CA2410972A1 - Compounds to treat alzheimer's disease - Google Patents
Compounds to treat alzheimer's disease Download PDFInfo
- Publication number
- CA2410972A1 CA2410972A1 CA002410972A CA2410972A CA2410972A1 CA 2410972 A1 CA2410972 A1 CA 2410972A1 CA 002410972 A CA002410972 A CA 002410972A CA 2410972 A CA2410972 A CA 2410972A CA 2410972 A1 CA2410972 A1 CA 2410972A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- defined above
- aryl
- heteroaryl
- group
- 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.)
- Abandoned
Links
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 54
- 150000001875 compounds Chemical class 0.000 title claims description 65
- 150000001412 amines Chemical class 0.000 claims abstract description 80
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
- 201000010099 disease Diseases 0.000 claims abstract description 28
- -1 dihydronaphthalyl Chemical group 0.000 claims description 862
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 495
- 125000001424 substituent group Chemical group 0.000 claims description 446
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 418
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 296
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 291
- 125000000623 heterocyclic group Chemical group 0.000 claims description 252
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 247
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 205
- 125000000217 alkyl group Chemical group 0.000 claims description 188
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 141
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 141
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 119
- 238000000034 method Methods 0.000 claims description 104
- 125000003118 aryl group Chemical group 0.000 claims description 78
- 125000001072 heteroaryl group Chemical group 0.000 claims description 73
- 229910052799 carbon Inorganic materials 0.000 claims description 66
- 238000011282 treatment Methods 0.000 claims description 65
- 229910052739 hydrogen Inorganic materials 0.000 claims description 61
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 59
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 58
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 55
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 53
- 125000003342 alkenyl group Chemical group 0.000 claims description 52
- 125000003545 alkoxy group Chemical group 0.000 claims description 49
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 38
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 37
- 125000002541 furyl group Chemical group 0.000 claims description 37
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 37
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 37
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 37
- 125000002971 oxazolyl group Chemical group 0.000 claims description 37
- 125000004076 pyridyl group Chemical group 0.000 claims description 37
- 125000000335 thiazolyl group Chemical group 0.000 claims description 37
- 125000001544 thienyl group Chemical group 0.000 claims description 37
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 37
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 36
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 36
- 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 claims description 36
- 125000001188 haloalkyl group Chemical group 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 36
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 36
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 36
- 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 claims description 34
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 34
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 32
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 32
- 125000003386 piperidinyl group Chemical group 0.000 claims description 28
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 27
- 125000004193 piperazinyl group Chemical group 0.000 claims description 27
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 27
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 27
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 27
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 26
- 229910052801 chlorine Inorganic materials 0.000 claims description 26
- 229910052731 fluorine Inorganic materials 0.000 claims description 26
- 125000002757 morpholinyl group Chemical group 0.000 claims description 26
- 150000001721 carbon Chemical group 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- 125000005842 heteroatom Chemical group 0.000 claims description 25
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 claims description 24
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 206010012289 Dementia Diseases 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 19
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 19
- 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 claims description 19
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 19
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 19
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 19
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 125000002883 imidazolyl group Chemical group 0.000 claims description 19
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 19
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 19
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 19
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 19
- 125000001041 indolyl group Chemical group 0.000 claims description 19
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 19
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 19
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 19
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 19
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 19
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 19
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 19
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 19
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 19
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 19
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 19
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 19
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 19
- 125000001425 triazolyl group Chemical group 0.000 claims description 19
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 claims description 18
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 18
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 18
- 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims description 18
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 18
- 125000003282 alkyl amino group Chemical group 0.000 claims description 18
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 18
- 125000006196 aroyl alkyl group Chemical group 0.000 claims description 18
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims description 18
- 125000004429 atom Chemical group 0.000 claims description 18
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 18
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 18
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 claims description 18
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 18
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 18
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 18
- 125000005243 carbonyl alkyl group Chemical group 0.000 claims description 18
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 18
- 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 claims description 18
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 18
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 claims description 18
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 18
- 125000005992 dihydrobenzisothiazinyl group Chemical group 0.000 claims description 18
- 125000005993 dihydrobenzisoxazinyl group Chemical group 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 18
- 125000005994 isobenzotetrahydrofuranyl group Chemical group 0.000 claims description 18
- 125000005995 isobenzotetrahydrothienyl group Chemical group 0.000 claims description 18
- 125000005990 isobenzothienyl group Chemical group 0.000 claims description 18
- 125000003151 isocoumarinyl group Chemical group C1(=O)OC(=CC2=CC=CC=C12)* 0.000 claims description 18
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 18
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 18
- 125000005429 oxyalkyl group Chemical group 0.000 claims description 18
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 claims description 18
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 claims description 18
- 125000004620 quinolinyl-N-oxide group Chemical group 0.000 claims description 18
- 125000004963 sulfonylalkyl group Chemical group 0.000 claims description 18
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 18
- 125000004001 thioalkyl group Chemical group 0.000 claims description 18
- 125000004306 triazinyl group Chemical group 0.000 claims description 18
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 18
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 claims description 17
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 claims description 17
- 125000004858 cycloalkoxyalkyl group Chemical group 0.000 claims description 17
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 17
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 claims description 17
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 17
- 125000005127 aryl alkoxy alkyl group Chemical group 0.000 claims description 16
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 16
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 16
- 208000010877 cognitive disease Diseases 0.000 claims description 15
- 208000027061 mild cognitive impairment Diseases 0.000 claims description 15
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims description 14
- 102000013455 Amyloid beta-Peptides Human genes 0.000 claims description 14
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 14
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 13
- 230000002401 inhibitory effect Effects 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 10
- 210000004556 brain Anatomy 0.000 claims description 10
- 230000003412 degenerative effect Effects 0.000 claims description 10
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 claims description 9
- 201000010374 Down Syndrome Diseases 0.000 claims description 9
- 206010044688 Trisomy 21 Diseases 0.000 claims description 9
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 9
- 125000005046 dihydronaphthyl group Chemical group 0.000 claims description 9
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 9
- 125000005051 dihydropyrazinyl group Chemical group N1(CC=NC=C1)* 0.000 claims description 9
- 125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 claims description 9
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 9
- 125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 claims description 9
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 claims description 9
- 125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 claims description 9
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 9
- 125000006413 ring segment Chemical group 0.000 claims description 9
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 9
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 9
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 8
- 208000018282 ACys amyloidosis Diseases 0.000 claims description 8
- 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 claims description 8
- 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 claims description 8
- 238000003776 cleavage reaction Methods 0.000 claims description 8
- 230000007017 scission Effects 0.000 claims description 8
- 241001465754 Metazoa Species 0.000 claims description 7
- 210000004558 lewy body Anatomy 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- 208000037259 Amyloid Plaque Diseases 0.000 claims description 5
- 241000282412 Homo Species 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- 230000002792 vascular Effects 0.000 claims description 5
- 208000032843 Hemorrhage Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 230000001054 cortical effect Effects 0.000 claims description 4
- 230000007850 degeneration Effects 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 4
- 230000000306 recurrent effect Effects 0.000 claims description 4
- 229910006069 SO3H Inorganic materials 0.000 claims 16
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 16
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims 16
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 14
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 14
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims 14
- 238000006467 substitution reaction Methods 0.000 claims 12
- 210000004027 cell Anatomy 0.000 claims 8
- 150000002431 hydrogen Chemical class 0.000 claims 8
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims 7
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims 7
- 239000011541 reaction mixture Substances 0.000 claims 6
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims 4
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 claims 4
- OTTXCOAOKOEENK-UHFFFAOYSA-N 2,2-difluoroethenone Chemical group FC(F)=C=O OTTXCOAOKOEENK-UHFFFAOYSA-N 0.000 claims 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 4
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims 4
- FGIVSGPRGVABAB-UHFFFAOYSA-N fluoren-9-ylmethyl hydrogen carbonate Chemical compound C1=CC=C2C(COC(=O)O)C3=CC=CC=C3C2=C1 FGIVSGPRGVABAB-UHFFFAOYSA-N 0.000 claims 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 4
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims 4
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims 4
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 4
- 125000006288 3,5-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(C([H])=C1F)C([H])([H])* 0.000 claims 3
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical class [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 claims 3
- 239000002253 acid Substances 0.000 claims 3
- 150000007513 acids Chemical class 0.000 claims 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 3
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 claims 3
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 claims 3
- 238000000338 in vitro Methods 0.000 claims 3
- 230000035772 mutation Effects 0.000 claims 3
- 239000002674 ointment Substances 0.000 claims 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 3
- 101710148027 Ribulose bisphosphate carboxylase/oxygenase activase 1, chloroplastic Proteins 0.000 claims 2
- 101710201629 Ribulose bisphosphate carboxylase/oxygenase activase 2, chloroplastic Proteins 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 239000006071 cream Substances 0.000 claims 2
- 125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- KQCOOWKXGUMXCK-UHFFFAOYSA-N 1-n-[1-(3,5-difluorophenyl)-3-hydroxy-4-(2-methyl-2-phenylhydrazinyl)butan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=C(F)C=C(F)C=2)C(O)CNN(C)C=2C=CC=CC=2)=C1 KQCOOWKXGUMXCK-UHFFFAOYSA-N 0.000 claims 1
- JNZJUAKUKIDRKO-UHFFFAOYSA-N 1-n-[1-(3,5-difluorophenyl)-3-hydroxy-4-(phenoxyamino)butan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=C(F)C=C(F)C=2)C(O)CNOC=2C=CC=CC=2)=C1 JNZJUAKUKIDRKO-UHFFFAOYSA-N 0.000 claims 1
- ZDWFSWVQSUHAOP-UHFFFAOYSA-N 1-n-[1-(3,5-difluorophenyl)-3-hydroxy-4-[2-methyl-2-(4-methylpentanoyl)hydrazinyl]butan-2-yl]-5-methyl-3-n,3-n-dipropylbenzene-1,3-dicarboxamide Chemical compound CCCN(CCC)C(=O)C1=CC(C)=CC(C(=O)NC(CC=2C=C(F)C=C(F)C=2)C(O)CNN(C)C(=O)CCC(C)C)=C1 ZDWFSWVQSUHAOP-UHFFFAOYSA-N 0.000 claims 1
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 claims 1
- UOACKFBJUYNSLK-XRKIENNPSA-N Estradiol Cypionate Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H](C4=CC=C(O)C=C4CC3)CC[C@@]21C)C(=O)CCC1CCCC1 UOACKFBJUYNSLK-XRKIENNPSA-N 0.000 claims 1
- 229940125373 Gamma-Secretase Inhibitor Drugs 0.000 claims 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 1
- 239000003708 ampul Substances 0.000 claims 1
- 210000004102 animal cell Anatomy 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 claims 1
- 239000003963 antioxidant agent Substances 0.000 claims 1
- 230000003078 antioxidant effect Effects 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
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- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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- C07D277/04—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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| US21532300P | 2000-06-30 | 2000-06-30 | |
| US60/215,323 | 2000-06-30 | ||
| PCT/US2001/020930 WO2002002506A2 (en) | 2000-06-30 | 2001-06-29 | Compounds to treat alzheimer's disease |
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| CA002410972A Abandoned CA2410972A1 (en) | 2000-06-30 | 2001-06-29 | Compounds to treat alzheimer's disease |
| CA002410680A Abandoned CA2410680A1 (en) | 2000-06-30 | 2001-06-29 | Compounds to treat alzheimer's disease |
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| CA002410680A Abandoned CA2410680A1 (en) | 2000-06-30 | 2001-06-29 | Compounds to treat alzheimer's disease |
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| US6846813B2 (en) | 2000-06-30 | 2005-01-25 | Pharmacia & Upjohn Company | Compounds to treat alzheimer's disease |
| US6960664B2 (en) | 2001-05-22 | 2005-11-01 | Pharmacia & Upjohn Company | Aza hydroxylated ethyl amine compounds |
| WO2002098849A2 (en) | 2001-06-01 | 2002-12-12 | Elan Pharmaceuticals, Inc. | Hydroxy alkyl amine derivatives as beta-secretase inhibitors and their use for the treatment of alzheimer’s disease and similar diseases |
| RS50504A (sr) | 2001-11-08 | 2007-04-10 | Elan Pharmaceuticals Inc., | Derivati n,n'-supstituisanog-1,3- diamino-2-hidroksipropana |
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2001
- 2001-06-29 JP JP2002507763A patent/JP2004502665A/ja active Pending
- 2001-06-29 CA CA002410972A patent/CA2410972A1/en not_active Abandoned
- 2001-06-29 DE DE60112942T patent/DE60112942T2/de not_active Expired - Fee Related
- 2001-06-29 MX MXPA02012560A patent/MXPA02012560A/es active IP Right Grant
- 2001-06-29 EP EP01950719A patent/EP1299349B1/en not_active Expired - Lifetime
- 2001-06-29 CA CA002410680A patent/CA2410680A1/en not_active Abandoned
- 2001-06-29 AU AU2001273094A patent/AU2001273094A1/en not_active Abandoned
- 2001-06-29 AU AU2001273113A patent/AU2001273113A1/en not_active Abandoned
- 2001-06-29 WO PCT/US2001/020930 patent/WO2002002506A2/en not_active Ceased
- 2001-06-29 BR BR0111980-0A patent/BR0111980A/pt not_active IP Right Cessation
- 2001-06-29 DE DE60116313T patent/DE60116313T2/de not_active Expired - Fee Related
- 2001-06-29 AT AT01950719T patent/ATE302751T1/de not_active IP Right Cessation
- 2001-06-29 NZ NZ523005A patent/NZ523005A/en unknown
- 2001-06-29 JP JP2002507762A patent/JP2004502664A/ja not_active Abandoned
- 2001-06-29 CN CN01812058XA patent/CN1217920C/zh not_active Expired - Fee Related
- 2001-06-29 WO PCT/US2001/020856 patent/WO2002002518A2/en not_active Ceased
- 2001-06-29 EP EP01952352A patent/EP1299352B1/en not_active Expired - Lifetime
- 2001-06-29 AT AT01952352T patent/ATE314343T1/de not_active IP Right Cessation
- 2001-06-29 ES ES01952352T patent/ES2252257T3/es not_active Expired - Lifetime
- 2001-06-29 AU AU2001271686A patent/AU2001271686A1/en not_active Abandoned
- 2001-06-29 WO PCT/US2001/020852 patent/WO2002002505A2/en not_active Ceased
- 2001-06-29 KR KR1020027018013A patent/KR20030058959A/ko not_active Abandoned
- 2001-06-29 US US09/896,874 patent/US7034182B2/en not_active Expired - Fee Related
- 2001-06-29 ES ES01950719T patent/ES2248356T3/es not_active Expired - Lifetime
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2002
- 2002-12-10 ZA ZA200209991A patent/ZA200209991B/en unknown
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2003
- 2003-01-13 ZA ZA200300327A patent/ZA200300327B/en unknown
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2006
- 2006-03-07 US US11/370,073 patent/US7432389B2/en not_active Expired - Fee Related
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