KR20090041387A - 마크로시클릭 락탐 - Google Patents
마크로시클릭 락탐 Download PDFInfo
- Publication number
- KR20090041387A KR20090041387A KR1020097001068A KR20097001068A KR20090041387A KR 20090041387 A KR20090041387 A KR 20090041387A KR 1020097001068 A KR1020097001068 A KR 1020097001068A KR 20097001068 A KR20097001068 A KR 20097001068A KR 20090041387 A KR20090041387 A KR 20090041387A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- tetrahydro
- benzo
- cycloalkyl
- dioxo
- 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- Withdrawn
Links
- 150000003951 lactams Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 66
- 239000002253 acid Substances 0.000 claims abstract description 20
- 150000003839 salts Chemical group 0.000 claims abstract description 20
- 239000012458 free base Substances 0.000 claims abstract description 19
- 239000003814 drug Substances 0.000 claims abstract description 12
- -1 chroman-4-yl Chemical group 0.000 claims description 155
- 125000000217 alkyl group Chemical group 0.000 claims description 111
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 71
- 125000001072 heteroaryl group Chemical group 0.000 claims description 52
- 125000003118 aryl group Chemical group 0.000 claims description 49
- 239000001257 hydrogen Substances 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 34
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical group 0.000 claims description 15
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- 238000004220 aggregation Methods 0.000 claims description 13
- 230000002776 aggregation Effects 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 102000013455 Amyloid beta-Peptides Human genes 0.000 claims description 12
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 10
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000004043 oxo group Chemical group O=* 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 7
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 7
- 210000004204 blood vessel Anatomy 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 210000000653 nervous system Anatomy 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 5
- 238000003776 cleavage reaction Methods 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- 230000007017 scission Effects 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000005529 alkyleneoxy group Chemical group 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000006413 ring segment Chemical group 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000005237 alkyleneamino group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 claims description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 2
- 238000007306 functionalization reaction Methods 0.000 claims description 2
- 229910052750 molybdenum Inorganic materials 0.000 claims description 2
- 239000011733 molybdenum Substances 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 229910052707 ruthenium Inorganic materials 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 claims description 2
- 229910052721 tungsten Inorganic materials 0.000 claims description 2
- 239000010937 tungsten Substances 0.000 claims description 2
- 229910052720 vanadium Inorganic materials 0.000 claims description 2
- 208000019553 vascular disease Diseases 0.000 claims 4
- 206010059245 Angiopathy Diseases 0.000 claims 2
- 208000012902 Nervous system disease Diseases 0.000 claims 2
- 208000025966 Neurological disease Diseases 0.000 claims 2
- 230000000926 neurological effect Effects 0.000 claims 2
- 229940088679 drug related substance Drugs 0.000 claims 1
- 239000008024 pharmaceutical diluent Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 3
- 150000002678 macrocyclic compounds Chemical class 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 16
- 239000000203 mixture Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 201000010099 disease Diseases 0.000 description 10
- 208000035475 disorder Diseases 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 9
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- 125000004076 pyridyl group Chemical group 0.000 description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- RWNJOXUVHRXHSD-UHFFFAOYSA-N hept-6-enoic acid Chemical compound OC(=O)CCCCC=C RWNJOXUVHRXHSD-UHFFFAOYSA-N 0.000 description 5
- 230000001394 metastastic effect Effects 0.000 description 5
- 206010061289 metastatic neoplasm Diseases 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 125000003107 substituted aryl group Chemical group 0.000 description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 4
- 102000003908 Cathepsin D Human genes 0.000 description 4
- 108090000258 Cathepsin D Proteins 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ALEZWDWARSRIRW-UHFFFAOYSA-N 1-(3-propan-2-ylphenyl)cyclopropan-1-amine Chemical compound CC(C)C1=CC=CC(C2(N)CC2)=C1 ALEZWDWARSRIRW-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 241000701447 unidentified baculovirus Species 0.000 description 3
- HWUWVNZQHHMGEX-YFQNEARWSA-N (3s,14r,16s)-16-[(1r)-1-hydroxy-2-[[1-(3-propan-2-ylphenyl)cyclopropyl]amino]ethyl]-3,4,14-trimethyl-1,4-diazacyclohexadecane-2,5-dione Chemical compound CC(C)C1=CC=CC(C2(CC2)NC[C@@H](O)[C@H]2NC(=O)[C@H](C)N(C)C(=O)CCCCCCCC[C@@H](C)C2)=C1 HWUWVNZQHHMGEX-YFQNEARWSA-N 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N 1-ethenoxybutane Chemical compound CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- XXOQJWXDRPURJK-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1-benzoxepine Chemical group O1CCCCC2=CC=CC=C21 XXOQJWXDRPURJK-UHFFFAOYSA-N 0.000 description 2
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 2
- LWYFMTMRWRGREZ-UHFFFAOYSA-N 3-propan-2-ylbenzonitrile Chemical compound CC(C)C1=CC=CC(C#N)=C1 LWYFMTMRWRGREZ-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 2
- 102100021257 Beta-secretase 1 Human genes 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
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- 239000004280 Sodium formate Substances 0.000 description 2
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- 206010002022 amyloidosis Diseases 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
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- 238000004440 column chromatography Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 2
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
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- QQRLQQQKCIEUJA-UHFFFAOYSA-N 1-(3-propan-2-yloxyphenyl)cyclopropan-1-amine Chemical compound CC(C)OC1=CC=CC(C2(N)CC2)=C1 QQRLQQQKCIEUJA-UHFFFAOYSA-N 0.000 description 1
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- RPYKMZGMPZPSNA-UHFFFAOYSA-N 1-(4-propan-2-ylpyridin-2-yl)cyclopropan-1-amine Chemical compound CC(C)C1=CC=NC(C2(N)CC2)=C1 RPYKMZGMPZPSNA-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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- 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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D245/00—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms
- C07D245/02—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
- C07D273/02—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 having two nitrogen atoms and only one oxygen atom
-
- 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
-
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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| BRPI0606636A2 (pt) * | 2005-01-13 | 2009-07-07 | Novartis Ag | compostos macrocìclicos úteis como inibidores de bace |
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| CA2657280A1 (en) * | 2006-07-20 | 2008-01-24 | Novartis Ag | Macrocyclic compounds useful as bace inhibitors |
| EP3653609B1 (en) | 2013-02-12 | 2024-04-03 | Buck Institute for Research on Aging | Hydantoins that modulate bace-mediated app processing |
| US11834515B2 (en) | 2017-10-11 | 2023-12-05 | Cornell University | Macrocyclic compounds as proteasome inhibitors |
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|---|---|---|---|---|
| EP1395257A1 (en) * | 2001-06-12 | 2004-03-10 | Elan Pharmaceuticals, Inc. | Macrocycles useful in the treatment of alzheimer's disease |
| JP2004534064A (ja) * | 2001-06-12 | 2004-11-11 | イーラン ファーマスーティカルズ、インコーポレイテッド | アルツハイマー病の治療に有用な大環状分子 |
| GB0325830D0 (en) * | 2003-11-05 | 2003-12-10 | Novartis Ag | Organic compounds |
| CA2575340A1 (en) * | 2004-07-28 | 2006-02-09 | Schering Corporation | Macrocyclic beta-secretase inhibitors |
| BRPI0606636A2 (pt) * | 2005-01-13 | 2009-07-07 | Novartis Ag | compostos macrocìclicos úteis como inibidores de bace |
| GB0500683D0 (en) * | 2005-01-13 | 2005-02-23 | Novartis Ag | Organic compounds |
| GB0526614D0 (en) * | 2005-12-30 | 2006-02-08 | Novartis Ag | Organic compounds |
| CA2657280A1 (en) * | 2006-07-20 | 2008-01-24 | Novartis Ag | Macrocyclic compounds useful as bace inhibitors |
-
2007
- 2007-07-19 KR KR1020097001068A patent/KR20090041387A/ko not_active Withdrawn
- 2007-07-19 WO PCT/EP2007/057492 patent/WO2008009734A1/en not_active Ceased
- 2007-07-19 BR BRPI0715437-2A patent/BRPI0715437A2/pt not_active Application Discontinuation
- 2007-07-19 JP JP2009519989A patent/JP2009544597A/ja not_active Withdrawn
- 2007-07-19 MX MX2009000768A patent/MX2009000768A/es unknown
- 2007-07-19 US US12/374,469 patent/US20090170878A1/en not_active Abandoned
- 2007-07-19 RU RU2009105764/04A patent/RU2009105764A/ru not_active Application Discontinuation
- 2007-07-19 AU AU2007275132A patent/AU2007275132A1/en not_active Abandoned
- 2007-07-19 CN CNA2007800255206A patent/CN101484431A/zh active Pending
- 2007-07-19 EP EP07819907A patent/EP2046760A1/en not_active Withdrawn
- 2007-07-19 CA CA002656869A patent/CA2656869A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN101484431A (zh) | 2009-07-15 |
| WO2008009734A1 (en) | 2008-01-24 |
| MX2009000768A (es) | 2009-01-28 |
| US20090170878A1 (en) | 2009-07-02 |
| BRPI0715437A2 (pt) | 2013-04-16 |
| CA2656869A1 (en) | 2008-01-24 |
| AU2007275132A1 (en) | 2008-01-24 |
| JP2009544597A (ja) | 2009-12-17 |
| EP2046760A1 (en) | 2009-04-15 |
| RU2009105764A (ru) | 2010-08-27 |
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