ES2524892T3 - 2-(Benciloxi)benzamidas como inhibidores de LRRK2 quinasa - Google Patents
2-(Benciloxi)benzamidas como inhibidores de LRRK2 quinasa Download PDFInfo
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- ES2524892T3 ES2524892T3 ES11757574.6T ES11757574T ES2524892T3 ES 2524892 T3 ES2524892 T3 ES 2524892T3 ES 11757574 T ES11757574 T ES 11757574T ES 2524892 T3 ES2524892 T3 ES 2524892T3
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- Prior art keywords
- methyl
- oxy
- mmol
- phenylmethyl
- pyrazol
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- 239000003112 inhibitor Substances 0.000 title description 6
- 102000009784 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Human genes 0.000 title 1
- 108010020246 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Proteins 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 540
- 150000001875 compounds Chemical class 0.000 claims abstract description 295
- -1 pyrimidine- 5 5-yl Chemical group 0.000 claims abstract description 129
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 111
- 150000003839 salts Chemical class 0.000 claims abstract description 82
- 125000005843 halogen group Chemical group 0.000 claims abstract description 68
- 239000001257 hydrogen Substances 0.000 claims abstract description 61
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 42
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 40
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 36
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 32
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 19
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 18
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims abstract description 13
- 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims abstract description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 9
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims abstract description 8
- 125000000842 isoxazolyl group Chemical group 0.000 claims abstract description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 8
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims abstract description 7
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 5
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims abstract description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 2
- 238000011282 treatment Methods 0.000 claims description 39
- 208000018737 Parkinson disease Diseases 0.000 claims description 35
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 9
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 8
- WVKCJEGOEIKIEW-UHFFFAOYSA-N n-(3-chlorophenyl)-5-(1-methylpyrazol-4-yl)-4-(morpholin-4-ylmethyl)-2-phenylmethoxybenzamide Chemical compound C1=NN(C)C=C1C(C(=C1)CN2CCOCC2)=CC(C(=O)NC=2C=C(Cl)C=CC=2)=C1OCC1=CC=CC=C1 WVKCJEGOEIKIEW-UHFFFAOYSA-N 0.000 claims description 8
- 238000011321 prophylaxis Methods 0.000 claims description 8
- PNLFSZXNKSYCIK-UHFFFAOYSA-N 5-bromo-2-[(4-fluorophenyl)methoxy]-n-(3-methyl-1,2-oxazol-4-yl)-4-(morpholin-4-ylmethyl)benzamide Chemical compound CC1=NOC=C1NC(=O)C(C(=C1)OCC=2C=CC(F)=CC=2)=CC(Br)=C1CN1CCOCC1 PNLFSZXNKSYCIK-UHFFFAOYSA-N 0.000 claims description 6
- PCQTUHNOEGXOGA-UHFFFAOYSA-N 2-[(4-fluorophenyl)methoxy]-5-(1-methylpyrazol-4-yl)-4-(morpholine-4-carbonyl)-n-pyridazin-4-ylbenzamide Chemical compound C1=NN(C)C=C1C(C(=C1)C(=O)N2CCOCC2)=CC(C(=O)NC=2C=NN=CC=2)=C1OCC1=CC=C(F)C=C1 PCQTUHNOEGXOGA-UHFFFAOYSA-N 0.000 claims description 5
- PETDKGFNLJTKFY-UHFFFAOYSA-N 4-bromo-5-methyl-2-phenylmethoxy-n-pyridazin-4-ylbenzamide Chemical compound C=1C=CC=CC=1COC=1C=C(Br)C(C)=CC=1C(=O)NC1=CC=NN=C1 PETDKGFNLJTKFY-UHFFFAOYSA-N 0.000 claims description 5
- KSPCWJFRHRJBTA-UHFFFAOYSA-N 4-bromo-5-methyl-2-phenylmethoxy-n-pyridin-3-ylbenzamide Chemical compound C=1C=CC=CC=1COC=1C=C(Br)C(C)=CC=1C(=O)NC1=CC=CN=C1 KSPCWJFRHRJBTA-UHFFFAOYSA-N 0.000 claims description 5
- WYLCYMKCMSZZGE-UHFFFAOYSA-N 4-methyl-5-(1-methylpyrazol-4-yl)-2-phenylmethoxy-n-pyridazin-4-ylbenzamide Chemical compound C=1C=NN=CC=1NC(=O)C=1C=C(C2=CN(C)N=C2)C(C)=CC=1OCC1=CC=CC=C1 WYLCYMKCMSZZGE-UHFFFAOYSA-N 0.000 claims description 5
- NRTJPQGNYRYDBO-UHFFFAOYSA-N 5-bromo-2-[(2,4-difluorophenyl)methoxy]-4-(morpholin-4-ylmethyl)-n-pyridin-3-ylbenzamide Chemical compound FC1=CC(F)=CC=C1COC1=CC(CN2CCOCC2)=C(Br)C=C1C(=O)NC1=CC=CN=C1 NRTJPQGNYRYDBO-UHFFFAOYSA-N 0.000 claims description 5
- WFQPMLJLFKCPFN-UHFFFAOYSA-N 5-bromo-2-[(4-fluorophenyl)methoxy]-4-(morpholin-4-ylmethyl)-n-pyridin-3-ylbenzamide Chemical compound C1=CC(F)=CC=C1COC1=CC(CN2CCOCC2)=C(Br)C=C1C(=O)NC1=CC=CN=C1 WFQPMLJLFKCPFN-UHFFFAOYSA-N 0.000 claims description 5
- YGQUQCZUNVIFSC-UHFFFAOYSA-N 5-bromo-4-(morpholin-4-ylmethyl)-2-phenylmethoxy-n-pyridazin-4-ylbenzamide Chemical compound C=1C=CC=CC=1COC=1C=C(CN2CCOCC2)C(Br)=CC=1C(=O)NC1=CC=NN=C1 YGQUQCZUNVIFSC-UHFFFAOYSA-N 0.000 claims description 5
- DSNCIOWRWZUOME-UHFFFAOYSA-N 5-bromo-4-methyl-2-phenylmethoxy-n-pyridazin-4-ylbenzamide Chemical compound C=1C=NN=CC=1NC(=O)C=1C=C(Br)C(C)=CC=1OCC1=CC=CC=C1 DSNCIOWRWZUOME-UHFFFAOYSA-N 0.000 claims description 5
- VXPAEGIGRDIXNY-UHFFFAOYSA-N 5-bromo-4-methyl-2-phenylmethoxy-n-pyridin-3-ylbenzamide Chemical compound C=1C=CN=CC=1NC(=O)C=1C=C(Br)C(C)=CC=1OCC1=CC=CC=C1 VXPAEGIGRDIXNY-UHFFFAOYSA-N 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 5
- ZNZAYRZVOSKGDF-UHFFFAOYSA-N 1-n,1-n-dimethyl-2-(1-methylpyrazol-4-yl)-5-phenylmethoxy-4-n-pyridin-3-ylbenzene-1,4-dicarboxamide Chemical compound C=1C=CN=CC=1NC(=O)C=1C=C(C2=CN(C)N=C2)C(C(=O)N(C)C)=CC=1OCC1=CC=CC=C1 ZNZAYRZVOSKGDF-UHFFFAOYSA-N 0.000 claims description 4
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 4
- ACZUDGFGMAICLB-UHFFFAOYSA-N 2-[(4-fluorophenyl)methoxy]-4-(1-methylpyrazol-4-yl)-5-(morpholin-4-ylmethyl)-n-pyridazin-4-ylbenzamide Chemical compound C1=NN(C)C=C1C1=CC(OCC=2C=CC(F)=CC=2)=C(C(=O)NC=2C=NN=CC=2)C=C1CN1CCOCC1 ACZUDGFGMAICLB-UHFFFAOYSA-N 0.000 claims description 4
- ICVNHGOJUXSGHB-UHFFFAOYSA-N 2-[(4-fluorophenyl)methoxy]-4-(1-methylpyrazol-4-yl)-5-(morpholin-4-ylmethyl)-n-pyridin-3-ylbenzamide Chemical compound C1=NN(C)C=C1C1=CC(OCC=2C=CC(F)=CC=2)=C(C(=O)NC=2C=NC=CC=2)C=C1CN1CCOCC1 ICVNHGOJUXSGHB-UHFFFAOYSA-N 0.000 claims description 4
- ZOCPONDHNCZYMF-UHFFFAOYSA-N 2-[(4-fluorophenyl)methoxy]-4-(1-methylpyrazol-4-yl)-5-(morpholine-4-carbonyl)-n-pyridazin-4-ylbenzamide Chemical compound C1=NN(C)C=C1C1=CC(OCC=2C=CC(F)=CC=2)=C(C(=O)NC=2C=NN=CC=2)C=C1C(=O)N1CCOCC1 ZOCPONDHNCZYMF-UHFFFAOYSA-N 0.000 claims description 4
- OTMDMMQDZAMHTA-UHFFFAOYSA-N 2-[(4-fluorophenyl)methoxy]-4-(1-methylpyrazol-4-yl)-5-(morpholine-4-carbonyl)-n-pyridin-3-ylbenzamide Chemical compound C1=NN(C)C=C1C1=CC(OCC=2C=CC(F)=CC=2)=C(C(=O)NC=2C=NC=CC=2)C=C1C(=O)N1CCOCC1 OTMDMMQDZAMHTA-UHFFFAOYSA-N 0.000 claims description 4
- FMCJXTLGQHSVTJ-UHFFFAOYSA-N 2-[(4-fluorophenyl)methoxy]-5-(1-methylpyrazol-4-yl)-4-(morpholin-4-ylmethyl)-n-pyridin-3-ylbenzamide Chemical compound C1=NN(C)C=C1C(C(=C1)CN2CCOCC2)=CC(C(=O)NC=2C=NC=CC=2)=C1OCC1=CC=C(F)C=C1 FMCJXTLGQHSVTJ-UHFFFAOYSA-N 0.000 claims description 4
- AJIPXNGNCZRRPQ-UHFFFAOYSA-N 2-[(4-fluorophenyl)methoxy]-n-(3-methyl-1,2-oxazol-4-yl)-5-(1-methylpyrazol-4-yl)-4-(morpholin-4-ylmethyl)benzamide Chemical compound CC1=NOC=C1NC(=O)C(C(=C1)OCC=2C=CC(F)=CC=2)=CC(C2=CN(C)N=C2)=C1CN1CCOCC1 AJIPXNGNCZRRPQ-UHFFFAOYSA-N 0.000 claims description 4
- ZGBITSVINYLREK-UHFFFAOYSA-N 2-phenylmethoxy-4-(piperidin-1-ylmethyl)-n-pyridazin-4-yl-5-(trifluoromethyl)benzamide Chemical compound C=1C=CC=CC=1COC=1C=C(CN2CCCCC2)C(C(F)(F)F)=CC=1C(=O)NC1=CC=NN=C1 ZGBITSVINYLREK-UHFFFAOYSA-N 0.000 claims description 4
- XXXQDKGSXAWNPL-UHFFFAOYSA-N 2-phenylmethoxy-4-(piperidin-1-ylmethyl)-n-pyridin-3-yl-5-(trifluoromethyl)benzamide Chemical compound C=1C=CC=CC=1COC=1C=C(CN2CCCCC2)C(C(F)(F)F)=CC=1C(=O)NC1=CC=CN=C1 XXXQDKGSXAWNPL-UHFFFAOYSA-N 0.000 claims description 4
- QEQWBOBNBKHVAA-UHFFFAOYSA-N 2-phenylmethoxy-4-(piperidine-1-carbonyl)-n-pyridazin-4-yl-5-(trifluoromethyl)benzamide Chemical compound C=1C=CC=CC=1COC=1C=C(C(=O)N2CCCCC2)C(C(F)(F)F)=CC=1C(=O)NC1=CC=NN=C1 QEQWBOBNBKHVAA-UHFFFAOYSA-N 0.000 claims description 4
- VVVAMQDCNJYXGL-UHFFFAOYSA-N 4-(morpholin-4-ylmethyl)-2-phenylmethoxy-n-pyridazin-4-yl-5-(trifluoromethyl)benzamide Chemical compound C=1C=CC=CC=1COC=1C=C(CN2CCOCC2)C(C(F)(F)F)=CC=1C(=O)NC1=CC=NN=C1 VVVAMQDCNJYXGL-UHFFFAOYSA-N 0.000 claims description 4
- PMMSDHXESWWTGW-UHFFFAOYSA-N 4-(morpholin-4-ylmethyl)-2-phenylmethoxy-n-pyridin-3-yl-5-(trifluoromethyl)benzamide Chemical compound C=1C=CC=CC=1COC=1C=C(CN2CCOCC2)C(C(F)(F)F)=CC=1C(=O)NC1=CC=CN=C1 PMMSDHXESWWTGW-UHFFFAOYSA-N 0.000 claims description 4
- PVIVCPFJFILPFP-UHFFFAOYSA-N 4-(morpholine-4-carbonyl)-2-phenylmethoxy-n-pyridazin-4-yl-5-(trifluoromethyl)benzamide Chemical compound C=1C=CC=CC=1COC=1C=C(C(=O)N2CCOCC2)C(C(F)(F)F)=CC=1C(=O)NC1=CC=NN=C1 PVIVCPFJFILPFP-UHFFFAOYSA-N 0.000 claims description 4
- XZCUBMJXCFBXGI-UHFFFAOYSA-N 4-(morpholine-4-carbonyl)-2-phenylmethoxy-n-pyridin-3-yl-5-(trifluoromethyl)benzamide Chemical compound C=1C=CC=CC=1COC=1C=C(C(=O)N2CCOCC2)C(C(F)(F)F)=CC=1C(=O)NC1=CC=CN=C1 XZCUBMJXCFBXGI-UHFFFAOYSA-N 0.000 claims description 4
- TXKMZQCYNZWDKR-UHFFFAOYSA-N 5-(1-methylpyrazol-4-yl)-2-phenylmethoxy-4-(piperidine-1-carbonyl)-n-pyridin-3-ylbenzamide Chemical compound C1=NN(C)C=C1C(C(=C1)C(=O)N2CCCCC2)=CC(C(=O)NC=2C=NC=CC=2)=C1OCC1=CC=CC=C1 TXKMZQCYNZWDKR-UHFFFAOYSA-N 0.000 claims description 4
- ANGYFPHUVAZUDG-UHFFFAOYSA-N 5-(1-methylpyrazol-4-yl)-4-(morpholin-4-ylmethyl)-2-phenylmethoxy-n-pyridazin-4-ylbenzamide Chemical compound C1=NN(C)C=C1C(C(=C1)CN2CCOCC2)=CC(C(=O)NC=2C=NN=CC=2)=C1OCC1=CC=CC=C1 ANGYFPHUVAZUDG-UHFFFAOYSA-N 0.000 claims description 4
- INTSBGSQDNKPIA-UHFFFAOYSA-N 5-(1-methylpyrazol-4-yl)-4-(morpholin-4-ylmethyl)-2-phenylmethoxy-n-pyridin-3-ylbenzamide Chemical compound C1=NN(C)C=C1C(C(=C1)CN2CCOCC2)=CC(C(=O)NC=2C=NC=CC=2)=C1OCC1=CC=CC=C1 INTSBGSQDNKPIA-UHFFFAOYSA-N 0.000 claims description 4
- NHBSVMHIINESQN-UHFFFAOYSA-N 5-(1-methylpyrazol-4-yl)-4-(morpholine-4-carbonyl)-2-phenylmethoxy-n-pyridazin-4-ylbenzamide Chemical compound C1=NN(C)C=C1C(C(=C1)C(=O)N2CCOCC2)=CC(C(=O)NC=2C=NN=CC=2)=C1OCC1=CC=CC=C1 NHBSVMHIINESQN-UHFFFAOYSA-N 0.000 claims description 4
- BZMDESXKILFDBN-UHFFFAOYSA-N 5-(1-methylpyrazol-4-yl)-4-(morpholine-4-carbonyl)-2-phenylmethoxy-n-pyridin-3-ylbenzamide Chemical compound C1=NN(C)C=C1C(C(=C1)C(=O)N2CCOCC2)=CC(C(=O)NC=2C=NC=CC=2)=C1OCC1=CC=CC=C1 BZMDESXKILFDBN-UHFFFAOYSA-N 0.000 claims description 4
- KNSYFGFJFCYPEV-UHFFFAOYSA-N 5-bromo-2-[(2,4-difluorophenyl)methoxy]-n-(3-methyl-1,2-oxazol-4-yl)-4-(morpholin-4-ylmethyl)benzamide Chemical compound CC1=NOC=C1NC(=O)C(C(=C1)OCC=2C(=CC(F)=CC=2)F)=CC(Br)=C1CN1CCOCC1 KNSYFGFJFCYPEV-UHFFFAOYSA-N 0.000 claims description 4
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- HNNRSNAGYWQHNZ-UHFFFAOYSA-N 5-chloro-4-(3,3-difluoropyrrolidine-1-carbonyl)-2-phenylmethoxy-n-pyridazin-4-ylbenzamide Chemical compound C1C(F)(F)CCN1C(=O)C1=CC(OCC=2C=CC=CC=2)=C(C(=O)NC=2C=NN=CC=2)C=C1Cl HNNRSNAGYWQHNZ-UHFFFAOYSA-N 0.000 claims description 4
- RACZIHSWOWWRDP-UHFFFAOYSA-N 5-chloro-4-(3,3-difluoropyrrolidine-1-carbonyl)-2-phenylmethoxy-n-pyridin-3-ylbenzamide Chemical compound C1C(F)(F)CCN1C(=O)C1=CC(OCC=2C=CC=CC=2)=C(C(=O)NC=2C=NC=CC=2)C=C1Cl RACZIHSWOWWRDP-UHFFFAOYSA-N 0.000 claims description 4
- VHLQWNCVVZDRJZ-UHFFFAOYSA-N 5-chloro-4-(3,3-difluoropyrrolidine-1-carbonyl)-n-(3-methyl-1,2-oxazol-4-yl)-2-phenylmethoxybenzamide Chemical compound CC1=NOC=C1NC(=O)C1=CC(Cl)=C(C(=O)N2CC(F)(F)CC2)C=C1OCC1=CC=CC=C1 VHLQWNCVVZDRJZ-UHFFFAOYSA-N 0.000 claims description 4
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract description 28
- 125000004429 atom Chemical group 0.000 abstract description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/20—Nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/14—Nitrogen atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
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- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| WOPCT/CN2010/076557 | 2010-09-02 | ||
| CN2010076557 | 2010-09-02 | ||
| WOPCT/CN2011/000511 | 2011-03-28 | ||
| CN2011000511 | 2011-03-28 | ||
| CN2011001227 | 2011-07-26 | ||
| WOPCT/CN2011/001227 | 2011-07-26 | ||
| PCT/EP2011/064943 WO2012028629A1 (en) | 2010-09-02 | 2011-08-31 | 2 - (benzyloxy) benzamides as lrrk2 kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
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| ES2524892T3 true ES2524892T3 (es) | 2014-12-15 |
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| ES11757574.6T Active ES2524892T3 (es) | 2010-09-02 | 2011-08-31 | 2-(Benciloxi)benzamidas como inhibidores de LRRK2 quinasa |
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| TW (1) | TW201305109A (enExample) |
| WO (1) | WO2012028629A1 (enExample) |
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| MD20140130A2 (ro) | 2012-06-29 | 2015-04-30 | Pfizer Inc. | 4-(amino-substituite)-7H-pirolo[2,3-d]pirimidine noi ca inhibitori de LRRK2 |
| US9725463B2 (en) | 2013-06-21 | 2017-08-08 | Lupin Limited | Substituted heterocyclic compounds as CRAC modulators |
| WO2014207648A1 (en) | 2013-06-24 | 2014-12-31 | Lupin Limited | Chromane and chromene derivatives and their use as crac modulators |
| WO2015092592A1 (en) | 2013-12-17 | 2015-06-25 | Pfizer Inc. | Novel 3,4-disubstituted-1h-pyrrolo[2,3-b]pyridines and 4,5-disubstituted-7h-pyrrolo[2,3-c]pyridazines as lrrk2 inhibitors |
| US10004751B2 (en) | 2014-07-10 | 2018-06-26 | The J. David Gladstone Institutes | Compositions and methods for treating Dengue virus infection |
| EP3623371A1 (en) | 2014-12-16 | 2020-03-18 | Axovant Sciences GmbH | Geminal substituted quinuclidine amide compounds as agonists of alpha-7 nicotinic acetylcholine receptors |
| US10875844B2 (en) | 2015-03-04 | 2020-12-29 | Dana-Farber Cancer Institute, Inc. | Salicylate inhibitors of MELK and methods of use |
| CA2988968A1 (en) | 2015-06-10 | 2016-12-15 | Forum Pharmaceuticals, Inc. | Aminobenzisoxazole compounds as agonists of a7-nicotinic acetylcholine receptors |
| JP2018523707A (ja) | 2015-08-12 | 2018-08-23 | アクソバント サイエンシズ ゲーエムベーハー | α7−ニコチン性アセチルコリン受容体のアゴニストとしてのジェミナル置換アミノベンゾイソオキサゾール化合物 |
| RU2722149C1 (ru) | 2015-09-14 | 2020-05-27 | Пфайзер Инк. | Новые производные имидазо[4,5-c] хинолинов и имидазо[4,5-c][1,5] нафтиридинов в качестве ингибиторов LRRK2 |
| EP3592741B1 (en) | 2017-03-10 | 2023-02-15 | Pfizer Inc. | Novel imidazo[4,5-c]quinoline derivatives as lrrk2 inhibitors |
| EP3592740B1 (en) | 2017-03-10 | 2022-02-09 | Pfizer Inc. | Cyclic substituted imidazo[4,5-c]quinoline derivatives |
| WO2023076404A1 (en) | 2021-10-27 | 2023-05-04 | Aria Pharmaceuticals, Inc. | Methods for treating systemic lupus erythematosus |
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| US5236931A (en) * | 1992-03-26 | 1993-08-17 | A. H. Robins Company, Incorporated | 2-substituted benzamide and benzoate derivatives of 3-aminoquinuclidine and 3-quinuclidinol |
| PL202623B1 (pl) | 2000-06-28 | 2009-07-31 | Smithkline Beecham Plc | Sposób wytwarzania drobno zmielonego preparatu substancji leczniczej, drobno zmielona substancja lecznicza wytworzona tym sposobem i zawierająca ją kompozycja farmaceutyczna |
| WO2006045392A2 (en) | 2004-10-21 | 2006-05-04 | GSF-Forschungszentrum für Umwelt und Gesundheit GmbH | Kaspp (lrrke) gene, its production and use for the detection and treatment of neurodegenerative disorders |
| NO323175B1 (no) | 2004-12-23 | 2007-01-15 | Jan O Aasly | Framgangsmate for a pavise en mutasjon som forarsaker arvelig parkinsonisme |
| BRPI0713738A2 (pt) | 2006-06-20 | 2014-06-24 | Novartis Ag | Biomarcadores para a progressão de doença alzheimer |
| WO2009127642A2 (en) | 2008-04-15 | 2009-10-22 | Cellzome Limited | Use of lrrk2 inhibitors for neurodegenerative diseases |
| BR112012006859A2 (pt) * | 2009-09-29 | 2019-09-24 | Glaxo Group Ltd | compostos |
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| JP2013540712A (ja) | 2013-11-07 |
| US9365551B2 (en) | 2016-06-14 |
| AR082827A1 (es) | 2013-01-09 |
| JP5781611B2 (ja) | 2015-09-24 |
| TW201305109A (zh) | 2013-02-01 |
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| EP2611772B1 (en) | 2014-09-24 |
| EP2611772A1 (en) | 2013-07-10 |
| US20130225584A1 (en) | 2013-08-29 |
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