ES2829550T3 - Ureas cíclicas espiro-condensadas como inhibidores de ROCK - Google Patents

Info

Publication number

ES2829550T3

ES2829550T3 ES17739834T ES17739834T ES2829550T3 ES 2829550 T3 ES2829550 T3 ES 2829550T3 ES 17739834 T ES17739834 T ES 17739834T ES 17739834 T ES17739834 T ES 17739834T ES 2829550 T3 ES2829550 T3 ES 2829550T3

Authority

ES

Spain

Prior art keywords

pyrazol

substituted

decan

triazaspiro

independently selected

Prior art date

2016-07-07

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Active

Links

• Espacenet
• Global Dossier
• Discuss

• -1 cyclic ureas Chemical class 0.000 title claims abstract description 192
• 239000011435 rock Substances 0.000 title description 35
• 239000003112 inhibitor Substances 0.000 title description 11
• 235000013877 carbamide Nutrition 0.000 title description 9
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 153
• 150000001875 compounds Chemical class 0.000 claims abstract description 145
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 125
• 229910052801 chlorine Inorganic materials 0.000 claims abstract description 113
• 229910052731 fluorine Inorganic materials 0.000 claims abstract description 113
• 229910052794 bromium Inorganic materials 0.000 claims abstract description 99
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 99
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 84
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 79
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 74
• 229910021481 rutherfordium Inorganic materials 0.000 claims abstract description 71
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 56
• 150000003839 salts Chemical class 0.000 claims abstract description 54
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 46
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 43
• 101150105130 RORB gene Proteins 0.000 claims abstract description 39
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 39
• 125000003118 aryl group Chemical group 0.000 claims abstract description 30
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 28
• 125000004452 carbocyclyl group Chemical group 0.000 claims abstract description 28
• 229910052702 rhenium Inorganic materials 0.000 claims abstract description 27
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 23
• 229910052701 rubidium Inorganic materials 0.000 claims abstract description 23
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 20
• 125000006706 (C3-C6) carbocyclyl group Chemical group 0.000 claims abstract description 12
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 9
• 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims abstract description 6
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract description 5
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims abstract description 4
• 229910052700 potassium Inorganic materials 0.000 claims abstract description 3
• 238000011282 treatment Methods 0.000 claims description 28
• 125000004432 carbon atom Chemical group C* 0.000 claims description 24
• 229910052799 carbon Inorganic materials 0.000 claims description 23
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
• 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 18
• 125000005842 heteroatom Chemical group 0.000 claims description 17
• 230000000694 effects Effects 0.000 claims description 15
• 239000008194 pharmaceutical composition Substances 0.000 claims description 15
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 15
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 13
• 201000010099 disease Diseases 0.000 claims description 13
• 239000003937 drug carrier Substances 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 206010020772 Hypertension Diseases 0.000 claims description 10
• ZAJNGDIORYACQU-UHFFFAOYSA-N decan-2-one Chemical compound CCCCCCCCC(C)=O ZAJNGDIORYACQU-UHFFFAOYSA-N 0.000 claims description 10
• 238000011321 prophylaxis Methods 0.000 claims description 10
• 108010041788 rho-Associated Kinases Proteins 0.000 claims description 9
• 102000000568 rho-Associated Kinases Human genes 0.000 claims description 9
• 208000006011 Stroke Diseases 0.000 claims description 8
• JTQMDDLVQXVUKH-UHFFFAOYSA-N 3-(4-bromophenyl)-1-[(3-methoxyphenyl)methyl]-8-methyl-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(C)CC2)C2=CC=C(Br)C=C2)=C1 JTQMDDLVQXVUKH-UHFFFAOYSA-N 0.000 claims description 7
• 208000035475 disorder Diseases 0.000 claims description 7
• XHBZKKFNCZNQFW-UHFFFAOYSA-N tert-butyl 2-ethylnonanoate Chemical compound CCCCCCCC(CC)C(=O)OC(C)(C)C XHBZKKFNCZNQFW-UHFFFAOYSA-N 0.000 claims description 7
• VRZQEUPIPNZMNU-UHFFFAOYSA-N 3-(4-bromophenyl)-8-(2-hydroxy-2-methylpropyl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CC(C)(C)O)CC2)C2=CC=C(Br)C=C2)=C1 VRZQEUPIPNZMNU-UHFFFAOYSA-N 0.000 claims description 6
• UNGQCMHGZQXWBJ-UHFFFAOYSA-N 8-acetyl-3-(4-bromophenyl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CC2)C(C)=O)C2=CC=C(Br)C=C2)=C1 UNGQCMHGZQXWBJ-UHFFFAOYSA-N 0.000 claims description 6
• 125000000304 alkynyl group Chemical group 0.000 claims description 6
• UKCXKXHOZRWSMB-UHFFFAOYSA-N 3-(4-bromophenyl)-1-[(3-methoxyphenyl)methyl]-8-methylsulfonyl-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CC2)S(C)(=O)=O)C2=CC=C(Br)C=C2)=C1 UKCXKXHOZRWSMB-UHFFFAOYSA-N 0.000 claims description 5
• 206010019280 Heart failures Diseases 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• OWQKCHBSZBHZTL-UHFFFAOYSA-N methyl 3-(4-bromophenyl)-1-[(3-methoxyphenyl)methyl]-2-oxo-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound COC(=O)N1CCC2(CN(C(=O)N2CC2=CC(OC)=CC=C2)C2=CC=C(Br)C=C2)CC1 OWQKCHBSZBHZTL-UHFFFAOYSA-N 0.000 claims description 5
• 210000002460 smooth muscle Anatomy 0.000 claims description 5
• OFWHRTPIAAYJQV-UHFFFAOYSA-N tert-butyl 6-(4-bromophenyl)-8-(3-methoxyanilino)-7-oxo-2,6-diazaspiro[3.4]octane-2-carboxylate Chemical compound BrC1=CC=C(C=C1)N1CC2(CN(C2)C(=O)OC(C)(C)C)C(C1=O)NC1=CC(=CC=C1)OC OFWHRTPIAAYJQV-UHFFFAOYSA-N 0.000 claims description 5
• BROSREAJJVLOIF-UHFFFAOYSA-N 4-[(3-methoxyphenyl)methyl]-6-[4-(1H-pyrazol-4-yl)phenyl]-4,6-diazaspiro[2.4]heptan-5-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(CC2)C1)CC1=CC(=CC=C1)OC)=O BROSREAJJVLOIF-UHFFFAOYSA-N 0.000 claims description 4
• 206010002383 Angina Pectoris Diseases 0.000 claims description 4
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• CNCGPNHRKQTYOH-UHFFFAOYSA-N N-methyl-3-[[2-oxo-3-[4-(1H-pyrazol-4-yl)phenyl]-8-oxa-1,3-diazaspiro[4.5]decan-1-yl]methyl]benzamide Chemical compound CNC(=O)C1=CC(CN2C(=O)N(CC22CCOCC2)C2=CC=C(C=C2)C2=CNN=C2)=CC=C1 CNCGPNHRKQTYOH-UHFFFAOYSA-N 0.000 claims description 4
• 229910001850 copernicium Inorganic materials 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 230000003176 fibrotic effect Effects 0.000 claims description 4
• WMRXZLMVHTVUNT-UHFFFAOYSA-N methyl 2-ethylnonanoate Chemical compound CCCCCCCC(CC)C(=O)OC WMRXZLMVHTVUNT-UHFFFAOYSA-N 0.000 claims description 4
• 208000002815 pulmonary hypertension Diseases 0.000 claims description 4
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
• XOPDCJXPZUSRAA-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCOCC2)C2=CC=C(C=C2)C2=CNN=C2)=C1 XOPDCJXPZUSRAA-UHFFFAOYSA-N 0.000 claims description 3
• WNJQJLMDIBUEEY-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-N-methyl-2-oxo-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decane-8-carboxamide Chemical compound CNC(=O)N1CCC2(CN(C(=O)N2CC2=CC(OC)=CC=C2)C2=CC=C(C=C2)C2=CNN=C2)CC1 WNJQJLMDIBUEEY-UHFFFAOYSA-N 0.000 claims description 3
• OOZRFCRBNSPYQA-UHFFFAOYSA-N 2-[1-[(3-methoxyphenyl)methyl]-2-oxo-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-8-yl]-N-methylacetamide Chemical compound O=C(NC)CN1CCC2(CN(C3=CC=C(C=4C=NNC=4)C=C3)C(=O)N2CC2=CC=CC(=C2)OC)CC1 OOZRFCRBNSPYQA-UHFFFAOYSA-N 0.000 claims description 3
• RCLOXRNEJNVIJQ-UHFFFAOYSA-N 4-[1-(3-methoxyphenyl)ethyl]-6-[4-(1H-pyrazol-4-yl)phenyl]-4,6-diazaspiro[2.4]heptan-5-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(CC2)C1)C(C)C1=CC(=CC=C1)OC)=O RCLOXRNEJNVIJQ-UHFFFAOYSA-N 0.000 claims description 3
• 208000029078 coronary artery disease Diseases 0.000 claims description 3
• 208000027866 inflammatory disease Diseases 0.000 claims description 3
• WNIMBIZDEUDZOC-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-8-(oxetan-3-yl)-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CC2)C2COC2)C2=CC=C(C=C2)C2=CNN=C2)=C1 WNIMBIZDEUDZOC-UHFFFAOYSA-N 0.000 claims description 2
• KVRFCRXDZPUGDD-UHFFFAOYSA-N 4-(3-methoxyanilino)-2-[4-methoxy-5-(1H-pyrazol-4-yl)pyrimidin-2-yl]-8-(pyrazolo[1,5-a]pyridine-3-carbonyl)-2,8-diazaspiro[4.5]decan-3-one Chemical compound COC1=NC(=NC=C1C=1C=NNC=1)N1CC2(C(C1=O)NC1=CC(=CC=C1)OC)CCN(CC2)C(=O)C=1C=NN2C=1C=CC=C2 KVRFCRXDZPUGDD-UHFFFAOYSA-N 0.000 claims description 2
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 2
• MTZLWOMJPMXXGV-UHFFFAOYSA-N tert-butyl 1-[(3-methoxyphenyl)methyl]-2-oxo-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 MTZLWOMJPMXXGV-UHFFFAOYSA-N 0.000 claims description 2
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 8
• CFUXHLBWJKIHMV-UHFFFAOYSA-N 8-acetyl-1-[(3-methoxyphenyl)methyl]-3-(5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC=C(C=C4)C5CNNC5 CFUXHLBWJKIHMV-UHFFFAOYSA-N 0.000 claims 2
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
• VGXOPPWAECNIRG-UHFFFAOYSA-N 1-(cyclohexylmethyl)-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCNCC2)CC1CCCCC1)=O VGXOPPWAECNIRG-UHFFFAOYSA-N 0.000 claims 1
• HAQQVROBXWGKFI-UHFFFAOYSA-N 1-(oxan-4-ylmethyl)-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCNCC2)CC1CCOCC1)=O HAQQVROBXWGKFI-UHFFFAOYSA-N 0.000 claims 1
• QSXFJHJYWUHGOH-UHFFFAOYSA-N 1-[(2,3-difluorophenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCNCC2)CC1=C(C(=CC=C1)F)F)=O QSXFJHJYWUHGOH-UHFFFAOYSA-N 0.000 claims 1
• MMUZHHMVWYJSPK-UHFFFAOYSA-N 1-[(2,4-difluorophenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1COCCC12CN(C(=O)N2CC3=C(C=C(C=C3)F)F)C4=CC=C(C=C4)C5CNNC5 MMUZHHMVWYJSPK-UHFFFAOYSA-N 0.000 claims 1
• RQJKBLWPSHXKPD-UHFFFAOYSA-N 1-[(2,4-difluorophenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCNCC2)CC1=C(C=C(C=C1)F)F)=O RQJKBLWPSHXKPD-UHFFFAOYSA-N 0.000 claims 1
• UCJMSAJUANGOLI-UHFFFAOYSA-N 1-[(2,5-difluorophenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCNCC2)CC1=C(C=CC(=C1)F)F)=O UCJMSAJUANGOLI-UHFFFAOYSA-N 0.000 claims 1
• CAUKWAZOLCTIBG-UHFFFAOYSA-N 1-[(2,6-difluorophenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound FC1=CC=CC(F)=C1CN1C(=O)N(CC11CCOCC1)C1=CC=C(C=C1)C1=CNN=C1 CAUKWAZOLCTIBG-UHFFFAOYSA-N 0.000 claims 1
• GYOLGFKCWIYCTN-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1COCCC12CN(C(=O)N2CC3=CC=CC=C3F)C4=CC=C(C=C4)C5CNNC5 GYOLGFKCWIYCTN-UHFFFAOYSA-N 0.000 claims 1
• FZXWJVZSWFDKPK-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCNCC2)CC1=C(C=CC=C1)F)=O FZXWJVZSWFDKPK-UHFFFAOYSA-N 0.000 claims 1
• ZXENQYUNTGCTFF-UHFFFAOYSA-N 1-[(3,4-dichlorophenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1COCCC12CN(C(=O)N2CC3=CC(=C(C=C3)Cl)Cl)C4=CC=C(C=C4)C5CNNC5 ZXENQYUNTGCTFF-UHFFFAOYSA-N 0.000 claims 1
• CSTRVLBMFSFVHH-UHFFFAOYSA-N 1-[(3,4-difluorophenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1COCCC12CN(C(=O)N2CC3=CC(=C(C=C3)F)F)C4=CC=C(C=C4)C5CNNC5 CSTRVLBMFSFVHH-UHFFFAOYSA-N 0.000 claims 1
• RPWPXEOKQAZVQV-UHFFFAOYSA-N 1-[(3,5-difluorophenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1COCCC12CN(C(=O)N2CC3=CC(=CC(=C3)F)F)C4=CC=C(C=C4)C5CNNC5 RPWPXEOKQAZVQV-UHFFFAOYSA-N 0.000 claims 1
• SDOHYAUBJQTZJP-UHFFFAOYSA-N 1-[(3-fluoro-2-methylphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC=C1F)CN2C(=O)N(CC23CCOCC3)C4=CC=C(C=C4)C5CNNC5 SDOHYAUBJQTZJP-UHFFFAOYSA-N 0.000 claims 1
• YZDOFSSAMQEIHX-UHFFFAOYSA-N 1-[(3-fluoro-2-methylphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-8-(3-phenylbutanoyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC=C1F)CN2C(=O)N(CC23CCN(CC3)C(=O)CC(C)C4=CC=CC=C4)C5=NC(=C(C=C5)C6CNNC6)OC YZDOFSSAMQEIHX-UHFFFAOYSA-N 0.000 claims 1
• OUILEGKXBJPOQT-UHFFFAOYSA-N 1-[(3-fluoro-2-methylphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-8-[3-(2-oxopyrrolidin-1-yl)propanoyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC=C1F)CN2C(=O)N(CC23CCN(CC3)C(=O)CCN4CCCC4=O)C5=NC(=C(C=C5)C6CNNC6)OC OUILEGKXBJPOQT-UHFFFAOYSA-N 0.000 claims 1
• AOAXWMANQJZBLS-UHFFFAOYSA-N 1-[(3-fluoro-2-methylphenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCNCC2)CC1=C(C(=CC=C1)F)C)=O AOAXWMANQJZBLS-UHFFFAOYSA-N 0.000 claims 1
• QCLPWXBIXVIJIQ-UHFFFAOYSA-N 1-[(3-fluoro-2-methylphenyl)methyl]-8-(2-hydroxy-2-methylpropanoyl)-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC=C1F)CN2C(=O)N(CC23CCN(CC3)C(=O)C(C)(C)O)C4=NC(=C(C=C4)C5CNNC5)OC QCLPWXBIXVIJIQ-UHFFFAOYSA-N 0.000 claims 1
• CQMDVUYJQOSQII-UHFFFAOYSA-N 1-[(3-fluoro-2-methylphenyl)methyl]-8-(2-hydroxyacetyl)-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC=C1F)CN2C(=O)N(CC23CCN(CC3)C(=O)CO)C4=NC(=C(C=C4)C5CNNC5)OC CQMDVUYJQOSQII-UHFFFAOYSA-N 0.000 claims 1
• MRLHWLRQPXUJJR-UHFFFAOYSA-N 1-[(3-fluoro-2-methylphenyl)methyl]-8-(2-hydroxyethyl)-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCN(CC2)CCO)CC1=C(C(=CC=C1)F)C)=O MRLHWLRQPXUJJR-UHFFFAOYSA-N 0.000 claims 1
• ZNODHHGLTRAMQJ-UHFFFAOYSA-N 1-[(3-fluoro-2-methylphenyl)methyl]-8-(2-hydroxypropyl)-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC=C1F)CN2C(=O)N(CC23CCN(CC3)CC(C)O)C4=NC(=C(C=C4)C5CNNC5)OC ZNODHHGLTRAMQJ-UHFFFAOYSA-N 0.000 claims 1
• KQFOZPBHEPDTCK-UHFFFAOYSA-N 1-[(3-fluoro-2-methylphenyl)methyl]-8-(2-methoxyacetyl)-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC=C1F)CN2C(=O)N(CC23CCN(CC3)C(=O)COC)C4=NC(=C(C=C4)C5CNNC5)OC KQFOZPBHEPDTCK-UHFFFAOYSA-N 0.000 claims 1
• WBRQXXXNHSLFQP-UHFFFAOYSA-N 1-[(3-fluoro-2-methylphenyl)methyl]-8-(2-methoxyethyl)-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC=C1F)CN2C(=O)N(CC23CCN(CC3)CCOC)C4=NC(=C(C=C4)C5CNNC5)OC WBRQXXXNHSLFQP-UHFFFAOYSA-N 0.000 claims 1
• OFWCREWZNVSOQE-UHFFFAOYSA-N 1-[(3-fluoro-2-methylphenyl)methyl]-8-(3-hydroxy-2,2-dimethylpropanoyl)-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC=C1F)CN2C(=O)N(CC23CCN(CC3)C(=O)C(C)(C)CO)C4=NC(=C(C=C4)C5CNNC5)OC OFWCREWZNVSOQE-UHFFFAOYSA-N 0.000 claims 1
• YXJVSDPZGVHJBV-UHFFFAOYSA-N 1-[(3-fluoro-5-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC(=CC(=C1)CN2C(=O)N(CC23CCNCC3)C4=CC=C(C=C4)C5CNNC5)F YXJVSDPZGVHJBV-UHFFFAOYSA-N 0.000 claims 1
• GSDRRDTWQNOHPO-UHFFFAOYSA-N 1-[(3-fluoro-5-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound COC1=CC(=CC(=C1)CN2C(=O)N(CC23CCOCC3)C4=CC=C(C=C4)C5CNNC5)F GSDRRDTWQNOHPO-UHFFFAOYSA-N 0.000 claims 1
• JOQJCDJPODRYLQ-UHFFFAOYSA-N 1-[(3-fluoro-5-methoxyphenyl)methyl]-8-(2-hydroxy-2-methylpropanoyl)-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(C)(C(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC(=C3)F)OC)C4=CC=C(C=C4)C5CNNC5)O JOQJCDJPODRYLQ-UHFFFAOYSA-N 0.000 claims 1
• HSURVVJSSLDVGJ-UHFFFAOYSA-N 1-[(3-fluoro-5-methoxyphenyl)methyl]-8-(2-hydroxyethyl)-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC(=CC(=C1)CN2C(=O)N(CC23CCN(CC3)CCO)C4=CC=C(C=C4)C5CNNC5)F HSURVVJSSLDVGJ-UHFFFAOYSA-N 0.000 claims 1
• ARKQSPMMAMDEKD-UHFFFAOYSA-N 1-[(3-fluoro-5-methoxyphenyl)methyl]-8-(2-hydroxypropyl)-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC(=C3)F)OC)C4=CC=C(C=C4)C5CNNC5)O ARKQSPMMAMDEKD-UHFFFAOYSA-N 0.000 claims 1
• VPYJUHSGXRVLTL-UHFFFAOYSA-N 1-[(3-fluoro-5-methoxyphenyl)methyl]-8-(oxetan-3-yl)-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC(=CC(=C1)CN2C(=O)N(CC23CCN(CC3)C4COC4)C5=CC=C(C=C5)C6CNNC6)F VPYJUHSGXRVLTL-UHFFFAOYSA-N 0.000 claims 1
• FCIBCLCNCTWNGM-UHFFFAOYSA-N 1-[(3-fluorophenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1COCCC12CN(C(=O)N2CC3=CC(=CC=C3)F)C4=CC=C(C=C4)C5CNNC5 FCIBCLCNCTWNGM-UHFFFAOYSA-N 0.000 claims 1
• HODFQWBFOSEABZ-UHFFFAOYSA-N 1-[(3-fluorophenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCNCC2)CC1=CC(=CC=C1)F)=O HODFQWBFOSEABZ-UHFFFAOYSA-N 0.000 claims 1
• DWRGMVZPIJATTE-UHFFFAOYSA-N 1-[(3-hydroxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C1CNCCC12CN(C(=O)N2CC3=CC(=CC=C3)O)C4=CC=C(C=C4)C5CNNC5 DWRGMVZPIJATTE-UHFFFAOYSA-N 0.000 claims 1
• QOIVKJGHXLLUHV-UHFFFAOYSA-N 1-[(3-hydroxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1COCCC12CN(C(=O)N2CC3=CC(=CC=C3)O)C4=CC=C(C=C4)C5CNNC5 QOIVKJGHXLLUHV-UHFFFAOYSA-N 0.000 claims 1
• USFDVOAMKBFRMF-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-2-oxo-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decane-8-carboxamide Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)C(=O)N)C4=CC=C(C=C4)C5CNNC5 USFDVOAMKBFRMF-UHFFFAOYSA-N 0.000 claims 1
• FHPBWZAPMDRPAA-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-3-(4-methoxy-5-pyrazolidin-4-ylpyrimidin-2-yl)-8-(3,3,3-trifluoropropyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)CCC(F)(F)F)C4=NC=C(C(=N4)OC)C5CNNC5 FHPBWZAPMDRPAA-UHFFFAOYSA-N 0.000 claims 1
• MQQFHIAKFYSZKO-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-3-(4-methoxy-5-pyrazolidin-4-ylpyrimidin-2-yl)-8-(3-methylbutanoyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(C)CC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC=C(C(=N4)OC)C5CNNC5 MQQFHIAKFYSZKO-UHFFFAOYSA-N 0.000 claims 1
• YUTKHERVPTXECV-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-(pyrazolo[1,5-a]pyridine-3-carbonyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)C(=O)C4=C5C=CC=CN5N=C4)C6=CC=C(C=C6)C7CNNC7 YUTKHERVPTXECV-UHFFFAOYSA-N 0.000 claims 1
• LFZVXLHQCPAXNB-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-3-(5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCNCC3)C4=NC=C(C=C4)C5CNNC5 LFZVXLHQCPAXNB-UHFFFAOYSA-N 0.000 claims 1
• FHVDRXSNFSOUFP-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-3-(5-pyrazolidin-4-ylpyridin-2-yl)-8-(3,3,3-trifluoropropyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)CCC(F)(F)F)C4=NC=C(C=C4)C5CNNC5 FHVDRXSNFSOUFP-UHFFFAOYSA-N 0.000 claims 1
• SKTKJPKFFFSWSB-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-8-(oxetan-3-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)C4COC4)C5=NC(=C(C=C5)C6CNNC6)OC SKTKJPKFFFSWSB-UHFFFAOYSA-N 0.000 claims 1
• APQTXCPFCZYGDR-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-8-(oxetane-3-carbonyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)C(=O)C4COC4)C5=NC(=C(C=C5)C6CNNC6)OC APQTXCPFCZYGDR-UHFFFAOYSA-N 0.000 claims 1
• RMJBBOWIWYPNCJ-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-3-[6-methyl-5-(1H-pyrazol-4-yl)pyridin-2-yl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC=1C=C(CN2C(N(CC22CCNCC2)C2=NC(=C(C=C2)C=2C=NNC=2)C)=O)C=CC=1 RMJBBOWIWYPNCJ-UHFFFAOYSA-N 0.000 claims 1
• FRYDLZYDQJNVSM-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-8-(2-methylpropyl)-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(C)CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 FRYDLZYDQJNVSM-UHFFFAOYSA-N 0.000 claims 1
• LXOYGGCNPKLFDT-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-8-(2-phenylethyl)-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)CCC4=CC=CC=C4)C5=CC=C(C=C5)C6CNNC6 LXOYGGCNPKLFDT-UHFFFAOYSA-N 0.000 claims 1
• IKFDDSUFRADXQR-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-8-(3-methylbutyl)-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(C)CCN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 IKFDDSUFRADXQR-UHFFFAOYSA-N 0.000 claims 1
• KLROLIVQJLATTG-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-8-(oxan-4-ylmethyl)-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCN(CC2)CC1CCOCC1)CC1=CC(=CC=C1)OC)=O KLROLIVQJLATTG-UHFFFAOYSA-N 0.000 claims 1
• HTBYAJUVCCSMPG-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-8-(oxane-4-carbonyl)-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)C(=O)C4CCOCC4)C5=CC=C(C=C5)C6CNNC6 HTBYAJUVCCSMPG-UHFFFAOYSA-N 0.000 claims 1
• CNQIQYAXDZEXIA-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-8-(oxetan-3-yl)-3-(5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)C4COC4)C5=NC=C(C=C5)C6CNNC6 CNQIQYAXDZEXIA-UHFFFAOYSA-N 0.000 claims 1
• MHAZUOSDOXXQRA-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-8-(oxetane-3-carbonyl)-3-(5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)C(=O)C4COC4)C5=NC=C(C=C5)C6CNNC6 MHAZUOSDOXXQRA-UHFFFAOYSA-N 0.000 claims 1
• XIZRFXPRFVSPOX-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-8-propyl-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCCN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 XIZRFXPRFVSPOX-UHFFFAOYSA-N 0.000 claims 1
• WILDKSMPGSOPLO-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-N,N-dimethyl-2-oxo-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decane-8-carboxamide Chemical compound CN(C)C(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 WILDKSMPGSOPLO-UHFFFAOYSA-N 0.000 claims 1
• KUXUXRWOPFZRFC-UHFFFAOYSA-N 1-[(4-fluoro-2-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound COC1=C(C=CC(=C1)F)CN2C(=O)N(CC23CCOCC3)C4=CC=C(C=C4)C5CNNC5 KUXUXRWOPFZRFC-UHFFFAOYSA-N 0.000 claims 1
• CXIGXVAGPFRKPP-UHFFFAOYSA-N 1-[(4-fluoro-2-methylphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC(=C1)F)CN2C(=O)N(CC23CCOCC3)C4=CC=C(C=C4)C5CNNC5 CXIGXVAGPFRKPP-UHFFFAOYSA-N 0.000 claims 1
• PIAORSBWFKEBRR-UHFFFAOYSA-N 1-[(4-fluoro-3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=C(C=CC(=C1)CN2C(=O)N(CC23CCNCC3)C4=CC=C(C=C4)C5CNNC5)F PIAORSBWFKEBRR-UHFFFAOYSA-N 0.000 claims 1
• JQLMAWMVEXHIDU-UHFFFAOYSA-N 1-[(5-fluoro-2-methylphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=C(C=C1)F)CN2C(=O)N(CC23CCOCC3)C4=CC=C(C=C4)C5CNNC5 JQLMAWMVEXHIDU-UHFFFAOYSA-N 0.000 claims 1
• DJYVLSDJVJJPJR-UHFFFAOYSA-N 1-[[2-fluoro-3-(trifluoromethoxy)phenyl]methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1COCCC12CN(C(=O)N2CC3=C(C(=CC=C3)OC(F)(F)F)F)C4=CC=C(C=C4)C5CNNC5 DJYVLSDJVJJPJR-UHFFFAOYSA-N 0.000 claims 1
• GHXCRQFAXBXOHY-UHFFFAOYSA-N 1-[[3-(cyclopropylmethoxy)phenyl]methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C1CC1COC2=CC=CC(=C2)CN3C(=O)N(CC34CCNCC4)C5=CC=C(C=C5)C6CNNC6 GHXCRQFAXBXOHY-UHFFFAOYSA-N 0.000 claims 1
• XDXGXINVVSCYCL-UHFFFAOYSA-N 1-[[3-(cyclopropylmethoxy)phenyl]methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1CC1COC2=CC=CC(=C2)CN3C(=O)N(CC34CCOCC4)C5=CC=C(C=C5)C6CNNC6 XDXGXINVVSCYCL-UHFFFAOYSA-N 0.000 claims 1
• TXWFYJNQGHVFIR-UHFFFAOYSA-N 1-[[3-(difluoromethoxy)phenyl]methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C1CNCCC12CN(C(=O)N2CC3=CC(=CC=C3)OC(F)F)C4=CC=C(C=C4)C5CNNC5 TXWFYJNQGHVFIR-UHFFFAOYSA-N 0.000 claims 1
• PXZJDZFAMRCBER-VWLOTQADSA-N 1-[[3-[(3S)-3-hydroxypyrrolidine-1-carbonyl]phenyl]methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1CN(C[C@H]1O)C(=O)C2=CC=CC(=C2)CN3C(=O)N(CC34CCOCC4)C5=CC=C(C=C5)C6CNNC6 PXZJDZFAMRCBER-VWLOTQADSA-N 0.000 claims 1
• NOWZSMAKLSIARZ-UHFFFAOYSA-N 1-[[3-[3-(dimethylamino)azetidine-1-carbonyl]phenyl]methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCOCC2)CC1=CC(=CC=C1)C(=O)N1CC(C1)N(C)C)=O NOWZSMAKLSIARZ-UHFFFAOYSA-N 0.000 claims 1
• YKUHCCTUVHZEFW-UHFFFAOYSA-N 1-[[3-[4-(hydroxymethyl)piperidine-1-carbonyl]phenyl]methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1CN(CCC1CO)C(=O)C2=CC=CC(=C2)CN3C(=O)N(CC34CCOCC4)C5=CC=C(C=C5)C6CNNC6 YKUHCCTUVHZEFW-UHFFFAOYSA-N 0.000 claims 1
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims 1
• PCMKFMSDONFORN-UHFFFAOYSA-N 2,2-dimethylpropyl 1-[(3-methoxyphenyl)methyl]-2-oxo-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound COC1=CC(CN2C(=O)N(CC22CCN(CC2)C(=O)OCC(C)(C)C)C2=CC=C(C=C2)C2=CNN=C2)=CC=C1 PCMKFMSDONFORN-UHFFFAOYSA-N 0.000 claims 1
• GSMXNJRZZZEKLL-UHFFFAOYSA-N 2-(2-hydroxy-2-methylpropanoyl)-8-(3-methoxyanilino)-6-[4-(1H-pyrazol-4-yl)phenyl]-2,6-diazaspiro[3.4]octan-7-one Chemical compound COC1=CC=CC(NC2C(=O)N(CC22CN(C2)C(=O)C(C)(C)O)C2=CC=C(C=C2)C2=CNN=C2)=C1 GSMXNJRZZZEKLL-UHFFFAOYSA-N 0.000 claims 1
• BHHHTLJSSYZUNZ-UHFFFAOYSA-N 2-[1-[(3-methoxyphenyl)methyl]-2-oxo-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-8-yl]acetamide Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)CC(=O)N)C4=CC=C(C=C4)C5CNNC5 BHHHTLJSSYZUNZ-UHFFFAOYSA-N 0.000 claims 1
• XOMHMDGPENYGDC-UHFFFAOYSA-N 2-[1-[(3-methoxyphenyl)methyl]-2-oxo-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-8-yl]-N,N-dimethylacetamide Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCN(CC2)CC(=O)N(C)C)CC1=CC(=CC=C1)OC)=O XOMHMDGPENYGDC-UHFFFAOYSA-N 0.000 claims 1
• YYXSMUFYRXSZBL-UHFFFAOYSA-N 2-acetyl-8-(3-methoxyanilino)-6-[4-(1H-pyrazol-4-yl)phenyl]-2,6-diazaspiro[3.4]octan-7-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1CC2(CN(C2)C(C)=O)C(C1=O)NC1=CC(=CC=C1)OC YYXSMUFYRXSZBL-UHFFFAOYSA-N 0.000 claims 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
• RYQKUYMPRPJMDP-UHFFFAOYSA-N 2-methoxyethyl 1-[(3-methoxyphenyl)methyl]-2-oxo-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound COCCOC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 RYQKUYMPRPJMDP-UHFFFAOYSA-N 0.000 claims 1
• YJVOHVQKJGTXBI-UHFFFAOYSA-N 2-methylpropyl 1-[(3-methoxyphenyl)methyl]-2-oxo-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound CC(C)COC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 YJVOHVQKJGTXBI-UHFFFAOYSA-N 0.000 claims 1
• WUFMSSPYKKPJLV-UHFFFAOYSA-N 3-(4-pyrazolidin-4-ylphenyl)-1-[[3-(trifluoromethoxy)phenyl]methyl]-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1COCCC12CN(C(=O)N2CC3=CC(=CC=C3)OC(F)(F)F)C4=CC=C(C=C4)C5CNNC5 WUFMSSPYKKPJLV-UHFFFAOYSA-N 0.000 claims 1
• NTDAEJMQCATBIH-UHFFFAOYSA-N 3-(4-pyrazolidin-4-ylphenyl)-1-[[3-(trifluoromethyl)phenyl]methyl]-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1COCCC12CN(C(=O)N2CC3=CC(=CC=C3)C(F)(F)F)C4=CC=C(C=C4)C5CNNC5 NTDAEJMQCATBIH-UHFFFAOYSA-N 0.000 claims 1
• DDXCSQPIUCOJEQ-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-fluoro-2-methylphenyl)methyl]-8-(2-hydroxyacetyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)C(=O)CO)N(C2=O)CC4=C(C(=CC=C4)F)C)C5CNNC5 DDXCSQPIUCOJEQ-UHFFFAOYSA-N 0.000 claims 1
• IQJXAWIIZHGWAY-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-fluoro-2-methylphenyl)methyl]-8-(2-hydroxyethyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)CCO)N(C2=O)CC4=C(C(=CC=C4)F)C)C5CNNC5 IQJXAWIIZHGWAY-UHFFFAOYSA-N 0.000 claims 1
• VXVQPCSHSWCYKS-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-fluoro-2-methylphenyl)methyl]-8-(3,3,3-trifluoropropyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)CCC(F)(F)F)N(C2=O)CC4=C(C(=CC=C4)F)C)C5CNNC5 VXVQPCSHSWCYKS-UHFFFAOYSA-N 0.000 claims 1
• VELZLGSAHPTMMZ-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-fluoro-5-methoxyphenyl)methyl]-8-(2-hydroxy-2-methylpropanoyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)C(=O)C(C)(C)O)N(C2=O)CC4=CC(=CC(=C4)F)OC)C5CNNC5 VELZLGSAHPTMMZ-UHFFFAOYSA-N 0.000 claims 1
• DNVIAQLPANEGGH-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-fluoro-5-methoxyphenyl)methyl]-8-(2-hydroxy-2-methylpropyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)CC(C)(C)O)N(C2=O)CC4=CC(=CC(=C4)F)OC)C5CNNC5 DNVIAQLPANEGGH-UHFFFAOYSA-N 0.000 claims 1
• FUGKXHGJRHIYIT-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-fluoro-5-methoxyphenyl)methyl]-8-(2-hydroxyacetyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)C(=O)CO)N(C2=O)CC4=CC(=CC(=C4)F)OC)C5CNNC5 FUGKXHGJRHIYIT-UHFFFAOYSA-N 0.000 claims 1
• USANVQCTEPTZPN-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-fluoro-5-methoxyphenyl)methyl]-8-(2-hydroxyethyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)CCO)N(C2=O)CC4=CC(=CC(=C4)F)OC)C5CNNC5 USANVQCTEPTZPN-UHFFFAOYSA-N 0.000 claims 1
• OWSUTFUECKPMEP-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-fluoro-5-methoxyphenyl)methyl]-8-(2-hydroxypropanoyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)C(=O)C(C)O)N(C2=O)CC4=CC(=CC(=C4)F)OC)C5CNNC5 OWSUTFUECKPMEP-UHFFFAOYSA-N 0.000 claims 1
• NLCNNEPKHPLPEE-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-fluoro-5-methoxyphenyl)methyl]-8-(2-hydroxypropyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)CC(C)O)N(C2=O)CC4=CC(=CC(=C4)F)OC)C5CNNC5 NLCNNEPKHPLPEE-UHFFFAOYSA-N 0.000 claims 1
• NNTOODLAZGVNHH-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCNCC3)N(C2=O)CC4=CC(=CC=C4)OC)C5CNNC5 NNTOODLAZGVNHH-UHFFFAOYSA-N 0.000 claims 1
• JIABLDCSUPAFDX-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-methoxyphenyl)methyl]-8-(2-methylpropanoyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)C(=O)C(C)C)N(C2=O)CC4=CC(=CC=C4)OC)C5CNNC5 JIABLDCSUPAFDX-UHFFFAOYSA-N 0.000 claims 1
• ZOQDPATYIBTHTD-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-methoxyphenyl)methyl]-8-(3,3,3-trifluoropropyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)CCC(F)(F)F)N(C2=O)CC4=CC(=CC=C4)OC)C5CNNC5 ZOQDPATYIBTHTD-UHFFFAOYSA-N 0.000 claims 1
• PRTLBJIROKLALF-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-methoxyphenyl)methyl]-8-(3-methylbutanoyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)C(=O)CC(C)C)N(C2=O)CC4=CC(=CC=C4)OC)C5CNNC5 PRTLBJIROKLALF-UHFFFAOYSA-N 0.000 claims 1
• JCXHFGTYONZXIY-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-8-(2-hydroxy-2-methylpropanoyl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)C(=O)C(C)(C)O)N(C2=O)CC4=CC(=CC=C4)OC)C5CNNC5 JCXHFGTYONZXIY-UHFFFAOYSA-N 0.000 claims 1
• XHYJFZQFPHDLQY-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-8-(2-hydroxyacetyl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)C(=O)CO)N(C2=O)CC4=CC(=CC=C4)OC)C5CNNC5 XHYJFZQFPHDLQY-UHFFFAOYSA-N 0.000 claims 1
• AWQYRQVVMDLZAC-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-8-(2-hydroxypropyl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)CC(C)O)N(C2=O)CC4=CC(=CC=C4)OC)C5CNNC5 AWQYRQVVMDLZAC-UHFFFAOYSA-N 0.000 claims 1
• CTUUDNXREWJTCH-UHFFFAOYSA-N 3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-8-(2-methoxyacetyl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)C(=O)COC)N(C2=O)CC4=CC(=CC=C4)OC)C5CNNC5 CTUUDNXREWJTCH-UHFFFAOYSA-N 0.000 claims 1
• KMEFGUXFSGOAHU-UHFFFAOYSA-N 3-[4-(1H-pyrazol-4-yl)phenyl]-1-(quinolin-8-ylmethyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCOCC2)CC=1C=CC=C2C=CC=NC=12)=O KMEFGUXFSGOAHU-UHFFFAOYSA-N 0.000 claims 1
• RYNAERWDRFFVFQ-UHFFFAOYSA-N 3-[6-ethyl-5-(1H-pyrazol-4-yl)pyridin-2-yl]-1-[(3-fluoro-2-methylphenyl)methyl]-8-(oxetane-3-carbonyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C(C)C1=C(C=CC(=N1)N1C(N(C2(C1)CCN(CC2)C(=O)C1COC1)CC1=C(C(=CC=C1)F)C)=O)C=1C=NNC=1 RYNAERWDRFFVFQ-UHFFFAOYSA-N 0.000 claims 1
• PELLSFUNUFGKPC-UHFFFAOYSA-N 3-[6-ethyl-5-(1H-pyrazol-4-yl)pyridin-2-yl]-1-[(3-fluoro-5-methoxyphenyl)methyl]-8-(3,3,3-trifluoropropyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N1CC2(CCN(CCC(F)(F)F)CC2)N(CC2=CC(F)=CC(OC)=C2)C1=O)C1=CNN=C1 PELLSFUNUFGKPC-UHFFFAOYSA-N 0.000 claims 1
• MKUKTOBOZNPJPW-UHFFFAOYSA-N 3-[6-ethyl-5-(1H-pyrazol-4-yl)pyridin-2-yl]-1-[(3-methoxyphenyl)methyl]-8-(oxolane-2-carbonyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C(C)C1=C(C=CC(=N1)N1C(N(C2(C1)CCN(CC2)C(=O)C1OCCC1)CC1=CC(=CC=C1)OC)=O)C=1C=NNC=1 MKUKTOBOZNPJPW-UHFFFAOYSA-N 0.000 claims 1
• ICESESSNNCQZJO-UHFFFAOYSA-N 3-[6-ethyl-5-(1H-pyrazol-4-yl)pyridin-2-yl]-8-(2-hydroxy-2-methylpropyl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C(C)C1=C(C=CC(=N1)N1C(N(C2(C1)CCN(CC2)CC(C)(C)O)CC1=CC(=CC=C1)OC)=O)C=1C=NNC=1 ICESESSNNCQZJO-UHFFFAOYSA-N 0.000 claims 1
• BQUZSTACQNYFHD-UHFFFAOYSA-N 3-[6-ethyl-5-(1H-pyrazol-4-yl)pyridin-2-yl]-8-(2-hydroxyethyl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C(C)C1=C(C=CC(=N1)N1C(N(C2(C1)CCN(CC2)CCO)CC1=CC(=CC=C1)OC)=O)C=1C=NNC=1 BQUZSTACQNYFHD-UHFFFAOYSA-N 0.000 claims 1
• IFWMGOWOTKZIHK-UHFFFAOYSA-N 3-[6-ethyl-5-(1H-pyrazol-4-yl)pyridin-2-yl]-8-(3-hydroxy-2,2-dimethylpropanoyl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C(C)C1=C(C=CC(=N1)N1C(N(C2(C1)CCN(CC2)C(C(CO)(C)C)=O)CC1=CC(=CC=C1)OC)=O)C=1C=NNC=1 IFWMGOWOTKZIHK-UHFFFAOYSA-N 0.000 claims 1
• IZIYOHWFXCHIGR-UHFFFAOYSA-N 3-[[2-oxo-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-1-yl]methyl]benzonitrile Chemical compound C1COCCC12CN(C(=O)N2CC3=CC(=CC=C3)C#N)C4=CC=C(C=C4)C5CNNC5 IZIYOHWFXCHIGR-UHFFFAOYSA-N 0.000 claims 1
• STNHQOJXJKLCLN-UHFFFAOYSA-N 4-(3-methoxyanilino)-8-(3-phenylbutanoyl)-2-(5-pyrazolidin-4-ylpyridin-2-yl)-2,8-diazaspiro[4.5]decan-3-one Chemical compound CC(CC(=O)N1CCC2(CC1)CN(C(=O)C2NC3=CC(=CC=C3)OC)C4=NC=C(C=C4)C5CNNC5)C6=CC=CC=C6 STNHQOJXJKLCLN-UHFFFAOYSA-N 0.000 claims 1
• YTLAMUNXADCUQG-UHFFFAOYSA-N 4-(3-methoxyanilino)-8-[2-(2-methyl-1,3-thiazol-4-yl)acetyl]-2-(5-pyrazolidin-4-ylpyridin-2-yl)-2,8-diazaspiro[4.5]decan-3-one Chemical compound CC1=NC(=CS1)CC(=O)N2CCC3(CC2)CN(C(=O)C3NC4=CC(=CC=C4)OC)C5=NC=C(C=C5)C6CNNC6 YTLAMUNXADCUQG-UHFFFAOYSA-N 0.000 claims 1
• PEEZTQRQUJNPQH-UHFFFAOYSA-N 4-(3-methoxyanilino)-8-[3-(2-oxopyrrolidin-1-yl)propanoyl]-2-(5-pyrazolidin-4-ylpyridin-2-yl)-2,8-diazaspiro[4.5]decan-3-one Chemical compound COC1=CC=CC(=C1)NC2C(=O)N(CC23CCN(CC3)C(=O)CCN4CCCC4=O)C5=NC=C(C=C5)C6CNNC6 PEEZTQRQUJNPQH-UHFFFAOYSA-N 0.000 claims 1
• CSQPKWTURSLWPZ-UHFFFAOYSA-N 4-(3-methoxyanilino)-8-[3-(3-methylindol-1-yl)propanoyl]-2-(5-pyrazolidin-4-ylpyridin-2-yl)-2,8-diazaspiro[4.5]decan-3-one Chemical compound CC1=CN(C2=CC=CC=C12)CCC(=O)N3CCC4(CC3)CN(C(=O)C4NC5=CC(=CC=C5)OC)C6=NC=C(C=C6)C7CNNC7 CSQPKWTURSLWPZ-UHFFFAOYSA-N 0.000 claims 1
• LNMNQIZJZGQCCN-UHFFFAOYSA-N 4-(3-methoxyanilino)-8-[3-(5-phenyl-1,3,4-oxadiazol-2-yl)propanoyl]-2-[5-(1H-pyrazol-4-yl)pyridin-2-yl]-2,8-diazaspiro[4.5]decan-3-one Chemical compound COc1cccc(NC2C(=O)N(CC22CCN(CC2)C(=O)CCc2nnc(o2)-c2ccccc2)c2ccc(cn2)-c2cn[nH]c2)c1 LNMNQIZJZGQCCN-UHFFFAOYSA-N 0.000 claims 1
• JFSRBPJJCNEKDZ-UHFFFAOYSA-N 4-[(3-fluoro-5-methoxyphenyl)methyl]-6-[4-(1H-pyrazol-4-yl)phenyl]-4,6-diazaspiro[2.4]heptan-5-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(CC2)C1)CC1=CC(=CC(=C1)OC)F)=O JFSRBPJJCNEKDZ-UHFFFAOYSA-N 0.000 claims 1
• KPGJFDXUXJJYKS-UHFFFAOYSA-N 4-[(4-fluoro-3-methoxyphenyl)methyl]-6-[4-(1H-pyrazol-4-yl)phenyl]-4,6-diazaspiro[2.4]heptan-5-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(CC2)C1)CC1=CC(=C(C=C1)F)OC)=O KPGJFDXUXJJYKS-UHFFFAOYSA-N 0.000 claims 1
• FVBOLLBSCYOTRP-UHFFFAOYSA-N 4-[[3-(cyclopropylmethoxy)phenyl]methyl]-6-[4-(1H-pyrazol-4-yl)phenyl]-4,6-diazaspiro[2.4]heptan-5-one Chemical compound O=C1N(CC2=CC=CC(OCC3CC3)=C2)C2(CC2)CN1C1=CC=C(C=C1)C1=CNN=C1 FVBOLLBSCYOTRP-UHFFFAOYSA-N 0.000 claims 1
• DDZZRBFFMUVYCA-UHFFFAOYSA-N 6-[3-ethyl-4-(1H-pyrazol-4-yl)phenyl]-4-[(3-fluoro-5-methoxyphenyl)methyl]-4,6-diazaspiro[2.4]heptan-5-one Chemical compound C(C)C=1C=C(C=CC=1C=1C=NNC=1)N1C(N(C2(CC2)C1)CC1=CC(=CC(=C1)OC)F)=O DDZZRBFFMUVYCA-UHFFFAOYSA-N 0.000 claims 1
• KBNKRDYUMJIIRU-UHFFFAOYSA-N 6-[3-ethyl-4-(1H-pyrazol-4-yl)phenyl]-4-[(3-methoxyphenyl)methyl]-4,6-diazaspiro[2.4]heptan-5-one Chemical compound C(C)C=1C=C(C=CC=1C=1C=NNC=1)N1C(N(C2(CC2)C1)CC1=CC(=CC=C1)OC)=O KBNKRDYUMJIIRU-UHFFFAOYSA-N 0.000 claims 1
• ZLSPNLQZGBLMGM-UHFFFAOYSA-N 8-(1H-indole-6-carbonyl)-1-[(3-methoxyphenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCN(CC2)C(=O)C1=CC=C2C=CNC2=C1)CC1=CC(=CC=C1)OC)=O ZLSPNLQZGBLMGM-UHFFFAOYSA-N 0.000 claims 1
• NZZRTRXYFDJPBG-UHFFFAOYSA-N 8-(2,2-difluoroacetyl)-1-[(3-methoxyphenyl)methyl]-3-(5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)C(=O)C(F)F)C4=NC=C(C=C4)C5CNNC5 NZZRTRXYFDJPBG-UHFFFAOYSA-N 0.000 claims 1
• LIBLJYKSDDIGHL-UHFFFAOYSA-N 8-(2,2-difluoroacetyl)-3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)C(=O)C(F)F)N(C2=O)CC4=CC(=CC=C4)OC)C5CNNC5 LIBLJYKSDDIGHL-UHFFFAOYSA-N 0.000 claims 1
• MEJFSKDEKHPBHJ-UHFFFAOYSA-N 8-(2,2-difluoroethyl)-1-[(3-fluoro-2-methylphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC=C1F)CN2C(=O)N(CC23CCN(CC3)CC(F)F)C4=CC=C(C=C4)C5CNNC5 MEJFSKDEKHPBHJ-UHFFFAOYSA-N 0.000 claims 1
• CFTFWMADVNPWLP-UHFFFAOYSA-N 8-(2,2-difluoroethyl)-1-[(3-fluoro-2-methylphenyl)methyl]-3-[6-methoxy-5-(1H-pyrazol-4-yl)pyridin-2-yl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COc1nc(ccc1-c1cn[nH]c1)N1CC2(CCN(CC(F)F)CC2)N(Cc2cccc(F)c2C)C1=O CFTFWMADVNPWLP-UHFFFAOYSA-N 0.000 claims 1
• ZOBGXVLVUBLRPY-UHFFFAOYSA-N 8-(2,2-difluoroethyl)-1-[(3-fluoro-5-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC(=CC(=C1)CN2C(=O)N(CC23CCN(CC3)CC(F)F)C4=CC=C(C=C4)C5CNNC5)F ZOBGXVLVUBLRPY-UHFFFAOYSA-N 0.000 claims 1
• MBIOQIXZMNADLU-UHFFFAOYSA-N 8-(2,2-difluoroethyl)-1-[(3-methoxyphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)CC(F)F)C4=NC(=C(C=C4)C5CNNC5)OC MBIOQIXZMNADLU-UHFFFAOYSA-N 0.000 claims 1
• YVNYQVXTJNCHOI-UHFFFAOYSA-N 8-(2,2-difluoroethyl)-3-[6-ethyl-5-(1H-pyrazol-4-yl)pyridin-2-yl]-1-[(3-fluoro-2-methylphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound FC(CN1CCC2(CN(C(N2CC2=C(C(=CC=C2)F)C)=O)C2=NC(=C(C=C2)C=2C=NNC=2)CC)CC1)F YVNYQVXTJNCHOI-UHFFFAOYSA-N 0.000 claims 1
• ZTQYOXPCDGXXBM-UHFFFAOYSA-N 8-(2,2-difluoroethyl)-3-[6-ethyl-5-(1H-pyrazol-4-yl)pyridin-2-yl]-1-[(3-fluoro-5-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound FC(CN1CCC2(CN(C(N2CC2=CC(=CC(=C2)OC)F)=O)C2=NC(=C(C=C2)C=2C=NNC=2)CC)CC1)F ZTQYOXPCDGXXBM-UHFFFAOYSA-N 0.000 claims 1
• ZJGAPPDTKFOOCS-UHFFFAOYSA-N 8-(2,3-dihydroxypropyl)-1-[(3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)CC(CO)O)C4=CC=C(C=C4)C5CNNC5 ZJGAPPDTKFOOCS-UHFFFAOYSA-N 0.000 claims 1
• BEGTUFYXQXJMTN-UHFFFAOYSA-N 8-(2-ethylbutyl)-1-[(3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC(CC)CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 BEGTUFYXQXJMTN-UHFFFAOYSA-N 0.000 claims 1
• UHJDFHKCRVOOLL-UHFFFAOYSA-N 8-(2-hydroxy-2-methylpropanoyl)-1-[(3-methoxyphenyl)methyl]-3-(4-methoxy-5-pyrazolidin-4-ylpyrimidin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(C)(C(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC=C(C(=N4)OC)C5CNNC5)O UHJDFHKCRVOOLL-UHFFFAOYSA-N 0.000 claims 1
• FBSAEEJGQYQULT-UHFFFAOYSA-N 8-(2-hydroxy-2-methylpropanoyl)-1-[(3-methoxyphenyl)methyl]-3-(5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(C)(C(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC=C(C=C4)C5CNNC5)O FBSAEEJGQYQULT-UHFFFAOYSA-N 0.000 claims 1
• XODNDTVHTDQSGA-UHFFFAOYSA-N 8-(2-hydroxy-2-methylpropanoyl)-1-[(3-methoxyphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(C)(C(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC(=C(C=C4)C5CNNC5)OC)O XODNDTVHTDQSGA-UHFFFAOYSA-N 0.000 claims 1
• CESQVIQNSBGHHU-UHFFFAOYSA-N 8-(2-hydroxy-2-methylpropanoyl)-1-[(3-methoxyphenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCN(CC2)C(C(C)(C)O)=O)CC1=CC(=CC=C1)OC)=O CESQVIQNSBGHHU-UHFFFAOYSA-N 0.000 claims 1
• CBBZPZGJOXIRLO-UHFFFAOYSA-N 8-(2-hydroxy-2-methylpropyl)-1-[(3-methoxyphenyl)methyl]-3-(5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(C)(CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC=C(C=C4)C5CNNC5)O CBBZPZGJOXIRLO-UHFFFAOYSA-N 0.000 claims 1
• MEYGPBBMIUXCGJ-UHFFFAOYSA-N 8-(2-hydroxy-2-methylpropyl)-1-[(3-methoxyphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(C)(CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC(=C(C=C4)C5CNNC5)OC)O MEYGPBBMIUXCGJ-UHFFFAOYSA-N 0.000 claims 1
• KKWUKQHNTVIRPK-UHFFFAOYSA-N 8-(2-hydroxy-2-methylpropyl)-4-(3-methoxyanilino)-2-(4-pyrazolidin-4-ylphenyl)-2,8-diazaspiro[4.5]decan-3-one Chemical compound CC(C)(CN1CCC2(CC1)CN(C(=O)C2NC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5)O KKWUKQHNTVIRPK-UHFFFAOYSA-N 0.000 claims 1
• FOPJPLDKOYCNEI-UHFFFAOYSA-N 8-(2-hydroxyacetyl)-1-[(3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)C(=O)CO)C4=CC=C(C=C4)C5CNNC5 FOPJPLDKOYCNEI-UHFFFAOYSA-N 0.000 claims 1
• XKLZTWSTDUWQCG-UHFFFAOYSA-N 8-(2-hydroxyacetyl)-1-[(3-methoxyphenyl)methyl]-3-(5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)C(=O)CO)C4=NC=C(C=C4)C5CNNC5 XKLZTWSTDUWQCG-UHFFFAOYSA-N 0.000 claims 1
• KJSXRIBXBNWSOK-UHFFFAOYSA-N 8-(2-hydroxyacetyl)-1-[(3-methoxyphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)C(=O)CO)C4=NC(=C(C=C4)C5CNNC5)OC KJSXRIBXBNWSOK-UHFFFAOYSA-N 0.000 claims 1
• IOTIXZZCHCQJEW-UHFFFAOYSA-N 8-(2-hydroxyacetyl)-4-(3-methoxyanilino)-2-(4-pyrazolidin-4-ylphenyl)-2,8-diazaspiro[4.5]decan-3-one Chemical compound COC1=CC=CC(=C1)NC2C(=O)N(CC23CCN(CC3)C(=O)CO)C4=CC=C(C=C4)C5CNNC5 IOTIXZZCHCQJEW-UHFFFAOYSA-N 0.000 claims 1
• KIVYQUUSULZBIW-UHFFFAOYSA-N 8-(2-hydroxyethyl)-1-[(3-methoxyphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)CCO)C4=NC(=C(C=C4)C5CNNC5)OC KIVYQUUSULZBIW-UHFFFAOYSA-N 0.000 claims 1
• WVZRXGWIIFZFHK-UHFFFAOYSA-N 8-(2-hydroxyethyl)-1-[(3-methoxyphenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCN(CC2)CCO)CC1=CC(=CC=C1)OC)=O WVZRXGWIIFZFHK-UHFFFAOYSA-N 0.000 claims 1
• XBNFOZVSUQEKGC-UHFFFAOYSA-N 8-(2-hydroxyethyl)-1-[(3-methoxyphenyl)methyl]-8-oxido-3-(4-pyrazolidin-4-ylphenyl)-1,3-diaza-8-azoniaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CC[N+](CC3)(CCO)[O-])C4=CC=C(C=C4)C5CNNC5 XBNFOZVSUQEKGC-UHFFFAOYSA-N 0.000 claims 1
• FCVSBZULJAMPKF-UHFFFAOYSA-N 8-(2-hydroxyethyl)-4-(3-methoxyanilino)-2-(4-pyrazolidin-4-ylphenyl)-2,8-diazaspiro[4.5]decan-3-one Chemical compound COC1=CC=CC(=C1)NC2C(=O)N(CC23CCN(CC3)CCO)C4=CC=C(C=C4)C5CNNC5 FCVSBZULJAMPKF-UHFFFAOYSA-N 0.000 claims 1
• NPRMTGUOGLPFCR-UHFFFAOYSA-N 8-(2-hydroxypropanoyl)-1-[(3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(C(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5)O NPRMTGUOGLPFCR-UHFFFAOYSA-N 0.000 claims 1
• OKFCQQRXCKOXJB-UHFFFAOYSA-N 8-(2-hydroxypropanoyl)-1-[(3-methoxyphenyl)methyl]-3-(5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(C(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC=C(C=C4)C5CNNC5)O OKFCQQRXCKOXJB-UHFFFAOYSA-N 0.000 claims 1
• DGYJWEJHYASGQT-UHFFFAOYSA-N 8-(2-hydroxypropanoyl)-1-[(3-methoxyphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(C(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC(=C(C=C4)C5CNNC5)OC)O DGYJWEJHYASGQT-UHFFFAOYSA-N 0.000 claims 1
• JDWSZUCRUVPSPY-UHFFFAOYSA-N 8-(2-hydroxypropyl)-1-[(3-methoxyphenyl)methyl]-3-(5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC=C(C=C4)C5CNNC5)O JDWSZUCRUVPSPY-UHFFFAOYSA-N 0.000 claims 1
• OCAIVEUDVMLYEG-UHFFFAOYSA-N 8-(2-hydroxypropyl)-1-[(3-methoxyphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC(=C(C=C4)C5CNNC5)OC)O OCAIVEUDVMLYEG-UHFFFAOYSA-N 0.000 claims 1
• MAMAYKLTUKRNDG-UHFFFAOYSA-N 8-(2-methoxyacetyl)-1-[(3-methoxyphenyl)methyl]-3-(5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COCC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC=C(C=C4)C5CNNC5 MAMAYKLTUKRNDG-UHFFFAOYSA-N 0.000 claims 1
• UJBXESMEBNYGDA-UHFFFAOYSA-N 8-(2-methoxyacetyl)-1-[(3-methoxyphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COCC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC(=C(C=C4)C5CNNC5)OC UJBXESMEBNYGDA-UHFFFAOYSA-N 0.000 claims 1
• ADPHTYNKJZXPSG-UHFFFAOYSA-N 8-(2-methoxyethyl)-1-[(3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COCCN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 ADPHTYNKJZXPSG-UHFFFAOYSA-N 0.000 claims 1
• QOTSVEXEIIYDFK-UHFFFAOYSA-N 8-(2-methoxyethyl)-1-[(3-methoxyphenyl)methyl]-3-(5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COCCN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC=C(C=C4)C5CNNC5 QOTSVEXEIIYDFK-UHFFFAOYSA-N 0.000 claims 1
• JACIPNLETCILQA-UHFFFAOYSA-N 8-(3-hydroxy-2,2-dimethylpropanoyl)-1-[(3-methoxyphenyl)methyl]-3-[4-methoxy-5-(1H-pyrazol-4-yl)pyrimidin-2-yl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound OCC(C(=O)N1CCC2(CN(C(N2CC2=CC(=CC=C2)OC)=O)C2=NC=C(C(=N2)OC)C=2C=NNC=2)CC1)(C)C JACIPNLETCILQA-UHFFFAOYSA-N 0.000 claims 1
• DQURXMGNVQBDBA-UHFFFAOYSA-N 8-(cyclopentylmethyl)-1-[(3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)CC4CCCC4)C5=CC=C(C=C5)C6CNNC6 DQURXMGNVQBDBA-UHFFFAOYSA-N 0.000 claims 1
• FSQRQOAZIXHGTG-UHFFFAOYSA-N 8-(cyclopropylmethyl)-1-[(3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)CC4CC4)C5=CC=C(C=C5)C6CNNC6 FSQRQOAZIXHGTG-UHFFFAOYSA-N 0.000 claims 1
• NPRMTGUOGLPFCR-LJQANCHMSA-N 8-[(2R)-2-hydroxypropanoyl]-1-[(3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](C(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5)O NPRMTGUOGLPFCR-LJQANCHMSA-N 0.000 claims 1
• NPRMTGUOGLPFCR-IBGZPJMESA-N 8-[(2S)-2-hydroxypropanoyl]-1-[(3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@@H](C(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5)O NPRMTGUOGLPFCR-IBGZPJMESA-N 0.000 claims 1
• JXEFKEBXNBZAOB-UHFFFAOYSA-N 8-[2-(dimethylamino)acetyl]-1-[(3-fluoro-2-methylphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC=C1F)CN2C(=O)N(CC23CCN(CC3)C(=O)CN(C)C)C4=NC(=C(C=C4)C5CNNC5)OC JXEFKEBXNBZAOB-UHFFFAOYSA-N 0.000 claims 1
• XDFOGPPNTRUWPE-UHFFFAOYSA-N 8-[2-(dimethylamino)acetyl]-1-[(3-methoxyphenyl)methyl]-3-(4-methoxy-5-pyrazolidin-4-ylpyrimidin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CN(C)CC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC=C(C(=N4)OC)C5CNNC5 XDFOGPPNTRUWPE-UHFFFAOYSA-N 0.000 claims 1
• JNVPJMOXWLUYPL-UHFFFAOYSA-N 8-[2-(dimethylamino)acetyl]-1-[(3-methoxyphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CN(C)CC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC(=C(C=C4)C5CNNC5)OC JNVPJMOXWLUYPL-UHFFFAOYSA-N 0.000 claims 1
• DIYYMYDLFZTPKJ-UHFFFAOYSA-N 8-[2-(dimethylamino)acetyl]-3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)C(=O)CN(C)C)N(C2=O)CC4=CC(=CC=C4)OC)C5CNNC5 DIYYMYDLFZTPKJ-UHFFFAOYSA-N 0.000 claims 1
• HROGATHOYMBQCO-UHFFFAOYSA-N 8-acetyl-1-(cyclohexylmethyl)-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(=O)N1CCC2(CC1)CN(C(=O)N2CC3CCCCC3)C4=CC=C(C=C4)C5CNNC5 HROGATHOYMBQCO-UHFFFAOYSA-N 0.000 claims 1
• ANNZNJVDAWYIJZ-UHFFFAOYSA-N 8-acetyl-1-[(2,3-difluorophenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCN(CC2)C(C)=O)CC1=C(C(=CC=C1)F)F)=O ANNZNJVDAWYIJZ-UHFFFAOYSA-N 0.000 claims 1
• KKXMWIKJPUDTBW-UHFFFAOYSA-N 8-acetyl-1-[(2,4-difluorophenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCN(CC2)C(C)=O)CC1=C(C=C(C=C1)F)F)=O KKXMWIKJPUDTBW-UHFFFAOYSA-N 0.000 claims 1
• UEAAGILCHTVHKS-UHFFFAOYSA-N 8-acetyl-1-[(2,5-difluorophenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCN(CC2)C(C)=O)CC1=C(C=CC(=C1)F)F)=O UEAAGILCHTVHKS-UHFFFAOYSA-N 0.000 claims 1
• IYXZXPOXVOJBBD-UHFFFAOYSA-N 8-acetyl-1-[(3-fluoro-2-methylphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC=C1F)CN2C(=O)N(CC23CCN(CC3)C(=O)C)C4=NC(=C(C=C4)C5CNNC5)OC IYXZXPOXVOJBBD-UHFFFAOYSA-N 0.000 claims 1
• LNBNAZMEXYAFFR-UHFFFAOYSA-N 8-acetyl-1-[(3-fluoro-2-methylphenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(N(C2(C1)CCN(CC2)C(C)=O)CC1=C(C(=CC=C1)F)C)=O LNBNAZMEXYAFFR-UHFFFAOYSA-N 0.000 claims 1
• WMOFPEHCLPBRTL-UHFFFAOYSA-N 8-acetyl-1-[(3-methoxyphenyl)methyl]-3-(4-methoxy-5-pyrazolidin-4-ylpyrimidin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC=C(C(=N4)OC)C5CNNC5 WMOFPEHCLPBRTL-UHFFFAOYSA-N 0.000 claims 1
• OVAXEVLCLVFIGF-UHFFFAOYSA-N 8-acetyl-1-[(3-methoxyphenyl)methyl]-3-(6-methoxy-5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC(=C(C=C4)C5CNNC5)OC OVAXEVLCLVFIGF-UHFFFAOYSA-N 0.000 claims 1
• LSBXGFGHKJZSCK-UHFFFAOYSA-N 8-acetyl-1-[(4-fluoro-2-methylphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=CC(=C1)F)CN2C(=O)N(CC23CCN(CC3)C(=O)C)C4=CC=C(C=C4)C5CNNC5 LSBXGFGHKJZSCK-UHFFFAOYSA-N 0.000 claims 1
• JLPUGTWKNRNJIF-UHFFFAOYSA-N 8-acetyl-1-[(5-fluoro-2-methylphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CC1=C(C=C(C=C1)F)CN2C(=O)N(CC23CCN(CC3)C(=O)C)C4=CC=C(C=C4)C5CNNC5 JLPUGTWKNRNJIF-UHFFFAOYSA-N 0.000 claims 1
• GNRNSZZUOBPJRD-UHFFFAOYSA-N 8-acetyl-3-(6-ethyl-5-pyrazolidin-4-ylpyridin-2-yl)-1-[(3-fluoro-5-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCC1=C(C=CC(=N1)N2CC3(CCN(CC3)C(=O)C)N(C2=O)CC4=CC(=CC(=C4)F)OC)C5CNNC5 GNRNSZZUOBPJRD-UHFFFAOYSA-N 0.000 claims 1
• QEKIIWDTJLDFSP-UHFFFAOYSA-N 8-ethyl-1-[(3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound CCN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 QEKIIWDTJLDFSP-UHFFFAOYSA-N 0.000 claims 1
• 208000023275 Autoimmune disease Diseases 0.000 claims 1
• JVSSEKOUHXNNOB-UHFFFAOYSA-N N,N-dimethyl-3-[[2-oxo-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-1-yl]methyl]benzamide Chemical compound CN(C)C(=O)C1=CC=CC(=C1)CN2C(=O)N(CC23CCOCC3)C4=CC=C(C=C4)C5CNNC5 JVSSEKOUHXNNOB-UHFFFAOYSA-N 0.000 claims 1
• BSRBMIUACVZFQY-UHFFFAOYSA-N N-(2-hydroxyethyl)-3-[[2-oxo-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-1-yl]methyl]benzamide Chemical compound C1COCCC12CN(C(=O)N2CC3=CC(=CC=C3)C(=O)NCCO)C4=CC=C(C=C4)C5CNNC5 BSRBMIUACVZFQY-UHFFFAOYSA-N 0.000 claims 1
• NQZCRLCBOLSWQQ-UHFFFAOYSA-N N-(2-methylpropyl)-3-[[2-oxo-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-1-yl]methyl]benzamide Chemical compound CC(C)CNC(=O)C1=CC=CC(=C1)CN2C(=O)N(CC23CCOCC3)C4=CC=C(C=C4)C5CNNC5 NQZCRLCBOLSWQQ-UHFFFAOYSA-N 0.000 claims 1
• OVLNETWWNGCLDL-UHFFFAOYSA-N N-ethyl-N-methyl-3-[[2-oxo-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-1-yl]methyl]benzamide Chemical compound CCN(C)C(=O)C1=CC=CC(=C1)CN2C(=O)N(CC23CCOCC3)C4=CC=C(C=C4)C5CNNC5 OVLNETWWNGCLDL-UHFFFAOYSA-N 0.000 claims 1
• 208000031481 Pathologic Constriction Diseases 0.000 claims 1
• 208000018262 Peripheral vascular disease Diseases 0.000 claims 1
• 206010047163 Vasospasm Diseases 0.000 claims 1
• 230000002159 abnormal effect Effects 0.000 claims 1
• 208000026106 cerebrovascular disease Diseases 0.000 claims 1
• MJURPJITNZRTNF-UHFFFAOYSA-N ethyl 1-[(3-methoxyphenyl)methyl]-2-oxo-3-(5-pyrazolidin-4-ylpyridin-2-yl)-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound CCOC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=NC=C(C=C4)C5CNNC5 MJURPJITNZRTNF-UHFFFAOYSA-N 0.000 claims 1
• ILQNURBRVXNUOA-UHFFFAOYSA-N ethyl 2-ethylnonanoate Chemical compound CCCCCCCC(CC)C(=O)OCC ILQNURBRVXNUOA-UHFFFAOYSA-N 0.000 claims 1
• NZPAXGFTEPFMEB-UHFFFAOYSA-N methyl 1-[(3-fluoro-2-methylphenyl)methyl]-2-oxo-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound CC1=C(C=CC=C1F)CN2C(=O)N(CC23CCN(CC3)C(=O)OC)C4=CC=C(C=C4)C5CNNC5 NZPAXGFTEPFMEB-UHFFFAOYSA-N 0.000 claims 1
• DAYCRDHUYCCKBF-UHFFFAOYSA-N methyl 4-(3-methoxyanilino)-3-oxo-2-(4-pyrazolidin-4-ylphenyl)-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound COC1=CC=CC(=C1)NC2C(=O)N(CC23CCN(CC3)C(=O)OC)C4=CC=C(C=C4)C5CNNC5 DAYCRDHUYCCKBF-UHFFFAOYSA-N 0.000 claims 1
• OSBOEMLLPKKPNR-UHFFFAOYSA-N methyl 8-(3-methoxyanilino)-7-oxo-6-[4-(1H-pyrazol-4-yl)phenyl]-2,6-diazaspiro[3.4]octane-2-carboxylate Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1CC2(CN(C2)C(=O)OC)C(C1=O)NC1=CC(=CC=C1)OC OSBOEMLLPKKPNR-UHFFFAOYSA-N 0.000 claims 1
• 208000010125 myocardial infarction Diseases 0.000 claims 1
• 230000002981 neuropathic effect Effects 0.000 claims 1
• 230000000771 oncological effect Effects 0.000 claims 1
• JBZWTRCHHJLEDC-UHFFFAOYSA-N propan-2-yl 1-[(3-methoxyphenyl)methyl]-2-oxo-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound CC(C)OC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 JBZWTRCHHJLEDC-UHFFFAOYSA-N 0.000 claims 1
• FWYYZQPXWIJWTI-UHFFFAOYSA-N propyl 1-[(3-methoxyphenyl)methyl]-2-oxo-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound CCCOC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 FWYYZQPXWIJWTI-UHFFFAOYSA-N 0.000 claims 1
• 208000037804 stenosis Diseases 0.000 claims 1
• 230000036262 stenosis Effects 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 150
• 239000011541 reaction mixture Substances 0.000 description 131
• 238000000034 method Methods 0.000 description 105
• 229910001868 water Inorganic materials 0.000 description 90
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 89
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 84
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 76
• 239000000243 solution Substances 0.000 description 69
• 239000007787 solid Substances 0.000 description 68
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 67
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
• 239000000460 chlorine Substances 0.000 description 56
• 235000019439 ethyl acetate Nutrition 0.000 description 56
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 56
• 238000002360 preparation method Methods 0.000 description 54
• 239000000543 intermediate Substances 0.000 description 53
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 52
• 238000005160 1H NMR spectroscopy Methods 0.000 description 47
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
• 239000002904 solvent Substances 0.000 description 44
• 235000002639 sodium chloride Nutrition 0.000 description 40
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 33
• 239000000203 mixture Substances 0.000 description 32
• 229910000027 potassium carbonate Inorganic materials 0.000 description 28
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 25
• 235000015320 potassium carbonate Nutrition 0.000 description 25
• 229910052938 sodium sulfate Inorganic materials 0.000 description 25
• 235000011152 sodium sulphate Nutrition 0.000 description 25
• 239000012453 solvate Substances 0.000 description 25
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
• 238000006243 chemical reaction Methods 0.000 description 23
• 239000007832 Na2SO4 Substances 0.000 description 22
• 238000002953 preparative HPLC Methods 0.000 description 22
• 239000012267 brine Substances 0.000 description 21
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
• 239000010410 layer Substances 0.000 description 19
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
• 239000012391 XPhos Pd G2 Substances 0.000 description 18
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 18
• 239000000706 filtrate Substances 0.000 description 18
• IPISOFJLWYBCAV-UHFFFAOYSA-N tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole-1-carboxylate Chemical compound C1=NN(C(=O)OC(C)(C)C)C=C1B1OC(C)(C)C(C)(C)O1 IPISOFJLWYBCAV-UHFFFAOYSA-N 0.000 description 18
• 239000003814 drug Substances 0.000 description 17
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
• 238000010828 elution Methods 0.000 description 16
• 238000003818 flash chromatography Methods 0.000 description 16
• 239000002585 base Substances 0.000 description 15
• 125000001424 substituent group Chemical group 0.000 description 15
• 229910052717 sulfur Inorganic materials 0.000 description 14
• 239000000725 suspension Substances 0.000 description 14
• DBVXKCHMLPTQJR-UHFFFAOYSA-N 3-(4-bromophenyl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCNCC2)C2=CC=C(Br)C=C2)=C1 DBVXKCHMLPTQJR-UHFFFAOYSA-N 0.000 description 13
• 125000004429 atom Chemical group 0.000 description 13
• 238000003756 stirring Methods 0.000 description 13
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 12
• 239000002245 particle Substances 0.000 description 12
• 238000003786 synthesis reaction Methods 0.000 description 12
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 11
• 239000003153 chemical reaction reagent Substances 0.000 description 11
• 238000004128 high performance liquid chromatography Methods 0.000 description 11
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• 230000007170 pathology Effects 0.000 description 11
• 239000000047 product Substances 0.000 description 11
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
• 239000006184 cosolvent Substances 0.000 description 10
• 239000012071 phase Substances 0.000 description 10
• 239000000651 prodrug Substances 0.000 description 10
• 229940002612 prodrug Drugs 0.000 description 10
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• 229910052796 boron Inorganic materials 0.000 description 9
• 229940079593 drug Drugs 0.000 description 9
• 125000002950 monocyclic group Chemical group 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 235000017557 sodium bicarbonate Nutrition 0.000 description 9
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
• 229910000104 sodium hydride Inorganic materials 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 9
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 239000011324 bead Substances 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 150000001721 carbon Chemical group 0.000 description 8
• 238000004519 manufacturing process Methods 0.000 description 8
• 229910052760 oxygen Inorganic materials 0.000 description 8
• 230000008569 process Effects 0.000 description 8
• 238000004808 supercritical fluid chromatography Methods 0.000 description 8
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 8
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 125000003545 alkoxy group Chemical group 0.000 description 7
• 238000003556 assay Methods 0.000 description 7
• 125000002619 bicyclic group Chemical group 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 150000002148 esters Chemical class 0.000 description 7
• IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 7
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
• YHMGODFIAQQIDP-UHFFFAOYSA-N 3-(4-bromophenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound BrC1=CC=C(C=C1)N1CC2(CCOCC2)NC1=O YHMGODFIAQQIDP-UHFFFAOYSA-N 0.000 description 6
• QEPAOUDRVKBDFE-UHFFFAOYSA-N 6-(4-bromophenyl)-4,6-diazaspiro[2.4]heptan-5-one Chemical compound BrC1=CC=C(C=C1)N1C(NC2(CC2)C1)=O QEPAOUDRVKBDFE-UHFFFAOYSA-N 0.000 description 6
• 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
• 101000669921 Homo sapiens Rho-associated protein kinase 2 Proteins 0.000 description 6
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
• 101150111584 RHOA gene Proteins 0.000 description 6
• 102100039314 Rho-associated protein kinase 2 Human genes 0.000 description 6
• 125000004438 haloalkoxy group Chemical group 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 239000012044 organic layer Substances 0.000 description 6
• 125000002971 oxazolyl group Chemical group 0.000 description 6
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 6
• 239000000523 sample Substances 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 241000894007 species Species 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• 229940124597 therapeutic agent Drugs 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
• 241000124008 Mammalia Species 0.000 description 5
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 5
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
• 239000004202 carbamide Substances 0.000 description 5
• 125000001188 haloalkyl group Chemical group 0.000 description 5
• 239000001257 hydrogen Substances 0.000 description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
• 125000001041 indolyl group Chemical group 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 208000017169 kidney disease Diseases 0.000 description 5
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 5
• 231100000252 nontoxic Toxicity 0.000 description 5
• 230000003000 nontoxic effect Effects 0.000 description 5
• 108090000623 proteins and genes Proteins 0.000 description 5
• 230000019491 signal transduction Effects 0.000 description 5
• 125000004434 sulfur atom Chemical group 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• 125000001544 thienyl group Chemical group 0.000 description 5
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 5
• 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 4
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• IMTQCSZFSSQPOU-UHFFFAOYSA-N 1-(4-bromophenyl)-3-[4-(hydroxymethyl)oxan-4-yl]urea Chemical compound OCC1(CCOCC1)NC(=O)NC1=CC=C(Br)C=C1 IMTQCSZFSSQPOU-UHFFFAOYSA-N 0.000 description 4
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
• PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 4
• HRZOBKMWNGQPOK-UHFFFAOYSA-N 3-(4-bromophenyl)-1-[(3-methoxyphenyl)methyl]-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCOCC2)C2=CC=C(Br)C=C2)=C1 HRZOBKMWNGQPOK-UHFFFAOYSA-N 0.000 description 4
• LNVYSDUXYYCOIW-UHFFFAOYSA-N 3-(4-bromophenyl)-8-(4,4-difluorocyclohexanecarbonyl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CC2)C(=O)C2CCC(F)(F)CC2)C2=CC=C(Br)C=C2)=C1 LNVYSDUXYYCOIW-UHFFFAOYSA-N 0.000 description 4
• PLWHZCBDPVGOHA-UHFFFAOYSA-N 8-(2-hydroxypropyl)-1-[(3-methoxyphenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CC(C)O)CC2)C2=CC=C(C=C2)C2=CNN=C2)=C1 PLWHZCBDPVGOHA-UHFFFAOYSA-N 0.000 description 4
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
• 239000005695 Ammonium acetate Substances 0.000 description 4
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
• 208000010228 Erectile Dysfunction Diseases 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
• 239000004793 Polystyrene Substances 0.000 description 4
• 241000700159 Rattus Species 0.000 description 4
• 229920002472 Starch Polymers 0.000 description 4
• 238000006069 Suzuki reaction reaction Methods 0.000 description 4
• 230000001594 aberrant effect Effects 0.000 description 4
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
• 150000001413 amino acids Chemical class 0.000 description 4
• 235000019257 ammonium acetate Nutrition 0.000 description 4
• 229940043376 ammonium acetate Drugs 0.000 description 4
• 235000019270 ammonium chloride Nutrition 0.000 description 4
• 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 4
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
• YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 4
• 229910000024 caesium carbonate Inorganic materials 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• 239000003054 catalyst Substances 0.000 description 4
• 239000012043 crude product Substances 0.000 description 4
• NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical compound C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 description 4
• 229910052805 deuterium Inorganic materials 0.000 description 4
• NGOGFTYYXHNFQH-UHFFFAOYSA-N fasudil Chemical compound C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N1CCCNCC1 NGOGFTYYXHNFQH-UHFFFAOYSA-N 0.000 description 4
• 229960002435 fasudil Drugs 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 125000002541 furyl group Chemical group 0.000 description 4
• 125000002883 imidazolyl group Chemical group 0.000 description 4
• 201000001881 impotence Diseases 0.000 description 4
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• 208000001286 intracranial vasospasm Diseases 0.000 description 4
• 125000000842 isoxazolyl group Chemical group 0.000 description 4
• 125000005647 linker group Chemical group 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 125000001624 naphthyl group Chemical group 0.000 description 4
• 125000001715 oxadiazolyl group Chemical group 0.000 description 4
• 125000004430 oxygen atom Chemical group O* 0.000 description 4
• DFVROMJTBLOOGY-UHFFFAOYSA-N phenyl n-(4-bromophenyl)carbamate Chemical compound C1=CC(Br)=CC=C1NC(=O)OC1=CC=CC=C1 DFVROMJTBLOOGY-UHFFFAOYSA-N 0.000 description 4
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• 239000004033 plastic Substances 0.000 description 4
• 229920003023 plastic Polymers 0.000 description 4
• 102000004169 proteins and genes Human genes 0.000 description 4
• 125000004076 pyridyl group Chemical group 0.000 description 4
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
• 239000008107 starch Substances 0.000 description 4
• 235000019698 starch Nutrition 0.000 description 4
• ITRBCWSMRIMAGM-UHFFFAOYSA-N tert-butyl 3-(4-bromophenyl)-1-[(3-methoxyphenyl)methyl]-2-oxo-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CC2)C(=O)OC(C)(C)C)C2=CC=C(Br)C=C2)=C1 ITRBCWSMRIMAGM-UHFFFAOYSA-N 0.000 description 4
• JFBUNRXUEXKBFV-UHFFFAOYSA-N tert-butyl 3-(4-bromophenyl)-2-oxo-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC2(CN(C(=O)N2)C2=CC=C(Br)C=C2)CC1 JFBUNRXUEXKBFV-UHFFFAOYSA-N 0.000 description 4
• 125000000335 thiazolyl group Chemical group 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
• 125000004306 triazinyl group Chemical group 0.000 description 4
• 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 3
• ZKSOJQDNSNJIQW-UHFFFAOYSA-N 1-(bromomethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CBr)=C1 ZKSOJQDNSNJIQW-UHFFFAOYSA-N 0.000 description 3
• RYNJMGGCUJSOGW-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCNCC3)C4=CC=C(C=C4)C5CNNC5 RYNJMGGCUJSOGW-UHFFFAOYSA-N 0.000 description 3
• 238000004293 19F NMR spectroscopy Methods 0.000 description 3
• 125000005955 1H-indazolyl group Chemical group 0.000 description 3
• OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 3
• LPBQXBAZCGUTFM-UHFFFAOYSA-N 2-(5-bromo-4-methoxypyrimidin-2-yl)-4-(3-methoxyanilino)-2,8-diazaspiro[4.5]decan-3-one Chemical compound BrC=1C(=NC(=NC=1)N1CC2(C(C1=O)NC1=CC(=CC=C1)OC)CCNCC2)OC LPBQXBAZCGUTFM-UHFFFAOYSA-N 0.000 description 3
• SFTRBFXJZFWUEO-UHFFFAOYSA-N 2-(5-bromo-4-methoxypyrimidin-2-yl)-4-(3-methoxyanilino)-8-(pyrazolo[1,5-a]pyridine-3-carbonyl)-2,8-diazaspiro[4.5]decan-3-one Chemical compound COC1=CC=CC(NC2C(=O)N(CC22CCN(CC2)C(=O)C2=C3C=CC=CN3N=C2)C2=NC(OC)=C(Br)C=N2)=C1 SFTRBFXJZFWUEO-UHFFFAOYSA-N 0.000 description 3
• ZADUPKOTMHBQOV-UHFFFAOYSA-N 2-[3-(4-bromophenyl)-1-[(3-methoxyphenyl)methyl]-2-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]-N-methylacetamide Chemical compound CNC(=O)CN1CCC2(CN(C(=O)N2CC2=CC(OC)=CC=C2)C2=CC=C(Br)C=C2)CC1 ZADUPKOTMHBQOV-UHFFFAOYSA-N 0.000 description 3
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
• KJYIMWDAUCGCQZ-UHFFFAOYSA-N 3-(4-bromophenyl)-1-[(3-methoxyphenyl)methyl]-8-(oxetan-3-yl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CC2)C2COC2)C2=CC=C(Br)C=C2)=C1 KJYIMWDAUCGCQZ-UHFFFAOYSA-N 0.000 description 3
• NCAHMIAUVLZBLD-UHFFFAOYSA-N 3-(4-bromophenyl)-1-[(3-methoxyphenyl)methyl]-N-methyl-2-oxo-1,3,8-triazaspiro[4.5]decane-8-carboxamide Chemical compound CNC(=O)N1CCC2(CN(C(=O)N2CC2=CC(OC)=CC=C2)C2=CC=C(Br)C=C2)CC1 NCAHMIAUVLZBLD-UHFFFAOYSA-N 0.000 description 3
• VYAFNMNHLSPBKO-UHFFFAOYSA-N 3-[[3-(4-bromophenyl)-2-oxo-8-oxa-1,3-diazaspiro[4.5]decan-1-yl]methyl]-N-methylbenzamide Chemical compound CNC(=O)C1=CC(CN2C(=O)N(CC22CCOCC2)C2=CC=C(Br)C=C2)=CC=C1 VYAFNMNHLSPBKO-UHFFFAOYSA-N 0.000 description 3
• IYOZTVGMEWJPKR-VOMCLLRMSA-N 4-[(1R)-1-aminoethyl]-N-pyridin-4-yl-1-cyclohexanecarboxamide Chemical compound C1CC([C@H](N)C)CCC1C(=O)NC1=CC=NC=C1 IYOZTVGMEWJPKR-VOMCLLRMSA-N 0.000 description 3
• XYWIPYBIIRTJMM-IBGZPJMESA-N 4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide Chemical compound CC[C@H](N1C=C(OC)C(=CC1=O)C1=C(C=CC(Cl)=C1)N1C=C(N=N1)C(F)(F)F)C(=O)NC1=CC(F)=C(C=C1)C(N)=O XYWIPYBIIRTJMM-IBGZPJMESA-N 0.000 description 3
• LYVOCESKGSKZJK-UHFFFAOYSA-N 6-(4-bromophenyl)-4-[(3-methoxyphenyl)methyl]-4,6-diazaspiro[2.4]heptan-5-one Chemical compound BrC1=CC=C(C=C1)N1C(N(C2(CC2)C1)CC1=CC(=CC=C1)OC)=O LYVOCESKGSKZJK-UHFFFAOYSA-N 0.000 description 3
• RXYGRDKXQMFJNO-UHFFFAOYSA-N 6-(4-bromophenyl)-4-[1-(3-methoxyphenyl)ethyl]-4,6-diazaspiro[2.4]heptan-5-one Chemical compound BrC1=CC=C(C=C1)N1C(N(C2(CC2)C1)C(C)C1=CC(=CC=C1)OC)=O RXYGRDKXQMFJNO-UHFFFAOYSA-N 0.000 description 3
• 206010003225 Arteriospasm coronary Diseases 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 0 C*(C(*)*(C)N(C1(CN2c(nc3)nc(*)c3-c3c[n]nc3)CCN(*)CC1)C2=O)c1ccccc1 Chemical compound C*(C(*)*(C)N(C1(CN2c(nc3)nc(*)c3-c3c[n]nc3)CCN(*)CC1)C2=O)c1ccccc1 0.000 description 3
• 208000003890 Coronary Vasospasm Diseases 0.000 description 3
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
• 208000010412 Glaucoma Diseases 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 239000007821 HATU Substances 0.000 description 3
• 241000282414 Homo sapiens Species 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• 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 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• 206010028980 Neoplasm Diseases 0.000 description 3
• 108091000080 Phosphotransferase Proteins 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 206010063837 Reperfusion injury Diseases 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 125000001931 aliphatic group Chemical group 0.000 description 3
• 125000003342 alkenyl group Chemical group 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 208000006673 asthma Diseases 0.000 description 3
• 125000005605 benzo group Chemical group 0.000 description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 230000036772 blood pressure Effects 0.000 description 3
• MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• 201000011510 cancer Diseases 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 229940125904 compound 1 Drugs 0.000 description 3
• 238000007796 conventional method Methods 0.000 description 3
• 201000011634 coronary artery vasospasm Diseases 0.000 description 3
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
• 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 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 230000002526 effect on cardiovascular system Effects 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 239000011521 glass Substances 0.000 description 3
• 150000002430 hydrocarbons Chemical group 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 230000004047 hyperresponsiveness Effects 0.000 description 3
• 125000002632 imidazolidinyl group Chemical group 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 238000007918 intramuscular administration Methods 0.000 description 3
• 229910052740 iodine Inorganic materials 0.000 description 3
• 208000028867 ischemia Diseases 0.000 description 3
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 3
• 125000000468 ketone group Chemical group 0.000 description 3
• 150000002576 ketones Chemical class 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 239000000314 lubricant Substances 0.000 description 3
• NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 150000007522 mineralic acids Chemical class 0.000 description 3
• 230000003287 optical effect Effects 0.000 description 3
• 239000000123 paper Substances 0.000 description 3
• 238000007911 parenteral administration Methods 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 102000020233 phosphotransferase Human genes 0.000 description 3
• 125000004193 piperazinyl group Chemical group 0.000 description 3
• 125000003386 piperidinyl group Chemical group 0.000 description 3
• 229920002223 polystyrene Polymers 0.000 description 3
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 3
• 235000011181 potassium carbonates Nutrition 0.000 description 3
• 229910000160 potassium phosphate Inorganic materials 0.000 description 3
• 235000011009 potassium phosphates Nutrition 0.000 description 3
• 239000012041 precatalyst Substances 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 125000003373 pyrazinyl group Chemical group 0.000 description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 description 3
• 125000000168 pyrrolyl group Chemical group 0.000 description 3
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 3
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 235000010265 sodium sulphite Nutrition 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 235000000346 sugar Nutrition 0.000 description 3
• YIAGIPUMQSTQNW-UHFFFAOYSA-N tert-butyl 2-methyloctanoate Chemical compound CCCCCCC(C)C(=O)OC(C)(C)C YIAGIPUMQSTQNW-UHFFFAOYSA-N 0.000 description 3
• WAKBJSSVEFWGNI-UHFFFAOYSA-N tert-butyl 2-oxo-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11NC(=O)NC1 WAKBJSSVEFWGNI-UHFFFAOYSA-N 0.000 description 3
• DBSPPHJKYJUFLA-UHFFFAOYSA-N tert-butyl 4-bromo-2-(5-bromo-4-methoxypyrimidin-2-yl)-3-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound BrC1C(N(CC11CCN(CC1)C(=O)OC(C)(C)C)C1=NC=C(C(=N1)OC)Br)=O DBSPPHJKYJUFLA-UHFFFAOYSA-N 0.000 description 3
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
• 230000009466 transformation Effects 0.000 description 3
• 238000000844 transformation Methods 0.000 description 3
• 125000001425 triazolyl group Chemical group 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• AAZCFOYBTCRVEJ-YUMQZZPRSA-N (2S,5S)-2,5-diethylphospholane Chemical compound CC[C@H]1CC[C@H](CC)P1 AAZCFOYBTCRVEJ-YUMQZZPRSA-N 0.000 description 2
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 2
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
• JBBOKHAGKJRMKV-UHFFFAOYSA-N 1-(4-bromophenyl)-3-[1-(hydroxymethyl)cyclopropyl]urea Chemical compound BrC1=CC=C(C=C1)NC(=O)NC1(CC1)CO JBBOKHAGKJRMKV-UHFFFAOYSA-N 0.000 description 2
• PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical compound OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 description 2
• DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 2
• BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 2
• VSCBATMPTLKTOV-UHFFFAOYSA-N 2-tert-butylimino-n,n-diethyl-1,3-dimethyl-1,3,2$l^{5}-diazaphosphinan-2-amine Chemical compound CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C VSCBATMPTLKTOV-UHFFFAOYSA-N 0.000 description 2
• BYHQTRFJOGIQAO-UHFFFAOYSA-N 3-(4-bromophenyl)-8-(2-hydroxypropyl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CC(C)O)CC2)C2=CC=C(Br)C=C2)=C1 BYHQTRFJOGIQAO-UHFFFAOYSA-N 0.000 description 2
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 2
• CMAUNZAVWIDLTM-UHFFFAOYSA-N 3-(4-bromophenyl)-8-[(4,4-difluorocyclohexyl)methyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CC3CCC(F)(F)CC3)CC2)C2=CC=C(Br)C=C2)=C1 CMAUNZAVWIDLTM-UHFFFAOYSA-N 0.000 description 2
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
• BXZNWBXUUWDFRE-UHFFFAOYSA-N 3-[[3-(4-bromophenyl)-2-oxo-8-oxa-1,3-diazaspiro[4.5]decan-1-yl]methyl]benzoic acid Chemical compound OC(=O)C1=CC(CN2C(=O)N(CC22CCOCC2)C2=CC=C(Br)C=C2)=CC=C1 BXZNWBXUUWDFRE-UHFFFAOYSA-N 0.000 description 2
• NBDKSEHBSJDUBX-UHFFFAOYSA-N 3-[[3-(4-bromophenyl)-2-oxo-8-oxa-1,3-diazaspiro[4.5]decan-1-yl]methyl]benzoyl chloride Chemical compound ClC(=O)C1=CC(CN2C(=O)N(CC22CCOCC2)C2=CC=C(Br)C=C2)=CC=C1 NBDKSEHBSJDUBX-UHFFFAOYSA-N 0.000 description 2
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
• UTIISFYTUAJTDV-UHFFFAOYSA-N 4-[(4-bromophenyl)carbamoylamino]-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound BrC1=CC=C(C=C1)NC(NC1(CCN(CC1)C(=O)OC(C)(C)C)C(=O)O)=O UTIISFYTUAJTDV-UHFFFAOYSA-N 0.000 description 2
• ANXOJJJCXLSEET-UHFFFAOYSA-N 4-[(4-bromophenyl)carbamoylamino]oxane-4-carboxylic acid Chemical compound BrC1=CC=C(C=C1)NC(NC1(CCOCC1)C(=O)O)=O ANXOJJJCXLSEET-UHFFFAOYSA-N 0.000 description 2
• ZPPORMCRNCNFGX-UHFFFAOYSA-N 5-bromo-2-chloro-4-methoxypyrimidine Chemical compound COC1=NC(Cl)=NC=C1Br ZPPORMCRNCNFGX-UHFFFAOYSA-N 0.000 description 2
• 229920000936 Agarose Polymers 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
• XVOQRFFINGKGSD-UHFFFAOYSA-N CC(C)(C)C(N=C(N=C1OC)Cl)=C1Br Chemical compound CC(C)(C)C(N=C(N=C1OC)Cl)=C1Br XVOQRFFINGKGSD-UHFFFAOYSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 201000000057 Coronary Stenosis Diseases 0.000 description 2
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• GSCCALZHGUWNJW-UHFFFAOYSA-N N-Cyclohexyl-N-methylcyclohexanamine Chemical compound C1CCCCC1N(C)C1CCCCC1 GSCCALZHGUWNJW-UHFFFAOYSA-N 0.000 description 2
• 150000001204 N-oxides Chemical class 0.000 description 2
• 238000005481 NMR spectroscopy Methods 0.000 description 2
• 208000012902 Nervous system disease Diseases 0.000 description 2
• 208000025966 Neurological disease Diseases 0.000 description 2
• 239000004677 Nylon Substances 0.000 description 2
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
• 229920000954 Polyglycolide Polymers 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
• RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
• 125000004450 alkenylene group Chemical group 0.000 description 2
• 125000004414 alkyl thio group Chemical group 0.000 description 2
• 125000002947 alkylene group Chemical group 0.000 description 2
• 125000004419 alkynylene group Chemical group 0.000 description 2
• 239000001099 ammonium carbonate Substances 0.000 description 2
• 235000012501 ammonium carbonate Nutrition 0.000 description 2
• 235000011114 ammonium hydroxide Nutrition 0.000 description 2
• 238000006254 arylation reaction Methods 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 2
• 125000004935 benzoxazolinyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 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 2
• 230000037396 body weight Effects 0.000 description 2
• 229910000085 borane Inorganic materials 0.000 description 2
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
• 125000002837 carbocyclic group Chemical group 0.000 description 2
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 239000011111 cardboard Substances 0.000 description 2
• 230000012292 cell migration Effects 0.000 description 2
• DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 2
• 239000007795 chemical reaction product Substances 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 229910052681 coesite Inorganic materials 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 239000002299 complementary DNA Substances 0.000 description 2
• 230000008602 contraction Effects 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
• 229910052906 cristobalite Inorganic materials 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 2
• 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 2
• 230000034994 death Effects 0.000 description 2
• 231100000517 death Toxicity 0.000 description 2
• NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 235000003599 food sweetener Nutrition 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 239000003292 glue Substances 0.000 description 2
• 229910052736 halogen Inorganic materials 0.000 description 2
• 125000005843 halogen group Chemical group 0.000 description 2
• 150000002367 halogens Chemical class 0.000 description 2
• 230000001631 hypertensive effect Effects 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 125000004926 indolenyl group Chemical group 0.000 description 2
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• 125000004936 isatinoyl group Chemical group N1(C(=O)C(=O)C2=CC=CC=C12)C(=O)* 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• 239000012948 isocyanate Substances 0.000 description 2
• 150000002513 isocyanates Chemical class 0.000 description 2
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 125000001786 isothiazolyl group Chemical group 0.000 description 2
• 238000002372 labelling Methods 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
• 235000019341 magnesium sulphate Nutrition 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• 230000008692 neointimal formation Effects 0.000 description 2
• 208000004296 neuralgia Diseases 0.000 description 2
• 208000021722 neuropathic pain Diseases 0.000 description 2
• 239000002547 new drug Substances 0.000 description 2
• 229920001778 nylon Polymers 0.000 description 2
• 239000003921 oil Substances 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 125000004095 oxindolyl group Chemical group N1(C(CC2=CC=CC=C12)=O)* 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 239000003182 parenteral nutrition solution Substances 0.000 description 2
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 2
• 229920000747 poly(lactic acid) Polymers 0.000 description 2
• 125000003367 polycyclic group Chemical group 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 239000004633 polyglycolic acid Substances 0.000 description 2
• 239000004626 polylactic acid Substances 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
• 238000001556 precipitation Methods 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 238000009117 preventive therapy Methods 0.000 description 2
• 238000011324 primary prophylaxis Methods 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 125000003226 pyrazolyl group Chemical group 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 208000037803 restenosis Diseases 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 description 2
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
• 235000012239 silicon dioxide Nutrition 0.000 description 2
• 150000003413 spiro compounds Chemical class 0.000 description 2
• 238000011699 spontaneously hypertensive rat Methods 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 235000011150 stannous chloride Nutrition 0.000 description 2
• 229910052682 stishovite Inorganic materials 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 150000008163 sugars Chemical class 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• 238000013268 sustained release Methods 0.000 description 2
• 239000012730 sustained-release form Substances 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• DHJXKTPWDXJQEK-UHFFFAOYSA-N tert-butyl 2,4-dioxo-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC21C(=O)NC(=O)N2 DHJXKTPWDXJQEK-UHFFFAOYSA-N 0.000 description 2
• VLUYHJFEWCRYOV-UHFFFAOYSA-N tert-butyl 2-(5-bromo-4-methoxypyrimidin-2-yl)-3-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound BrC=1C(=NC(=NC=1)N1CC2(CC1=O)CCN(CC2)C(=O)OC(C)(C)C)OC VLUYHJFEWCRYOV-UHFFFAOYSA-N 0.000 description 2
• ISPMGSDJJKFTEA-UHFFFAOYSA-N tert-butyl 3-(5-bromo-4-methoxypyrimidin-2-yl)-2-oxo-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound COC1=C(Br)C=NC(=N1)N1CC2(CCN(CC2)C(=O)OC(C)(C)C)NC1=O ISPMGSDJJKFTEA-UHFFFAOYSA-N 0.000 description 2
• FFPCUGVVDMIPIG-UHFFFAOYSA-N tert-butyl 6-(4-bromophenyl)-7-oxo-2,6-diazaspiro[3.4]octane-2-carboxylate Chemical compound BrC1=CC=C(C=C1)N1CC2(CN(C2)C(=O)OC(C)(C)C)CC1=O FFPCUGVVDMIPIG-UHFFFAOYSA-N 0.000 description 2
• YISDQEWWIMFORF-UHFFFAOYSA-N tert-butyl 8-bromo-6-(4-bromophenyl)-7-oxo-2,6-diazaspiro[3.4]octane-2-carboxylate Chemical compound BrC1C(N(CC11CN(C1)C(=O)OC(C)(C)C)C1=CC=C(C=C1)Br)=O YISDQEWWIMFORF-UHFFFAOYSA-N 0.000 description 2
• DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
• 125000003831 tetrazolyl group Chemical group 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 125000004525 thiadiazinyl group Chemical group S1NN=C(C=C1)* 0.000 description 2
• 125000001113 thiadiazolyl group Chemical group 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• 229910052905 tridymite Inorganic materials 0.000 description 2
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
• ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
• 239000002691 unilamellar liposome Substances 0.000 description 2
• 239000003643 water by type Substances 0.000 description 2
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 2
• SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
• XFQNWPYGEGCIMF-HCUGAJCMSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].[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.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 XFQNWPYGEGCIMF-HCUGAJCMSA-N 0.000 description 1
• XDIYNQZUNSSENW-UUBOPVPUSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• YUXKOWPNKJSTPQ-AXWWPMSFSA-N (2s,3r)-2-amino-3-hydroxybutanoic acid;(2s)-2-amino-3-hydroxypropanoic acid Chemical compound OC[C@H](N)C(O)=O.C[C@@H](O)[C@H](N)C(O)=O YUXKOWPNKJSTPQ-AXWWPMSFSA-N 0.000 description 1
• CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
• VAVHMEQFYYBAPR-ITWZMISCSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-1-phenyl-2-propan-2-ylpyrrol-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound CC(C)C1=C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=CN1C1=CC=CC=C1 VAVHMEQFYYBAPR-ITWZMISCSA-N 0.000 description 1
• FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
• 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
• 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
• LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 1
• YGBWEVLCLQXBKI-UHFFFAOYSA-N 1-(1-bromoethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(C(C)Br)=C1 YGBWEVLCLQXBKI-UHFFFAOYSA-N 0.000 description 1
• BGRAJZILUVNVIS-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCOCC3)C4=CC=C(C=C4)C5CNNC5 BGRAJZILUVNVIS-UHFFFAOYSA-N 0.000 description 1
• YSMBQPANVSYAKZ-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-8-(oxetan-3-yl)-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(CC23CCN(CC3)C4COC4)C5=CC=C(C=C5)C6CNNC6 YSMBQPANVSYAKZ-UHFFFAOYSA-N 0.000 description 1
• NHCFUFMMWMTGGK-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-N-methyl-2-oxo-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decane-8-carboxamide Chemical compound CNC(=O)N1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 NHCFUFMMWMTGGK-UHFFFAOYSA-N 0.000 description 1
• AFLJZPTXEVIOFA-UHFFFAOYSA-N 1-[(4-bromophenyl)carbamoylamino]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(Br)C=CC=1NC(=O)NC1(C(=O)O)CC1 AFLJZPTXEVIOFA-UHFFFAOYSA-N 0.000 description 1
• AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
• WEGOLYBUWCMMMY-UHFFFAOYSA-N 1-bromo-2-propanol Chemical compound CC(O)CBr WEGOLYBUWCMMMY-UHFFFAOYSA-N 0.000 description 1
• UCCUXODGPMAHRL-UHFFFAOYSA-N 1-bromo-4-iodobenzene Chemical compound BrC1=CC=C(I)C=C1 UCCUXODGPMAHRL-UHFFFAOYSA-N 0.000 description 1
• CZQIJQFTRGDODI-UHFFFAOYSA-N 1-bromo-4-isocyanatobenzene Chemical compound BrC1=CC=C(N=C=O)C=C1 CZQIJQFTRGDODI-UHFFFAOYSA-N 0.000 description 1
• MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
• JNOZGFXJZQXOSU-UHFFFAOYSA-N 1-chloro-2-methylpropan-2-ol Chemical compound CC(C)(O)CCl JNOZGFXJZQXOSU-UHFFFAOYSA-N 0.000 description 1
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• YOIQWEPLWVOUGA-UHFFFAOYSA-N 2-[1-[(3-methoxyphenyl)methyl]-2-oxo-3-(4-pyrazolidin-4-ylphenyl)-1,3,8-triazaspiro[4.5]decan-8-yl]-N-methylacetamide Chemical compound CNC(=O)CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)C5CNNC5 YOIQWEPLWVOUGA-UHFFFAOYSA-N 0.000 description 1
• IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
• 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
• MLONYBFKXHEPCD-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound OCC(N)(CO)CO.OCC(N)(CO)CO MLONYBFKXHEPCD-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• HOZLOOPIXHWKCI-UHFFFAOYSA-N 2-chloro-n-methylacetamide Chemical compound CNC(=O)CCl HOZLOOPIXHWKCI-UHFFFAOYSA-N 0.000 description 1
• 125000006040 2-hexenyl group Chemical group 0.000 description 1
• 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
• YSEQNZOXHCKLOG-UHFFFAOYSA-N 2-methyl-octanoic acid Chemical compound CCCCCCC(C)C(O)=O YSEQNZOXHCKLOG-UHFFFAOYSA-N 0.000 description 1
• 125000006024 2-pentenyl group Chemical group 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• MSRAZUGPWHWDHN-UHFFFAOYSA-N 2h-pyran-4-carboxylic acid Chemical compound OC(=O)C1=CCOC=C1 MSRAZUGPWHWDHN-UHFFFAOYSA-N 0.000 description 1
• BEPZZGYEDSKCMB-UHFFFAOYSA-N 3-(4-bromophenyl)-8-(2-hydroxyethyl)-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CCO)CC2)C2=CC=C(Br)C=C2)=C1 BEPZZGYEDSKCMB-UHFFFAOYSA-N 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• 125000006041 3-hexenyl group Chemical group 0.000 description 1
• ROADCYAOHVSOLQ-UHFFFAOYSA-N 3-oxetanone Chemical compound O=C1COC1 ROADCYAOHVSOLQ-UHFFFAOYSA-N 0.000 description 1
• HYIUDFLDFSIXTR-UHFFFAOYSA-N 4,4-difluorocyclohexane-1-carboxylic acid Chemical compound OC(=O)C1CCC(F)(F)CC1 HYIUDFLDFSIXTR-UHFFFAOYSA-N 0.000 description 1
• OMOWLHCKRBLDLR-UHFFFAOYSA-N 4-(3-methoxyanilino)-2-(4-methoxy-5-pyrazolidin-4-ylpyrimidin-2-yl)-8-(pyrazolo[1,5-a]pyridine-3-carbonyl)-2,8-diazaspiro[4.5]decan-3-one Chemical compound COC1=CC=CC(=C1)NC2C(=O)N(CC23CCN(CC3)C(=O)C4=C5C=CC=CN5N=C4)C6=NC=C(C(=N6)OC)C7CNNC7 OMOWLHCKRBLDLR-UHFFFAOYSA-N 0.000 description 1
• FCXAYEPBCJFGPO-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole-1-carboxylic acid Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(C(O)=O)N=C1 FCXAYEPBCJFGPO-UHFFFAOYSA-N 0.000 description 1
• YNHLVALLAURVJF-UHFFFAOYSA-N 4-amino-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC(N)(C(O)=O)CC1 YNHLVALLAURVJF-UHFFFAOYSA-N 0.000 description 1
• DPDPQQHHTHKSRN-UHFFFAOYSA-N 4-aminooxane-4-carboxylic acid Chemical compound OC(=O)C1(N)CCOCC1 DPDPQQHHTHKSRN-UHFFFAOYSA-N 0.000 description 1
• WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 1
• 125000006042 4-hexenyl group Chemical group 0.000 description 1
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000003119 4-methyl-3-pentenyl group Chemical group [H]\C(=C(/C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
• FLDSMVTWEZKONL-AWEZNQCLSA-N 5,5-dimethyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1,4,7,8-tetrahydrooxepino[4,5-c]pyrazole-3-carboxamide Chemical compound CC1(CC2=C(NN=C2C(=O)N[C@@H]2C(N(C3=C(OC2)C=CC=C3)C)=O)CCO1)C FLDSMVTWEZKONL-AWEZNQCLSA-N 0.000 description 1
• 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 description 1
• ZMGMDXCADSRNCX-UHFFFAOYSA-N 5,6-dihydroxy-1,3-diazepan-2-one Chemical compound OC1CNC(=O)NCC1O ZMGMDXCADSRNCX-UHFFFAOYSA-N 0.000 description 1
• SIKXIUWKPGWBBF-UHFFFAOYSA-N 5-bromo-2,4-dichloropyrimidine Chemical compound ClC1=NC=C(Br)C(Cl)=N1 SIKXIUWKPGWBBF-UHFFFAOYSA-N 0.000 description 1
• 125000006043 5-hexenyl group Chemical group 0.000 description 1
• 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
• CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Chemical group O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• VGIRGDRNPWHJNL-UHFFFAOYSA-N 8-(2-hydroxy-2-methylpropyl)-1-[(3-methoxyphenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CC(C)(C)O)CC2)C2=CC=C(C=C2)C2=CNN=C2)=C1 VGIRGDRNPWHJNL-UHFFFAOYSA-N 0.000 description 1
• BBHSJBWSVZIKFI-UHFFFAOYSA-N 8-[(4,4-difluorocyclohexyl)methyl]-1-[(3-methoxyphenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CC3CCC(F)(F)CC3)CC2)C2=CC=C(C=C2)C2=CNN=C2)=C1 BBHSJBWSVZIKFI-UHFFFAOYSA-N 0.000 description 1
• XCLDTSIVQWWTGZ-UHFFFAOYSA-N 8-acetyl-1-[(3-methoxyphenyl)methyl]-3-[4-(1H-pyrazol-4-yl)phenyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound COC1=CC=CC(CN2C(=O)N(CC22CCN(CC2)C(C)=O)C2=CC=C(C=C2)C2=CNN=C2)=C1 XCLDTSIVQWWTGZ-UHFFFAOYSA-N 0.000 description 1
• 239000005541 ACE inhibitor Substances 0.000 description 1
• OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 102000007469 Actins Human genes 0.000 description 1
• 108010085238 Actins Proteins 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 229920000856 Amylose Polymers 0.000 description 1
• 102400000345 Angiotensin-2 Human genes 0.000 description 1
• 101800000733 Angiotensin-2 Proteins 0.000 description 1
• 102000015427 Angiotensins Human genes 0.000 description 1
• 108010064733 Angiotensins Proteins 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 229910015845 BBr3 Inorganic materials 0.000 description 1
• GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
• 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
• QTGRLXCDAWOXPD-KQQUZDAGSA-N C/C(/C(/C)=N/C)=N\C Chemical compound C/C(/C(/C)=N/C)=N\C QTGRLXCDAWOXPD-KQQUZDAGSA-N 0.000 description 1
• 125000000041 C6-C10 aryl group Chemical group 0.000 description 1
• NRLMBJAXBSSZLH-UHFFFAOYSA-N CC(C)(C)OC(N(C1)CC1(CN(C1=O)c(cc2)ccc2-c2c[nH]nc2)C1Nc1cccc(OC)c1)=O Chemical compound CC(C)(C)OC(N(C1)CC1(CN(C1=O)c(cc2)ccc2-c2c[nH]nc2)C1Nc1cccc(OC)c1)=O NRLMBJAXBSSZLH-UHFFFAOYSA-N 0.000 description 1
• TTWNXXXZMABTEX-UHFFFAOYSA-N CC1C(CNC)=CC(CN(C2(CN3c(cc4)ccc4Br)CCOCC2)C3=O)=CC1 Chemical compound CC1C(CNC)=CC(CN(C2(CN3c(cc4)ccc4Br)CCOCC2)C3=O)=CC1 TTWNXXXZMABTEX-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 206010007559 Cardiac failure congestive Diseases 0.000 description 1
• 229930186147 Cephalosporin Natural products 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 108020004635 Complementary DNA Proteins 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical group OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
• 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 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
• 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 102400000686 Endothelin-1 Human genes 0.000 description 1
• 101800004490 Endothelin-1 Proteins 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
• XNLWZFDLOBDYSS-UHFFFAOYSA-M FC(S(=O)(=O)[O-])(F)F.[Rh+].C1=CCCC=CCC1.C1=CC=CC=C1 Chemical compound FC(S(=O)(=O)[O-])(F)F.[Rh+].C1=CCCC=CCC1.C1=CC=CC=C1 XNLWZFDLOBDYSS-UHFFFAOYSA-M 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 108091006027 G proteins Proteins 0.000 description 1
• 102000030782 GTP binding Human genes 0.000 description 1
• 108091000058 GTP-Binding Proteins 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 229910004373 HOAc Inorganic materials 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000684275 Homo sapiens ADP-ribosylation factor 3 Proteins 0.000 description 1
• 101001000061 Homo sapiens Protein phosphatase 1 regulatory subunit 12A Proteins 0.000 description 1
• 101001130437 Homo sapiens Ras-related protein Rap-2b Proteins 0.000 description 1
• 101000669917 Homo sapiens Rho-associated protein kinase 1 Proteins 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
• 206010061216 Infarction Diseases 0.000 description 1
• 102000003777 Interleukin-1 beta Human genes 0.000 description 1
• 108090000193 Interleukin-1 beta Proteins 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 229920001410 Microfiber Polymers 0.000 description 1
• 108010037801 Myosin-Light-Chain Phosphatase Proteins 0.000 description 1
• 102000011131 Myosin-Light-Chain Phosphatase Human genes 0.000 description 1
• JCRZEVOVVSCTKH-UHFFFAOYSA-N N-methyl-3-[[2-oxo-3-(4-pyrazolidin-4-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]decan-1-yl]methyl]benzamide Chemical compound CNC(=O)C1=CC=CC(=C1)CN2C(=O)N(CC23CCOCC3)C4=CC=C(C=C4)C5CNNC5 JCRZEVOVVSCTKH-UHFFFAOYSA-N 0.000 description 1
• YRYXLWNXHJIZQN-UHFFFAOYSA-N NC1=[I][I]=C(Br)[I]=[I]1 Chemical compound NC1=[I][I]=C(Br)[I]=[I]1 YRYXLWNXHJIZQN-UHFFFAOYSA-N 0.000 description 1
• 208000034827 Neointima Diseases 0.000 description 1
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
• HWPDAGQTJYPVLX-UHFFFAOYSA-N O=C(NC1=[I][I]=C(Br)[I]=[I]1)Oc1ccccc1 Chemical compound O=C(NC1=[I][I]=C(Br)[I]=[I]1)Oc1ccccc1 HWPDAGQTJYPVLX-UHFFFAOYSA-N 0.000 description 1
• REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
• 102000015636 Oligopeptides Human genes 0.000 description 1
• 108010038807 Oligopeptides Chemical group 0.000 description 1
• 229910019213 POCl3 Inorganic materials 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 229910002666 PdCl2 Inorganic materials 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
• 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 102100036547 Protein phosphatase 1 regulatory subunit 12A Human genes 0.000 description 1
• 229910000564 Raney nickel Inorganic materials 0.000 description 1
• 102100031421 Ras-related protein Rap-2b Human genes 0.000 description 1
• 208000001647 Renal Insufficiency Diseases 0.000 description 1
• 206010062237 Renal impairment Diseases 0.000 description 1
• 208000002200 Respiratory Hypersensitivity Diseases 0.000 description 1
• 102100039313 Rho-associated protein kinase 1 Human genes 0.000 description 1
• 102100027609 Rho-related GTP-binding protein RhoD Human genes 0.000 description 1
• 229940124639 Selective inhibitor Drugs 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
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 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 1
• 229930006000 Sucrose Natural products 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 102000050488 Urotensin II Human genes 0.000 description 1
• 108010018369 Urotensin II Proteins 0.000 description 1
• 206010047295 Ventricular hypertrophy Diseases 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• WGOBPPNNYVSJTE-HSZRJFAPSA-N [(2r)-1-diphenylphosphanylpropan-2-yl]-diphenylphosphane Chemical compound C([C@@H](C)P(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)C1=CC=CC=C1 WGOBPPNNYVSJTE-HSZRJFAPSA-N 0.000 description 1
• UJQAHAANAPEYLR-UHFFFAOYSA-N [2-chloro-6-[2,4,6-tri(propan-2-yl)phenyl]phenyl]-dicyclohexylphosphane Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC(Cl)=C1P(C1CCCCC1)C1CCCCC1 UJQAHAANAPEYLR-UHFFFAOYSA-N 0.000 description 1
• CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical group [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 1
• JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 description 1
• 159000000021 acetate salts Chemical class 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
• 150000008043 acidic salts Chemical class 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 230000001070 adhesive effect Effects 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 208000037883 airway inflammation Diseases 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000001447 alkali salts Chemical class 0.000 description 1
• 125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 1
• 125000006177 alkyl benzyl group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• XKMRRTOUMJRJIA-UHFFFAOYSA-N ammonia nh3 Chemical compound N.N XKMRRTOUMJRJIA-UHFFFAOYSA-N 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 229950006323 angiotensin ii Drugs 0.000 description 1
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
• 150000001502 aryl halides Chemical class 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
• 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 239000000440 bentonite Substances 0.000 description 1
• 229910000278 bentonite Inorganic materials 0.000 description 1
• 235000012216 bentonite Nutrition 0.000 description 1
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
• 229960000686 benzalkonium chloride Drugs 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical group C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
• RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• 125000005512 benztetrazolyl group Chemical group 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
• FCDPQMAOJARMTG-UHFFFAOYSA-L benzylidene-[1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene]-dichlororuthenium;tricyclohexylphosphane Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1.CC1=CC(C)=CC(C)=C1N(CCN1C=2C(=CC(C)=CC=2C)C)C1=[Ru](Cl)(Cl)=CC1=CC=CC=C1 FCDPQMAOJARMTG-UHFFFAOYSA-L 0.000 description 1
• FCDPQMAOJARMTG-UHFFFAOYSA-M benzylidene-[1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene]-dichlororuthenium;tricyclohexylphosphanium Chemical compound C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.CC1=CC(C)=CC(C)=C1N(CCN1C=2C(=CC(C)=CC=2C)C)C1=[Ru](Cl)(Cl)=CC1=CC=CC=C1 FCDPQMAOJARMTG-UHFFFAOYSA-M 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 239000002876 beta blocker Substances 0.000 description 1
• 229940097320 beta blocking agent Drugs 0.000 description 1
• 239000012867 bioactive agent Substances 0.000 description 1
• 230000000975 bioactive effect Effects 0.000 description 1
• 229920002988 biodegradable polymer Polymers 0.000 description 1
• 239000004621 biodegradable polymer Substances 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 229920001400 block copolymer Polymers 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• KZMGYPLQYOPHEL-UHFFFAOYSA-N boron trifluoride etherate Substances FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 238000010804 cDNA synthesis Methods 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 235000011132 calcium sulphate Nutrition 0.000 description 1
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 150000001735 carboxylic acids Chemical group 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 229940105329 carboxymethylcellulose Drugs 0.000 description 1
• 210000004027 cell Anatomy 0.000 description 1
• 230000021164 cell adhesion Effects 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 230000005754 cellular signaling Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 229940124587 cephalosporin Drugs 0.000 description 1
• 150000001780 cephalosporins Chemical class 0.000 description 1
• CDVMXMZPDJHSCC-UHFFFAOYSA-N chembl1684662 Chemical compound C=1C=C2C=C(C=3C4=NC=CC=C4NN=3)NC2=CC=1CC(=O)C1=CC=CC=C1 CDVMXMZPDJHSCC-UHFFFAOYSA-N 0.000 description 1
• 125000003636 chemical group Chemical group 0.000 description 1
• 238000005229 chemical vapour deposition Methods 0.000 description 1
• 230000035605 chemotaxis Effects 0.000 description 1
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
• 208000037998 chronic venous disease Diseases 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 238000013267 controlled drug release Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
• XSYZCZPCBXYQTE-UHFFFAOYSA-N cyclodecylcyclodecane Chemical compound C1CCCCCCCCC1C1CCCCCCCCC1 XSYZCZPCBXYQTE-UHFFFAOYSA-N 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
• 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 230000021953 cytokinesis Effects 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 125000001295 dansyl group Chemical group [H]C1=C([H])C(N(C([H])([H])[H])C([H])([H])[H])=C2C([H])=C([H])C([H])=C(C2=C1[H])S(*)(=O)=O 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
• 239000007933 dermal patch Substances 0.000 description 1
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
• 150000001975 deuterium Chemical group 0.000 description 1
• DIXBSCZRIZDQGC-UHFFFAOYSA-N diaziridine Chemical group C1NN1 DIXBSCZRIZDQGC-UHFFFAOYSA-N 0.000 description 1
• 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• ASWXNYNXAOQCCD-UHFFFAOYSA-N dichloro(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Cl)(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 ASWXNYNXAOQCCD-UHFFFAOYSA-N 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 102000038379 digestive enzymes Human genes 0.000 description 1
• 108091007734 digestive enzymes Proteins 0.000 description 1
• BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 150000002016 disaccharides Chemical class 0.000 description 1
• 239000002934 diuretic Substances 0.000 description 1
• 229940030606 diuretics Drugs 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 239000012039 electrophile Substances 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000002124 endocrine Effects 0.000 description 1
• 238000006911 enzymatic reaction Methods 0.000 description 1
• 230000001856 erectile effect Effects 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• OLAMWIPURJGSKE-UHFFFAOYSA-N et2o diethylether Chemical compound CCOCC.CCOCC OLAMWIPURJGSKE-UHFFFAOYSA-N 0.000 description 1
• OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
• VJYFKVYYMZPMAB-UHFFFAOYSA-N ethoprophos Chemical compound CCCSP(=O)(OCC)SCCC VJYFKVYYMZPMAB-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 210000001105 femoral artery Anatomy 0.000 description 1
• 230000004761 fibrosis Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical group O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 238000001215 fluorescent labelling Methods 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 125000003709 fluoroalkyl group Chemical group 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 125000003838 furazanyl group Chemical group 0.000 description 1
• 229930182830 galactose Chemical group 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 125000004995 haloalkylthio group Chemical group 0.000 description 1
• 125000001475 halogen functional group Chemical group 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 229910001385 heavy metal Inorganic materials 0.000 description 1
• 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000005980 hexynyl group Chemical group 0.000 description 1
• 238000004896 high resolution mass spectrometry Methods 0.000 description 1
• WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
• 229940091173 hydantoin Drugs 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 238000013299 hypertensive rat model Methods 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 210000002865 immune cell Anatomy 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 230000007574 infarction Effects 0.000 description 1
• 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• SYJRVVFAAIUVDH-UHFFFAOYSA-N ipa isopropanol Chemical compound CC(C)O.CC(C)O SYJRVVFAAIUVDH-UHFFFAOYSA-N 0.000 description 1
• 230000007794 irritation Effects 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
• 125000005438 isoindazolyl group Chemical group 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 201000006370 kidney failure Diseases 0.000 description 1
• 230000003907 kidney function Effects 0.000 description 1
• 150000003951 lactams Chemical class 0.000 description 1
• 229910052747 lanthanoid Inorganic materials 0.000 description 1
• 150000002602 lanthanoids Chemical class 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 239000008297 liquid dosage form Substances 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 230000003908 liver function Effects 0.000 description 1
• 238000011866 long-term treatment Methods 0.000 description 1
• HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical group O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
• 229910021645 metal ion Inorganic materials 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
• YUHSMQQNPRLEEJ-UHFFFAOYSA-N methyl 3-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC(CBr)=C1 YUHSMQQNPRLEEJ-UHFFFAOYSA-N 0.000 description 1
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 239000003658 microfiber Substances 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 150000002772 monosaccharides Chemical class 0.000 description 1
• PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• GRRYSIXDUIAUGY-UHFFFAOYSA-N n-methylcarbamoyl chloride Chemical compound CNC(Cl)=O GRRYSIXDUIAUGY-UHFFFAOYSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000007971 neurological deficit Effects 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
• SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
• 229960002748 norepinephrine Drugs 0.000 description 1
• 238000004958 nuclear spectroscopy Methods 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 229940126701 oral medication Drugs 0.000 description 1
• 239000007935 oral tablet Substances 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
• MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 125000005981 pentynyl group Chemical group 0.000 description 1
• 239000002304 perfume Substances 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 229940127557 pharmaceutical product Drugs 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
• 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
• 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
• 125000005954 phenoxathiinyl group Chemical group 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• 150000008105 phosphatidylcholines Chemical class 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 1
• 125000004928 piperidonyl group Chemical group 0.000 description 1
• LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 1
• 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229920000656 polylysine Polymers 0.000 description 1
• 229920006324 polyoxymethylene Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 230000003449 preventive effect Effects 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 230000012743 protein tagging Effects 0.000 description 1
• 210000001243 pseudopodia Anatomy 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• HRSDPDBQVZHCRC-UHFFFAOYSA-N pyrazolo[1,5-a]pyridine-3-carboxylic acid Chemical compound C1=CC=CC2=C(C(=O)O)C=NN21 HRSDPDBQVZHCRC-UHFFFAOYSA-N 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 238000003908 quality control method Methods 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 102000016914 ras Proteins Human genes 0.000 description 1
• 108010014186 ras Proteins Proteins 0.000 description 1
• 238000011552 rat model Methods 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 230000016487 regulation of smooth muscle contraction Effects 0.000 description 1
• 238000007634 remodeling Methods 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 125000006413 ring segment Chemical group 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 239000008299 semisolid dosage form Substances 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 229940076279 serotonin Drugs 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000015424 sodium Nutrition 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
• RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
• PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
• WGRULTCAYDOGQK-UHFFFAOYSA-M sodium;sodium;hydroxide Chemical compound [OH-].[Na].[Na+] WGRULTCAYDOGQK-UHFFFAOYSA-M 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 238000007614 solvation Methods 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 208000020431 spinal cord injury Diseases 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• QYJKXSHVEMVDFH-UHFFFAOYSA-N tert-butyl 2-(5-bromo-4-methoxypyrimidin-2-yl)-4-(3-methoxyanilino)-3-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound BrC=1C(=NC(=NC=1)N1CC2(C(C1=O)NC1=CC(=CC=C1)OC)CCN(CC2)C(=O)OC(C)(C)C)OC QYJKXSHVEMVDFH-UHFFFAOYSA-N 0.000 description 1
• HNMWIKVFYHYBKX-UHFFFAOYSA-N tert-butyl 3-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11CC(=O)NC1 HNMWIKVFYHYBKX-UHFFFAOYSA-N 0.000 description 1
• ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
• IRALTYPUIGPWFA-UHFFFAOYSA-N tert-butyl 6-oxo-2,7-diazaspiro[3.4]octane-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC21CC(=O)NC2 IRALTYPUIGPWFA-UHFFFAOYSA-N 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
• PHCBRBWANGJMHS-UHFFFAOYSA-J tetrasodium;disulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O PHCBRBWANGJMHS-UHFFFAOYSA-J 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
• 125000005309 thioalkoxy group Chemical group 0.000 description 1
• 125000005403 thiohaloalkoxy group Chemical group 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 229940062627 tribasic potassium phosphate Drugs 0.000 description 1
• FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• 125000006168 tricyclic group Chemical group 0.000 description 1
• GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-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
• 229910052722 tritium Inorganic materials 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Chemical group Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
• ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical group C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
• HFNHAPQMXICKCF-USJMABIRSA-N urotensin-ii Chemical compound N([C@@H](CC(O)=O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@@H](C(C)C)C(O)=O)C(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](N)CCC(O)=O)[C@@H](C)O HFNHAPQMXICKCF-USJMABIRSA-N 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 230000002227 vasoactive effect Effects 0.000 description 1
• PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
• 229930195724 β-lactose Natural products 0.000 description 1
• PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1