KR20190121404A - 소마토스타틴 조절제 및 이의 용도 - Google Patents

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Publication number

KR20190121404A

KR20190121404A KR1020197030515A KR20197030515A KR20190121404A KR 20190121404 A KR20190121404 A KR 20190121404A KR 1020197030515 A KR1020197030515 A KR 1020197030515A KR 20197030515 A KR20197030515 A KR 20197030515A KR 20190121404 A KR20190121404 A KR 20190121404A

Authority

KR

South Korea

Prior art keywords

substituted

unsubstituted

fluoro

methylphenyl

amine

Prior art date

2017-03-16

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.)

Withdrawn

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• 108010056088 Somatostatin Proteins 0.000 title abstract description 22
• 102000005157 Somatostatin Human genes 0.000 title abstract description 21
• NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 title abstract description 19
• 229960000553 somatostatin Drugs 0.000 title abstract description 19
• 150000001875 compounds Chemical class 0.000 claims abstract description 380
• 238000000034 method Methods 0.000 claims abstract description 81
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 60
• 201000010099 disease Diseases 0.000 claims abstract description 46
• 230000000694 effects Effects 0.000 claims abstract description 29
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 29
• 238000011282 treatment Methods 0.000 claims abstract description 29
• -1 oxeta Nil Chemical group 0.000 claims description 319
• 239000000203 mixture Substances 0.000 claims description 187
• 229910052739 hydrogen Inorganic materials 0.000 claims description 165
• 239000001257 hydrogen Substances 0.000 claims description 164
• 150000003839 salts Chemical class 0.000 claims description 126
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 102
• 150000002431 hydrogen Chemical class 0.000 claims description 92
• 239000012453 solvate Substances 0.000 claims description 88
• 239000000243 solution Substances 0.000 claims description 76
• 238000002360 preparation method Methods 0.000 claims description 75
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 70
• 229910052801 chlorine Inorganic materials 0.000 claims description 51
• 229910052731 fluorine Inorganic materials 0.000 claims description 51
• 229910052794 bromium Inorganic materials 0.000 claims description 47
• 239000000651 prodrug Substances 0.000 claims description 45
• 229940002612 prodrug Drugs 0.000 claims description 45
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 43
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 43
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 42
• 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 40
• 241000124008 Mammalia Species 0.000 claims description 39
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 35
• 108050001286 Somatostatin Receptor Proteins 0.000 claims description 34
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 34
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 32
• 102000011096 Somatostatin receptor Human genes 0.000 claims description 32
• 229910052757 nitrogen Inorganic materials 0.000 claims description 32
• 125000000623 heterocyclic group Chemical group 0.000 claims description 30
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 28
• BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 claims description 27
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 26
• 229910052736 halogen Inorganic materials 0.000 claims description 26
• 150000002367 halogens Chemical class 0.000 claims description 26
• 125000002950 monocyclic group Chemical group 0.000 claims description 26
• 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 claims description 25
• 125000004429 atom Chemical group 0.000 claims description 25
• 239000002904 solvent Substances 0.000 claims description 25
• 125000002393 azetidinyl group Chemical group 0.000 claims description 24
• 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 20
• 229910052799 carbon Inorganic materials 0.000 claims description 19
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 17
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 16
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 16
• 125000002757 morpholinyl group Chemical group 0.000 claims description 16
• 125000004193 piperazinyl group Chemical group 0.000 claims description 16
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
• 125000003386 piperidinyl group Chemical group 0.000 claims description 15
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 15
• 125000001620 monocyclic carbocycle group Chemical group 0.000 claims description 14
• 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
• 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 14
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 13
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
• 239000007788 liquid Substances 0.000 claims description 12
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 12
• 239000000725 suspension Substances 0.000 claims description 12
• 239000003826 tablet Substances 0.000 claims description 12
• 239000002775 capsule Substances 0.000 claims description 11
• CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims description 10
• 125000003725 azepanyl group Chemical group 0.000 claims description 9
• 229920006395 saturated elastomer Polymers 0.000 claims description 9
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 8
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 8
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 8
• 206010000599 Acromegaly Diseases 0.000 claims description 7
• 208000002193 Pain Diseases 0.000 claims description 7
• 238000001990 intravenous administration Methods 0.000 claims description 7
• 230000036407 pain Effects 0.000 claims description 7
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 7
• 239000000839 emulsion Substances 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 239000000499 gel Substances 0.000 claims description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
• 206010028980 Neoplasm Diseases 0.000 claims description 5
• 208000017169 kidney disease Diseases 0.000 claims description 5
• 230000007823 neuropathy Effects 0.000 claims description 5
• 201000001119 neuropathy Diseases 0.000 claims description 5
• 208000033808 peripheral neuropathy Diseases 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• 239000006187 pill Substances 0.000 claims description 5
• 238000007920 subcutaneous administration Methods 0.000 claims description 5
• TYFOIVBYLRTMBZ-UHFFFAOYSA-N 4-(4-aminopiperidin-1-yl)-5-(3,5-dimethylphenyl)-3-(6-fluoro-4-methoxy-1H-benzimidazol-2-yl)pyridin-2-amine Chemical compound COC1=C2N=C(NC2=CC(F)=C1)C1=C(N2CCC(N)CC2)C(=CN=C1N)C1=CC(C)=CC(C)=C1 TYFOIVBYLRTMBZ-UHFFFAOYSA-N 0.000 claims description 4
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 4
• 201000011510 cancer Diseases 0.000 claims description 4
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
• 201000011519 neuroendocrine tumor Diseases 0.000 claims description 4
• 239000002674 ointment Substances 0.000 claims description 4
• 208000023504 respiratory system disease Diseases 0.000 claims description 4
• FJCBXWHOENKMPR-UHFFFAOYSA-N 1-[3-(6-fluoro-4-methoxy-1H-benzimidazol-2-yl)-5-(3-fluoro-5-methylphenyl)-2-methylpyridin-4-yl]piperidin-4-amine Chemical compound COC1=C2NC(=NC2=CC(F)=C1)C1=C(N2CCC(N)CC2)C(=CN=C1C)C1=CC(F)=CC(C)=C1 FJCBXWHOENKMPR-UHFFFAOYSA-N 0.000 claims description 3
• 239000006210 lotion Substances 0.000 claims description 3
• 230000004770 neurodegeneration Effects 0.000 claims description 3
• 208000020016 psychiatric disease Diseases 0.000 claims description 3
• BCRNGLKUJYOOLU-NFBKMPQASA-N (3R,4R)-1-[3-(6-chloro-1H-indol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridazin-4-yl]-3-methoxypiperidin-4-amine Chemical compound ClC1=CC=C2C=C(NC2=C1)C=1N=NC=C(C=1N1C[C@H]([C@@H](CC1)N)OC)C1=CC(=CC(=C1)C)F BCRNGLKUJYOOLU-NFBKMPQASA-N 0.000 claims description 2
• UPEDCKFLNFMCCW-YLJYHZDGSA-N (3R,4R)-4-amino-1-[2-amino-3-(6-chloro-1H-benzimidazol-2-yl)-5-(3,5-dimethylphenyl)pyridin-4-yl]piperidine-3-carbonitrile Chemical compound N[C@H]1[C@@H](CN(CC1)C1=C(C(=NC=C1C1=CC(=CC(=C1)C)C)N)C1=NC2=C(N1)C=CC(=C2)Cl)C#N UPEDCKFLNFMCCW-YLJYHZDGSA-N 0.000 claims description 2
• IITNRQXUVUEFEC-DNVCBOLYSA-N (3R,4R)-4-amino-1-[2-amino-3-(6-chloro-1H-benzimidazol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridin-4-yl]piperidine-3-carbonitrile Chemical compound N[C@H]1[C@@H](CN(CC1)C1=C(C(=NC=C1C1=CC(=CC(=C1)C)F)N)C1=NC2=C(N1)C=CC(=C2)Cl)C#N IITNRQXUVUEFEC-DNVCBOLYSA-N 0.000 claims description 2
• DHUVTGPVLQUQMN-UHFFFAOYSA-N 1-[2-(3-fluoroazetidin-1-yl)-3-(6-fluoro-4-methoxy-1H-benzimidazol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridin-4-yl]piperidin-4-amine Chemical compound FC1=CC2=C(NC(=N2)C=2C(=NC=C(C=2N2CCC(CC2)N)C2=CC(=CC(=C2)C)F)N2CC(C2)F)C(=C1)OC DHUVTGPVLQUQMN-UHFFFAOYSA-N 0.000 claims description 2
• BHPQOEOAPQDIEN-UHFFFAOYSA-N 1-[2-(3-fluoroazetidin-1-yl)-3-(6-fluoro-4-methoxy-1H-benzimidazol-2-yl)-5-(3-fluorophenyl)pyridin-4-yl]piperidin-4-amine Chemical compound FC1=CC2=C(NC(=N2)C=2C(=NC=C(C=2N2CCC(CC2)N)C2=CC(=CC=C2)F)N2CC(C2)F)C(=C1)OC BHPQOEOAPQDIEN-UHFFFAOYSA-N 0.000 claims description 2
• RNQZIASPEMRGMD-UHFFFAOYSA-N 1-[2-[2-amino-4-(4-aminopiperidin-1-yl)-5-(3-fluoro-5-methylphenyl)pyridin-3-yl]-3H-benzimidazol-5-yl]-3-methoxyurea Chemical compound CONC(=O)NC1=CC=C2NC(=NC2=C1)C1=C(N2CCC(N)CC2)C(=CN=C1N)C1=CC(F)=CC(C)=C1 RNQZIASPEMRGMD-UHFFFAOYSA-N 0.000 claims description 2
• OETDALONENHPFH-UHFFFAOYSA-N 1-[3-(3,6-dichloro-1H-indol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridazin-4-yl]piperidin-4-amine Chemical class CC1=CC(=CC(F)=C1)C1=CN=NC(C2=C(Cl)C3=CC=C(Cl)C=C3N2)=C1N1CCC(N)CC1 OETDALONENHPFH-UHFFFAOYSA-N 0.000 claims description 2
• XOPIPOWCTBDWET-UHFFFAOYSA-N 1-[3-(3-chloro-6-methoxy-1H-indol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridazin-4-yl]piperidin-4-amine Chemical compound COC1=CC=C2C(NC(=C2Cl)C2=C(N3CCC(N)CC3)C(=CN=N2)C2=CC(F)=CC(C)=C2)=C1 XOPIPOWCTBDWET-UHFFFAOYSA-N 0.000 claims description 2
• VKUKHUYITZGFFE-UHFFFAOYSA-N 1-[3-(4,6-difluoro-1H-benzimidazol-2-yl)-5-(3-fluoro-5-methylphenyl)-2-methoxypyridin-4-yl]piperidin-4-amine Chemical compound COC1=NC=C(C2=CC(F)=CC(C)=C2)C(N2CCC(N)CC2)=C1C1=NC2=CC(F)=CC(F)=C2N1 VKUKHUYITZGFFE-UHFFFAOYSA-N 0.000 claims description 2
• SQXXHFGZRMUIRD-UHFFFAOYSA-N 1-[3-(4-chloro-1H-indol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridazin-4-yl]piperidin-4-amine Chemical compound ClC1=C2C=C(NC2=CC=C1)C=1N=NC=C(C=1N1CCC(CC1)N)C1=CC(=CC(=C1)C)F SQXXHFGZRMUIRD-UHFFFAOYSA-N 0.000 claims description 2
• RNGUJUXDBHUSKQ-UHFFFAOYSA-N 1-[3-(5-chloro-1H-imidazo[4,5-b]pyridin-2-yl)-5-(3-fluoro-5-methylphenyl)-2-methoxypyridin-4-yl]piperidin-4-amine Chemical compound COC1=NC=C(C2=CC(F)=CC(C)=C2)C(N2CCC(N)CC2)=C1C1=NC2=C(N1)C=CC(Cl)=N2 RNGUJUXDBHUSKQ-UHFFFAOYSA-N 0.000 claims description 2
• HCZPDGOCDZLWFR-UHFFFAOYSA-N 1-[3-(5-chloro-1H-indol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridazin-4-yl]piperidin-4-amine Chemical compound CC1=CC(=CC(F)=C1)C1=CN=NC(C2=CC3=CC(Cl)=CC=C3N2)=C1N1CCC(N)CC1 HCZPDGOCDZLWFR-UHFFFAOYSA-N 0.000 claims description 2
• KAXWUJDWJRBISJ-UHFFFAOYSA-N 1-[3-(5-fluoro-1H-indol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridazin-4-yl]piperidin-4-amine Chemical compound FC=1C=C2C=C(NC2=CC=1)C=1N=NC=C(C=1N1CCC(CC1)N)C1=CC(=CC(=C1)C)F KAXWUJDWJRBISJ-UHFFFAOYSA-N 0.000 claims description 2
• UUQAUJHYBJQDDY-UHFFFAOYSA-N 1-[3-(6-chloro-1H-benzimidazol-2-yl)-5-(3-fluoro-5-methylphenyl)-2-piperazin-1-ylpyridin-4-yl]piperidin-4-amine Chemical compound ClC1=CC2=C(NC(=N2)C=2C(=NC=C(C=2N2CCC(CC2)N)C2=CC(=CC(=C2)C)F)N2CCNCC2)C=C1 UUQAUJHYBJQDDY-UHFFFAOYSA-N 0.000 claims description 2
• UHPPYUNDJACSOI-UHFFFAOYSA-N 1-[3-(6-chloro-1H-benzimidazol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridazin-4-yl]piperidin-4-amine Chemical compound CC1=CC(=CC(F)=C1)C1=CN=NC(C2=NC3=CC(Cl)=CC=C3N2)=C1N1CCC(N)CC1 UHPPYUNDJACSOI-UHFFFAOYSA-N 0.000 claims description 2
• WWEPPGZPTSQIRU-UHFFFAOYSA-N 1-[3-(6-chloro-1H-indol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridazin-4-yl]piperidin-4-amine Chemical compound ClC1=CC=C2C=C(NC2=C1)C=1N=NC=C(C=1N1CCC(CC1)N)C1=CC(=CC(=C1)C)F WWEPPGZPTSQIRU-UHFFFAOYSA-N 0.000 claims description 2
• SRJOVPUDSWWJAL-UHFFFAOYSA-N 1-[3-(6-chloro-3H-imidazo[4,5-c]pyridin-2-yl)-5-(3-fluoro-5-methylphenyl)-2-methoxypyridin-4-yl]piperidin-4-amine Chemical compound ClC1=CC2=C(C=N1)NC(=N2)C=1C(=NC=C(C=1N1CCC(CC1)N)C1=CC(=CC(=C1)C)F)OC SRJOVPUDSWWJAL-UHFFFAOYSA-N 0.000 claims description 2
• FSRFOIVPJVCVDC-UHFFFAOYSA-N 1-[3-(6-fluoro-1H-benzimidazol-2-yl)-5-(3-fluoro-5-methylphenyl)-2-methoxypyridin-4-yl]piperidin-4-amine Chemical compound COC1=NC=C(C2=CC(F)=CC(C)=C2)C(N2CCC(N)CC2)=C1C1=NC2=CC(F)=CC=C2N1 FSRFOIVPJVCVDC-UHFFFAOYSA-N 0.000 claims description 2
• RMOSEWLIPWUBQP-UHFFFAOYSA-N 1-[3-(6-fluoro-1H-indol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridazin-4-yl]piperidin-4-amine Chemical compound CC1=CC(=CC(F)=C1)C1=CN=NC(C2=CC3=CC=C(F)C=C3N2)=C1N1CCC(N)CC1 RMOSEWLIPWUBQP-UHFFFAOYSA-N 0.000 claims description 2
• PLBUDSGTVDRMOP-UHFFFAOYSA-N 1-[3-(7-chloro-1H-indol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridazin-4-yl]piperidin-4-amine Chemical compound ClC=1C=CC=C2C=C(NC=12)C=1N=NC=C(C=1N1CCC(CC1)N)C1=CC(=CC(=C1)C)F PLBUDSGTVDRMOP-UHFFFAOYSA-N 0.000 claims description 2
• BHSJDBBBIWDEKP-UHFFFAOYSA-N 1-[5-(3-fluoro-5-methylphenyl)-2-methoxy-3-(6-methoxy-1H-benzimidazol-2-yl)pyridin-4-yl]piperidin-4-amine Chemical compound COC1=CC=C2NC(=NC2=C1)C1=C(N2CCC(N)CC2)C(=CN=C1OC)C1=CC(F)=CC(C)=C1 BHSJDBBBIWDEKP-UHFFFAOYSA-N 0.000 claims description 2
• AUPCBUYYKUYLJK-UHFFFAOYSA-N 1-[5-(3-fluoro-5-methylphenyl)-3-(5-methoxy-1H-indol-2-yl)pyridazin-4-yl]piperidin-4-amine Chemical compound COC1=CC=C2NC(=CC2=C1)C1=C(N2CCC(N)CC2)C(=CN=N1)C1=CC(F)=CC(C)=C1 AUPCBUYYKUYLJK-UHFFFAOYSA-N 0.000 claims description 2
• VNLPEVPXNGOIFD-UHFFFAOYSA-N 1-[5-(3-fluoro-5-methylphenyl)-3-(6-methoxy-1H-indol-2-yl)pyridazin-4-yl]piperidin-4-amine Chemical compound COC1=CC=C2C=C(NC2=C1)C1=C(N2CCC(N)CC2)C(=CN=N1)C1=CC(F)=CC(C)=C1 VNLPEVPXNGOIFD-UHFFFAOYSA-N 0.000 claims description 2
• NHEASOBRMDJZKE-UHFFFAOYSA-N 1-[5-(3-fluoro-5-methylphenyl)-3-(6-methyl-1H-indol-2-yl)pyridazin-4-yl]piperidin-4-amine Chemical compound CC1=CC=C2C=C(NC2=C1)C1=C(N2CCC(N)CC2)C(=CN=N1)C1=CC(F)=CC(C)=C1 NHEASOBRMDJZKE-UHFFFAOYSA-N 0.000 claims description 2
• PCVFDYVBMPXZRA-UHFFFAOYSA-N 1-[5-(3-fluoro-5-methylphenyl)-3-[6-(2H-tetrazol-5-yl)-1H-indol-2-yl]pyridazin-4-yl]piperidin-4-amine Chemical compound CC1=CC(=CC(F)=C1)C1=CN=NC(C2=CC3=CC=C(C=C3N2)C2=NNN=N2)=C1N1CCC(N)CC1 PCVFDYVBMPXZRA-UHFFFAOYSA-N 0.000 claims description 2
• JQVMUGNWAUNANO-UHFFFAOYSA-N 2-[2-amino-4-(4-aminopiperidin-1-yl)-5-(3-chloro-5-fluorophenyl)pyridin-3-yl]-7-fluoro-3H-benzimidazole-5-carbonitrile Chemical compound NC1CCN(CC1)C1=C(C2=NC3=CC(=CC(F)=C3N2)C#N)C(N)=NC=C1C1=CC(Cl)=CC(F)=C1 JQVMUGNWAUNANO-UHFFFAOYSA-N 0.000 claims description 2
• VAERIDPTRUIBSE-UHFFFAOYSA-N 2-[2-amino-4-(4-aminopiperidin-1-yl)-5-(3-fluoro-5-methylphenyl)pyridin-3-yl]-1H-benzimidazole-4-carbonitrile Chemical compound NC1=NC=C(C(=C1C1=NC2=C(N1)C(=CC=C2)C#N)N1CCC(CC1)N)C1=CC(=CC(=C1)C)F VAERIDPTRUIBSE-UHFFFAOYSA-N 0.000 claims description 2
• FNHZZNBSQHPAKT-UHFFFAOYSA-N 2-[2-amino-4-(4-aminopiperidin-1-yl)-5-(3-fluoro-5-methylphenyl)pyridin-3-yl]-1H-indole-6-carbonitrile Chemical compound NC1=NC=C(C(=C1C=1NC2=CC(=CC=C2C=1)C#N)N1CCC(CC1)N)C1=CC(=CC(=C1)C)F FNHZZNBSQHPAKT-UHFFFAOYSA-N 0.000 claims description 2
• FHSLBGSYYAWDBT-UHFFFAOYSA-N 2-[2-amino-4-(4-aminopiperidin-1-yl)-5-(3-fluoro-5-methylphenyl)pyridin-3-yl]-3H-benzimidazole-5-carbonitrile Chemical compound CC1=CC(=CC(F)=C1)C1=CN=C(N)C(C2=NC3=CC(=CC=C3N2)C#N)=C1N1CCC(N)CC1 FHSLBGSYYAWDBT-UHFFFAOYSA-N 0.000 claims description 2
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• RIMFGGAVAYMNAK-UHFFFAOYSA-N 2-[2-amino-4-(4-aminopiperidin-1-yl)-5-(3-fluoro-5-methylphenyl)pyridin-3-yl]-N-methoxy-3H-benzimidazole-5-carboxamide Chemical compound CONC(=O)C1=CC=C2NC(=NC2=C1)C1=C(N2CCC(N)CC2)C(=CN=C1N)C1=CC(F)=CC(C)=C1 RIMFGGAVAYMNAK-UHFFFAOYSA-N 0.000 claims description 2
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• PYVPEITXHJPGKY-UHFFFAOYSA-N 2-[4-(4-aminopiperidin-1-yl)-5-(3-fluoro-5-methylphenyl)pyridazin-3-yl]-3-chloro-1H-indole-6-carbonitrile Chemical compound NC1CCN(CC1)C1=C(N=NC=C1C1=CC(=CC(=C1)C)F)C=1NC2=CC(=CC=C2C=1Cl)C#N PYVPEITXHJPGKY-UHFFFAOYSA-N 0.000 claims description 2
• HUMXWYQFUJFMBG-UHFFFAOYSA-N 2-[4-(4-aminopiperidin-1-yl)-5-(3-fluoro-5-methylphenyl)pyridazin-3-yl]-N-methoxy-1H-indole-6-carboxamide Chemical compound NC1CCN(CC1)C1=C(N=NC=C1C1=CC(=CC(=C1)C)F)C=1NC2=CC(=CC=C2C=1)C(=O)NOC HUMXWYQFUJFMBG-UHFFFAOYSA-N 0.000 claims description 2
• VXEKZTDHOQMNBL-UHFFFAOYSA-N 2-[[2-[2-amino-4-(4-aminopiperidin-1-yl)-5-(3-chloro-5-fluorophenyl)pyridin-3-yl]-6-fluoro-1H-benzimidazol-4-yl]oxy]acetonitrile Chemical compound NC1=NC=C(C(=C1C1=NC2=C(N1)C(=CC(=C2)F)OCC#N)N1CCC(CC1)N)C1=CC(=CC(=C1)F)Cl VXEKZTDHOQMNBL-UHFFFAOYSA-N 0.000 claims description 2
• HLJWRTVDEHNIEE-UHFFFAOYSA-N 2-[[2-[2-amino-4-(4-aminopiperidin-1-yl)-5-(3-chloro-5-fluorophenyl)pyridin-3-yl]-7-fluoro-3H-benzimidazol-5-yl]oxy]acetonitrile Chemical compound NC1=NC=C(C(=C1C1=NC2=C(N1)C(=CC(=C2)OCC#N)F)N1CCC(CC1)N)C1=CC(=CC(=C1)F)Cl HLJWRTVDEHNIEE-UHFFFAOYSA-N 0.000 claims description 2
• RTNVXWYTPYYQLA-UHFFFAOYSA-N 2-[[2-[2-amino-4-(4-aminopiperidin-1-yl)-5-(3-fluoro-5-methylphenyl)pyridin-3-yl]-6-fluoro-1H-benzimidazol-4-yl]oxy]acetonitrile Chemical compound NC1=NC=C(C(=C1C1=NC2=C(N1)C(=CC(=C2)F)OCC#N)N1CCC(CC1)N)C1=CC(=CC(=C1)C)F RTNVXWYTPYYQLA-UHFFFAOYSA-N 0.000 claims description 2
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• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 2
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• NRYHSWFTYVKYRW-UHFFFAOYSA-N 4-(4-aminopiperidin-1-yl)-3-(4,6-difluoro-1H-benzimidazol-2-yl)-N-ethyl-5-(3-fluoro-5-methylphenyl)pyridin-2-amine Chemical compound CCNC1=NC=C(C2=CC(F)=CC(C)=C2)C(N2CCC(N)CC2)=C1C1=NC2=CC(F)=CC(F)=C2N1 NRYHSWFTYVKYRW-UHFFFAOYSA-N 0.000 claims description 2
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