HRP20210931T1 - Alkil-amin harminski derivati za poticanje rasta kostiju - Google Patents
Alkil-amin harminski derivati za poticanje rasta kostiju Download PDFInfo
- Publication number
- HRP20210931T1 HRP20210931T1 HRP20210931TT HRP20210931T HRP20210931T1 HR P20210931 T1 HRP20210931 T1 HR P20210931T1 HR P20210931T T HRP20210931T T HR P20210931TT HR P20210931 T HRP20210931 T HR P20210931T HR P20210931 T1 HRP20210931 T1 HR P20210931T1
- Authority
- HR
- Croatia
- Prior art keywords
- pyrido
- methoxy
- indol
- methyl
- ethyl
- Prior art date
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- -1 Alkyl-amine harmine derivatives Chemical class 0.000 title claims 3
- 230000008468 bone growth Effects 0.000 title 1
- 230000001737 promoting effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 20
- 150000003839 salts Chemical class 0.000 claims 11
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 229910052799 carbon Inorganic materials 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 230000011164 ossification Effects 0.000 claims 4
- 230000009885 systemic effect Effects 0.000 claims 4
- 125000003545 alkoxy group Chemical group 0.000 claims 3
- 230000000123 anti-resoprtive effect Effects 0.000 claims 3
- 229940079593 drug Drugs 0.000 claims 3
- 239000003112 inhibitor Substances 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 2
- 150000001204 N-oxides Chemical class 0.000 claims 2
- 208000001132 Osteoporosis Diseases 0.000 claims 2
- 101150074062 Tnfsf11 gene Proteins 0.000 claims 2
- 229930003316 Vitamin D Natural products 0.000 claims 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 125000004104 aryloxy group Chemical group 0.000 claims 2
- 210000000988 bone and bone Anatomy 0.000 claims 2
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 201000001937 osteoporosis-pseudoglioma syndrome Diseases 0.000 claims 2
- 239000000333 selective estrogen receptor modulator Substances 0.000 claims 2
- 229940095743 selective estrogen receptor modulator Drugs 0.000 claims 2
- 235000019166 vitamin D Nutrition 0.000 claims 2
- 239000011710 vitamin D Substances 0.000 claims 2
- 150000003710 vitamin D derivatives Chemical class 0.000 claims 2
- 229940046008 vitamin d Drugs 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims 1
- WKTCZWNJRJKXAO-UHFFFAOYSA-N 1-(2-methoxycarbazol-9-yl)-n,n-dimethylpropan-2-amine Chemical compound C1=CC=C2C3=CC=C(OC)C=C3N(CC(C)N(C)C)C2=C1 WKTCZWNJRJKXAO-UHFFFAOYSA-N 0.000 claims 1
- WFJXCZIZWDZCAC-UHFFFAOYSA-N 1-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)-N,N-dimethylpropan-2-amine Chemical compound COc1ccc2c(c1)n(CC(C)N(C)C)c1c(C)nccc21 WFJXCZIZWDZCAC-UHFFFAOYSA-N 0.000 claims 1
- ZPRZEEZIJUGABT-UHFFFAOYSA-N 1-(7-methoxypyrido[3,4-b]indol-9-yl)-n,n-dimethylpropan-2-amine Chemical compound N1=CC=C2C3=CC=C(OC)C=C3N(CC(C)N(C)C)C2=C1 ZPRZEEZIJUGABT-UHFFFAOYSA-N 0.000 claims 1
- ASGQPUIZVLKBQG-UHFFFAOYSA-N 1-[7-methoxy-1-(trifluoromethyl)pyrido[3,4-b]indol-9-yl]-N,N-dimethylpropan-2-amine Chemical compound N1=CC=C2C3=CC=C(OC)C=C3N(CC(C)N(C)C)C2=C1C(F)(F)F ASGQPUIZVLKBQG-UHFFFAOYSA-N 0.000 claims 1
- BCVBMFNQYJBGNN-UHFFFAOYSA-N 1-carbazol-9-yl-n,n-dimethylpropan-2-amine Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3C2=C1 BCVBMFNQYJBGNN-UHFFFAOYSA-N 0.000 claims 1
- MOPUAJCKFRRYRF-UHFFFAOYSA-N 2-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)-N,N-dimethylethanamine Chemical compound N1=CC=C2C3=CC=C(OC)C=C3N(CCN(C)C)C2=C1C MOPUAJCKFRRYRF-UHFFFAOYSA-N 0.000 claims 1
- UIXJGDMFGANPOO-UHFFFAOYSA-N 2-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)-N,N-dimethylpropan-1-amine Chemical compound N1=CC=C2C3=CC=C(OC)C=C3N(C(C)CN(C)C)C2=C1C UIXJGDMFGANPOO-UHFFFAOYSA-N 0.000 claims 1
- HIHKOJJFNQRLIC-UHFFFAOYSA-N 2-[2-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)ethyl-methylamino]ethanol Chemical compound N1=CC=C2C3=CC=C(OC)C=C3N(CCN(C)CCO)C2=C1C HIHKOJJFNQRLIC-UHFFFAOYSA-N 0.000 claims 1
- FCENLLJVXGSQOU-UHFFFAOYSA-N 2-[2-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)ethyl]-1,3,4-oxadiazole Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCC1=NN=CO1 FCENLLJVXGSQOU-UHFFFAOYSA-N 0.000 claims 1
- HNRHYCYFOGOPJC-UHFFFAOYSA-N 2-[2-[7-methoxy-1-(trifluoromethyl)pyrido[3,4-b]indol-9-yl]ethyl-methylamino]ethanol Chemical compound COc1ccc2c(c1)n(CCN(C)CCO)c1c(nccc21)C(F)(F)F HNRHYCYFOGOPJC-UHFFFAOYSA-N 0.000 claims 1
- ITODGJFZJRVILM-UHFFFAOYSA-N 2-[2-[7-methoxy-1-(trifluoromethyl)pyrido[3,4-b]indol-9-yl]ethylamino]ethanol Chemical compound N1=CC=C2C3=CC=C(OC)C=C3N(CCNCCO)C2=C1C(F)(F)F ITODGJFZJRVILM-UHFFFAOYSA-N 0.000 claims 1
- OKMJTCSWBOAKOG-UHFFFAOYSA-N 2-[2-hydroxyethyl-[2-[7-methoxy-1-(trifluoromethyl)pyrido[3,4-b]indol-9-yl]ethyl]amino]ethanol Chemical compound N1=CC=C2C3=CC=C(OC)C=C3N(CCN(CCO)CCO)C2=C1C(F)(F)F OKMJTCSWBOAKOG-UHFFFAOYSA-N 0.000 claims 1
- BOZSOJDHNLWOST-UHFFFAOYSA-N 2-[3-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)propyl]-1,3,4-oxadiazole Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCCC1=NN=CO1 BOZSOJDHNLWOST-UHFFFAOYSA-N 0.000 claims 1
- ULDBONUMQPGMEL-UHFFFAOYSA-N 3-fluoro-7-methoxy-1-methyl-9-(2-piperidin-1-ylethyl)pyrido[3,4-b]indole Chemical compound C=1C(OC)=CC=C(C2=CC(F)=NC(C)=C22)C=1N2CCN1CCCCC1 ULDBONUMQPGMEL-UHFFFAOYSA-N 0.000 claims 1
- INGXPYLWNWFCMP-UHFFFAOYSA-N 4-[1-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)propan-2-yl]morpholine Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CC(C)N1CCOCC1 INGXPYLWNWFCMP-UHFFFAOYSA-N 0.000 claims 1
- MEPHWIHMAWNRMX-UHFFFAOYSA-N 4-[1-[7-methoxy-1-(trifluoromethyl)pyrido[3,4-b]indol-9-yl]propan-2-yl]morpholine Chemical compound C=1C(OC)=CC=C(C2=CC=NC(=C22)C(F)(F)F)C=1N2CC(C)N1CCOCC1 MEPHWIHMAWNRMX-UHFFFAOYSA-N 0.000 claims 1
- XKBMZXCWPNTOBC-UHFFFAOYSA-N 4-[2-(3-fluoro-7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)ethyl]morpholine Chemical compound COc1ccc2c(c1)n(CCN1CCOCC1)c1c(C)nc(F)cc21 XKBMZXCWPNTOBC-UHFFFAOYSA-N 0.000 claims 1
- QTUOYYRDSDTGJJ-UHFFFAOYSA-N 4-[2-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)ethyl]morpholine Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCN1CCOCC1 QTUOYYRDSDTGJJ-UHFFFAOYSA-N 0.000 claims 1
- LGEHUKFEPQDZFT-UHFFFAOYSA-N 4-[2-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)propyl]morpholine Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2C(C)CN1CCOCC1 LGEHUKFEPQDZFT-UHFFFAOYSA-N 0.000 claims 1
- RMWLCCMYIIGIPN-UHFFFAOYSA-N 4-[2-[7-methoxy-1-(trifluoromethyl)pyrido[3,4-b]indol-9-yl]ethyl]-3-methylmorpholine Chemical compound C=1C(OC)=CC=C(C2=CC=NC(=C22)C(F)(F)F)C=1N2CCN1CCOCC1C RMWLCCMYIIGIPN-UHFFFAOYSA-N 0.000 claims 1
- HQNUHDPVMZYMQK-UHFFFAOYSA-N 4-[2-[7-methoxy-1-(trifluoromethyl)pyrido[3,4-b]indol-9-yl]ethyl]morpholine Chemical compound C=1C(OC)=CC=C(C2=CC=NC(=C22)C(F)(F)F)C=1N2CCN1CCOCC1 HQNUHDPVMZYMQK-UHFFFAOYSA-N 0.000 claims 1
- QMAFSWDVIBXMHP-UHFFFAOYSA-N 4-[3-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)propyl]morpholine Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCCN1CCOCC1 QMAFSWDVIBXMHP-UHFFFAOYSA-N 0.000 claims 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- YTYVERVTSZVXFF-UHFFFAOYSA-N 5-[2-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)ethyl]-1,2,4-oxadiazole Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCC1=NC=NO1 YTYVERVTSZVXFF-UHFFFAOYSA-N 0.000 claims 1
- CLHZKABZRWVEQD-UHFFFAOYSA-N 5-[3-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)propyl]-1,2,4-oxadiazole Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCCC1=NC=NO1 CLHZKABZRWVEQD-UHFFFAOYSA-N 0.000 claims 1
- XLCYHDXHLSBKSZ-UHFFFAOYSA-N 7-methoxy-1-methyl-9-(1-piperidin-1-ylpropan-2-yl)pyrido[3,4-b]indole Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2C(C)CN1CCCCC1 XLCYHDXHLSBKSZ-UHFFFAOYSA-N 0.000 claims 1
- NHKUUSNNGFVBDB-UHFFFAOYSA-N 7-methoxy-1-methyl-9-(2-piperazin-1-ylethyl)pyrido[3,4-b]indole Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCN1CCNCC1 NHKUUSNNGFVBDB-UHFFFAOYSA-N 0.000 claims 1
- LPKYJYPNDXMKNT-UHFFFAOYSA-N 7-methoxy-1-methyl-9-(2-piperidin-1-ylethyl)pyrido[3,4-b]indole Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCN1CCCCC1 LPKYJYPNDXMKNT-UHFFFAOYSA-N 0.000 claims 1
- NJKZKIHFIMNASZ-UHFFFAOYSA-N 7-methoxy-1-methyl-9-(2-piperidin-1-ylpropyl)pyrido[3,4-b]indole Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CC(C)N1CCCCC1 NJKZKIHFIMNASZ-UHFFFAOYSA-N 0.000 claims 1
- BEDVZTSPJGOAHL-UHFFFAOYSA-N 7-methoxy-1-methyl-9-(3-piperazin-1-ylpropyl)pyrido[3,4-b]indole Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCCN1CCNCC1 BEDVZTSPJGOAHL-UHFFFAOYSA-N 0.000 claims 1
- PARVISVZOIWQKP-UHFFFAOYSA-N 7-methoxy-1-methyl-9-[2-(1,2,4-triazol-1-yl)ethyl]pyrido[3,4-b]indole Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCN1C=NC=N1 PARVISVZOIWQKP-UHFFFAOYSA-N 0.000 claims 1
- BGLGUULRIOHOML-UHFFFAOYSA-N 7-methoxy-1-methyl-9-[2-(1h-1,2,4-triazol-5-yl)ethyl]pyrido[3,4-b]indole Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCC1=NN=CN1 BGLGUULRIOHOML-UHFFFAOYSA-N 0.000 claims 1
- VWZMJZFDXISWCJ-UHFFFAOYSA-N 7-methoxy-1-methyl-9-[3-(1,2,4-triazol-1-yl)propyl]pyrido[3,4-b]indole Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCCN1C=NC=N1 VWZMJZFDXISWCJ-UHFFFAOYSA-N 0.000 claims 1
- OLXJUVVUPRPACM-UHFFFAOYSA-N 7-methoxy-1-methyl-9-[3-(1h-1,2,4-triazol-5-yl)propyl]pyrido[3,4-b]indole Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCCC1=NN=CN1 OLXJUVVUPRPACM-UHFFFAOYSA-N 0.000 claims 1
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- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 claims 1
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- 102000055006 Calcitonin Human genes 0.000 claims 1
- 108060001064 Calcitonin Proteins 0.000 claims 1
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- 108090000625 Cathepsin K Proteins 0.000 claims 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 1
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- 125000004432 carbon atom Chemical group C* 0.000 claims 1
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
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- 150000004677 hydrates Chemical class 0.000 claims 1
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- 125000002757 morpholinyl group Chemical group 0.000 claims 1
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- JRPSMXUOKGFTRV-UHFFFAOYSA-N n,n-diethyl-3-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)propan-1-amine Chemical compound C1=NC(C)=C2N(CCCN(CC)CC)C3=CC(OC)=CC=C3C2=C1 JRPSMXUOKGFTRV-UHFFFAOYSA-N 0.000 claims 1
- ULWNQNZJXNXIQA-UHFFFAOYSA-N n,n-dimethyl-1-pyrido[2,3-b]indol-9-ylpropan-2-amine Chemical compound C1=CN=C2N(CC(C)N(C)C)C3=CC=CC=C3C2=C1 ULWNQNZJXNXIQA-UHFFFAOYSA-N 0.000 claims 1
- MVOVLYWWEVJBAE-UHFFFAOYSA-N n,n-dimethyl-1-pyrido[3,4-b]indol-9-ylpropan-2-amine Chemical compound C1=NC=C2N(CC(C)N(C)C)C3=CC=CC=C3C2=C1 MVOVLYWWEVJBAE-UHFFFAOYSA-N 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 238000011275 oncology therapy Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 125000006413 ring segment Chemical group 0.000 claims 1
- 230000004936 stimulating effect Effects 0.000 claims 1
- 230000000638 stimulation Effects 0.000 claims 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims 1
- DMIDCCHBGQPVGO-UHFFFAOYSA-N tert-butyl 4-[2-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)ethyl]piperazine-1-carboxylate Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCN1CCN(C(=O)OC(C)(C)C)CC1 DMIDCCHBGQPVGO-UHFFFAOYSA-N 0.000 claims 1
- IBIOLMQVRUQALS-UHFFFAOYSA-N tert-butyl 4-[2-[7-methoxy-1-(trifluoromethyl)pyrido[3,4-b]indol-9-yl]ethyl]piperazine-1-carboxylate Chemical compound C=1C(OC)=CC=C(C2=CC=NC(=C22)C(F)(F)F)C=1N2CCN1CCN(C(=O)OC(C)(C)C)CC1 IBIOLMQVRUQALS-UHFFFAOYSA-N 0.000 claims 1
- HKCIYSGWQLQJHZ-UHFFFAOYSA-N tert-butyl 4-[3-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)propyl]piperazine-1-carboxylate Chemical compound C=1C(OC)=CC=C(C2=CC=NC(C)=C22)C=1N2CCCN1CCN(C(=O)OC(C)(C)C)CC1 HKCIYSGWQLQJHZ-UHFFFAOYSA-N 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P19/00—Drugs for skeletal disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- C07C59/235—Saturated compounds containing more than one carboxyl group
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- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
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- C07D209/86—Carbazoles; Hydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
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Claims (17)
1. Spoj u skladu s Formulom I:
[image]
ili njegova sol ili hidrat; pri čemu
W je CR3a;
X je CR3b;
Y je N, pri čemu je N izborno oksidiran u odgovarajući N-oksid;
Z je CR3d;
RNje izabran iz grupe koja se sastoji od NR6R7, heterociklila i heteroarila, pri čemu heterociklil i heteroaril sadrže od 5 do 10 atoma u prstenu, od kojih je najmanje jedan azot;
svako R1a, R1b, i R1cje nezavisno izabran između H, metila i etila, pri čemu ukupni broj atoma ugljika u grupi -C(R1a)2-[C(R1b)2]q-[C(R1c)2]t- ne prelazi šest;
svako R2, R3a, R3bi R3dje nezavisno izabrano iz grupe koja se sastoji od H, halogena, C1-6 alkila, C1-6haloalkila, C2-6 alkenila, C2-6 alkinila, C1-6 alkoksi, C1-6 haloalkoksi, ariloksi, C1-6 alkila-OH, -OR4, -C0-6 alkila-NR4R5, -SR4, -C(O)R4, -C0-6 alkila-C(O)OR4, -C(O)NR4R5, -N(R4)C(O)R5, -N(R4)C(O)OR5, -N(R4)C(O)NR4R5, -OP(O)(OR4)2, -S(O)2OR4, -S(O)2NR4R5, -CN, cikloalkila, heterocikloalkila, arila i heteroarila;
svako R4, R5, R6, i R7je nezavisno izabrano iz grupe koja se sastoji od H, C1-6 alkila i C1-6 alkila-OH;
pri čemu je indeks q jednak 0 i indeks t je 1, ili pri čemu je indeks q jednak 1 i indeks t je 0, ili pri čemu su indeks q i indeks t jednaki 1;
pod uvjetom da:
a) zbroj q i t je 1, i
b) bilo R6iliR7, ako je prisutno, je H ili C1-6 alkil,
najmanje jedno od R1ai R1bje drugačije od H; i
pod uvjetom da je zbroj q i t jednak 2,
a) R2je drugačije od H, i
b) najmanje jedno od R6i R7, ako je prisutno, je drugačije od H ili metila.
2. Spoj prema zahtjevu 1 koje ima strukturu:
[image]
ili njegova sol ili hidrat; pri čemu
R2je izabrano iz grupe koja se sastoji od C1-6 alkoksi, -OH, i C1-6 alkila-OH;
R3ai R3bsu nezavisno izabrani iz grupe koja se sastoji od H, halo, C1-6 alkoksi, -OH, i
R3dje izabrano iz grupe koja se sastoji od H, C1-6 alkila i C1-6 haloalkila.
3. Spoj prema zahtjevu 2, pri čemu
R2je izabrano iz grupe koja se sastoji od metoksi i -OH; i
R3dje izabrano iz grupe koja se sastoji od metila i trifluorometila; ili njegova sol ili hidrat.
4. Spoj prema zahtjevu 3, pri čemu R3ai R3bjesu H; ili njegova sol ili hidrat.
5. Spoj prema zahtjevu 1 koje ima strukturu:
[image]
ili njegova sol ili hidrat; pri čemu
R2je izabrano iz grupe koja se sastoji od -OH, C1-6 alkoksi, i ariloksi; i R3dje izabrano iz grupe koja se sastoji od C1-6 alkila, arila i heteroarila.
6. Spoj prema zahtjevu 5, pri čemu
R2je izabrano između -OH i metoksi; i
R3dje izabrano iz grupe koja se sastoji od 4-metoksifenila; 1,2,3-triazolila; 1,2,4-oksadiazolila; i 1,3,4-oksadiazolila;
ili njegova sol ili hidrat.
7. Spoj prema zahtjevima 1-6, pri čemu je bilo koje N u RNoksidirano u odgovarajući N-oksid; pri čemu je RNizabrano iz grupe koja se sastoji od piperidinil, homopiperidinil, piperazinil, homopiperazinil, morfolinil, pirolidinil i azetidinil grupe.
8. Spoj prema zahtjevima 1-7, pri čemu je grupa -C(R1a)2-[C(R1b)2]q-[C(R1c)2]t-RNizabrana iz grupe koja se sastoji od:
[image]
ili njegova sol ili hidrat.
9. Spoj prema bilo kojem od zahtjeva 1 ili 2, pri čemu je grupa -C(R1a)2-[C(R1b)2]q-[C(R1c)2]t-RNizabrana iz grupe koja se sastoji od:
[image]
ili njegova sol ili hidrat.
10. Spoj prema bilo kojem od zahtjeva 1 ili 2, pri čemu je grupa C(R1a)2 [C(R1b)2]q [C(R1c)2]t-RNizabrana iz grupe koja se sastoji od:
[image]
ili njegova sol ili hidrat.
11. Spoj prema zahtjevu 1, koje je izabrano iz grupe koja se sastoji od:
7-metoksi-1-metil-9-(3-(piperazin-1-il)propil)-9H-pirido[3,4-b]indola;
7-metoksi-1-metil-9-(2-(piperazin-1-il)etil)-9H-pirido[3,4-b]indola;
7-metoksi-1-metil-9-(1-(piperidin-1-il)propan-2-il)-9H-pirido[3,4-b]indola;
4-(3-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)propil)morfolina;
4-(2-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)etil)morfolina;
4-(2-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)propil)morfolina;
9-(2-morfolinoetil)-1-(trifluorometil)-9H-pirido[3,4-b]indol-7-ola;
4-(1-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)propan-2-il)morfolina;
7-metoksi-1-metil-9-(2-(piperidin-1-il)etil)-9H-pirido[3,4-b]indola;
1-metil-9-(2-morfolinoetil)-9H-pirido[3,4-b]indol-7-ola;
terc-butil 4-(2-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)etil)piperazin-1-karboksilata;
terc-butil 4-(3-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)propil)piperazin-1-karboksilata;
terc-butil 4-(2-(7-metoksi-1-(trifluorometil)-9H-pirido[3,4-b]indol-9-il)etil)piperazin-1-karboksilata;
4-(1-(7-metoksi-1-(trifluorometil)-9H-pirido[3,4-b]indol-9-il)propan-2-il)morfolina;
4-(2-(7-metoksi-l-(trifluorometil)-9H-pirido[3,4-b]indol-9-il)etil)morfolina;
9-(2-(3-metilmorfolino)etil)-1-(trifluorometil)-9H-pirido[3,4-b]indol-7-ola;
9-(2-(2,6-dimetilmorfolino)etil)-1-(trifluorometil)-9H-pirido[3,4-b]indol-7-ola;
9-(2-(3,3-dimetilmorfolino)etil)-1-(trifluorometil)-9H-pirido[3,4-b]indol-7-ola;
7-metoksi-9-(2-(piperidin-1-il)etil)-1-(trifluorometil)-9H-pirido[3,4-b]indola;
3-fluoro-7-metoksi-1-metil-9-(2-(piperidin-1-il)etil)-9H-pirido[3,4-b]indola;
4-(2-(3-fluoro-7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)etil)morfolina;
7-metoksi-1-metil-9-(2-(piperidin-1-il)propil)-9H-pirido[3,4-b]indola;
2-((2-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)etil)(metil)amino)etanola;
1-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)-N,N-dimetilpropan-2-amina;
2,2’-((2-(7-metoksi-1-(trifluorometil)-9H-pirido[3,4-b]indol-9-il)etil)azanediil)dietanola;
2-((2-(7-metoksi-1-(trifluorometil)-9H-pirido[3,4-b]indol-9-il)etil)amino)etanola;
2,2’-((2-(7-hidroksi-1-(trifluorometil)-9H-pirido[3,4-b]indol-9-il)etil)azanediil)dietanola;
2-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)-N,N-dimetiletanamina;
1-(7 -metoksi-1-(trifluorometil)-9H-pirido[3,4-b]indol-9-il)-N,N-dimetilpropan-2-amina;
2-((2-(7-metoksi-1-(trifluorometil)-9H-pirido[3,4-b]indol-9-il)etil)(metil)amino)etanola;
9-(2-(dimetilamino)propil)-9H-pirido [3,4-b] indol-7-ola;
9-(2-(dimetilamino)propil)-1-metil-9H-pirido[3,4-b]indol-7-ola;
N,N-dimetil-1-(9H-pirido[3,4-b]indol-9-il)propan-2-amina;
1-(7-metoksi-9H-pirido[3,4-b]indol-9-il)-N,N-dimetilpropan-2-amina;
1-(2-metoksi-9H-karbazol-9-il)-N,N-dimetilpropan-2-amina;
N,N-dietil-3-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)propan-1-amina;
2-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)-N,N-dimetilpropan-1-amina;
N,N-dietil-2-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)propan-1-amina;
9-(2-(4H-1, 2,4-triazol-3-il)etil)-7-metoksi-1-metil-9H-pirido[3,4-b]indola;
2-(2-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)etil)-1,3,4-oksadiazola;
5-(2-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)etil)-1,2,4-oksadiazola;
9-(2-(1H-1,2,4-triazol-1-il)etil)-7-metoksi-1-metil-9H-pirido[3,4-b]indola;
9-(3-(4H-1,2,4-triazol-3-il)propil)-7-metoksi-1-metil-9H-pirido[3,4-b]indola;
2-(3-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)propil)-1,3,4-oksadiazola;
5-(3-(7-metoksi-1-metil-9H-pirido[3,4-b]indol-9-il)propil)-1,2,4-oksadiazola;
9-(3-(1H-1,2,4-triazol-1-il)propil)-7-metoksi-1-metil-9H-pirido[3,4-b]indola;
N,N-dimetil-1-(9H-pirido[2,3-b]indol-9-il)propan-2-amina;
1-(9H-karbazol-9-il)-N,N-dimetilpropan-2-amina;
4-(2-(7-metoksi-1-(trifluorometil)-9H-pirido[3,4-b]indol-9-il)etil)-3-metilmorfolina;
ili njegove soli ili hidrati.
12. Spoj prema bilo kojem od zahtjeva 1-11, pri čemu je sol formatna, citratna, acetatna ili sulfatna sol; ili, hidrokloridna sol.
13. Farmaceutska kompozicija koja sadrži spoj prema bilo kojem od zahtjeva 1-12 i farmaceutski prihvatljivi ekscipijens.
14. Spoj prema bilo kojem od zahtjeva 1-12 za primjenu u poticanju sistemskog formiranja kostiju kod subjekta; za primjenu u terapiji oštećenja bubrega; ili za primjenu u terapiji raka, zbog čega se spoj primjenjuje sistemski.
15. Spoj za primjenu prema zahtjevu 14, pri čemu se potiče sistemsko formiranje kostiju radi liječenja oslabljene kosti, slomljene kosti, ili bolesti ili stanja naznačenog malom koštanom masom.
16. Spoj za primjenu prema zahtjevu 14, pri čemu se potiče sistemsko formiranje kostiju radi liječenja osteoporoze, osteogenesis imperfecta, osteopenije, sekundarno inducirane osteoporoze, Pagetove bolesti ili sindroma osteoporoze-pseudoglioma (OPPG).
17. Spoj za primjenu prema zahtjevu 14 ili 15, pri čemu je primjena stimulacija sistemskog formiranja kostiju i pri čemu se spoj primjenjuje u kombinaciji sa jednim ili više drugih terapijskih sredstava ili pri čemu se spoj primjenjuje na pacijentu koji je liječen antiresorptivnim lijekom ili je prethodno bio liječen antiresorptivnim lijekom;
pri čemu je izborno antiresorptivni lijek izabran iz grupe koja se sastoji od RankL inhibitora, bisfosfonata, selektivnog modulatora estrogenih receptora (SERM), kalcitonina, analoga kalcitonina, vitamina D, analoga vitamina D i inhibitora katepsina K;
pri čemu je izborno RankL inhibitor denosumab ili je biofosfonat alendronat.
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EP14770052.0A EP2968284B1 (en) | 2013-03-14 | 2014-03-14 | Alkyl-amine harmine derivatives for promoting bone growth |
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EP2968284A2 (en) | 2016-01-20 |
PT2968284T (pt) | 2021-06-28 |
US10501457B2 (en) | 2019-12-10 |
EP3915987B1 (en) | 2023-12-13 |
HUE055455T2 (hu) | 2021-11-29 |
JP2016519082A (ja) | 2016-06-30 |
US9540365B2 (en) | 2017-01-10 |
SI2968284T1 (sl) | 2021-08-31 |
PL2968284T3 (pl) | 2021-09-27 |
LT2968284T (lt) | 2021-07-12 |
WO2014153203A3 (en) | 2014-11-13 |
RS62053B1 (sr) | 2021-07-30 |
DK2968284T3 (da) | 2021-06-14 |
CN105120863A (zh) | 2015-12-02 |
ES2875874T3 (es) | 2021-11-11 |
US11267814B2 (en) | 2022-03-08 |
JP6721499B2 (ja) | 2020-07-15 |
CN105120863B (zh) | 2021-06-04 |
WO2014153203A2 (en) | 2014-09-25 |
HK1218259A1 (zh) | 2017-02-10 |
US20200172538A1 (en) | 2020-06-04 |
CN113416187A (zh) | 2021-09-21 |
EP3915987A1 (en) | 2021-12-01 |
EP3915987C0 (en) | 2023-12-13 |
CA2899247C (en) | 2023-04-04 |
EP2968284A4 (en) | 2016-08-17 |
CA2899247A1 (en) | 2014-09-25 |
EP2968284B1 (en) | 2021-04-21 |
US20170298059A1 (en) | 2017-10-19 |
US20140288068A1 (en) | 2014-09-25 |
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