ES2781309T3 - Triazolonas y tetrazolonas como inhibidores de ROCK - Google Patents

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Publication number

ES2781309T3

ES2781309T3 ES17728029T ES17728029T ES2781309T3 ES 2781309 T3 ES2781309 T3 ES 2781309T3 ES 17728029 T ES17728029 T ES 17728029T ES 17728029 T ES17728029 T ES 17728029T ES 2781309 T3 ES2781309 T3 ES 2781309T3

Authority

ES

Spain

Prior art keywords

substituted

phenyl

pyrazol

independently selected

triazol

Prior art date

2016-05-27

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

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• 239000011435 rock Substances 0.000 title description 37
• 239000003112 inhibitor Substances 0.000 title description 11
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 319
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 204
• 150000001875 compounds Chemical class 0.000 claims abstract description 142
• 229910052702 rhenium Inorganic materials 0.000 claims abstract description 136
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 124
• 229910052801 chlorine Inorganic materials 0.000 claims abstract description 115
• 229910052731 fluorine Inorganic materials 0.000 claims abstract description 115
• 229910052794 bromium Inorganic materials 0.000 claims abstract description 109
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 76
• 229910021481 rutherfordium Inorganic materials 0.000 claims abstract description 73
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 64
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 63
• 150000003839 salts Chemical class 0.000 claims abstract description 56
• 101150105130 RORB gene Proteins 0.000 claims abstract description 52
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 46
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 40
• 125000003118 aryl group Chemical group 0.000 claims abstract description 40
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 30
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 26
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 25
• 229910052701 rubidium Inorganic materials 0.000 claims abstract description 23
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 15
• 125000004452 carbocyclyl group Chemical group 0.000 claims abstract description 13
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims abstract description 5
• 229910052700 potassium Inorganic materials 0.000 claims abstract description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 3
• 229910052799 carbon Inorganic materials 0.000 claims description 201
• -1 1H-pyrazol-4-yl Chemical group 0.000 claims description 107
• 238000002360 preparation method Methods 0.000 claims description 44
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
• 229910052760 oxygen Inorganic materials 0.000 claims description 30
• 238000011282 treatment Methods 0.000 claims description 24
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 23
• 201000010099 disease Diseases 0.000 claims description 22
• 239000008194 pharmaceutical composition Substances 0.000 claims description 16
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 15
• 208000035475 disorder Diseases 0.000 claims description 15
• 230000000694 effects Effects 0.000 claims description 15
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 14
• 206010020772 Hypertension Diseases 0.000 claims description 10
• 239000003937 drug carrier Substances 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
• 102100033380 Chordin Human genes 0.000 claims description 8
• 101000943798 Homo sapiens Chordin Proteins 0.000 claims description 8
• 208000006011 Stroke Diseases 0.000 claims description 8
• 238000011321 prophylaxis Methods 0.000 claims description 8
• 125000003342 alkenyl group Chemical group 0.000 claims description 7
• 210000002460 smooth muscle Anatomy 0.000 claims description 7
• WIOWHADKSXUKEZ-UHFFFAOYSA-N dicyclohexyl-[3-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC(P(C2CCCCC2)C2CCCCC2)=C1 WIOWHADKSXUKEZ-UHFFFAOYSA-N 0.000 claims description 6
• 230000003176 fibrotic effect Effects 0.000 claims description 6
• HCOWWJVVBRBXBF-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-4-[4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1N=NN(C1=O)CC1=CC(=CC=C1)OC HCOWWJVVBRBXBF-UHFFFAOYSA-N 0.000 claims description 5
• 206010019280 Heart failures Diseases 0.000 claims description 5
• 208000027866 inflammatory disease Diseases 0.000 claims description 5
• YLSCUWQFIKOKIZ-UHFFFAOYSA-N 2-[(2,5-difluorophenyl)methyl]-4-(2-methoxy-4-pyrazolidin-4-ylphenyl)-1,2,4-triazol-3-one Chemical compound COC1=C(C=CC(=C1)C2CNNC2)N3C=NN(C3=O)CC4=C(C=CC(=C4)F)F YLSCUWQFIKOKIZ-UHFFFAOYSA-N 0.000 claims description 4
• CHUAJBPDNHOOAT-UHFFFAOYSA-N 4-benzyl-2-[4-(1H-pyrazol-4-yl)phenyl]-1,2,4-triazol-3-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1N=CN(C1=O)CC1=CC=CC=C1 CHUAJBPDNHOOAT-UHFFFAOYSA-N 0.000 claims description 4
• KQVZWUDGYVEWPK-UHFFFAOYSA-N 5-(hydroxymethyl)-4-[(3-methoxyphenyl)methyl]-2-[4-(1H-pyrazol-4-yl)phenyl]-1,2,4-triazol-3-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1N=C(N(C1=O)CC1=CC(=CC=C1)OC)CO KQVZWUDGYVEWPK-UHFFFAOYSA-N 0.000 claims description 4
• 206010002383 Angina Pectoris Diseases 0.000 claims description 4
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 208000002815 pulmonary hypertension Diseases 0.000 claims description 4
• CNLAYXDKLHCQMA-UHFFFAOYSA-N 2-[4-(2-aminopyridin-4-yl)phenyl]-4-[(3-methoxyphenyl)methyl]-5-methyl-1,2,4-triazol-3-one Chemical compound NC1=NC=CC(=C1)C1=CC=C(C=C1)N1N=C(N(C1=O)CC1=CC(=CC=C1)OC)C CNLAYXDKLHCQMA-UHFFFAOYSA-N 0.000 claims description 3
• NZPUJHVXZQBLFP-UHFFFAOYSA-N 2-benzyl-5-methyl-4-[4-(1H-pyrazol-4-yl)phenyl]-1,2,4-triazol-3-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1C(=NN(C1=O)CC1=CC=CC=C1)C NZPUJHVXZQBLFP-UHFFFAOYSA-N 0.000 claims description 3
• WJEJXTSVSCSNIW-UHFFFAOYSA-N 4-benzyl-5-methyl-2-[4-(1H-pyrazol-4-yl)phenyl]-1,2,4-triazol-3-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1N=C(N(C1=O)CC1=CC=CC=C1)C WJEJXTSVSCSNIW-UHFFFAOYSA-N 0.000 claims description 3
• 208000023275 Autoimmune disease Diseases 0.000 claims description 3
• 230000002159 abnormal effect Effects 0.000 claims description 3
• 208000029078 coronary artery disease Diseases 0.000 claims description 3
• 230000002981 neuropathic effect Effects 0.000 claims description 3
• 230000000771 oncological effect Effects 0.000 claims description 3
• SBXZSRBIFZQTFW-UHFFFAOYSA-N 1-(1-phenylethyl)-4-[4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1N=NN(C1=O)C(C)C1=CC=CC=C1 SBXZSRBIFZQTFW-UHFFFAOYSA-N 0.000 claims description 2
• MZHVBGWMFTZTIN-UHFFFAOYSA-N 1-[(2,5-difluorophenyl)methyl]-4-[3-methoxy-4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound FC1=C(CN2N=NN(C2=O)C2=CC(=C(C=C2)C=2C=NNC=2)OC)C=C(C=C1)F MZHVBGWMFTZTIN-UHFFFAOYSA-N 0.000 claims description 2
• KWULMTIIAPDEDB-UHFFFAOYSA-N 1-[(2,5-difluorophenyl)methyl]-4-[4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1N=NN(C1=O)CC1=C(C=CC(=C1)F)F KWULMTIIAPDEDB-UHFFFAOYSA-N 0.000 claims description 2
• WRYSVXYAJBVPFV-UHFFFAOYSA-N 1-[(2,6-difluorophenyl)methyl]-4-[3-methoxy-4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound FC1=C(CN2N=NN(C2=O)C2=CC(=C(C=C2)C=2C=NNC=2)OC)C(=CC=C1)F WRYSVXYAJBVPFV-UHFFFAOYSA-N 0.000 claims description 2
• HGWQMEPVCKVODS-UHFFFAOYSA-N 1-[(2-chlorophenyl)methyl]-4-[4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1N=NN(C1=O)CC1=C(C=CC=C1)Cl HGWQMEPVCKVODS-UHFFFAOYSA-N 0.000 claims description 2
• VYCJFSPNVUUXKJ-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]-4-[3-methoxy-4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound FC1=C(CN2N=NN(C2=O)C2=CC(=C(C=C2)C=2C=NNC=2)OC)C=CC=C1 VYCJFSPNVUUXKJ-UHFFFAOYSA-N 0.000 claims description 2
• FDFIDSBCANZIPW-UHFFFAOYSA-N 1-[(3-fluoro-5-methoxyphenyl)methyl]-4-[3-methoxy-4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound FC=1C=C(CN2N=NN(C2=O)C2=CC(=C(C=C2)C=2C=NNC=2)OC)C=C(C=1)OC FDFIDSBCANZIPW-UHFFFAOYSA-N 0.000 claims description 2
• AGOHQYODEKRYLB-UHFFFAOYSA-N 1-[(3-fluoro-5-methoxyphenyl)methyl]-4-[4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1N=NN(C1=O)CC1=CC(=CC(=C1)OC)F AGOHQYODEKRYLB-UHFFFAOYSA-N 0.000 claims description 2
• WBBFQRUOAIEACE-UHFFFAOYSA-N 1-[(3-fluorophenyl)methyl]-4-[3-methoxy-4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound FC=1C=C(CN2N=NN(C2=O)C2=CC(=C(C=C2)C=2C=NNC=2)OC)C=CC=1 WBBFQRUOAIEACE-UHFFFAOYSA-N 0.000 claims description 2
• HXZNRIGBNUJHRG-UHFFFAOYSA-N 1-[(3-fluorophenyl)methyl]-4-[4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1N=NN(C1=O)CC1=CC(=CC=C1)F HXZNRIGBNUJHRG-UHFFFAOYSA-N 0.000 claims description 2
• AMOIAMLLRYOOID-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-4-[3-methoxy-4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound COC=1C=C(C=CC=1C=1C=NNC=1)N1N=NN(C1=O)CC1=CC(=CC=C1)OC AMOIAMLLRYOOID-UHFFFAOYSA-N 0.000 claims description 2
• KJKGFOYVLLMZFK-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]-4-[3-methoxy-4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound FC1=CC=C(CN2N=NN(C2=O)C2=CC(=C(C=C2)C=2C=NNC=2)OC)C=C1 KJKGFOYVLLMZFK-UHFFFAOYSA-N 0.000 claims description 2
• MFKSHWINVZRZCI-UHFFFAOYSA-N 1-benzyl-4-[3-methoxy-4-(1H-pyrazol-4-yl)phenyl]tetrazol-5-one Chemical compound C(C1=CC=CC=C1)N1N=NN(C1=O)C1=CC(=C(C=C1)C=1C=NNC=1)OC MFKSHWINVZRZCI-UHFFFAOYSA-N 0.000 claims description 2
• WIJFUYFJFZKXGF-UHFFFAOYSA-N 2-(3-ethyl-4-pyrazolidin-4-ylphenyl)-4-(1-phenylethyl)-1,2,4-triazol-3-one Chemical compound CCC1=C(C=CC(=C1)N2C(=O)N(C=N2)C(C)C3=CC=CC=C3)C4CNNC4 WIJFUYFJFZKXGF-UHFFFAOYSA-N 0.000 claims description 2
• QTBSWLFVOJJIAZ-UHFFFAOYSA-N 2-(3-ethyl-4-pyrazolidin-4-ylphenyl)-4-[(2-fluorophenyl)methyl]-1,2,4-triazol-3-one Chemical compound CCC1=C(C=CC(=C1)N2C(=O)N(C=N2)CC3=CC=CC=C3F)C4CNNC4 QTBSWLFVOJJIAZ-UHFFFAOYSA-N 0.000 claims description 2
• BFDUHUMHBNAQOL-UHFFFAOYSA-N 2-(3-ethyl-4-pyrazolidin-4-ylphenyl)-4-[(3-fluoro-5-methoxyphenyl)methyl]-1,2,4-triazol-3-one Chemical compound CCC1=C(C=CC(=C1)N2C(=O)N(C=N2)CC3=CC(=CC(=C3)F)OC)C4CNNC4 BFDUHUMHBNAQOL-UHFFFAOYSA-N 0.000 claims description 2
• PDAZITHKSFDQJY-UHFFFAOYSA-N 2-(3-ethyl-4-pyrazolidin-4-ylphenyl)-4-[(3-methoxyphenyl)methyl]-1,2,4-triazol-3-one Chemical compound CCC1=C(C=CC(=C1)N2C(=O)N(C=N2)CC3=CC(=CC=C3)OC)C4CNNC4 PDAZITHKSFDQJY-UHFFFAOYSA-N 0.000 claims description 2
• RKMZFMAGJQZXES-UHFFFAOYSA-N 2-(3-ethyl-4-pyrazolidin-4-ylphenyl)-4-[(4-fluorophenyl)methyl]-1,2,4-triazol-3-one Chemical compound CCC1=C(C=CC(=C1)N2C(=O)N(C=N2)CC3=CC=C(C=C3)F)C4CNNC4 RKMZFMAGJQZXES-UHFFFAOYSA-N 0.000 claims description 2
• OIGFVWHLBMBSRW-UHFFFAOYSA-N 2-(3-methoxy-4-pyrazolidin-4-ylphenyl)-4-(1-phenylethyl)-1,2,4-triazol-3-one Chemical compound CC(C1=CC=CC=C1)N2C=NN(C2=O)C3=CC(=C(C=C3)C4CNNC4)OC OIGFVWHLBMBSRW-UHFFFAOYSA-N 0.000 claims description 2
• KFLMMLCFQYWZKX-UHFFFAOYSA-N 2-[(2,5-difluorophenyl)methyl]-4-(4-pyrazolidin-4-ylphenyl)-1,2,4-triazol-3-one Chemical compound C1C(CNN1)C2=CC=C(C=C2)N3C=NN(C3=O)CC4=C(C=CC(=C4)F)F KFLMMLCFQYWZKX-UHFFFAOYSA-N 0.000 claims description 2
• DTDMGKPJTKVHSR-UHFFFAOYSA-N 2-[(3-fluorophenyl)methyl]-4-(2-methoxy-4-pyrazolidin-4-ylphenyl)-1,2,4-triazol-3-one Chemical compound COC1=C(C=CC(=C1)C2CNNC2)N3C=NN(C3=O)CC4=CC(=CC=C4)F DTDMGKPJTKVHSR-UHFFFAOYSA-N 0.000 claims description 2
• YTKKNFVKRRWYLT-UHFFFAOYSA-N 2-[(3-fluorophenyl)methyl]-4-(3-methoxy-4-pyrazolidin-4-ylphenyl)-1,2,4-triazol-3-one Chemical compound COC1=C(C=CC(=C1)N2C=NN(C2=O)CC3=CC(=CC=C3)F)C4CNNC4 YTKKNFVKRRWYLT-UHFFFAOYSA-N 0.000 claims description 2
• HDAVZKNSAMZBJV-UHFFFAOYSA-N 2-[(3-fluorophenyl)methyl]-4-(3-methoxy-4-pyrazolidin-4-ylphenyl)-5-methyl-1,2,4-triazol-3-one Chemical compound CC1=NN(C(=O)N1C2=CC(=C(C=C2)C3CNNC3)OC)CC4=CC(=CC=C4)F HDAVZKNSAMZBJV-UHFFFAOYSA-N 0.000 claims description 2
• NDRZUYBYPGHWKV-UHFFFAOYSA-N 2-[(3-methoxyphenyl)methyl]-4-(2-methoxy-4-pyrazolidin-4-ylphenyl)-1,2,4-triazol-3-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(C=N2)C3=C(C=C(C=C3)C4CNNC4)OC NDRZUYBYPGHWKV-UHFFFAOYSA-N 0.000 claims description 2
• HKYRWIHBNOQEKQ-UHFFFAOYSA-N 2-[(3-methoxyphenyl)methyl]-4-(2-methoxy-4-pyrazolidin-4-ylphenyl)-5-methyl-1,2,4-triazol-3-one Chemical compound CC1=NN(C(=O)N1C2=C(C=C(C=C2)C3CNNC3)OC)CC4=CC(=CC=C4)OC HKYRWIHBNOQEKQ-UHFFFAOYSA-N 0.000 claims description 2
• NPRKWFHCLZRFSI-UHFFFAOYSA-N 2-[(3-methoxyphenyl)methyl]-4-(3-methoxy-4-pyrazolidin-4-ylphenyl)-1,2,4-triazol-3-one Chemical compound COC1=CC=CC(=C1)CN2C(=O)N(C=N2)C3=CC(=C(C=C3)C4CNNC4)OC NPRKWFHCLZRFSI-UHFFFAOYSA-N 0.000 claims description 2
• RDFCSIFWQKZZHL-UHFFFAOYSA-N 2-[(3-methoxyphenyl)methyl]-4-(3-methoxy-4-pyrazolidin-4-ylphenyl)-5-methyl-1,2,4-triazol-3-one Chemical compound CC1=NN(C(=O)N1C2=CC(=C(C=C2)C3CNNC3)OC)CC4=CC(=CC=C4)OC RDFCSIFWQKZZHL-UHFFFAOYSA-N 0.000 claims description 2
• SRPKQFCVYVRFEW-UHFFFAOYSA-N 2-[4-(2-aminopyridin-4-yl)phenyl]-4-[(3-methoxyphenyl)methyl]-1,2,4-triazol-3-one Chemical compound NC1=NC=CC(=C1)C1=CC=C(C=C1)N1N=CN(C1=O)CC1=CC(=CC=C1)OC SRPKQFCVYVRFEW-UHFFFAOYSA-N 0.000 claims description 2
• ZKTDPAIJEHULQD-UHFFFAOYSA-N 2-[4-(2-aminopyrimidin-4-yl)phenyl]-4-[(3-methoxyphenyl)methyl]-1,2,4-triazol-3-one Chemical compound NC1=NC=CC(=N1)C1=CC=C(C=C1)N1N=CN(C1=O)CC1=CC(=CC=C1)OC ZKTDPAIJEHULQD-UHFFFAOYSA-N 0.000 claims description 2
• DVTGDFKKWMOPNI-UHFFFAOYSA-N 2-[4-(2-aminopyrimidin-4-yl)phenyl]-4-[(3-methoxyphenyl)methyl]-5-methyl-1,2,4-triazol-3-one Chemical compound NC1=NC=CC(=N1)C1=CC=C(C=C1)N1N=C(N(C1=O)CC1=CC(=CC=C1)OC)C DVTGDFKKWMOPNI-UHFFFAOYSA-N 0.000 claims description 2
• PUHOAJIPYCNNAC-UHFFFAOYSA-N 2-benzyl-4-(2-methoxy-4-pyrazolidin-4-ylphenyl)-1,2,4-triazol-3-one Chemical compound COC1=C(C=CC(=C1)C2CNNC2)N3C=NN(C3=O)CC4=CC=CC=C4 PUHOAJIPYCNNAC-UHFFFAOYSA-N 0.000 claims description 2
• IDOPWFRPDWWRCY-UHFFFAOYSA-N 2-benzyl-4-(2-methoxy-4-pyrazolidin-4-ylphenyl)-5-methyl-1,2,4-triazol-3-one Chemical compound CC1=NN(C(=O)N1C2=C(C=C(C=C2)C3CNNC3)OC)CC4=CC=CC=C4 IDOPWFRPDWWRCY-UHFFFAOYSA-N 0.000 claims description 2
• MBKPCXHKJSWZFH-UHFFFAOYSA-N 2-benzyl-4-(3-methoxy-4-pyrazolidin-4-ylphenyl)-1,2,4-triazol-3-one Chemical compound COC1=C(C=CC(=C1)N2C=NN(C2=O)CC3=CC=CC=C3)C4CNNC4 MBKPCXHKJSWZFH-UHFFFAOYSA-N 0.000 claims description 2
• JKLGHSMWNQAVHS-UHFFFAOYSA-N 2-benzyl-4-(3-methoxy-4-pyrazolidin-4-ylphenyl)-5-methyl-1,2,4-triazol-3-one Chemical compound CC1=NN(C(=O)N1C2=CC(=C(C=C2)C3CNNC3)OC)CC4=CC=CC=C4 JKLGHSMWNQAVHS-UHFFFAOYSA-N 0.000 claims description 2
• GJVUXYIITRNGPQ-UHFFFAOYSA-N 3-[[1-(3-ethyl-4-pyrazolidin-4-ylphenyl)-5-oxo-1,2,4-triazol-4-yl]methyl]benzonitrile Chemical compound CCC1=C(C=CC(=C1)N2C(=O)N(C=N2)CC3=CC(=CC=C3)C#N)C4CNNC4 GJVUXYIITRNGPQ-UHFFFAOYSA-N 0.000 claims description 2
• BSCBWXXZRBKFRI-UHFFFAOYSA-N 3-[[1-(3-methoxy-4-pyrazolidin-4-ylphenyl)-5-oxo-1,2,4-triazol-4-yl]methyl]benzonitrile Chemical compound COC1=C(C=CC(=C1)N2C(=O)N(C=N2)CC3=CC(=CC=C3)C#N)C4CNNC4 BSCBWXXZRBKFRI-UHFFFAOYSA-N 0.000 claims description 2
• XAQMENZYZGPFNK-UHFFFAOYSA-N 3-[[4-[3-methoxy-4-(1H-pyrazol-4-yl)phenyl]-5-oxotetrazol-1-yl]methyl]benzonitrile Chemical compound COC=1C=C(C=CC=1C=1C=NNC=1)N1N=NN(C1=O)CC=1C=C(C#N)C=CC=1 XAQMENZYZGPFNK-UHFFFAOYSA-N 0.000 claims description 2
• UWIHBYUZOOEJOX-UHFFFAOYSA-N 3-[[5-oxo-1-(4-pyrazolidin-4-ylphenyl)-1,2,4-triazol-4-yl]methyl]benzonitrile Chemical compound C1C(CNN1)C2=CC=C(C=C2)N3C(=O)N(C=N3)CC4=CC(=CC=C4)C#N UWIHBYUZOOEJOX-UHFFFAOYSA-N 0.000 claims description 2
• 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 2
• HDSGDUHTERWRNZ-UHFFFAOYSA-N 4-(1-phenylethyl)-2-(4-pyrazolidin-4-ylphenyl)-1,2,4-triazol-3-one Chemical compound CC(C1=CC=CC=C1)N2C=NN(C2=O)C3=CC=C(C=C3)C4CNNC4 HDSGDUHTERWRNZ-UHFFFAOYSA-N 0.000 claims description 2
• GADQDULBPZEJPR-UHFFFAOYSA-N 4-(2-methoxy-4-pyrazolidin-4-ylphenyl)-2-(2-phenylethyl)-1,2,4-triazol-3-one Chemical compound COC1=C(C=CC(=C1)C2CNNC2)N3C=NN(C3=O)CCC4=CC=CC=C4 GADQDULBPZEJPR-UHFFFAOYSA-N 0.000 claims description 2
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• JRMMFXHSAYUMQP-UHFFFAOYSA-N 4-(3-methoxy-4-pyrazolidin-4-ylphenyl)-5-methyl-2-(1-phenylethyl)-1,2,4-triazol-3-one Chemical compound CC1=NN(C(=O)N1C2=CC(=C(C=C2)C3CNNC3)OC)C(C)C4=CC=CC=C4 JRMMFXHSAYUMQP-UHFFFAOYSA-N 0.000 claims description 2
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• QFXZBNJMEYMIDK-UHFFFAOYSA-N 5-(2-hydroxypropan-2-yl)-4-[(3-methoxyphenyl)methyl]-2-[4-(1H-pyrazol-4-yl)phenyl]-1,2,4-triazol-3-one Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)N1N=C(N(C1=O)CC1=CC(=CC=C1)OC)C(C)(C)O QFXZBNJMEYMIDK-UHFFFAOYSA-N 0.000 claims description 2
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• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• UIMPNNDUBWZREU-UHFFFAOYSA-N 2-(3-ethyl-4-pyrazolidin-4-ylphenyl)-4-[(2-fluorophenyl)methyl]-5-methyl-1,2,4-triazol-3-one Chemical compound CCC1=C(C=CC(=C1)N2C(=O)N(C(=N2)C)CC3=CC=CC=C3F)C4CNNC4 UIMPNNDUBWZREU-UHFFFAOYSA-N 0.000 claims 1
• DFYVMDCTDRJFGI-UHFFFAOYSA-N 2-(3-ethyl-4-pyrazolidin-4-ylphenyl)-4-[(3-methoxyphenyl)methyl]-5-methyl-1,2,4-triazol-3-one Chemical compound CCC1=C(C=CC(=C1)N2C(=O)N(C(=N2)C)CC3=CC(=CC=C3)OC)C4CNNC4 DFYVMDCTDRJFGI-UHFFFAOYSA-N 0.000 claims 1
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• RNTOFBAWHVQMQH-UHFFFAOYSA-N 2-[(2,5-difluorophenyl)methyl]-4-[2-methoxy-4-(1H-pyrazol-4-yl)phenyl]-5-methyl-1,2,4-triazol-3-one Chemical compound FC1=C(CN2N=C(N(C2=O)C2=C(C=C(C=C2)C=2C=NNC=2)OC)C)C=C(C=C1)F RNTOFBAWHVQMQH-UHFFFAOYSA-N 0.000 claims 1
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