HRP970705A2 - CYCLOALKYL, LACTAM, LACTONE AND RELATED COMPOUNDS, PHARMACEUTICAL COMPOSITIONS COMPRISING SAME, AND METHODS FOR INHIBITING "beta" -AMYLOID PEPTIDE RELEASE AND/OR ITS SYNTHESIS BY USE OF SUCH COMPOUNDS - Google Patents
CYCLOALKYL, LACTAM, LACTONE AND RELATED COMPOUNDS, PHARMACEUTICAL COMPOSITIONS COMPRISING SAME, AND METHODS FOR INHIBITING "beta" -AMYLOID PEPTIDE RELEASE AND/OR ITS SYNTHESIS BY USE OF SUCH COMPOUNDS Download PDFInfo
- Publication number
- HRP970705A2 HRP970705A2 HR08/780,025A HRP970705A HRP970705A2 HR P970705 A2 HRP970705 A2 HR P970705A2 HR P970705 A HRP970705 A HR P970705A HR P970705 A2 HRP970705 A2 HR P970705A2
- Authority
- HR
- Croatia
- Prior art keywords
- amino
- dihydro
- alaninyl
- benzodiazepine
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 240
- 150000001875 compounds Chemical class 0.000 title claims description 176
- 230000015572 biosynthetic process Effects 0.000 title claims description 153
- 238000003786 synthesis reaction Methods 0.000 title claims description 147
- 150000003951 lactams Chemical class 0.000 title claims description 80
- 150000002596 lactones Chemical class 0.000 title claims description 14
- 230000002401 inhibitory effect Effects 0.000 title claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 title description 8
- 108090000765 processed proteins & peptides Proteins 0.000 title description 5
- -1 cyano, carboxyl Chemical group 0.000 claims description 277
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 209
- 125000000217 alkyl group Chemical group 0.000 claims description 150
- 125000004450 alkenylene group Chemical group 0.000 claims description 142
- 125000003118 aryl group Chemical group 0.000 claims description 136
- 125000001072 heteroaryl group Chemical group 0.000 claims description 127
- 239000000203 mixture Substances 0.000 claims description 111
- 125000002947 alkylene group Chemical group 0.000 claims description 110
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 107
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 97
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 91
- 150000002391 heterocyclic compounds Chemical class 0.000 claims description 78
- 125000003342 alkenyl group Chemical group 0.000 claims description 73
- 125000001424 substituent group Chemical group 0.000 claims description 73
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 70
- 125000000304 alkynyl group Chemical group 0.000 claims description 66
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 64
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 63
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 61
- 125000003545 alkoxy group Chemical group 0.000 claims description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 52
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 51
- 125000005843 halogen group Chemical group 0.000 claims description 50
- 229910052757 nitrogen Inorganic materials 0.000 claims description 50
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 49
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 45
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 43
- 125000004432 carbon atom Chemical group C* 0.000 claims description 41
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 39
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 38
- 125000004122 cyclic group Chemical group 0.000 claims description 36
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 35
- 208000024827 Alzheimer disease Diseases 0.000 claims description 34
- 239000004471 Glycine Substances 0.000 claims description 32
- 125000002252 acyl group Chemical group 0.000 claims description 31
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 31
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- 239000002131 composite material Substances 0.000 claims description 25
- 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 24
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 24
- 229920006395 saturated elastomer Polymers 0.000 claims description 23
- 125000004104 aryloxy group Chemical group 0.000 claims description 22
- 125000003282 alkyl amino group Chemical group 0.000 claims description 21
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 20
- 150000003573 thiols Chemical class 0.000 claims description 18
- 125000004043 oxo group Chemical group O=* 0.000 claims description 17
- 125000004423 acyloxy group Chemical group 0.000 claims description 16
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 15
- PLZWYQYDWCXHTF-UHFFFAOYSA-N 1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(C)C2=CC=CC=C2C=1C1=CC=CC=C1 PLZWYQYDWCXHTF-UHFFFAOYSA-N 0.000 claims description 14
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- 239000011593 sulfur Substances 0.000 claims description 11
- 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 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 8
- 229910052701 rubidium Inorganic materials 0.000 claims description 8
- 150000003571 thiolactams Chemical class 0.000 claims description 8
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 8
- AYQMNFRCBKOMIA-UHFFFAOYSA-N 1-benzazepin-2-one Chemical compound O=C1C=CC=C2C=CC=CC2=N1 AYQMNFRCBKOMIA-UHFFFAOYSA-N 0.000 claims description 7
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical group O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 claims description 7
- KMADJPBGARDOAO-UHFFFAOYSA-N 7-bromo-5-(2-fluorophenyl)-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(C)C2=CC=C(Br)C=C2C=1C1=CC=CC=C1F KMADJPBGARDOAO-UHFFFAOYSA-N 0.000 claims description 7
- CIMVQIUIOSVWHR-UHFFFAOYSA-N 7-methyl-5,7-dihydrobenzo[d][1]benzazepin-6-one Chemical compound N1C(=O)C(C)C2=CC=CC=C2C2=CC=CC=C21 CIMVQIUIOSVWHR-UHFFFAOYSA-N 0.000 claims description 7
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 229940049706 benzodiazepine Drugs 0.000 claims description 7
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 7
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 7
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- ZWXPDGCFMMFNRW-UHFFFAOYSA-N N-methylcaprolactam Chemical group CN1CCCCCC1=O ZWXPDGCFMMFNRW-UHFFFAOYSA-N 0.000 claims description 6
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
- 230000001413 cellular effect Effects 0.000 claims description 6
- 125000003412 L-alanyl group Chemical group [H]N([H])[C@@](C([H])([H])[H])(C(=O)[*])[H] 0.000 claims description 5
- 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 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000005296 thioaryloxy group Chemical group 0.000 claims description 5
- DANRVXLYTJGYPM-UHFFFAOYSA-N 1,5-bis(2,2-dimethylpropyl)-1,5-benzodiazepine-2,4-dione Chemical compound CC(C)(C)CN1C(=O)CC(=O)N(CC(C)(C)C)C2=CC=CC=C21 DANRVXLYTJGYPM-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
- GHOCZDGJQOGXSZ-KRFIBBNCSA-N N-[(2S)-1-(1-amino-7-methyl-6-oxo-7H-benzo[d][1]benzazepin-5-yl)-4-methyl-1-oxohexan-2-yl]-2-(3,5-difluorophenyl)acetamide Chemical compound N([C@@H](CC(C)CC)C(=O)N1C(C(C)C2=CC=CC=C2C2=C(N)C=CC=C21)=O)C(=O)CC1=CC(F)=CC(F)=C1 GHOCZDGJQOGXSZ-KRFIBBNCSA-N 0.000 claims description 4
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 4
- 150000003997 cyclic ketones Chemical class 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- VFNGBJWKHOVSFR-WOVYWWTOSA-N (2s)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-[(1r,2s)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]propanamide Chemical compound N([C@@H](C)C(=O)N[C@@H]1C2=CC=CC=C2C[C@@H]1O)C(=O)CC1=CC(F)=CC(F)=C1 VFNGBJWKHOVSFR-WOVYWWTOSA-N 0.000 claims description 3
- VFNGBJWKHOVSFR-JVMOKEISSA-N (2s)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]propanamide Chemical compound N([C@@H](C)C(=O)N[C@H]1C2=CC=CC=C2C[C@H]1O)C(=O)CC1=CC(F)=CC(F)=C1 VFNGBJWKHOVSFR-JVMOKEISSA-N 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 230000006866 deterioration Effects 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 229950006098 orthocaine Drugs 0.000 claims description 3
- QEPBHBUUEMGNPR-NRFANRHFSA-N (2s)-2-[(2-cyclopentylacetyl)amino]-n-(2,4-dioxo-1,5-diphenyl-1,5-benzodiazepin-3-yl)propanamide Chemical compound N([C@@H](C)C(=O)NC1C(N(C=2C=CC=CC=2)C2=CC=CC=C2N(C=2C=CC=CC=2)C1=O)=O)C(=O)CC1CCCC1 QEPBHBUUEMGNPR-NRFANRHFSA-N 0.000 claims description 2
- MQFQHTAWAQYJMY-LBPRGKRZSA-N (2s)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-n-(1,5-dimethyl-2,4-dioxo-1,5-benzodiazepin-3-yl)propanamide Chemical compound N([C@@H](C)C(=O)NC1C(N(C)C2=CC=CC=C2N(C)C1=O)=O)C(=O)CC1=CC(F)=CC(F)=C1 MQFQHTAWAQYJMY-LBPRGKRZSA-N 0.000 claims description 2
- RRSKUDWFWIAKIO-LYKKTTPLSA-N 1-amino-7-methyl-5-[(2S)-2-[(4-phenyl-1,2,5-oxadiazol-3-yl)amino]propanoyl]-7H-benzo[d][1]benzazepin-6-one Chemical compound C1(=CC=CC=C1)C=1C(=NON=1)N[C@@H](C)C(=O)N1C2=C(C3=C(C(C1=O)C)C=CC=C3)C(=CC=C2)N RRSKUDWFWIAKIO-LYKKTTPLSA-N 0.000 claims description 2
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 2
- UMKTZUVQMLUKIV-UHFFFAOYSA-N 2-(3,5-difluorophenyl)-n-(1-ethyl-5,5-dimethyl-2-oxo-3,4-dihydro-1-benzazepin-3-yl)acetamide Chemical compound O=C1N(CC)C2=CC=CC=C2C(C)(C)CC1NC(=O)CC1=CC(F)=CC(F)=C1 UMKTZUVQMLUKIV-UHFFFAOYSA-N 0.000 claims description 2
- ACQGZNFECAFGFD-ZVAWYAOSSA-N 2-(n-acetylanilino)-n-[(2s)-1-(1-amino-7-methyl-6-oxo-7h-benzo[d][1]benzazepin-5-yl)-1-oxopropan-2-yl]acetamide Chemical compound N([C@@H](C)C(=O)N1C(C(C)C2=CC=CC=C2C2=C(N)C=CC=C21)=O)C(=O)CN(C(C)=O)C1=CC=CC=C1 ACQGZNFECAFGFD-ZVAWYAOSSA-N 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004362 3,4,5-trichlorophenyl group Chemical group [H]C1=C(Cl)C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
- 125000004361 3,4,5-trifluorophenyl group Chemical group [H]C1=C(F)C(F)=C(F)C([H])=C1* 0.000 claims description 2
- MWASGDJOVNIDEM-UHFFFAOYSA-N 3-amino-1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1C(N)C(=O)N(C)C2=CC=CC=C2C=1C1=CC=CC=C1 MWASGDJOVNIDEM-UHFFFAOYSA-N 0.000 claims description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
- 125000006291 3-hydroxybenzyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- 125000005917 3-methylpentyl group Chemical group 0.000 claims description 2
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 2
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- AKMASBOYQCWSTE-ODOSRFNGSA-N N-[(2S)-1-(1-amino-7-methyl-6-oxo-7H-benzo[d][1]benzazepin-5-yl)-3-cyclopropyl-1-oxopropan-2-yl]-2-(3,5-difluorophenyl)acetamide Chemical compound FC=1C=C(C=C(C=1)F)CC(=O)N[C@@H](CC1CC1)C(=O)N1C2=C(C3=C(C(C1=O)C)C=CC=C3)C(=CC=C2)N AKMASBOYQCWSTE-ODOSRFNGSA-N 0.000 claims description 2
- NBPZUDDPASJLCG-GPIXMLASSA-N N-[(2S)-1-(1-amino-7-methyl-6-oxo-7H-benzo[d][1]benzazepin-5-yl)-4-cyclohexyl-1-oxobutan-2-yl]-2-(2,4-difluorophenyl)acetamide Chemical compound C([C@@H](C(=O)N1C2=CC=CC(N)=C2C2=CC=CC=C2C(C1=O)C)NC(=O)CC=1C(=CC(F)=CC=1)F)CC1CCCCC1 NBPZUDDPASJLCG-GPIXMLASSA-N 0.000 claims description 2
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- KLGHHGGIANVJNM-QVWGJOIVSA-N N-[(2S)-1-(1-amino-7-methyl-6-oxo-7H-benzo[d][1]benzazepin-5-yl)-4-cyclohexyl-1-oxobutan-2-yl]-2-(3-fluorophenyl)acetamide Chemical compound FC=1C=C(C=CC=1)CC(=O)N[C@@H](CCC1CCCCC1)C(=O)N1C2=C(C3=C(C(C1=O)C)C=CC=C3)C(=CC=C2)N KLGHHGGIANVJNM-QVWGJOIVSA-N 0.000 claims description 2
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- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- AAAQKTZKLRYKHR-UHFFFAOYSA-N triphenylmethane Chemical compound C1=CC=CC=C1C(C=1C=CC=CC=1)C1=CC=CC=C1 AAAQKTZKLRYKHR-UHFFFAOYSA-N 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
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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
-
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
- C07D311/82—Xanthenes
- C07D311/90—Xanthenes with hydrocarbon radicals, substituted by amino radicals, directly attached in position 9
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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
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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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- 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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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
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- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—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 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, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
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- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/08—Oxygen atoms
- C07D223/10—Oxygen atoms attached in position 2
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/12—1,5-Benzodiazepines; Hydrogenated 1,5-benzodiazepines
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D267/02—Seven-membered rings
- C07D267/08—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D267/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D267/14—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/10—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings 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
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
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- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings 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
- C07D309/30—Oxygen atoms, e.g. delta-lactones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
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- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
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- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1021—Tetrapeptides with the first amino acid being acidic
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/32—All rings being cycloaliphatic the ring system containing at least eleven carbon atoms
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- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/30—Ortho- or ortho- and peri-condensed systems containing three rings containing seven-membered rings
- C07C2603/32—Dibenzocycloheptenes; Hydrogenated dibenzocycloheptenes
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- C12N2770/00011—Details
- C12N2770/24011—Flaviviridae
- C12N2770/24211—Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
- C12N2770/24222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
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- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
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- Hospice & Palliative Care (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Plural Heterocyclic Compounds (AREA)
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Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US78002596A | 1996-12-23 | 1996-12-23 |
Publications (1)
Publication Number | Publication Date |
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HRP970705A2 true HRP970705A2 (en) | 1998-10-31 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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HR08/780,025A HRP970705A2 (en) | 1996-12-23 | 1997-12-22 | CYCLOALKYL, LACTAM, LACTONE AND RELATED COMPOUNDS, PHARMACEUTICAL COMPOSITIONS COMPRISING SAME, AND METHODS FOR INHIBITING "beta" -AMYLOID PEPTIDE RELEASE AND/OR ITS SYNTHESIS BY USE OF SUCH COMPOUNDS |
Country Status (28)
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EP (1) | EP0951466B1 (fr) |
JP (1) | JP3812952B2 (fr) |
KR (1) | KR20000069654A (fr) |
CN (2) | CN1171878C (fr) |
AR (1) | AR010854A1 (fr) |
AT (1) | ATE421509T1 (fr) |
AU (1) | AU749658C (fr) |
BR (1) | BR9714517A (fr) |
CA (1) | CA2272305A1 (fr) |
CO (1) | CO4930282A1 (fr) |
DE (1) | DE69739236D1 (fr) |
DK (1) | DK0951466T3 (fr) |
EA (1) | EA002100B1 (fr) |
ES (1) | ES2319239T3 (fr) |
HR (1) | HRP970705A2 (fr) |
HU (1) | HUP0001232A3 (fr) |
ID (1) | ID22177A (fr) |
IL (2) | IL129820A0 (fr) |
NO (1) | NO993098L (fr) |
NZ (1) | NZ335583A (fr) |
PE (1) | PE52799A1 (fr) |
PL (1) | PL196641B1 (fr) |
PT (1) | PT951466E (fr) |
SI (1) | SI0951466T1 (fr) |
TR (1) | TR199901343T2 (fr) |
TW (1) | TW568914B (fr) |
WO (1) | WO1998028268A2 (fr) |
ZA (1) | ZA9711537B (fr) |
Families Citing this family (91)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999032453A1 (fr) * | 1997-12-22 | 1999-07-01 | Elan Pharmaceuticals, Inc. | ⊂-CAPROLACTAMES α-AMINO POLYCYCLIQUES ET COMPOSES CONNEXES |
US6509331B1 (en) | 1998-06-22 | 2003-01-21 | Elan Pharmaceuticals, Inc. | Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
US6552013B1 (en) | 1998-06-22 | 2003-04-22 | Elan Pharmaceuticals, Inc. | Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
US6569851B1 (en) | 1998-06-22 | 2003-05-27 | Elan Pharmaceutials, Inc. | Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
US6774125B2 (en) | 1998-06-22 | 2004-08-10 | Elan Pharmaceuticals, Inc. | Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
US6528505B1 (en) | 1998-06-22 | 2003-03-04 | Elan Pharmaceuticals, Inc. | Cyclic amino acid compounds pharmaceutical compositions comprising same and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
HRP990246A2 (en) | 1998-08-07 | 2000-06-30 | Du Pont Pharm Co | Succinoylamino benzodiazepines as inhibitors of a beta protein production |
NZ525513A (en) | 1998-08-07 | 2004-09-24 | Pont Pharmaceuticals Du | Succinoylamino lactams as inhibitors of Abeta protein production |
EP1131634A2 (fr) | 1998-09-30 | 2001-09-12 | Elan Pharmaceuticals, Inc. | Reactifs biologiques et procedes servant a determiner le mecanisme implique dans la generation du peptide beta-amyloide |
US6737038B1 (en) | 1998-11-12 | 2004-05-18 | Bristol-Myers Squibb Company | Use of small molecule radioligands to discover inhibitors of amyloid-beta peptide production and for diagnostic imaging |
EP1313426A4 (fr) | 1998-12-24 | 2003-05-28 | Bristol Myers Squibb Pharma Co | Benzodiazepines succinoylamino utilisees comme inhibiteurs de la production de proteine a-beta |
AU6071400A (en) | 1999-07-06 | 2001-01-22 | Vertex Pharmaceuticals Incorporated | Cyclized amide derivatives |
AU6420700A (en) * | 1999-08-05 | 2001-03-05 | Prescient Neuropharma Inc. | Novel 1,4-benzodiazepine compounds and derivatives thereof |
US6503902B2 (en) | 1999-09-13 | 2003-01-07 | Bristol-Myers Squibb Pharma Company | Hydroxyalkanoylaminolactams and related structures as inhibitors of a β protein production |
CA2377221A1 (fr) | 1999-09-13 | 2001-03-22 | Bristol-Myers Squibb Pharma Company | Hydroxyalkanoyl aminolactames et structures associees, inhibiteurs de la production de la proteine a.beta. |
US6960576B2 (en) | 1999-09-13 | 2005-11-01 | Bristol-Myers Squibb Pharma Company | Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production |
WO2001027108A1 (fr) | 1999-10-08 | 2001-04-19 | Bristol-Myers Squibb Pharma Company | AMINO SULFONAMIDES DE LACTAME UTILISES COMME INHIBITEURS DE LA PRODUCTION DE PROTEINE A$g(b) |
JP2003513958A (ja) * | 1999-11-09 | 2003-04-15 | イーライ・リリー・アンド・カンパニー | β−アミロイドペプチド放出および/またはその合成を阻害するために有用なβ−アミノ酸化合物 |
WO2001060826A2 (fr) * | 2000-02-17 | 2001-08-23 | Bristol-Myers Squibb Pharma Company | CARBOCYCLES ET HETEROCYCLES SUCCINOYLAMINO UTILISES EN TANT QU'INHIBITEURS DE LA PRODUCTION DE LA PROTEINE A$g(b) |
US6495540B2 (en) | 2000-03-28 | 2002-12-17 | Bristol - Myers Squibb Pharma Company | Lactams as inhibitors of A-β protein production |
CA2401120A1 (fr) * | 2000-03-28 | 2001-10-04 | Dupont Pharmaceuticals Company | Lactames en tant qu'inhibiteurs de production de proteines a-beta |
BR0110051A (pt) * | 2000-04-03 | 2004-12-07 | Bristol Myers Squibb Pharma Co | Composto, uso do composto, composição farmacêutica e método de tratamento do mal de alzheimer |
JP2003535046A (ja) | 2000-04-03 | 2003-11-25 | デュポン ファーマシューティカルズ カンパニー | Aβタンパク質産生の阻害剤としての環状ラクタム |
CA2404273A1 (fr) | 2000-04-11 | 2001-10-18 | Bristol-Myers Squibb Pharma Company | Lactames substitues utilises en tant qu'inhibiteurs de production de proteine a.beta. |
AU2001261728A1 (en) | 2000-05-17 | 2001-11-26 | Bristol-Myers Squibb Pharma Company | Use of small molecule radioligands for diagnostic imaging |
GB0012671D0 (en) | 2000-05-24 | 2000-07-19 | Merck Sharp & Dohme | Therapeutic agents |
EP1268450A1 (fr) | 2000-06-01 | 2003-01-02 | Bristol-Myers Squibb Pharma Company | Lactames substitues par des succinates cycliques en tant qu'inhibiteurs de la production de la proteine beta |
US6432944B1 (en) | 2000-07-06 | 2002-08-13 | Bristol-Myers Squibb Company | Benzodiazepinone β-amyloid inhibitors: arylacetamidoalanyl derivatives |
GB0025173D0 (en) | 2000-10-13 | 2000-11-29 | Merck Sharp & Dohme | Therapeutic agents |
UA77165C2 (en) * | 2000-11-17 | 2006-11-15 | Lilly Co Eli | (n)-((s)-2-hydroxy-3-methyl-butyryl)-1-(l-alaninyl)-(s)-1-amino-3-methyl-4,5,6,7-tetrahydro-2h-3-benzazepin-2-one dihydrate, processes for manufacturing and pharmaceutical composition |
AU2002224322A1 (en) * | 2000-11-17 | 2002-05-27 | Eli Lilly And Company | Lactam dipeptide and its use in inhibiting beta-amyloid peptiderelease |
US7468365B2 (en) | 2000-11-17 | 2008-12-23 | Eli Lilly And Company | Lactam compound |
UA74849C2 (en) * | 2000-11-17 | 2006-02-15 | Lilly Co Eli | Lactam |
US7132449B2 (en) | 2001-01-17 | 2006-11-07 | Amura Therapeutics Limited | Inhibitors of cruzipain and other cysteine proteases |
IL156776A0 (en) | 2001-01-17 | 2004-02-08 | Amura Therapeutics Ltd | Inhibitors of cruzipain and other cysteine proteases |
NZ526913A (en) | 2001-01-17 | 2004-12-24 | Amura Therapeutics Ltd | Inhibitors of cruzipain and other cysteine proteases |
NZ526914A (en) * | 2001-01-17 | 2005-02-25 | Amura Therapeutics Ltd | Cyclic 2-carbonylaminoketones as inhibitors of cruzipain and other cysteine proteases |
AR039059A1 (es) | 2001-08-06 | 2005-02-09 | Sanofi Aventis | Compuesto derivado de acilaminotiazol, su utilizacion, procedimientos para prepararlo, composicion farmaceutica que lo comprende, y compuestos intermediarios |
FR2840899B1 (fr) * | 2002-06-12 | 2005-02-25 | Sanofi Synthelabo | Derives d'acylaminothiazole, leur preparation et leur utilisation en therapeutique |
TW200502221A (en) | 2002-10-03 | 2005-01-16 | Astrazeneca Ab | Novel lactams and uses thereof |
US20060089371A1 (en) * | 2002-11-11 | 2006-04-27 | Bayer Healthcare Ag | Phenyl or heteroaryl amino alkane derivatives as ip receptor antagonist |
ATE496893T1 (de) | 2002-12-20 | 2011-02-15 | X Ceptor Therapeutics Inc | Isochinolinonderivate und deren verwendung als medikamente |
FR2850380B1 (fr) | 2003-01-23 | 2006-07-07 | Sanofi Synthelabo | Derives d'acylaminothiazole, leur preparation et leur utilisation en therapeutique |
US7342007B2 (en) | 2003-03-14 | 2008-03-11 | Astrazeneca Ab | Lactams and uses thereof |
ES2314418T3 (es) | 2003-05-02 | 2009-03-16 | Elan Pharmaceuticals, Inc. | Derivados de amidas del acido 4-bromo-5-(2-clorobenzoilamino)-1h-pirazol-3-carboxicilico y compuestos relacionados como antagonistas del receptor b1 de bradiquinina para el tratamiento de enfermedades inflamatorias. |
ITMI20032278A1 (it) | 2003-11-21 | 2005-05-22 | Ethicon Endo Surgery Inc | Dispositivo di diagnosi |
WO2005053702A2 (fr) * | 2003-12-01 | 2005-06-16 | Cambridge University Technical Services Limited | Agents anti-inflammatoires |
ES2375627T3 (es) | 2004-02-23 | 2012-03-02 | Eli Lilly And Company | Anticuerpos anti-abeta. |
WO2006034003A2 (fr) | 2004-09-17 | 2006-03-30 | Whitehead Institute For Biomedical Research | Composes, compositions et procedes d'inhibition de toxicite d'$g(a)-synucleine |
JP4519621B2 (ja) * | 2004-11-30 | 2010-08-04 | アイバイツ株式会社 | 光酸発生剤および感光性樹脂組成物 |
EP2094836B1 (fr) | 2006-11-15 | 2016-06-08 | Massachusetts Eye & Ear Infirmary | Génération de cellules de l'oreille interne |
AU2008215948A1 (en) | 2007-02-12 | 2008-08-21 | Merck & Co., Inc. | Piperazine derivatives for treatment of AD and related conditions |
CN101284828B (zh) * | 2007-04-12 | 2011-04-27 | 中国科学院上海药物研究所 | 环庚烷并吡啶类化合物、其制备方法、用途及包含此类化合物的药物组合物 |
KR101136260B1 (ko) * | 2007-08-14 | 2012-04-19 | 일라이 릴리 앤드 캄파니 | 감마-세크레타제 억제제로서의 아제핀 유도체 |
CA2709677C (fr) | 2007-12-21 | 2017-03-14 | Lin Zhi | Modulateurs selectifs du recepteur androgene (sarm) et leurs utilisations |
EP2291181B9 (fr) | 2008-04-18 | 2013-09-11 | University College Dublin National University Of Ireland, Dublin | Utilisation de la captodiamine pour le traitement des symptômes de la dépression |
US9776963B2 (en) | 2008-11-10 | 2017-10-03 | The Trustees Of The University Of Pennsylvania | Small molecule CD4 mimetics and uses thereof |
CA2743436C (fr) | 2008-11-24 | 2017-10-31 | Massachusetts Eye & Ear Infirmary | Voies pour generer des cellules pileuses |
CA2749700A1 (fr) * | 2009-01-23 | 2010-07-29 | Msd K.K. | Derives de benzodiazepin-2-one |
AU2010216632A1 (en) * | 2009-02-17 | 2011-08-04 | Msd K.K. | 1,4-benzodiazepin-2-on derivatives |
AR079170A1 (es) | 2009-12-10 | 2011-12-28 | Lilly Co Eli | Compuesto de ciclopropil-benzamida-imidazo-benzazepina inhibidor de diacil-glicerol aciltransferasa, sal del mismo, composicion farmaceutica que lo comprende, su uso para preparar un medicamento util para el tratamiento de obesidad o para mejorar la sensibilidad a insulina y compuesto intermedio par |
US8486967B2 (en) * | 2010-02-17 | 2013-07-16 | Hoffmann-La Roche Inc. | Heteroaryl substituted piperidines |
US9249161B2 (en) | 2010-12-02 | 2016-02-02 | Constellation Pharmaceuticals, Inc. | Bromodomain inhibitors and uses thereof |
AR084070A1 (es) | 2010-12-02 | 2013-04-17 | Constellation Pharmaceuticals Inc | Inhibidores del bromodominio y usos de los mismos |
EP2705039B1 (fr) | 2011-05-04 | 2017-07-26 | Constellation Pharmaceuticals, Inc. | Inhibiteurs de bromodomaines et leurs utilisations |
EP2721031B1 (fr) | 2011-06-17 | 2016-01-20 | Constellation Pharmaceuticals, Inc. | Inhibiteurs à bromodomaine et leurs utilisations |
JO3148B1 (ar) * | 2011-07-27 | 2017-09-20 | Lilly Co Eli | مركب مثبط لإشارات مسار notch |
WO2013090696A1 (fr) | 2011-12-14 | 2013-06-20 | Dana-Farber Cancer Institute, Inc. | Inhibiteurs de mimétiques du cd4 empêchant la pénétration du vih-1 et leurs méthodes d'utilisation |
TWI602820B (zh) | 2012-06-06 | 2017-10-21 | 星宿藥物公司 | 溴域抑制劑及其用途 |
WO2013184878A1 (fr) | 2012-06-06 | 2013-12-12 | Constellation Pharmaceuticals, Inc. | Inhibiteurs de bromo-domaine de benzo [b] isoxazoloazépines et applications associées |
WO2014039781A1 (fr) | 2012-09-07 | 2014-03-13 | Massachusetts Eye & Ear Infirmary | Traitement de la perte auditive |
CN103435549A (zh) * | 2013-08-14 | 2013-12-11 | 无锡惠飞生物医药技术有限公司 | 5-甲基-7-氨基-5H,7H-二苯并[b,d]氮杂环庚-6-酮的制备方法 |
EP3613418A1 (fr) | 2014-01-17 | 2020-02-26 | Ligand Pharmaceuticals, Inc. | Procédés et compositions de modulation des niveaux d'hormones |
DK3157928T3 (da) | 2014-06-20 | 2019-05-20 | Constellation Pharmaceuticals Inc | Krystallinske former af 2-((4s)-6-(4-chlorphenyl)-1-methyl-4h-benzo[c]isoxazolo[4,5-e]azepin-4-yl)acetamid |
WO2016022776A2 (fr) | 2014-08-06 | 2016-02-11 | Massachusetts Eye And Ear Infirmary | Augmentation de la durée de vie d'atoh1 pour diriger la différenciation des cellules ciliées neurosensorielles |
WO2016025681A1 (fr) | 2014-08-13 | 2016-02-18 | The Trustees Of The University Of Pennsylvania | Inhibiteurs de pénétration du vih-1 et leurs méthodes d'utilisation |
EP3212773B1 (fr) | 2014-10-29 | 2021-09-15 | Massachusetts Eye and Ear Infirmary | Administration efficace de molécules thérapeutiques en direction de cellules de l'oreille interne |
TWI609687B (zh) | 2015-04-14 | 2018-01-01 | 美國禮來大藥廠 | 平滑肌肉瘤之標靶性治療 |
WO2017096233A1 (fr) | 2015-12-04 | 2017-06-08 | Massachusetts Eye And Ear Infirmary | Traitement de perte auditive par inhibition de la caséine kinase 1 |
US11466252B2 (en) | 2016-01-29 | 2022-10-11 | Massachusetts Eye And Ear Infirmary | Expansion and differentiation of inner ear supporting cells and methods of use thereof |
EP3442529B1 (fr) | 2016-04-12 | 2021-05-26 | Eli Lilly and Company | Traitement d'association à base d'inhibiteurs de notch et de cdk4/6 pour le traitement du cancer du poumon |
KR102418766B1 (ko) | 2016-04-12 | 2022-07-08 | 일라이 릴리 앤드 캄파니 | 암 치료에 사용하기 위한 Notch 및 PI3K/mTOR 억제제의 조합 요법 |
CA3024424A1 (fr) | 2016-05-16 | 2017-11-23 | The General Hospital Corporation | Cellules souches de voies respiratoires humaines en ingenierie epitheliale pulmonaire |
IL263110B (en) | 2016-05-20 | 2022-07-01 | Lilly Co Eli | Combined treatment of notch and pd-1 or pd-l1 inhibitors |
CN106243050B (zh) * | 2016-08-10 | 2019-09-06 | 安徽恒星制药有限公司 | 一种适合工业化生产氯巴占的方法 |
WO2018071307A1 (fr) | 2016-10-12 | 2018-04-19 | Eli Lilly And Company | Traitement ciblé de lymphome à cellules t matures |
RU2757276C2 (ru) | 2016-12-16 | 2021-10-12 | Пайплайн Терапьютикс, Инк. | Способы лечения кохлеарной синаптопатии |
WO2018151836A1 (fr) | 2017-02-17 | 2018-08-23 | Fred Hutchinson Cancer Research Center | Traitements d'association pour le traitement de cancers associés à bcma et de troubles auto-immuns |
US11590152B2 (en) | 2018-01-26 | 2023-02-28 | Massachusetts Eye And Ear Infirmary | Treatment of hearing loss |
CN113754616B (zh) * | 2021-09-27 | 2023-07-18 | 北京工商大学 | 一种反式-3-苯硫基-γ-内酯的制备方法 |
CN116116396B (zh) * | 2023-02-20 | 2023-11-14 | 哈尔滨工程大学 | 一种偕胺肟基凝胶/氧化石墨/海绵复合材料的制备方法和应用 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IE42215B1 (en) * | 1973-12-28 | 1980-07-02 | Fujisawa Pharmaceutical Co | Azetidinone derivatives and process for preparation thereof |
FR2278335A1 (fr) * | 1974-07-04 | 1976-02-13 | Fujisawa Pharmaceutical Co | Derives d'azetidinones et leurs procedes de preparation |
CZ184194A3 (en) * | 1993-08-09 | 1995-03-15 | Lilly Co Eli | Aspartylprotease inhibitor and method of identifying thereof |
US5580979A (en) * | 1994-03-15 | 1996-12-03 | Trustees Of Tufts University | Phosphotyrosine peptidomimetics for inhibiting SH2 domain interactions |
US6251928B1 (en) * | 1994-03-16 | 2001-06-26 | Eli Lilly And Company | Treatment of alzheimer's disease employing inhibitors of cathepsin D |
US5849691A (en) * | 1996-02-20 | 1998-12-15 | The United States Of America As Represented By The Department Of Health And Human Services | Peptidomimetic inhibitors of cathepsin D and plasmepsins I and II |
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