KR20190121404A - 소마토스타틴 조절제 및 이의 용도 - Google Patents
소마토스타틴 조절제 및 이의 용도 Download PDFInfo
- 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
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- KR
- South Korea
- Prior art keywords
- substituted
- unsubstituted
- fluoro
- methylphenyl
- amine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Neurology (AREA)
- Ophthalmology & Optometry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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| US201762472480P | 2017-03-16 | 2017-03-16 | |
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| PCT/US2018/022665 WO2018170284A1 (en) | 2017-03-16 | 2018-03-15 | Somatostatin modulators and uses thereof |
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| KR20190121404A true KR20190121404A (ko) | 2019-10-25 |
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| EP (1) | EP3596062A4 (enExample) |
| JP (1) | JP7106564B2 (enExample) |
| KR (1) | KR20190121404A (enExample) |
| CN (1) | CN110650951B (enExample) |
| AU (1) | AU2018234806A1 (enExample) |
| BR (1) | BR112019019168A2 (enExample) |
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| TW (1) | TW201840550A (enExample) |
| UA (1) | UA127346C2 (enExample) |
| WO (1) | WO2018170284A1 (enExample) |
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| SG11201908512YA (en) | 2017-03-16 | 2019-10-30 | Crinetics Pharmaceuticals Inc | Somatostatin modulators and uses thereof |
| WO2019157458A1 (en) * | 2018-02-12 | 2019-08-15 | Crinetics Pharmaceuticals, Inc. | Somatostatin modulators and uses thereof |
| WO2019240246A1 (ja) * | 2018-06-15 | 2019-12-19 | 小野薬品工業株式会社 | ピペリジノール誘導体の新規な塩および新規結晶形 |
| US10696689B2 (en) | 2018-09-18 | 2020-06-30 | Crinetics Pharmaceuticals, Inc. | Somatostatin modulators and uses thereof |
| TWI841768B (zh) | 2019-08-14 | 2024-05-11 | 美商克林提克斯醫藥股份有限公司 | 非肽生長抑制素(somatostatin)5型受體激動劑及其用途 |
| WO2021076448A1 (en) * | 2019-10-14 | 2021-04-22 | Crinetics Pharmaceuticals, Inc. | Somatostatin modulators for treating pituitary adenomas |
| WO2021113625A1 (en) * | 2019-12-06 | 2021-06-10 | Plexxikon Inc. | Compounds and methods for cd73 modulation and indications therefor |
| AR121682A1 (es) | 2020-03-31 | 2022-06-29 | Takeda Pharmaceuticals Co | Derivados de n-(heterociclil y heterociclilalquil)-3-bencilpiridin-2-amina como agonistas de sstr4 |
| ES3040117T3 (en) | 2020-09-09 | 2025-10-28 | Crinetics Pharmaceuticals Inc | Formulations of a somatostatin modulator |
| CN117043149A (zh) | 2021-02-17 | 2023-11-10 | 克林提克斯医药股份有限公司 | 促生长素抑制素调节剂的结晶形式 |
| WO2022261221A1 (en) * | 2021-06-09 | 2022-12-15 | Crinetics Pharmaceuticals, Inc. | Non-peptide targeted therapeutics and uses thereof |
| CN114591326B (zh) * | 2022-02-28 | 2024-02-27 | 上海筛杰生物医药有限公司 | Cct-251921的中间体及其制备方法 |
| AU2023366475A1 (en) * | 2022-10-28 | 2025-05-29 | Exelixis, Inc. | Somatostatin receptor 2 agonists and uses thereof |
| KR20250117433A (ko) * | 2022-12-13 | 2025-08-04 | 크리네틱스 파마슈티칼스, 인크. | 소마토스타틴 아형-2 수용체(sst2r) 표적 치료제 및 이의 용도 |
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| US6127343A (en) | 1996-05-14 | 2000-10-03 | Novo Nordisk A/S | Somatostatin agonists and antagonists |
| US6025372A (en) | 1997-04-04 | 2000-02-15 | Merck & Co., Inc. | Somatostatin agonists |
| FR2802206B1 (fr) * | 1999-12-14 | 2005-04-22 | Sod Conseils Rech Applic | Derives de 4-aminopiperidine et leur utilisation en tant que medicament |
| US20060281764A1 (en) * | 2005-06-10 | 2006-12-14 | Gaul Michael D | Aminopyrimidines as kinase modulators |
| AU2007309708A1 (en) | 2006-03-13 | 2008-05-02 | Merck Sharp & Dohme Corp. | Somatostatin agonists |
| WO2008019967A2 (en) | 2006-08-15 | 2008-02-21 | F. Hoffmann-La Roche Ag | Phenyl, pyridine and quinoline derivatives |
| WO2009051705A1 (en) | 2007-10-18 | 2009-04-23 | Merck & Co., Inc. | Substituted 1,2,4-oxadiazoles and analogs thereof as cb2 receptor modulators, useful in the treatment of pain, respiratory and non-respiratory diseases |
| CA2729220A1 (en) | 2008-06-25 | 2009-12-30 | Envivo Pharmaceuticals, Inc. | Di-substituted phenyl compounds |
| GB0818241D0 (en) | 2008-10-06 | 2008-11-12 | Cancer Res Technology | Compounds and their use |
| JP2013503846A (ja) | 2009-09-01 | 2013-02-04 | ファイザー・インク | ベンズイミダゾール誘導体 |
| GB201008290D0 (en) | 2010-05-18 | 2010-06-30 | Syngenta Ltd | Chemical compounds |
| WO2011146324A1 (en) | 2010-05-18 | 2011-11-24 | Merck Sharp & Dohme Corp. | Spiro isoxazoline compounds as sstr5 antagonists |
| US9630976B2 (en) * | 2012-07-03 | 2017-04-25 | Ono Pharmaceutical Co., Ltd. | Compound having agonistic activity on somatostatin receptor, and use thereof for medical purposes |
| KR20160062023A (ko) | 2013-09-30 | 2016-06-01 | 오노 야꾸힝 고교 가부시키가이샤 | 소마토스타틴 수용체 작동 활성을 갖는 화합물 및 그 의약 용도 |
| US10093795B2 (en) | 2013-10-02 | 2018-10-09 | Kuraray Co., Ltd. | Resin composition, multilayer sheet, packaging material and container |
| PT3484865T (pt) | 2016-07-14 | 2022-11-03 | Crinetics Pharmaceuticals Inc | Moduladores da somatostatina e suas utilizações |
| SG11201907240XA (en) * | 2017-02-08 | 2019-09-27 | Ono Pharmaceutical Co | Compound having somatostatin receptor agonistic activity and pharmaceutical use thereof |
| SG11201908512YA (en) | 2017-03-16 | 2019-10-30 | Crinetics Pharmaceuticals Inc | Somatostatin modulators and uses thereof |
| EP3658560A4 (en) | 2017-07-25 | 2021-01-06 | Crinetics Pharmaceuticals, Inc. | SOMATOSTAT IN MODULATORS AND USES THEREOF |
| WO2019157458A1 (en) | 2018-02-12 | 2019-08-15 | Crinetics Pharmaceuticals, Inc. | Somatostatin modulators and uses thereof |
| US10696689B2 (en) | 2018-09-18 | 2020-06-30 | Crinetics Pharmaceuticals, Inc. | Somatostatin modulators and uses thereof |
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2018
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- 2018-03-15 KR KR1020197030515A patent/KR20190121404A/ko not_active Withdrawn
- 2018-03-15 WO PCT/US2018/022665 patent/WO2018170284A1/en not_active Ceased
- 2018-03-15 CN CN201880033113.8A patent/CN110650951B/zh active Active
- 2018-03-15 AU AU2018234806A patent/AU2018234806A1/en not_active Abandoned
- 2018-03-15 EA EA201992083A patent/EA201992083A1/ru unknown
- 2018-03-15 BR BR112019019168A patent/BR112019019168A2/pt not_active Application Discontinuation
- 2018-03-15 JP JP2019548905A patent/JP7106564B2/ja active Active
- 2018-03-15 EP EP18767082.3A patent/EP3596062A4/en active Pending
- 2018-03-15 MX MX2019010949A patent/MX2019010949A/es unknown
- 2018-03-15 UA UAA201910112A patent/UA127346C2/uk unknown
- 2018-03-15 NZ NZ757081A patent/NZ757081A/en unknown
- 2018-03-15 CA CA3056131A patent/CA3056131A1/en not_active Abandoned
- 2018-03-15 IL IL269241A patent/IL269241B/en unknown
- 2018-03-16 TW TW107109163A patent/TW201840550A/zh unknown
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2019
- 2019-09-16 US US16/572,453 patent/US11072598B2/en active Active
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| US11072598B2 (en) | 2021-07-27 |
| EA201992083A1 (ru) | 2020-03-18 |
| CA3056131A1 (en) | 2018-09-20 |
| EP3596062A4 (en) | 2020-08-26 |
| WO2018170284A1 (en) | 2018-09-20 |
| IL269241A (en) | 2019-11-28 |
| AU2018234806A1 (en) | 2019-10-03 |
| BR112019019168A2 (pt) | 2020-04-14 |
| CN110650951A (zh) | 2020-01-03 |
| UA127346C2 (uk) | 2023-07-26 |
| US20200010453A1 (en) | 2020-01-09 |
| EP3596062A1 (en) | 2020-01-22 |
| IL269241B (en) | 2022-09-01 |
| JP2020511452A (ja) | 2020-04-16 |
| JP7106564B2 (ja) | 2022-07-26 |
| SG11201908512YA (en) | 2019-10-30 |
| MX2019010949A (es) | 2019-10-24 |
| NZ757081A (en) | 2023-03-31 |
| TW201840550A (zh) | 2018-11-16 |
| CN110650951B (zh) | 2023-02-24 |
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| PA0105 | International application |
Patent event date: 20191016 Patent event code: PA01051R01D Comment text: International Patent Application |
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| PC1203 | Withdrawal of no request for examination |