UHFFFAOYSA-N 0.000 description 1
- CYIGKQSNDKHLDE-UHFFFAOYSA-N 6-[2-hydroxy-2-(3-quinolin-3-ylphenyl)acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC3=CC=CC=C3N=C2)=CC=C1 CYIGKQSNDKHLDE-UHFFFAOYSA-N 0.000 description 1
- DJLYEJFFEFQBSY-UHFFFAOYSA-N 6-[2-hydroxy-2-(6-methylpyridin-2-yl)acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=N1 DJLYEJFFEFQBSY-UHFFFAOYSA-N 0.000 description 1
- OLZZNVJLUZLISU-UHFFFAOYSA-N 6-[2-hydroxy-2-[2-(trifluoromethyl)pyridin-4-yl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C(F)(F)F)=NC=C1 OLZZNVJLUZLISU-UHFFFAOYSA-N 0.000 description 1
- RDZJOJDBEHVTGR-UHFFFAOYSA-N 6-[2-hydroxy-2-[2-[2-(trifluoromethyl)pyridin-4-yl]pyridin-4-yl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC(C(F)(F)F)=NC=C2)=NC=C1 RDZJOJDBEHVTGR-UHFFFAOYSA-N 0.000 description 1
- LUBHUDXXXSVPGI-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-(2,2,2-trifluoroethoxy)phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(OCC(F)(F)F)=CC=C1 LUBHUDXXXSVPGI-UHFFFAOYSA-N 0.000 description 1
- ISOJUMVIVTWQMK-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-(2-methoxypyrimidin-5-yl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound COC(N=C1)=NC=C1C1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=C1 ISOJUMVIVTWQMK-UHFFFAOYSA-N 0.000 description 1
- JCBSZJPHHQOICJ-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-(2-methylpyridin-3-yl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC1=NC=CC=C1C1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=C1 JCBSZJPHHQOICJ-UHFFFAOYSA-N 0.000 description 1
- FJAYVHDCMHICGX-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-(2-methylpyridin-4-yl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC1=NC=CC(C2=CC=CC(C(C(N(CC3)CC4=C3N=C(C3(CC3)C3=CC=CC=C3)NC4=O)=O)O)=C2)=C1 FJAYVHDCMHICGX-UHFFFAOYSA-N 0.000 description 1
- GXCNCVDZYNYNPX-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-(6-methoxypyridin-3-yl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound COC(N=C1)=CC=C1C1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=C1 GXCNCVDZYNYNPX-UHFFFAOYSA-N 0.000 description 1
- UAHMVDZWMCNPEA-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-(6-methylpyridin-3-yl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC(N=C1)=CC=C1C1=CC=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=C1 UAHMVDZWMCNPEA-UHFFFAOYSA-N 0.000 description 1
- QFTGDBLCUVDUCZ-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-(trifluoromethoxy)phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(OC(F)(F)F)=CC=C1 QFTGDBLCUVDUCZ-UHFFFAOYSA-N 0.000 description 1
- ORNSWLJBKUFBLU-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-(trifluoromethyl)phenyl]propanoyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)(C1=CC(C(F)(F)F)=CC=C1)O ORNSWLJBKUFBLU-UHFFFAOYSA-N 0.000 description 1
- ADQNHWXGWKXNEO-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-(trifluoromethylsulfanyl)phenyl]acetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C(C(C4=CC(SC(F)(F)F)=CC=C4)O)=O)=C3C2=O)=C1 ADQNHWXGWKXNEO-UHFFFAOYSA-N 0.000 description 1
- AIJXEKBBEAIQOV-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[2-(trifluoromethoxy)phenyl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=CC=C2)=C2OC(F)(F)F)=C1 AIJXEKBBEAIQOV-UHFFFAOYSA-N 0.000 description 1
- ILUVXSFVPKPVQP-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[2-(trifluoromethyl)pyridin-4-yl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC(C(F)(F)F)=NC=C2)=CC=C1 ILUVXSFVPKPVQP-UHFFFAOYSA-N 0.000 description 1
- VBSRLACFWZTAJD-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[2-(trifluoromethyl)pyridin-4-yl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC(C(F)(F)F)=NC=C2)=CC=C1 VBSRLACFWZTAJD-UHFFFAOYSA-N 0.000 description 1
- UCANSNLDRLESGT-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[3-(trifluoromethoxy)phenyl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(OC(F)(F)F)=CC=C2)=C1 UCANSNLDRLESGT-UHFFFAOYSA-N 0.000 description 1
- XGBREQNZHPBDPW-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[3-(trifluoromethoxy)phenyl]phenyl]acetyl]-2-(1-thiophen-2-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C1=CC=CC(C2=CC(OC(F)(F)F)=CC=C2)=C1 XGBREQNZHPBDPW-UHFFFAOYSA-N 0.000 description 1
- CKVXMBRBWXOPKI-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[3-(trifluoromethoxy)phenyl]phenyl]acetyl]-2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCCN(C3)C(C(C4=CC=CC(C5=CC(OC(F)(F)F)=CC=C5)=C4)O)=O)=C3C2=O)=C1 CKVXMBRBWXOPKI-UHFFFAOYSA-N 0.000 description 1
- WLQJYQVEUMMMNA-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[3-(trifluoromethyl)phenoxy]phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(OC2=CC(C(F)(F)F)=CC=C2)=CC=C1 WLQJYQVEUMMMNA-UHFFFAOYSA-N 0.000 description 1
- XNBGHHVGVXSMHJ-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[3-(trifluoromethyl)phenoxy]phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(OC2=CC(C(F)(F)F)=CC=C2)=CC=C1 XNBGHHVGVXSMHJ-UHFFFAOYSA-N 0.000 description 1
- YEXQOPQCLRWLIV-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(C(F)(F)F)=CC=C2)=C1 YEXQOPQCLRWLIV-UHFFFAOYSA-N 0.000 description 1
- XYUZCECGCKFALZ-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-2-(1-thiophen-2-ylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CS1)NC2=O)=O)C1=CC=CC(C2=CC(C(F)(F)F)=CC=C2)=C1 XYUZCECGCKFALZ-UHFFFAOYSA-N 0.000 description 1
- RFPONOCDAFZOFJ-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-2-[1-(3-propan-2-ylphenyl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C(C(C4=CC=CC(C5=CC(C(F)(F)F)=CC=C5)=C4)O)=O)=C3C2=O)=C1 RFPONOCDAFZOFJ-UHFFFAOYSA-N 0.000 description 1
- CPHVDHZGUDEOPQ-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-2-[1-(4-propan-2-ylthiophen-2-yl)cyclopropyl]-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound CC(C)C1=CSC(C2(CC2)C(N2)=NC(CCCN(C3)C(C(C4=CC=CC(C5=CC(C(F)(F)F)=CC=C5)=C4)O)=O)=C3C2=O)=C1 CPHVDHZGUDEOPQ-UHFFFAOYSA-N 0.000 description 1
- ACODISVRYFGYFT-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[3-(trifluoromethylsulfanyl)phenyl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(SC(F)(F)F)=CC=C2)=C1 ACODISVRYFGYFT-UHFFFAOYSA-N 0.000 description 1
- QKISVRXCJMWFDF-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[3-hydroxy-5-(trifluoromethyl)phenyl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC(O)=CC(C(F)(F)F)=C2)=C1 QKISVRXCJMWFDF-UHFFFAOYSA-N 0.000 description 1
- AXMIKYSVXVWIMJ-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[4-(trifluoromethoxy)phenyl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,7,8,9-tetrahydro-3H-pyrimido[5,4-c]azepin-4-one Chemical compound OC(C(N(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C(C=C2)=CC=C2OC(F)(F)F)=C1 AXMIKYSVXVWIMJ-UHFFFAOYSA-N 0.000 description 1
- MAPMGUYEOHZMAT-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[4-(trifluoromethyl)phenyl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=CC(C2=CC=C(C(F)(F)F)C=C2)=C1 MAPMGUYEOHZMAT-UHFFFAOYSA-N 0.000 description 1
- JEYLYTLVGAEDSY-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[5-(trifluoromethyl)pyridin-3-yl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC(C(F)(F)F)=CN=C2)=CC=C1 JEYLYTLVGAEDSY-UHFFFAOYSA-N 0.000 description 1
- MXOCBMYRQMPWEQ-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-[6-(trifluoromethyl)pyridin-3-yl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2=CC=C(C(F)(F)F)N=C2)=CC=C1 MXOCBMYRQMPWEQ-UHFFFAOYSA-N 0.000 description 1
- HKANIMZKFSDEGY-UHFFFAOYSA-N 6-[2-hydroxy-2-[3-methyl-5-(trifluoromethyl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CC1=CC(C(F)(F)F)=CC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=C1 HKANIMZKFSDEGY-UHFFFAOYSA-N 0.000 description 1
- YADDHKYORSVYHE-UHFFFAOYSA-N 6-[2-hydroxy-2-[4-(trifluoromethyl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC=C(C(F)(F)F)C=C1 YADDHKYORSVYHE-UHFFFAOYSA-N 0.000 description 1
- UHDBZBXKUQEWKI-UHFFFAOYSA-N 6-[2-hydroxy-2-[5-[2-(trifluoromethyl)pyridin-4-yl]pyridin-3-yl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CN=CC(C2=CC(C(F)(F)F)=NC=C2)=C1 UHDBZBXKUQEWKI-UHFFFAOYSA-N 0.000 description 1
- KATIBTXRCBLUOV-UHFFFAOYSA-N 6-[2-hydroxy-2-[6-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)pyridin-2-yl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound CN(CC1)CC=C1C1=NC(C(C(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)O)=CC=C1 KATIBTXRCBLUOV-UHFFFAOYSA-N 0.000 description 1
- NVSMZBIKPCZFLW-UHFFFAOYSA-N 6-[2-hydroxy-2-[6-[3-(trifluoromethoxy)phenyl]pyridin-2-yl]acetyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=NC(C2=CC(OC(F)(F)F)=CC=C2)=CC=C1 NVSMZBIKPCZFLW-UHFFFAOYSA-N 0.000 description 1
- WJIGZMUJXRSYKP-UHFFFAOYSA-N 6-[3-(1H-indol-3-yl)propanoyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CCC1=CNC2=CC=CC=C12)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O WJIGZMUJXRSYKP-UHFFFAOYSA-N 0.000 description 1
- RGLJXIHVSRBSNO-UHFFFAOYSA-N 6-[3-(2-chlorophenyl)propanoyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(CCC(C=CC=C1)=C1Cl)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O RGLJXIHVSRBSNO-UHFFFAOYSA-N 0.000 description 1
- GTZVMGIYCRBKCK-UHFFFAOYSA-N 6-[3-(2-fluorophenyl)-1H-pyrazole-5-carbonyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound O=C(C1=CC(C(C=CC=C2)=C2F)=NN1)N(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O GTZVMGIYCRBKCK-UHFFFAOYSA-N 0.000 description 1
- BTTBVLHBRQEVJA-UHFFFAOYSA-N 6-[3-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]propanoyl]-2-(1-phenylcyclopropyl)-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound COC(C=C1)=CC=C1C1=NOC(CCC(N(CC2)CC3=C2N=C(C2(CC2)C2=CC=CC=C2)NC3=O)=O)=N1 BTTBVLHBRQEVJA-UHFFFAOYSA-N 0.000 description 1
- HUIBIVMDGVOZCI-UHFFFAOYSA-N 6-methylsulfonyl-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-3-[[4-[2-(trifluoromethyl)pyrrolidin-1-yl]piperidin-1-yl]methyl]quinoline-4-carboxamide Chemical compound CS(=O)(=O)C1=CC2=C(C=C1)N=C(C(=C2C(=O)NC3(CC3)C4=CC=CC=C4)CN5CCC(CC5)N6CCCC6C(F)(F)F)C7=CC(=CC=C7)C(F)(F)F HUIBIVMDGVOZCI-UHFFFAOYSA-N 0.000 description 1
- KSBOLBDSCKSZQL-UHFFFAOYSA-N 6-methylsulfonyl-N-(1-phenylcyclopropyl)-3-[(4-pyrrolidin-1-ylpiperidin-1-yl)methyl]-2-[4-(trifluoromethyl)phenyl]quinoline-4-carboxamide Chemical compound C1CC1(C=1C=CC=CC=1)NC(=O)C=1C2=CC(S(=O)(=O)C)=CC=C2N=C(C=2C=CC(=CC=2)C(F)(F)F)C=1CN(CC1)CCC1N1CCCC1 KSBOLBDSCKSZQL-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- ASRFFBIZTLULIR-OAQYLSRUSA-N 7-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,6,8,9-tetrahydro-3H-pyrimido[4,5-d]azepin-4-one Chemical compound O[C@@H](C(N(CC1)CCC(N=C(C2(CC2)C2=CC=CC=C2)N2)=C1C2=O)=O)C1=CC(Cl)=CC=C1 ASRFFBIZTLULIR-OAQYLSRUSA-N 0.000 description 1
- IHXGUSLNSGEFPT-UHFFFAOYSA-N 7-[2-(2,3-difluorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-3,5,6,8-tetrahydropyrido[3,4-d]pyrimidin-4-one Chemical compound OC(C(N(CC1)CC(N=C(C2(CC2)C2=CC=CC=C2)N2)=C1C2=O)=O)C(C=CC=C1F)=C1F IHXGUSLNSGEFPT-UHFFFAOYSA-N 0.000 description 1
- YRGLMFFHRJCALL-SLQAJWMNSA-N 7-chloro-3-[[(5s,7s)-3-[2-methyl-2-(3-phenyl-1,2,4-oxadiazol-5-yl)propyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC(Cl)=C3N=C2)C#N)CCC1)C1)C(=O)N1CC(C)(C)C(ON=1)=NC=1C1=CC=CC=C1 YRGLMFFHRJCALL-SLQAJWMNSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QMQFIEHHIHGJKA-OAQYLSRUSA-N 8-[(2R)-2-(3-chlorophenyl)-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,6,7,9-tetrahydro-3H-pyrimido[4,5-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC(N=C(C2(CC2)C2=CC=CC=C2)N2)=C1C2=O)=O)C1=CC(Cl)=CC=C1 QMQFIEHHIHGJKA-OAQYLSRUSA-N 0.000 description 1
- SGOSNVOCSFSSRF-SSEXGKCCSA-N 8-[(2R)-2-[3-(3-tert-butylphenyl)phenyl]-2-hydroxyacetyl]-2-(1-phenylcyclopropyl)-5,6,7,9-tetrahydro-3H-pyrimido[4,5-c]azepin-4-one Chemical compound CC(C)(C)C1=CC=CC(C2=CC([C@H](C(N(CCC3)CC(N=C(C4(CC4)C4=CC=CC=C4)N4)=C3C4=O)=O)O)=CC=C2)=C1 SGOSNVOCSFSSRF-SSEXGKCCSA-N 0.000 description 1
- XISNXSSAHYDKNQ-SSEXGKCCSA-N 8-[(2R)-2-hydroxy-2-[3-(3-propan-2-ylphenyl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,6,7,9-tetrahydro-3H-pyrimido[4,5-c]azepin-4-one Chemical compound CC(C)C1=CC=CC(C2=CC([C@H](C(N(CCC3)CC(N=C(C4(CC4)C4=CC=CC=C4)N4)=C3C4=O)=O)O)=CC=C2)=C1 XISNXSSAHYDKNQ-SSEXGKCCSA-N 0.000 description 1
- NMRIFILWSIXUKQ-HHHXNRCGSA-N 8-[(2R)-2-hydroxy-2-[3-[3-(trifluoromethyl)phenyl]phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,6,7,9-tetrahydro-3H-pyrimido[4,5-c]azepin-4-one Chemical compound O[C@@H](C(N(CCC1)CC(N=C(C2(CC2)C2=CC=CC=C2)N2)=C1C2=O)=O)C1=CC=CC(C2=CC(C(F)(F)F)=CC=C2)=C1 NMRIFILWSIXUKQ-HHHXNRCGSA-N 0.000 description 1
- JYTGIJLMZMOIEL-UHFFFAOYSA-N 8-[2-[3-(3-chlorophenyl)phenyl]acetyl]-2-(1-phenylcyclopropyl)-5,6,7,9-tetrahydro-3H-pyrimido[4,5-c]azepin-4-one Chemical compound O=C(CC1=CC=CC(C2=CC(Cl)=CC=C2)=C1)N(CCC1)CC(N=C(C2(CC2)C2=CC=CC=C2)N2)=C1C2=O JYTGIJLMZMOIEL-UHFFFAOYSA-N 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical group OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
- SESFRYSPDFLNCH-UHFFFAOYSA-N Benzyl benzoate Natural products C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- RHLJLALHBZGAFM-UHFFFAOYSA-N Bunazosinum Chemical compound C1CN(C(=O)CCC)CCCN1C1=NC(N)=C(C=C(OC)C(OC)=C2)C2=N1 RHLJLALHBZGAFM-UHFFFAOYSA-N 0.000 description 1
- 125000006725 C1-C10 alkenyl group Chemical group 0.000 description 1
- FIYZCEHMAGGRHM-UHFFFAOYSA-N C1=C(Cl)C(C(F)(F)F)=CC(C=2C(=C(C(=O)NC3(CC3)C=3C=CC=CC=3)C3=CC(Cl)=CC=C3N=2)CN2CCC(CC2)N2CCOCC2)=C1 Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(C=2C(=C(C(=O)NC3(CC3)C=3C=CC=CC=3)C3=CC(Cl)=CC=C3N=2)CN2CCC(CC2)N2CCOCC2)=C1 FIYZCEHMAGGRHM-UHFFFAOYSA-N 0.000 description 1
- TUSYGRDQNOBEEA-UHFFFAOYSA-N C1CC(N2CCOCC2)CCN1CC1=C(C=2C=C(C=CC=2)C(F)(F)F)N=C2C(CC)=CC=CC2=C1C(=O)NC1(C=2C=CC=CC=2)CC1 Chemical compound C1CC(N2CCOCC2)CCN1CC1=C(C=2C=C(C=CC=2)C(F)(F)F)N=C2C(CC)=CC=CC2=C1C(=O)NC1(C=2C=CC=CC=2)CC1 TUSYGRDQNOBEEA-UHFFFAOYSA-N 0.000 description 1
- SKAPVPXANLDWLA-UHFFFAOYSA-N C1CC(N2CCOCC2)CCN1CC1=C(C=2C=C(C=CC=2)C(F)(F)F)N=C2C(F)=C(Br)C=CC2=C1C(=O)NC1(C=2C=CC=CC=2)CC1 Chemical compound C1CC(N2CCOCC2)CCN1CC1=C(C=2C=C(C=CC=2)C(F)(F)F)N=C2C(F)=C(Br)C=CC2=C1C(=O)NC1(C=2C=CC=CC=2)CC1 SKAPVPXANLDWLA-UHFFFAOYSA-N 0.000 description 1
- JUWCRSMONVWTET-UHFFFAOYSA-N C1CC(N2CCOCC2)CCN1CC1=C(C=2C=C(C=CC=2)C(F)(F)F)N=C2C=C(Cl)C(S(=O)(=O)C(C)C)=CC2=C1C(=O)NC1(C=2C=CC=CC=2)CC1 Chemical compound C1CC(N2CCOCC2)CCN1CC1=C(C=2C=C(C=CC=2)C(F)(F)F)N=C2C=C(Cl)C(S(=O)(=O)C(C)C)=CC2=C1C(=O)NC1(C=2C=CC=CC=2)CC1 JUWCRSMONVWTET-UHFFFAOYSA-N 0.000 description 1
- WCLSAWOWGNJOGY-UHFFFAOYSA-N C1CC(N2CCOCC2)CCN1CC1=C(C=2C=C(C=CC=2)C(F)(F)F)N=C2C=C(OC(C)C)C(OCC)=CC2=C1C(=O)NC1(C=2C=CC=CC=2)CC1 Chemical compound C1CC(N2CCOCC2)CCN1CC1=C(C=2C=C(C=CC=2)C(F)(F)F)N=C2C=C(OC(C)C)C(OCC)=CC2=C1C(=O)NC1(C=2C=CC=CC=2)CC1 WCLSAWOWGNJOGY-UHFFFAOYSA-N 0.000 description 1
- NNRZFICTEFPCRG-UHFFFAOYSA-N C1CC(N2CCOCC2)CCN1CC=1C(C=2C=C(C=CC=2)C(F)(F)F)=NC2=C(Cl)C(OCC)=CC=C2C=1C(=O)NC1(C=2C=CC=CC=2)CC1 Chemical compound C1CC(N2CCOCC2)CCN1CC=1C(C=2C=C(C=CC=2)C(F)(F)F)=NC2=C(Cl)C(OCC)=CC=C2C=1C(=O)NC1(C=2C=CC=CC=2)CC1 NNRZFICTEFPCRG-UHFFFAOYSA-N 0.000 description 1
- NXJNYWZRKUDODA-UHFFFAOYSA-N C1CC(N2CCOCC2)CCN1CC=1C(C=2C=C(C=CC=2)C(F)(F)F)=NC2=CC(OC(C)C)=CC(Br)=C2C=1C(=O)NC1(C=2C=CC=CC=2)CC1 Chemical compound C1CC(N2CCOCC2)CCN1CC=1C(C=2C=C(C=CC=2)C(F)(F)F)=NC2=CC(OC(C)C)=CC(Br)=C2C=1C(=O)NC1(C=2C=CC=CC=2)CC1 NXJNYWZRKUDODA-UHFFFAOYSA-N 0.000 description 1
- CRIOSKRATOWVMD-UHFFFAOYSA-N C1CC(N2CCOCC2)CCN1CC=1C(C=2C=C(C=CC=2)C(F)(F)F)=NC2=CC(OCCC)=CC=C2C=1C(=O)NC1(C=2C=CC=CC=2)CC1 Chemical compound C1CC(N2CCOCC2)CCN1CC=1C(C=2C=C(C=CC=2)C(F)(F)F)=NC2=CC(OCCC)=CC=C2C=1C(=O)NC1(C=2C=CC=CC=2)CC1 CRIOSKRATOWVMD-UHFFFAOYSA-N 0.000 description 1
- BPFRLKMVDDVYFV-UHFFFAOYSA-N C1CC1(C=1C=CC=CC=1)NC(=O)C1=C2C=C(C)C(OC(C)C)=CC2=NC(C=2C=C(C=CC=2)C(F)(F)F)=C1CN(CC1)CCC1N1CCOCC1 Chemical compound C1CC1(C=1C=CC=CC=1)NC(=O)C1=C2C=C(C)C(OC(C)C)=CC2=NC(C=2C=C(C=CC=2)C(F)(F)F)=C1CN(CC1)CCC1N1CCOCC1 BPFRLKMVDDVYFV-UHFFFAOYSA-N 0.000 description 1
- DEGIRVGENHMHLO-UHFFFAOYSA-N C1CC1(C=1C=CC=CC=1)NC(=O)C1=C2C=C(Cl)C(OCC)=CC2=NC(C=2C=C(C=CC=2)C(F)(F)F)=C1CN(CC1)CCC1N1CCOCC1 Chemical compound C1CC1(C=1C=CC=CC=1)NC(=O)C1=C2C=C(Cl)C(OCC)=CC2=NC(C=2C=C(C=CC=2)C(F)(F)F)=C1CN(CC1)CCC1N1CCOCC1 DEGIRVGENHMHLO-UHFFFAOYSA-N 0.000 description 1
- HWCQBWLIBAZENK-UHFFFAOYSA-N C1CC1(C=1C=CC=CC=1)NC(=O)C1=C2C=C(S(=O)(=O)C(C)C)C(OC)=CC2=NC(C=2C=C(C=CC=2)C(F)(F)F)=C1CN(CC1)CCC1N1CCOCC1 Chemical compound C1CC1(C=1C=CC=CC=1)NC(=O)C1=C2C=C(S(=O)(=O)C(C)C)C(OC)=CC2=NC(C=2C=C(C=CC=2)C(F)(F)F)=C1CN(CC1)CCC1N1CCOCC1 HWCQBWLIBAZENK-UHFFFAOYSA-N 0.000 description 1
- YINJBQGIKKSSGJ-UHFFFAOYSA-N C1CC1(C=1C=CC=CC=1)NC(=O)C=1C2=CC(S(=O)(=O)C)=CC=C2N=C(C=2C=C(C=CC=2)C(F)(F)F)C=1CN(CC1)CCC1N1CCCC1 Chemical compound C1CC1(C=1C=CC=CC=1)NC(=O)C=1C2=CC(S(=O)(=O)C)=CC=C2N=C(C=2C=C(C=CC=2)C(F)(F)F)C=1CN(CC1)CCC1N1CCCC1 YINJBQGIKKSSGJ-UHFFFAOYSA-N 0.000 description 1
- IWDBGUSHTKRDRN-UHFFFAOYSA-N C1CC1(C=1C=CC=CC=1)NC(=O)C=1C2=CC(S(=O)(=O)C)=CC=C2N=C(C=2C=C(Cl)C(Cl)=CC=2)C=1CN(CC1)CCC1N1CCCC1 Chemical compound C1CC1(C=1C=CC=CC=1)NC(=O)C=1C2=CC(S(=O)(=O)C)=CC=C2N=C(C=2C=C(Cl)C(Cl)=CC=2)C=1CN(CC1)CCC1N1CCCC1 IWDBGUSHTKRDRN-UHFFFAOYSA-N 0.000 description 1
- JZBIMVDAFKDOHE-UHFFFAOYSA-N C1CC1(C=1C=CC=CC=1)NC(=O)C=1C2=CC(S(=O)(=O)CC)=CC=C2N=C(C=2C=C(C=CC=2)C(F)(F)F)C=1CN(CC1)CCC1N1CCOCC1 Chemical compound C1CC1(C=1C=CC=CC=1)NC(=O)C=1C2=CC(S(=O)(=O)CC)=CC=C2N=C(C=2C=C(C=CC=2)C(F)(F)F)C=1CN(CC1)CCC1N1CCOCC1 JZBIMVDAFKDOHE-UHFFFAOYSA-N 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- UAMWXISOMAVDJT-UHFFFAOYSA-N CC(C)(C)C1=CC=CC(C(C(ON(CC2)CC3=C2N=C(C2(CC2)C2=CC=CS2)NC3=O)=O)O)=C1 Chemical compound CC(C)(C)C1=CC=CC(C(C(ON(CC2)CC3=C2N=C(C2(CC2)C2=CC=CS2)NC3=O)=O)O)=C1 UAMWXISOMAVDJT-UHFFFAOYSA-N 0.000 description 1
- BSPGMMGMAMNDMJ-UHFFFAOYSA-N CC(C)(C)C1=CC=CC(C(C(ON(CCC2)CC3=C2N=C(C2(CC2)C2=CC(Cl)=CC=C2)NC3=O)=O)O)=C1 Chemical compound CC(C)(C)C1=CC=CC(C(C(ON(CCC2)CC3=C2N=C(C2(CC2)C2=CC(Cl)=CC=C2)NC3=O)=O)O)=C1 BSPGMMGMAMNDMJ-UHFFFAOYSA-N 0.000 description 1
- VJPJQHMHUBVGIS-UHFFFAOYSA-N CC(C)(C)C1=CC=CC(CC(N(CCC2)CC3=C2N=C(C2(CC2)C2=CC(Cl)=CC=C2)NC3)=O)=C1 Chemical compound CC(C)(C)C1=CC=CC(CC(N(CCC2)CC3=C2N=C(C2(CC2)C2=CC(Cl)=CC=C2)NC3)=O)=C1 VJPJQHMHUBVGIS-UHFFFAOYSA-N 0.000 description 1
- JTWKWBCGTARMRW-PGUFJCEWSA-N CC(C)C(C(CC1)CCN1C(N=C1)=CC=C1C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(C(F)(F)F)=CC=C4)O)=O)=C3C2=O)=C1)=O Chemical compound CC(C)C(C(CC1)CCN1C(N=C1)=CC=C1C1=CC=CC(C2(CC2)C(N2)=NC(CCCN(C3)C([C@@H](C4=CC(C(F)(F)F)=CC=C4)O)=O)=C3C2=O)=C1)=O JTWKWBCGTARMRW-PGUFJCEWSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010007687 Carotid artery stenosis Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 108091005462 Cation channels Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 1
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 1
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- NGSVJEWIRKAKAZ-UHFFFAOYSA-N FC(F)(F)C1=CC=CC(C=2C(=C(C(=O)NC3(CC3)C=3C=CC=CC=3)C3=CC(Cl)=CC(Cl)=C3N=2)CN2CCC(CC2)N2CCOCC2)=C1 Chemical compound FC(F)(F)C1=CC=CC(C=2C(=C(C(=O)NC3(CC3)C=3C=CC=CC=3)C3=CC(Cl)=CC(Cl)=C3N=2)CN2CCC(CC2)N2CCOCC2)=C1 NGSVJEWIRKAKAZ-UHFFFAOYSA-N 0.000 description 1
- YVQDZMMIGINYBE-UHFFFAOYSA-N FC(F)(F)C1=CC=CC(C=2C(=C(C(=O)NC3(CC3)C=3C=CC=CC=3)C3=CC(Cl)=CC=C3N=2)CN2CCC(CC2)N2CCOCC2)=C1 Chemical compound FC(F)(F)C1=CC=CC(C=2C(=C(C(=O)NC3(CC3)C=3C=CC=CC=3)C3=CC(Cl)=CC=C3N=2)CN2CCC(CC2)N2CCOCC2)=C1 YVQDZMMIGINYBE-UHFFFAOYSA-N 0.000 description 1
- HOCKPRLJWSIEEK-UHFFFAOYSA-N FC(F)(F)C1=CC=CC(C=2C(=C(C(=O)NC3(CC3)C=3C=CC=CC=3)C3=CC=CC=C3N=2)CC2CCC(CC2)N2CCCCC2)=C1 Chemical compound FC(F)(F)C1=CC=CC(C=2C(=C(C(=O)NC3(CC3)C=3C=CC=CC=3)C3=CC=CC=C3N=2)CC2CCC(CC2)N2CCCCC2)=C1 HOCKPRLJWSIEEK-UHFFFAOYSA-N 0.000 description 1
- RXJOGRUUYSNLHJ-UHFFFAOYSA-N FC(F)(F)C1=CC=CC(C=2C(=C(C(=O)NC3(CC3)C=3C=CC=CC=3)C3=CC=CC=C3N=2)CN2CCC(CC2)N2CCOCC2)=C1 Chemical compound FC(F)(F)C1=CC=CC(C=2C(=C(C(=O)NC3(CC3)C=3C=CC=CC=3)C3=CC=CC=C3N=2)CN2CCC(CC2)N2CCOCC2)=C1 RXJOGRUUYSNLHJ-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 244000303040 Glycyrrhiza glabra Species 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- YHGJHDJZIOYZIR-URPSFYETSA-N Helenien Chemical compound CC1(C)C[C@H](OC(=O)CCCCCCCCCCCCCCC)CC(C)=C1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\[C@@H]1C(C)(C)C[C@@H](OC(=O)CCCCCCCCCCCCCCC)C=C1C YHGJHDJZIOYZIR-URPSFYETSA-N 0.000 description 1
- YHGJHDJZIOYZIR-KFTCWRDFSA-N Helenien Natural products O=C(O[C@H]1C=C(C)[C@H](/C=C/C(=C\C=C\C(=C/C=C/C=C(\C=C\C=C(/C=C/C=2C(C)(C)C[C@H](OC(=O)CCCCCCCCCCCCCCC)CC=2C)\C)/C)\C)/C)C(C)(C)C1)CCCCCCCCCCCCCCC YHGJHDJZIOYZIR-KFTCWRDFSA-N 0.000 description 1
- OMCPLEZZPVJJIS-UHFFFAOYSA-N Hypadil (TN) Chemical compound C1C(O[N+]([O-])=O)COC2=C1C=CC=C2OCC(O)CNC(C)C OMCPLEZZPVJJIS-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- FEXQDZTYJVXMOS-UHFFFAOYSA-N Isopropyl benzoate Chemical group CC(C)OC(=O)C1=CC=CC=C1 FEXQDZTYJVXMOS-UHFFFAOYSA-N 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
- 239000003798 L01XE11 - Pazopanib Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010065534 Macular ischaemia Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229920000057 Mannan Polymers 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 208000009857 Microaneurysm Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 150000001200 N-acyl ethanolamides Chemical class 0.000 description 1
- 238000006411 Negishi coupling reaction Methods 0.000 description 1
- 241000933095 Neotragus moschatus Species 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000005736 Nervous System Malformations Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010067013 Normal tension glaucoma Diseases 0.000 description 1
- 229920002292 Nylon 6 Polymers 0.000 description 1
- OSKZMSPAWSCGFM-UHFFFAOYSA-N O=C1NC(C2(CC2)C2=CC(Cl)=CC=C2)=NC2=C1CN(CC(C=C1)=CC=C1OC1=CC=CC=C1)CCC2 Chemical compound O=C1NC(C2(CC2)C2=CC(Cl)=CC=C2)=NC2=C1CN(CC(C=C1)=CC=C1OC1=CC=CC=C1)CCC2 OSKZMSPAWSCGFM-UHFFFAOYSA-N 0.000 description 1
- IWHUKTRGDKUQFF-UHFFFAOYSA-N O=C1NC(C2(CC2)C2=CC(Cl)=CC=C2)=NC2=C1CN(CC1=CC(OC3=CC=CC=C3)=CC=C1)CCC2 Chemical compound O=C1NC(C2(CC2)C2=CC(Cl)=CC=C2)=NC2=C1CN(CC1=CC(OC3=CC=CC=C3)=CC=C1)CCC2 IWHUKTRGDKUQFF-UHFFFAOYSA-N 0.000 description 1
- UDAPLLKQMCAVHC-UHFFFAOYSA-N OC(C(ON(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(Cl)=CC(Cl)=C1 Chemical compound OC(C(ON(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(Cl)=CC(Cl)=C1 UDAPLLKQMCAVHC-UHFFFAOYSA-N 0.000 description 1
- CIRLNFOTSNUFQL-UHFFFAOYSA-N OC(C(ON(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(F)=CC(C(F)(F)F)=C1 Chemical compound OC(C(ON(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(F)=CC(C(F)(F)F)=C1 CIRLNFOTSNUFQL-UHFFFAOYSA-N 0.000 description 1
- KEJCXPAVKKAYJD-UHFFFAOYSA-N OC(C(ON(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2CC2)=CC=C1 Chemical compound OC(C(ON(CCC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O)=O)C1=CC(C2CC2)=CC=C1 KEJCXPAVKKAYJD-UHFFFAOYSA-N 0.000 description 1
- NGEWEJBRNGGHAX-QGZVFWFLSA-N O[C@@H](C(ON(CC1)CC2=C1N=C(C1(CC1)C1=CN=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 Chemical compound O[C@@H](C(ON(CC1)CC2=C1N=C(C1(CC1)C1=CN=CS1)NC2=O)=O)C1=CC(Cl)=CC=C1 NGEWEJBRNGGHAX-QGZVFWFLSA-N 0.000 description 1
- RHYAOUCGFVGSQN-PGUFJCEWSA-N O[C@@H](C(ON(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCCC3)=CC=C1)NC2=O)=O)C1=CC(C2=COC3=C2C=CC=C3)=CC=C1 Chemical compound O[C@@H](C(ON(CCC1)CC2=C1N=C(C1(CC1)C1=CC(C3CCCCC3)=CC=C1)NC2=O)=O)C1=CC(C2=COC3=C2C=CC=C3)=CC=C1 RHYAOUCGFVGSQN-PGUFJCEWSA-N 0.000 description 1
- SUJXMTLRTGPTTB-OAQYLSRUSA-N O[C@H](CCC1=CC=CC=C1)CN(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O Chemical compound O[C@H](CCC1=CC=CC=C1)CN(CC1)CC2=C1N=C(C1(CC1)C1=CC=CC=C1)NC2=O SUJXMTLRTGPTTB-OAQYLSRUSA-N 0.000 description 1
- 206010030936 Optic nerve infarction Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 241000233805 Phoenix Species 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 101710096328 Phospholipase A2 Proteins 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920002701 Polyoxyl 40 Stearate Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- TVQZAMVBTVNYLA-UHFFFAOYSA-N Pranoprofen Chemical compound C1=CC=C2CC3=CC(C(C(O)=O)C)=CC=C3OC2=N1 TVQZAMVBTVNYLA-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 101710126089 Putative inactive carbonic anhydrase 5B-like protein Proteins 0.000 description 1
- 108091008103 RNA aptamers Proteins 0.000 description 1
- 208000035977 Rare disease Diseases 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 201000007737 Retinal degeneration Diseases 0.000 description 1
- 244000178231 Rosmarinus officinalis Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000004288 Sodium dehydroacetate Substances 0.000 description 1
- 206010042265 Sturge-Weber Syndrome Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 1
- 108060008564 TRPV Proteins 0.000 description 1
- 102000003563 TRPV Human genes 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- 102000000591 Tight Junction Proteins Human genes 0.000 description 1
- 108010002321 Tight Junction Proteins Proteins 0.000 description 1
- 102100029611 Transient receptor potential cation channel subfamily V member 4 Human genes 0.000 description 1
- 108700039205 Transient receptor potential cation channel subfamily V member 4 Proteins 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 206010058990 Venous occlusion Diseases 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- COERJHDMQUPDCV-UHFFFAOYSA-N [K].FB(F)F Chemical compound [K].FB(F)F COERJHDMQUPDCV-UHFFFAOYSA-N 0.000 description 1
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
- 229960000571 acetazolamide Drugs 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- RBYGDVHOECIAFC-UHFFFAOYSA-L acetonitrile;palladium(2+);dichloride Chemical compound [Cl-].[Cl-].[Pd+2].CC#N.CC#N RBYGDVHOECIAFC-UHFFFAOYSA-L 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 206010069351 acute lung injury Diseases 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002465 adenosine A2a receptor agonist Substances 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- YHGJHDJZIOYZIR-UHFFFAOYSA-N all-trans-lutein dipalmitate Natural products CC1(C)CC(OC(=O)CCCCCCCCCCCCCCC)CC(C)=C1C=CC(C)=CC=CC(C)=CC=CC=C(C)C=CC=C(C)C=CC1C(C)(C)CC(OC(=O)CCCCCCCCCCCCCCC)C=C1C YHGJHDJZIOYZIR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- WLDHEUZGFKACJH-UHFFFAOYSA-K amaranth Chemical compound [Na+].[Na+].[Na+].C12=CC=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(O)=C1N=NC1=CC=C(S([O-])(=O)=O)C2=CC=CC=C12 WLDHEUZGFKACJH-UHFFFAOYSA-K 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 229940030225 antihemorrhagics Drugs 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 229940120638 avastin Drugs 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 description 1
- 229960004347 betaxolol hydrochloride Drugs 0.000 description 1
- PUNFICOCZAPAJV-UHFFFAOYSA-N bicyclo[2.2.2]octane-4-carboxylic acid Chemical compound C1CC2CCC1(C(=O)O)CC2 PUNFICOCZAPAJV-UHFFFAOYSA-N 0.000 description 1
- AQOKCDNYWBIDND-FTOWTWDKSA-N bimatoprost Chemical compound CCNC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)CCC1=CC=CC=C1 AQOKCDNYWBIDND-FTOWTWDKSA-N 0.000 description 1
- 229960002470 bimatoprost Drugs 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
- 238000000071 blow moulding Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 201000005845 branch retinal artery occlusion Diseases 0.000 description 1
- 229960003679 brimonidine Drugs 0.000 description 1
- HCRKCZRJWPKOAR-JTQLQIEISA-N brinzolamide Chemical compound CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 HCRKCZRJWPKOAR-JTQLQIEISA-N 0.000 description 1
- 229960000722 brinzolamide Drugs 0.000 description 1
- 229950000025 brolucizumab Drugs 0.000 description 1
- 229960002716 bromfenac sodium Drugs 0.000 description 1
- HZFGMQJYAFHESD-UHFFFAOYSA-M bromfenac sodium Chemical compound [Na+].NC1=C(CC([O-])=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1 HZFGMQJYAFHESD-UHFFFAOYSA-M 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 210000001775 bruch membrane Anatomy 0.000 description 1
- 229960002467 bunazosin Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 208000001969 capillary hemangioma Diseases 0.000 description 1
- 229960004353 carbazochrome sodium sulfonate Drugs 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000004903 cardiac system Anatomy 0.000 description 1
- 210000004004 carotid artery internal Anatomy 0.000 description 1
- 208000006170 carotid stenosis Diseases 0.000 description 1
- LWAFSWPYPHEXKX-UHFFFAOYSA-N carteolol Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(O)CNC(C)(C)C LWAFSWPYPHEXKX-UHFFFAOYSA-N 0.000 description 1
- 229960001222 carteolol Drugs 0.000 description 1
- FYBXRCFPOTXTJF-UHFFFAOYSA-N carteolol hydrochloride Chemical compound [Cl-].N1C(=O)CCC2=C1C=CC=C2OCC(O)C[NH2+]C(C)(C)C FYBXRCFPOTXTJF-UHFFFAOYSA-N 0.000 description 1
- 229960002165 carteolol hydrochloride Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 201000005849 central retinal artery occlusion Diseases 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- OIQPTROHQCGFEF-UHFFFAOYSA-L chembl1371409 Chemical compound [Na+].[Na+].OC1=CC=C2C=C(S([O-])(=O)=O)C=CC2=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 OIQPTROHQCGFEF-UHFFFAOYSA-L 0.000 description 1
- BIXFMOUJSRCOMS-UHFFFAOYSA-M chloro(methyl)alumane Chemical compound C[AlH]Cl BIXFMOUJSRCOMS-UHFFFAOYSA-M 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- USJRLGNYCQWLPF-UHFFFAOYSA-N chlorophosphane Chemical compound ClP USJRLGNYCQWLPF-UHFFFAOYSA-N 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- RRGUKTPIGVIEKM-UHFFFAOYSA-N cilostazol Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCCC1=NN=NN1C1CCCCC1 RRGUKTPIGVIEKM-UHFFFAOYSA-N 0.000 description 1
- 229960004588 cilostazol Drugs 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- RFKZUAOAYVHBOY-UHFFFAOYSA-M copper(1+);acetate Chemical compound [Cu+].CC([O-])=O RFKZUAOAYVHBOY-UHFFFAOYSA-M 0.000 description 1
- YNYHGRUPNQLZHB-UHFFFAOYSA-M copper(1+);trifluoromethanesulfonate Chemical compound [Cu+].[O-]S(=O)(=O)C(F)(F)F YNYHGRUPNQLZHB-UHFFFAOYSA-M 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000004300 dark adaptation Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 201000011190 diabetic macular edema Diseases 0.000 description 1
- 238000013118 diabetic mouse model Methods 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- DXPIZCZNFUTPEI-UHFFFAOYSA-O diphenylphosphanium;azide Chemical compound [N-]=[N+]=[N-].C=1C=CC=CC=1[PH2+]C1=CC=CC=C1 DXPIZCZNFUTPEI-UHFFFAOYSA-O 0.000 description 1
- OCUJLLGVOUDECM-UHFFFAOYSA-N dipivefrin Chemical compound CNCC(O)C1=CC=C(OC(=O)C(C)(C)C)C(OC(=O)C(C)(C)C)=C1 OCUJLLGVOUDECM-UHFFFAOYSA-N 0.000 description 1
- 229960000966 dipivefrine Drugs 0.000 description 1
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical compound [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- RAGZEDHHTPQLAI-UHFFFAOYSA-L disodium;2',4',5',7'-tetraiodo-3-oxospiro[2-benzofuran-1,9'-xanthene]-3',6'-diolate Chemical compound [Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(I)=C([O-])C(I)=C1OC1=C(I)C([O-])=C(I)C=C21 RAGZEDHHTPQLAI-UHFFFAOYSA-L 0.000 description 1
- 229960001446 distigmine Drugs 0.000 description 1
- GJHSNEVFXQVOHR-UHFFFAOYSA-L distigmine bromide Chemical compound [Br-].[Br-].C=1C=C[N+](C)=CC=1OC(=O)N(C)CCCCCCN(C)C(=O)OC1=CC=C[N+](C)=C1 GJHSNEVFXQVOHR-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- OSRUSFPMRGDLAG-QMGYSKNISA-N dorzolamide hydrochloride Chemical compound [Cl-].CC[NH2+][C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 OSRUSFPMRGDLAG-QMGYSKNISA-N 0.000 description 1
- 229960002506 dorzolamide hydrochloride Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000002621 endocannabinoid Substances 0.000 description 1
- 230000008497 endothelial barrier function Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007159 enucleation Effects 0.000 description 1
- 230000004890 epithelial barrier function Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 208000024519 eye neoplasm Diseases 0.000 description 1
- 229940051306 eylea Drugs 0.000 description 1
- NGOGFTYYXHNFQH-UHFFFAOYSA-N fasudil Chemical compound C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N1CCCNCC1 NGOGFTYYXHNFQH-UHFFFAOYSA-N 0.000 description 1
- 229960002435 fasudil Drugs 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 229940043075 fluocinolone Drugs 0.000 description 1
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 1
- 238000002875 fluorescence polarization Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000000576 food coloring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N gamma-methylpyridine Natural products CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 1
- 210000000609 ganglia Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- BMXFPSYOCKSSBE-UHFFFAOYSA-N guanidine Chemical compound NC(N)=N.NC(N)=N BMXFPSYOCKSSBE-UHFFFAOYSA-N 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000004995 haloalkylthio group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 239000002874 hemostatic agent Substances 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 102000052948 human TRPV4 Human genes 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 239000004095 hydrolyase inhibitor Substances 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 230000000544 hyperemic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 208000010746 intraretinal hemorrhage Diseases 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection 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
- 229910052740 iodine Inorganic materials 0.000 description 1
- 208000023589 ischemic disease Diseases 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- XXUPXHKCPIKWLR-JHUOEJJVSA-N isopropyl unoprostone Chemical compound CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(=O)OC(C)C XXUPXHKCPIKWLR-JHUOEJJVSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 229960003709 kallidinogenase Drugs 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000001307 laser spectroscopy Methods 0.000 description 1
- GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 description 1
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 description 1
- 229960000831 levobunolol Drugs 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 1
- 229950007692 lomerizine Drugs 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 201000002978 low tension glaucoma Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229940076783 lucentis Drugs 0.000 description 1
- 229940092110 macugen Drugs 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000013227 male C57BL/6J mice Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960005321 mecobalamin Drugs 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 210000002752 melanocyte Anatomy 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 description 1
- 235000007672 methylcobalamin Nutrition 0.000 description 1
- 239000011585 methylcobalamin Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N monoethyl amine Natural products CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000000327 mueller cell Anatomy 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000004379 myopia Effects 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000005054 naphthyridines Chemical class 0.000 description 1
- 229960001002 nepafenac Drugs 0.000 description 1
- QEFAQIPZVLVERP-UHFFFAOYSA-N nepafenac Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N QEFAQIPZVLVERP-UHFFFAOYSA-N 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 229950000754 nipradilol Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 230000004493 normal intraocular pressure Effects 0.000 description 1
- 201000008106 ocular cancer Diseases 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 208000001749 optic atrophy Diseases 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000005968 oxazolinyl group Chemical group 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000001734 parasympathetic effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 1
- 229960000639 pazopanib Drugs 0.000 description 1
- 229960003407 pegaptanib Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000003668 pericyte Anatomy 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 1
- DGOSGFYDFDYMCW-MWRBZVGOSA-N phorbol dicaprate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)CCCCCCCCC)C1(C)C DGOSGFYDFDYMCW-MWRBZVGOSA-N 0.000 description 1
- 239000002644 phorbol ester Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 108091008695 photoreceptors Proteins 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 229960002139 pilocarpine hydrochloride Drugs 0.000 description 1
- RNAICSBVACLLGM-GNAZCLTHSA-N pilocarpine hydrochloride Chemical compound Cl.C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C RNAICSBVACLLGM-GNAZCLTHSA-N 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229940099429 polyoxyl 40 stearate Drugs 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 229960003101 pranoprofen Drugs 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- VIQCWEGEHRBLAC-UHFFFAOYSA-N propan-2-yl 2-[[6-[[(4-pyrazol-1-ylphenyl)methyl-pyridin-3-ylsulfonylamino]methyl]pyridin-2-yl]amino]acetate Chemical group CC(C)OC(=O)CNC1=CC=CC(CN(CC=2C=CC(=CC=2)N2N=CC=C2)S(=O)(=O)C=2C=NC=CC=2)=N1 VIQCWEGEHRBLAC-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 150000003169 prostaglandin F2α derivatives Chemical class 0.000 description 1
- 229940127293 prostanoid Drugs 0.000 description 1
- 150000003814 prostanoids Chemical class 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- LPPOVVJDAVMOET-UHFFFAOYSA-N pyrrolidine-1-sulfonamide Chemical class NS(=O)(=O)N1CCCC1 LPPOVVJDAVMOET-UHFFFAOYSA-N 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 210000001116 retinal neuron Anatomy 0.000 description 1
- 230000004250 retinal swelling Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- AZJPTIGZZTZIDR-UHFFFAOYSA-L rose bengal Chemical compound [K+].[K+].[O-]C(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C([O-])=C(I)C=C21 AZJPTIGZZTZIDR-UHFFFAOYSA-L 0.000 description 1
- 229940081623 rose bengal Drugs 0.000 description 1
- 229930187593 rose bengal Natural products 0.000 description 1
- STRXNPAVPKGJQR-UHFFFAOYSA-N rose bengal A Natural products O1C(=O)C(C(=CC=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 STRXNPAVPKGJQR-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 238000010187 selection method Methods 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
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 235000019259 sodium dehydroacetate Nutrition 0.000 description 1
- 229940079839 sodium dehydroacetate Drugs 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 1
- HLFCZZKCHVSOAP-WXIWBVQFSA-M sodium;(5e)-5-(carbamoylhydrazinylidene)-1-methyl-6-oxo-2,3-dihydroindole-2-sulfonate Chemical compound [Na+].NC(=O)N\N=C/1C(=O)C=C2N(C)C(S([O-])(=O)=O)CC2=C\1 HLFCZZKCHVSOAP-WXIWBVQFSA-M 0.000 description 1
- AYGJDUHQRFKLBG-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;dihydrate Chemical compound O.O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 AYGJDUHQRFKLBG-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 210000004500 stellate cell Anatomy 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 229960004458 tafluprost Drugs 0.000 description 1
- WSNODXPBBALQOF-VEJSHDCNSA-N tafluprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\C(F)(F)COC1=CC=CC=C1 WSNODXPBBALQOF-VEJSHDCNSA-N 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
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical compound C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 1
- 229940125670 thienopyridine Drugs 0.000 description 1
- 239000002175 thienopyridine Substances 0.000 description 1
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 229960005221 timolol maleate Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- MKPLKVHSHYCHOC-AHTXBMBWSA-N travoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(C(F)(F)F)=C1 MKPLKVHSHYCHOC-AHTXBMBWSA-N 0.000 description 1
- 229960002368 travoprost Drugs 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 150000003852 triazoles Chemical group 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 1
- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
- 238000013042 tunel staining Methods 0.000 description 1
- 229950008081 unoprostone isopropyl Drugs 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 230000004218 vascular function Effects 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 208000000318 vitreous detachment Diseases 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/423—Oxazoles condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—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
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/30—Animals modified by surgical methods
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/10—Screening for compounds of potential therapeutic value involving cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/16—Ophthalmology
- G01N2800/164—Retinal disorders, e.g. retinopathy
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Ophthalmology & Optometry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063052572P | 2020-07-16 | 2020-07-16 | |
| US63/052,572 | 2020-07-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202216143A true TW202216143A (zh) | 2022-05-01 |
Family
ID=79555653
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW110126328A TW202216143A (zh) | 2020-07-16 | 2021-07-16 | 作為眼疾病的治療藥之trpv4抑制藥 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20230255965A1 (https=) |
| EP (1) | EP4183415A4 (https=) |
| JP (1) | JPWO2022014707A1 (https=) |
| KR (1) | KR20230041680A (https=) |
| CN (1) | CN115776890A (https=) |
| BR (1) | BR112022024553A2 (https=) |
| CA (1) | CA3189206A1 (https=) |
| MX (1) | MX2023000610A (https=) |
| TW (1) | TW202216143A (https=) |
| WO (1) | WO2022014707A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN120641413A (zh) * | 2023-04-18 | 2025-09-12 | 河北乌图药业有限公司 | 化合物及其在慢性乙型肝炎、肝纤维化、肝癌的治疗中的应用 |
| WO2024217446A1 (zh) * | 2023-04-18 | 2024-10-24 | 河北乌图药业有限公司 | 化合物及其在慢性乙型肝炎、肝纤维化、肝癌的治疗中的应用 |
| WO2024217439A1 (zh) * | 2023-04-18 | 2024-10-24 | 河北乌图药业有限公司 | 化合物及其在慢性乙型肝炎、肝纤维化、肝癌的治疗中的应用 |
| CN116726013A (zh) * | 2023-04-25 | 2023-09-12 | 中国科学院大学深圳医院(光明) | Gsk2193874在防治痛性糖尿病周围神经病变中的应用 |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5409125A (en) | 1989-12-11 | 1995-04-25 | Aktiebolaget Astra | Unit dose container |
| DE4027320C2 (de) | 1990-08-29 | 1993-09-30 | Ursapharm Arzneimittel Gmbh | Fluid-Abgabeeinrichtung für keimfreies Fluid |
| EP0944530A1 (en) | 1996-12-09 | 1999-09-29 | Bausch & Lomb Incorporated | Single-use flexible container |
| US7087411B2 (en) | 1999-06-08 | 2006-08-08 | Regeneron Pharmaceuticals, Inc. | Fusion protein capable of binding VEGF |
| TW586946B (en) | 2000-12-22 | 2004-05-11 | Novartis Ag | Process to improve stability |
| US20080139648A1 (en) | 2004-12-09 | 2008-06-12 | Santen Pharmaceutical Co., Ltd. | Product Containing Prostaglandin Having Fluorine Atom In Its Molecule |
| WO2007082262A2 (en) | 2006-01-11 | 2007-07-19 | Smithkline Beecham Corporation | Novel compounds |
| JP2009527495A (ja) | 2006-02-17 | 2009-07-30 | スミスクライン・ビーチャム・コーポレイション | 新規化合物 |
| JP5294601B2 (ja) | 2007-09-28 | 2013-09-18 | 小林製薬株式会社 | Trpv4受容体抑制剤 |
| WO2009111680A1 (en) | 2008-03-07 | 2009-09-11 | Smithline Beecham Corporation | Trpv4 antagonists |
| WO2009146182A1 (en) | 2008-04-18 | 2009-12-03 | Smithkline Beecham Corporation | Trpv4 antagonists |
| WO2009146177A1 (en) | 2008-04-18 | 2009-12-03 | Smithkline Beecham Corporation | Trpv4 antagonists |
| WO2009139239A1 (ja) * | 2008-05-14 | 2009-11-19 | 日本電気株式会社 | 窒化物半導体レーザ及びその製造方法 |
| WO2010011912A1 (en) | 2008-07-25 | 2010-01-28 | Smithkline Beecham Corporation | Trpv4 antagonists |
| JP5607046B2 (ja) | 2008-07-25 | 2014-10-15 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | Trpv4拮抗薬 |
| WO2011091407A1 (en) | 2010-01-25 | 2011-07-28 | Glaxosmithkline Llp | Trpv4 antagonists |
| WO2011091410A1 (en) | 2010-01-25 | 2011-07-28 | Glaxos Smithkline Llc | Trpv4 antagonists |
| WO2011119694A1 (en) | 2010-03-23 | 2011-09-29 | Glaxosmithkline Llc | Trpv4 antagonists |
| WO2011119693A1 (en) | 2010-03-23 | 2011-09-29 | Glaxosmithkline Llc | Trpv4 antagonists |
| WO2011119704A1 (en) * | 2010-03-23 | 2011-09-29 | Glaxosmithkline Llc | Trpv4 antagonists |
| WO2011119701A1 (en) | 2010-03-23 | 2011-09-29 | Glaxosmithkline Llc | Trpv4 antagonists |
| WO2012144661A1 (en) | 2011-04-20 | 2012-10-26 | Shionogi & Co., Ltd. | Aromatic heterocyclic derivative having trpv4-inhibiting activity |
| JO3154B1 (ar) | 2011-06-17 | 2017-09-20 | Glaxosmithkline Llc | عوامل مضادة لـ trpv4 |
| EP2720546B1 (en) | 2011-06-17 | 2016-04-06 | Glaxosmithkline Intellectual Property (No. 2) Limited | Spiro-cyclic trpv4 antagonists |
| US8927585B2 (en) | 2011-06-17 | 2015-01-06 | Glaxosmithkline Intellectual Property (No.2) Limited | TRPV4 antagonists |
| WO2013146754A1 (ja) | 2012-03-27 | 2013-10-03 | 塩野義製薬株式会社 | Trpv4阻害活性を有する芳香族複素5員環誘導体 |
| CA2875842A1 (en) * | 2012-05-11 | 2013-11-14 | The University Of Utah Research Foundation | Compounds with trpv4 activity, compositions and associated methods thereof |
| WO2015046193A1 (ja) | 2013-09-25 | 2015-04-02 | 塩野義製薬株式会社 | Trpv4阻害活性を有する芳香族複素環式アミン誘導体 |
| WO2015199206A1 (ja) | 2014-06-27 | 2015-12-30 | 塩野義製薬株式会社 | Trpv4阻害活性を有する6員環誘導体 |
| CN109153672B (zh) | 2016-05-19 | 2021-12-07 | 葛兰素史密斯克莱知识产权(第2 号)有限公司 | Trpv4拮抗剂 |
| RU2019110821A (ru) | 2016-09-20 | 2020-10-22 | Глэксосмитклайн Интеллекчуал Проперти (Но.2) Лимитед | Антагонисты trpv4 |
| TW201825458A (zh) | 2016-09-20 | 2018-07-16 | 英商葛蘭素史克智慧財產(第二)有限公司 | Trpv4拮抗劑 |
| JP2019532054A (ja) | 2016-09-20 | 2019-11-07 | グラクソスミスクライン、インテレクチュアル、プロパティー、(ナンバー2)、リミテッドGlaxosmithkline Intellectual Property (No.2) Limited | Trpv4拮抗薬 |
| MX2017011166A (es) | 2017-08-31 | 2019-03-07 | Univ Mexico Nac Autonoma | Uso de los farmacos antagonistas del canal ionico transient receptor potential vaniloid 4 (trpv4) para el tratamiento del edema macular. |
| JP7195067B2 (ja) | 2018-06-20 | 2022-12-23 | 花王株式会社 | ロズマリン酸誘導体又はその塩 |
| WO2021170811A1 (en) * | 2020-02-27 | 2021-09-02 | Glaxosmithkline Intellectual Property (No.2) Limited | Method of treating eye disease using trpv4 antagonists |
| JP7692219B2 (ja) * | 2020-04-30 | 2025-06-13 | ラクオリア創薬株式会社 | Trpv4拮抗薬としてのピリミジン-4(3h)-オン誘導体 |
-
2021
- 2021-07-16 JP JP2022536464A patent/JPWO2022014707A1/ja active Pending
- 2021-07-16 TW TW110126328A patent/TW202216143A/zh unknown
- 2021-07-16 KR KR1020237000435A patent/KR20230041680A/ko active Pending
- 2021-07-16 CA CA3189206A patent/CA3189206A1/en active Pending
- 2021-07-16 BR BR112022024553A patent/BR112022024553A2/pt unknown
- 2021-07-16 MX MX2023000610A patent/MX2023000610A/es unknown
- 2021-07-16 WO PCT/JP2021/026829 patent/WO2022014707A1/ja not_active Ceased
- 2021-07-16 EP EP21842049.5A patent/EP4183415A4/en active Pending
- 2021-07-16 CN CN202180045312.2A patent/CN115776890A/zh active Pending
- 2021-07-16 US US18/014,367 patent/US20230255965A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| BR112022024553A2 (pt) | 2023-01-24 |
| WO2022014707A1 (ja) | 2022-01-20 |
| US20230255965A1 (en) | 2023-08-17 |
| JPWO2022014707A1 (https=) | 2022-01-20 |
| EP4183415A4 (en) | 2024-07-17 |
| MX2023000610A (es) | 2023-02-13 |
| KR20230041680A (ko) | 2023-03-24 |
| EP4183415A1 (en) | 2023-05-24 |
| CN115776890A (zh) | 2023-03-10 |
| CA3189206A1 (en) | 2022-01-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7730759B2 (ja) | Nlrp活性に関連する病態を治療するための化合物及び組成物 | |
| TW202216143A (zh) | 作為眼疾病的治療藥之trpv4抑制藥 | |
| CN113214287B (zh) | Hpk1抑制剂及其使用方法 | |
| CN116554168B (zh) | Cxcr4抑制剂及其用途 | |
| TWI818967B (zh) | 新穎雜環化合物 | |
| KR20220034739A (ko) | Tead 억제제 및 이의 용도 | |
| TWI884914B (zh) | 喋啶酮化合物及其用途 | |
| TW202142538A (zh) | 雜環glp-1促效劑 | |
| TW202220973A (zh) | 雜環glp-1促效劑 | |
| JP2023524493A (ja) | ヘテロ環glp-1アゴニスト | |
| CN103271906A (zh) | 螺-吲哚酮化合物作为治疗剂的用途 | |
| CN110177551B (zh) | 脂质合成的杂环调节剂 | |
| CN103429582A (zh) | Mst1激酶抑制剂及其用法 | |
| BR112016010041A2 (pt) | composto, medicamento, e, uso do composto ou sal | |
| KR20180094938A (ko) | 오피오이드 수용체 리간드와 시토크롬 p450 억제제의 결합 | |
| CN113316566A (zh) | 用于治疗与nlrp活性相关的病症的化合物和组合物 | |
| EP3914585A1 (en) | Sulfonimidamide compounds and compositions for treating conditions associated with nlrp activity | |
| US9549921B2 (en) | Heterocyclic compounds and methods of use thereof for the treatment of hepatitis C | |
| TW202525792A (zh) | 經取代之側氧異吲哚啉基哌啶-2,6-二酮化合物 | |
| CN114685453A (zh) | 杂环脯氨酰胺衍生物 | |
| HK40085364A (en) | Trpv4 inhibitor as therapeutic drug for eye disease | |
| TW201410649A (zh) | 吲哚衍生物及該吲哚衍生物在藥理學上可容許之鹽 | |
| HK40092802A (en) | Trpv4 inhibitor as therapeutic drug for eye disease | |
| WO2006132192A1 (ja) | 新規2-キノロン誘導体 | |
| HK40085148B (zh) | 杂环glp-1激动剂 |