ZA200601101B - Cyclic amine BACE-1 inhibitors having a heterocyclic substituent - Google Patents
Cyclic amine BACE-1 inhibitors having a heterocyclic substituent Download PDFInfo
- Publication number
- ZA200601101B ZA200601101B ZA200601101A ZA200601101A ZA200601101B ZA 200601101 B ZA200601101 B ZA 200601101B ZA 200601101 A ZA200601101 A ZA 200601101A ZA 200601101 A ZA200601101 A ZA 200601101A ZA 200601101 B ZA200601101 B ZA 200601101B
- Authority
- ZA
- South Africa
- Prior art keywords
- alkyl
- heteroaryl
- compound
- cycloalkylalkyl
- cycloalkyl
- Prior art date
Links
- -1 Cyclic amine Chemical class 0.000 title claims description 102
- 229940125759 BACE1 protease inhibitor Drugs 0.000 title description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 113
- 150000001875 compounds Chemical class 0.000 claims description 85
- 125000001072 heteroaryl group Chemical group 0.000 claims description 68
- 125000003118 aryl group Chemical group 0.000 claims description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 50
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 48
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 47
- 125000003342 alkenyl group Chemical group 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 38
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 37
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 35
- 125000000304 alkynyl group Chemical group 0.000 claims description 33
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 208000024827 Alzheimer disease Diseases 0.000 claims description 14
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 239000012453 solvate Substances 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 12
- 230000001149 cognitive effect Effects 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 9
- 239000000544 cholinesterase inhibitor Substances 0.000 claims description 9
- 208000010877 cognitive disease Diseases 0.000 claims description 9
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 230000004770 neurodegeneration Effects 0.000 claims description 9
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 9
- 229940121773 Secretase inhibitor Drugs 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 229940122041 Cholinesterase inhibitor Drugs 0.000 claims description 6
- 239000003540 gamma secretase inhibitor Substances 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 230000008021 deposition Effects 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 230000003637 steroidlike Effects 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 3
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 3
- 229940099433 NMDA receptor antagonist Drugs 0.000 claims description 3
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 3
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 claims description 3
- 230000000926 neurological effect Effects 0.000 claims description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
- 208000037259 Amyloid Plaque Diseases 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- 125000004984 dialkylaminoalkoxy group Chemical group 0.000 claims description 2
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 11
- 125000001475 halogen functional group Chemical group 0.000 claims 10
- 150000002431 hydrogen Chemical class 0.000 claims 6
- 229940125373 Gamma-Secretase Inhibitor Drugs 0.000 claims 3
- 229940044551 receptor antagonist Drugs 0.000 claims 3
- 239000002464 receptor antagonist Substances 0.000 claims 3
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 claims 2
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 claims 2
- 102000003914 Cholinesterases Human genes 0.000 claims 2
- 108090000322 Cholinesterases Proteins 0.000 claims 2
- 229940048961 cholinesterase Drugs 0.000 claims 2
- 230000000626 neurodegenerative effect Effects 0.000 claims 2
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 claims 1
- 229940123934 Reductase inhibitor Drugs 0.000 claims 1
- 229920000180 alkyd Polymers 0.000 claims 1
- 239000005557 antagonist Substances 0.000 claims 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
- 229960004717 insulin aspart Drugs 0.000 claims 1
- 239000003595 mist Substances 0.000 claims 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
- ICSAXRANXQSPQP-VUKDEKJYSA-M sodium;(5r,6s)-6-[(1r)-1-hydroxyethyl]-7-oxo-3-[(2r)-oxolan-2-yl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound [Na+].S([C@@H]1[C@H](C(N1C=1C([O-])=O)=O)[C@H](O)C)C=1[C@H]1CCCO1 ICSAXRANXQSPQP-VUKDEKJYSA-M 0.000 claims 1
- 239000002294 steroidal antiinflammatory agent Substances 0.000 claims 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 claims 1
- 235000013350 formula milk Nutrition 0.000 description 41
- 125000004432 carbon atom Chemical group C* 0.000 description 15
- 125000005843 halogen group Chemical group 0.000 description 12
- 125000004122 cyclic group Chemical group 0.000 description 10
- 125000006413 ring segment Chemical group 0.000 description 9
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 8
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 8
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 8
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 8
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 8
- 125000000623 heterocyclic group Chemical group 0.000 description 8
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- 125000004429 atom Chemical group 0.000 description 7
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
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- 125000005842 heteroatom Chemical group 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
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- 159000000001 potassium salts Chemical class 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
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- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
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- LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
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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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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones 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 other ring carbon atoms
- C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
-
- 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
- C07D403/14—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 three or more hetero rings
-
- 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
- C07D405/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Ceramic Engineering (AREA)
- Manufacturing & Machinery (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Structural Engineering (AREA)
- Materials Engineering (AREA)
- Neurosurgery (AREA)
- Inorganic Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49364603P | 2003-08-08 | 2003-08-08 |
Publications (1)
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|---|---|
| ZA200601101B true ZA200601101B (en) | 2007-05-30 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| ZA200601101A ZA200601101B (en) | 2003-08-08 | 2006-02-07 | Cyclic amine BACE-1 inhibitors having a heterocyclic substituent |
Country Status (17)
| Country | Link |
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| US (2) | US7598250B2 (es) |
| EP (1) | EP1660447B1 (es) |
| JP (2) | JP4472700B2 (es) |
| KR (1) | KR20060056376A (es) |
| CN (1) | CN1863770B (es) |
| AR (1) | AR045219A1 (es) |
| AT (1) | ATE402921T1 (es) |
| AU (1) | AU2004263532A1 (es) |
| CA (1) | CA2534672A1 (es) |
| DE (1) | DE602004015476D1 (es) |
| ES (1) | ES2308247T3 (es) |
| IL (1) | IL173534A0 (es) |
| MX (1) | MXPA06001558A (es) |
| PE (1) | PE20050354A1 (es) |
| TW (1) | TW200524910A (es) |
| WO (1) | WO2005014540A1 (es) |
| ZA (1) | ZA200601101B (es) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US7700603B2 (en) | 2003-12-15 | 2010-04-20 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| US7592348B2 (en) | 2003-12-15 | 2009-09-22 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| US7763609B2 (en) | 2003-12-15 | 2010-07-27 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| WO2005087752A2 (en) * | 2004-03-09 | 2005-09-22 | Elan Pharmaceuticals, Inc. | Substituted hydroxyethylamine aspartyl protease inhibitors |
| US20050239836A1 (en) * | 2004-03-09 | 2005-10-27 | Varghese John | Substituted hydroxyethylamine aspartyl protease inhibitors |
| US20060014737A1 (en) * | 2004-03-09 | 2006-01-19 | Varghese John | Methods of treatment of amyloidosis using bi-aryl aspartyl protease inhibitors |
| EP1740575A2 (en) | 2004-04-22 | 2007-01-10 | Eli Lilly And Company | Pyrrolidine derivatives useful as bace inhibitors |
| US7585885B2 (en) | 2004-04-22 | 2009-09-08 | Eli Lilly And Company | Pyrrolidine derivatives useful as BACE inhibitors |
| EP1745018A1 (en) * | 2004-04-29 | 2007-01-24 | Merck & Co., Inc. | Azetidine glycine transporter inhibitors |
| JP2008502684A (ja) | 2004-06-15 | 2008-01-31 | メルク エンド カムパニー インコーポレーテッド | アルツハイマー病を治療するためのベータ−セクレターゼ阻害剤として有用なピロリジン−３−イル化合物 |
| US7385085B2 (en) | 2004-07-09 | 2008-06-10 | Elan Pharmaceuticals, Inc. | Oxime derivative substituted hydroxyethylamine aspartyl protease inhibitors |
| JP2008505929A (ja) * | 2004-07-09 | 2008-02-28 | エラン ファーマシューティカルズ，インコーポレイテッド | オキシム誘導体ヒドロキシエチルアミン系のアスパラギン酸プロテアーゼ阻害薬 |
| JP2008511644A (ja) * | 2004-08-27 | 2008-04-17 | エラン ファーマシューティカルズ，インコーポレイテッド | エタノール環式アミンアスパラギン酸プロテアーゼ阻害剤を用いて、アミロイドーシスを治療する方法 |
| EP1789388A2 (en) * | 2004-08-27 | 2007-05-30 | Elan Pharmaceuticals, Inc. | Methods of treatment of amyloidosis using substituted ethanolcyclicamine aspartyl protease inhibitors |
| AU2005286844A1 (en) * | 2004-09-17 | 2006-03-30 | Comentis, Inc | Bicyclic compounds which inhibit beta-secretase activity and methods of use thereof |
| EP1871739A1 (en) * | 2005-04-08 | 2008-01-02 | Comentis, Inc. | Compounds which inhibit beta-secretase activity and methods of use thereof |
| MX2007016175A (es) * | 2005-06-14 | 2008-03-07 | Schering Corp | Inhibidor de aspartil proteasas. |
| KR20080029965A (ko) | 2005-06-14 | 2008-04-03 | 쉐링 코포레이션 | 아스파르틸 프로테아제 억제제 |
| EP1937638A1 (en) * | 2005-10-12 | 2008-07-02 | Elan Pharmaceuticals Inc. | Methods of treating amyloidosis using aryl-cyclopropyl derivative aspartyl protease inhibitors |
| WO2007047305A1 (en) * | 2005-10-12 | 2007-04-26 | Elan Pharmaceuticals, Inc. | Methods of treating amyloidosis using cyclopropyl derivative aspartyl protease inhibitors |
| ES2572263T3 (es) * | 2005-10-25 | 2016-05-31 | Shionogi & Co | Derivados de dihidrooxazina y tetrahidropirimidina como inhibidores de BACE 1 |
| CA2629317A1 (en) | 2005-11-16 | 2007-05-24 | Merck & Co., Inc. | Imidazolidinone compounds useful as beta-secretase inhibitors for the treatment of alzheimer's disease |
| CA2653650A1 (en) | 2006-06-12 | 2007-12-21 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| MX2009006228A (es) | 2006-12-12 | 2009-06-22 | Schering Corp | Inhibidores de aspartil proteasa. |
| KR20100051668A (ko) * | 2007-07-26 | 2010-05-17 | 코멘티스, 인코포레이티드 | 베타-세크레타제 활성을 억제하는 이소프탈아미드 유도체 |
| WO2009032277A1 (en) | 2007-09-06 | 2009-03-12 | Schering Corporation | Gamma secretase modulators |
| US8487099B2 (en) | 2007-11-05 | 2013-07-16 | Merck Sharp & Dohme Corp. | Gamma secretase modulators |
| MX2010006378A (es) * | 2007-12-11 | 2010-09-07 | Schering Corp | Moduladores de gamma secretasa. |
| EP2283016B1 (en) * | 2008-04-22 | 2014-09-24 | Merck Sharp & Dohme Corp. | Thiophenyl-substituted 2-imino-3-methyl pyrrolo pyrimidinone compounds as bace-1 inhibitors, compositions, and their use |
| WO2010013242A1 (en) * | 2008-07-29 | 2010-02-04 | Alcobra Ltd. | Substituted pyridoxine-lactam carboxylate salts |
| JP2012508182A (ja) * | 2008-11-06 | 2012-04-05 | シェーリング コーポレイション | γ−セクレターゼ調節剤 |
| CA2742486A1 (en) | 2008-11-13 | 2010-05-20 | Schering Corporation | Gamma secretase modulators |
| TW201034666A (en) | 2008-12-22 | 2010-10-01 | Schering Corp | Gamma secretase modulators |
| CA2747750A1 (en) | 2008-12-22 | 2010-07-01 | Theodros Asberom | Gamma secretase modulators |
| US20120214802A1 (en) * | 2009-03-25 | 2012-08-23 | Bilcer Geoffrey M | Pyrrolidine compounds which inhibit beta-secretase activity and methods of use thereof |
| EP2443118A1 (en) | 2009-06-16 | 2012-04-25 | Schering Corporation | Gamma secretase modulators |
| EP2443121A2 (en) | 2009-06-16 | 2012-04-25 | Schering Corporation | Gamma secretase modulators |
| US20120245158A1 (en) | 2009-06-16 | 2012-09-27 | Xianhai Huang | Gamma secretase modulators |
| UA108363C2 (uk) | 2009-10-08 | 2015-04-27 | Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування | |
| WO2011044187A1 (en) | 2009-10-08 | 2011-04-14 | Schering Corporation | Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| EP2485590B1 (en) | 2009-10-08 | 2015-01-07 | Merck Sharp & Dohme Corp. | Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use |
| WO2011044185A2 (en) | 2009-10-08 | 2011-04-14 | Schering Corporation | Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use |
| EP2694489B1 (en) | 2011-04-07 | 2017-09-06 | Merck Sharp & Dohme Corp. | C5-c6 oxacyclic-fused thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| AU2012266544A1 (en) * | 2011-06-07 | 2013-11-21 | F. Hoffmann-La Roche Ag | Halogen-alkyl-1,3 oxazines as BACE1 and/or BACE2 inhibitors |
| JP2014524472A (ja) | 2011-08-22 | 2014-09-22 | メルク・シャープ・アンド・ドーム・コーポレーション | Ｂａｃｅ阻害剤としての２−スピロ置換イミノチアジンならびにそのモノオキシドおよびジオキシド、組成物、ならびにそれらの使用 |
| USRE49873E1 (en) | 2012-03-19 | 2024-03-19 | Buck Institute For Research On Aging | APP specific bace inhibitors (ASBIs) and uses thereof |
| KR20150046259A (ko) | 2012-08-23 | 2015-04-29 | 앨리오스 바이오파마 인크. | 파라믹소바이러스 바이러스성 감염의 치료용 화합물 |
| US9422277B2 (en) | 2012-10-17 | 2016-08-23 | Merck Sharp & Dohme Corp. | Tricyclic substituted thiadiazine dioxide compounds as BACE inhibitors, compositions and their use |
| EP2908824B1 (en) | 2012-10-17 | 2018-05-02 | Merck Sharp & Dohme Corp. | Tricyclic substituted thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| CN104995176B (zh) | 2013-02-12 | 2019-02-22 | 巴克老龄化研究所 | 调节bace所介导的app加工的乙内酰脲 |
| CN105636936B (zh) * | 2013-08-21 | 2022-04-05 | 詹森生物制药有限公司 | 抗病毒化合物 |
| EP3082823B1 (en) | 2013-12-18 | 2020-04-22 | Merck Sharp & Dohme Corp. | Iminothiadiazepane dioxide compounds as bace inhibitors, compositions, and their use |
| US10420849B2 (en) * | 2014-09-14 | 2019-09-24 | Nanosynthons Llc | Pyrrolidone derivatives, oligomers and polymers |
| US10968176B2 (en) | 2014-09-14 | 2021-04-06 | Nanosynthons Llc | Pyrrolidone derivatives, oligomers and polymers |
| CN109942446B (zh) * | 2019-04-17 | 2021-09-07 | 黄冈鲁班药业股份有限公司 | 一种普瑞巴林的制备方法 |
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| EP0395664A1 (en) | 1987-10-21 | 1990-11-07 | The Upjohn Company | Renin inhibitors containing a (1-amino-2-hydroxy-2-heterocyclic) ethyl moiety |
| TW282460B (es) | 1993-12-28 | 1996-08-01 | Yamanouchi Pharma Co Ltd | |
| HRP990246A2 (en) | 1998-08-07 | 2000-06-30 | Du Pont Pharm Co | Succinoylamino benzodiazepines as inhibitors of a beta protein production |
| JP2002537376A (ja) | 1999-02-26 | 2002-11-05 | マーク・アンド・カンパニー・インコーポレイテッド | 新規スルホンアミドおよびそれらの使用 |
| EP1178800A4 (en) * | 1999-03-24 | 2002-07-31 | Univ California | TREATMENT OF NEURODEGENERATIVE DISEASES WITH ASPARTYL PROTEASE INHIBITORS |
| TW520575B (en) * | 2000-04-21 | 2003-02-11 | Sony Corp | Positive electrode material and nickel-zinc battery |
| EP1299352B1 (en) | 2000-06-30 | 2005-12-28 | Elan Pharmaceuticals, Inc. | Compounds to treat alzheimer's disease |
| PE20020276A1 (es) | 2000-06-30 | 2002-04-06 | Elan Pharm Inc | COMPUESTOS DE AMINA SUSTITUIDA COMO INHIBIDORES DE ß-SECRETASA PARA EL TRATAMIENTO DE ALZHEIMER |
| US6846813B2 (en) | 2000-06-30 | 2005-01-25 | Pharmacia & Upjohn Company | Compounds to treat alzheimer's disease |
| WO2002088101A2 (en) | 2001-04-27 | 2002-11-07 | Vertex Pharmaceuticals Incorporated | Inhibitors of bace |
| JP2005504042A (ja) | 2001-08-03 | 2005-02-10 | シェーリング コーポレイション | γセクレターゼインヒビターのようなスルホンアミド誘導体 |
| PL372212A1 (en) * | 2001-08-03 | 2005-07-11 | Schering Corporation | Novel gamma secretase inhibitors |
| HUP0401241A3 (en) | 2001-08-21 | 2008-03-28 | Merck Sharp & Dohme | Novel cyclohexyl sulphones, process for their preparation and pharmaceutical compositions containing them |
| BR0212787A (pt) * | 2001-09-24 | 2005-01-25 | Elan Pharm Inc | Composto ou sal farmaceuticamente aceitável do mesmo, métodos de tratamento ou prevenção de doenças e de preparação de um composto, uso de um composto ou sal, e, composição farmacêutica |
| TW200304374A (en) * | 2001-11-30 | 2003-10-01 | Smithkline Beecham Plc | Novel compounds |
| TW200302717A (en) | 2002-02-06 | 2003-08-16 | Schering Corp | Novel gamma secretase inhibitors |
| US20040171614A1 (en) * | 2002-02-06 | 2004-09-02 | Schering-Plough Corporation | Novel gamma secretase inhibitors |
-
2004
- 2004-08-04 US US10/911,030 patent/US7598250B2/en active Active
- 2004-08-04 CA CA002534672A patent/CA2534672A1/en not_active Abandoned
- 2004-08-04 WO PCT/US2004/025748 patent/WO2005014540A1/en active Application Filing
- 2004-08-04 TW TW093123376A patent/TW200524910A/zh unknown
- 2004-08-04 CN CN2004800290969A patent/CN1863770B/zh not_active Expired - Fee Related
- 2004-08-04 AT AT04780561T patent/ATE402921T1/de not_active IP Right Cessation
- 2004-08-04 MX MXPA06001558A patent/MXPA06001558A/es active IP Right Grant
- 2004-08-04 EP EP04780561A patent/EP1660447B1/en not_active Expired - Lifetime
- 2004-08-04 AR ARP040102781A patent/AR045219A1/es unknown
- 2004-08-04 DE DE602004015476T patent/DE602004015476D1/de not_active Expired - Lifetime
- 2004-08-04 JP JP2006522800A patent/JP4472700B2/ja not_active Expired - Fee Related
- 2004-08-04 KR KR1020067002698A patent/KR20060056376A/ko not_active Application Discontinuation
- 2004-08-04 ES ES04780561T patent/ES2308247T3/es not_active Expired - Lifetime
- 2004-08-04 AU AU2004263532A patent/AU2004263532A1/en not_active Abandoned
- 2004-08-05 PE PE2004000758A patent/PE20050354A1/es not_active Application Discontinuation
-
2006
- 2006-02-05 IL IL173534A patent/IL173534A0/en unknown
- 2006-02-07 ZA ZA200601101A patent/ZA200601101B/en unknown
-
2009
- 2009-06-24 US US12/490,884 patent/US7910590B2/en not_active Expired - Lifetime
- 2009-11-27 JP JP2009270850A patent/JP2010047610A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| DE602004015476D1 (de) | 2008-09-11 |
| ATE402921T1 (de) | 2008-08-15 |
| AR045219A1 (es) | 2005-10-19 |
| US7910590B2 (en) | 2011-03-22 |
| US7598250B2 (en) | 2009-10-06 |
| JP2010047610A (ja) | 2010-03-04 |
| PE20050354A1 (es) | 2005-05-17 |
| JP4472700B2 (ja) | 2010-06-02 |
| JP2007501803A (ja) | 2007-02-01 |
| IL173534A0 (en) | 2006-07-05 |
| CA2534672A1 (en) | 2005-02-17 |
| WO2005014540A1 (en) | 2005-02-17 |
| TW200524910A (en) | 2005-08-01 |
| EP1660447B1 (en) | 2008-07-30 |
| EP1660447A1 (en) | 2006-05-31 |
| US20090312341A1 (en) | 2009-12-17 |
| ES2308247T3 (es) | 2008-12-01 |
| AU2004263532A1 (en) | 2005-02-17 |
| KR20060056376A (ko) | 2006-05-24 |
| CN1863770A (zh) | 2006-11-15 |
| MXPA06001558A (es) | 2006-05-15 |
| CN1863770B (zh) | 2011-05-25 |
| US20050043290A1 (en) | 2005-02-24 |
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