OA12919A - Acetyl 2-hydroxy-1,3 diaminoalkanes. - Google Patents
Acetyl 2-hydroxy-1,3 diaminoalkanes. Download PDFInfo
- Publication number
- OA12919A OA12919A OA1200500066A OA1200500066A OA12919A OA 12919 A OA12919 A OA 12919A OA 1200500066 A OA1200500066 A OA 1200500066A OA 1200500066 A OA1200500066 A OA 1200500066A OA 12919 A OA12919 A OA 12919A
- Authority
- OA
- OAPI
- Prior art keywords
- alkyl
- amino
- difluorobenzyl
- acetamide
- groups
- Prior art date
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- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 406
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 52
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 31
- 201000010099 disease Diseases 0.000 claims abstract description 29
- 125000000217 alkyl group Chemical group 0.000 claims description 445
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 210
- 229910052736 halogen Inorganic materials 0.000 claims description 195
- 150000002367 halogens Chemical class 0.000 claims description 179
- -1 2-naphthylindanyl Chemical group 0.000 claims description 157
- 125000003545 alkoxy group Chemical group 0.000 claims description 149
- 238000000034 method Methods 0.000 claims description 143
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 134
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 128
- 125000003118 aryl group Chemical group 0.000 claims description 106
- 125000001072 heteroaryl group Chemical group 0.000 claims description 91
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 86
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 73
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 64
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 61
- 125000003342 alkenyl group Chemical group 0.000 claims description 60
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 57
- 125000000304 alkynyl group Chemical group 0.000 claims description 55
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 40
- 229910052799 carbon Inorganic materials 0.000 claims description 39
- 125000004432 carbon atom Chemical group C* 0.000 claims description 37
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 30
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 27
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 27
- 206010012289 Dementia Diseases 0.000 claims description 27
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 23
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 19
- 208000010877 cognitive disease Diseases 0.000 claims description 19
- 208000027061 mild cognitive impairment Diseases 0.000 claims description 19
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 17
- 229910052731 fluorine Inorganic materials 0.000 claims description 17
- 125000001188 haloalkyl group Chemical group 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 229910014585 C2-Ce Inorganic materials 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 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 13
- 230000003412 degenerative effect Effects 0.000 claims description 13
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 13
- 125000002883 imidazolyl group Chemical group 0.000 claims description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000000335 thiazolyl group Chemical group 0.000 claims description 12
- 125000001544 thienyl group Chemical group 0.000 claims description 12
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 11
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 11
- 125000002541 furyl group Chemical group 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000006288 3,5-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(C([H])=C1F)C([H])([H])* 0.000 claims description 10
- 206010059245 Angiopathy Diseases 0.000 claims description 10
- 208000032843 Hemorrhage Diseases 0.000 claims description 9
- AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 claims description 9
- 206010002022 amyloidosis Diseases 0.000 claims description 9
- 125000002619 bicyclic group Chemical group 0.000 claims description 9
- 210000004558 lewy body Anatomy 0.000 claims description 9
- 125000002971 oxazolyl group Chemical group 0.000 claims description 9
- 125000001475 halogen functional group Chemical group 0.000 claims description 8
- 201000010374 Down Syndrome Diseases 0.000 claims description 7
- 206010044688 Trisomy 21 Diseases 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 6
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 230000001054 cortical effect Effects 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 6
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 4
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 102200029950 rs35898499 Human genes 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 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 3
- JOTLFBOJCNGMEH-RWIDKHAYSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[[6-(2,2-dimethylpropyl)-4-methyl-2,3-dihydrochromen-4-yl]amino]-3-hydroxybutan-2-yl]acetamide Chemical compound C([C@H](NC(=O)C)[C@H](O)CNC1(C)C2=CC(CC(C)(C)C)=CC=C2OCC1)C1=CC(F)=CC(F)=C1 JOTLFBOJCNGMEH-RWIDKHAYSA-N 0.000 claims description 3
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 2
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 2
- 208000027089 Parkinsonian disease Diseases 0.000 claims description 2
- 206010034010 Parkinsonism Diseases 0.000 claims description 2
- 125000005046 dihydronaphthyl group Chemical group 0.000 claims description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 2
- XWRSCLXARRERCR-SLFFLAALSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[[(4s)-6-iodo-3,4-dihydro-2h-chromen-4-yl]amino]butan-2-yl]acetamide Chemical compound C([C@H](NC(=O)C)[C@H](O)CN[C@@H]1C2=CC(I)=CC=C2OCC1)C1=CC(F)=CC(F)=C1 XWRSCLXARRERCR-SLFFLAALSA-N 0.000 claims description 2
- XHXJXNDFQVVQIW-FDFHNCONSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[[(4s)-6-ethyl-3,4-dihydro-2h-chromen-4-yl]amino]-3-hydroxybutan-2-yl]acetamide Chemical compound C([C@@H]([C@H](O)CN[C@H]1CCOC2=CC=C(C=C21)CC)NC(C)=O)C1=CC(F)=CC(F)=C1 XHXJXNDFQVVQIW-FDFHNCONSA-N 0.000 claims description 2
- OAOZSVYTXSWPNZ-PCCBWWKXSA-N n-[(2s,3r)-4-[[(4s)-6-cyano-3,4-dihydro-2h-chromen-4-yl]amino]-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]acetamide Chemical compound C([C@H](NC(=O)C)[C@H](O)CN[C@@H]1C2=CC(=CC=C2OCC1)C#N)C1=CC(F)=CC(F)=C1 OAOZSVYTXSWPNZ-PCCBWWKXSA-N 0.000 claims description 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 2
- 229940080818 propionamide Drugs 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 4
- AXGWWGKUHKMPRX-ATTQYFOMSA-N methyl 3-[[(2r,3s)-3-acetamido-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino]-3-(3-ethylphenyl)propanoate Chemical compound CCC1=CC=CC(C(CC(=O)OC)NC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(C)=O)=C1 AXGWWGKUHKMPRX-ATTQYFOMSA-N 0.000 claims 3
- 125000001589 carboacyl group Chemical group 0.000 claims 2
- VWSIATNSQCPPMT-GJGLBJJNSA-N methyl 3-[[(2r,3s)-3-acetamido-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino]-3-(3-bromophenyl)propanoate Chemical compound C([C@@H]([C@H](O)CNC(CC(=O)OC)C=1C=C(Br)C=CC=1)NC(C)=O)C1=CC(F)=CC(F)=C1 VWSIATNSQCPPMT-GJGLBJJNSA-N 0.000 claims 2
- GUAHTUPTSSAPCN-KOEFPUPOSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(6-ethyl-3-methyl-2,2-dioxo-3,4-dihydro-1h-isothiochromen-4-yl)amino]-3-hydroxybutan-2-yl]acetamide Chemical compound C([C@@H]([C@H](O)CNC1C(C)S(=O)(=O)CC2=CC=C(C=C21)CC)NC(C)=O)C1=CC(F)=CC(F)=C1 GUAHTUPTSSAPCN-KOEFPUPOSA-N 0.000 claims 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 1
- 125000006279 3-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Br)=C1[H])C([H])([H])* 0.000 claims 1
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
- SDIXRDNYIMOKSG-UHFFFAOYSA-L disodium methyl arsenate Chemical compound [Na+].[Na+].C[As]([O-])([O-])=O SDIXRDNYIMOKSG-UHFFFAOYSA-L 0.000 claims 1
- OEBZIRQXECPRLZ-JBRSBNLGSA-N methyl (3r)-3-[[(2r,3s)-3-acetamido-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino]-3-(3-ethylphenyl)butanoate Chemical compound CCC1=CC=CC([C@@](C)(CC(=O)OC)NC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(C)=O)=C1 OEBZIRQXECPRLZ-JBRSBNLGSA-N 0.000 claims 1
- OEBZIRQXECPRLZ-ARNLJNQMSA-N methyl (3s)-3-[[(2r,3s)-3-acetamido-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino]-3-(3-ethylphenyl)butanoate Chemical compound CCC1=CC=CC([C@](C)(CC(=O)OC)NC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(C)=O)=C1 OEBZIRQXECPRLZ-ARNLJNQMSA-N 0.000 claims 1
- AOUJHXVXTOVWGN-JTGIGXABSA-N methyl 3-[[(2r,3s)-3-acetamido-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino]-3-(3-cyanophenyl)propanoate Chemical compound C([C@@H]([C@H](O)CNC(CC(=O)OC)C=1C=C(C=CC=1)C#N)NC(C)=O)C1=CC(F)=CC(F)=C1 AOUJHXVXTOVWGN-JTGIGXABSA-N 0.000 claims 1
- TYNXZNKYQRBNEY-NCPLZGKYSA-N methyl 3-[[(2r,3s)-3-acetamido-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino]-3-[3-(5-formylthiophen-2-yl)phenyl]propanoate Chemical compound C([C@@H]([C@H](O)CNC(CC(=O)OC)C=1C=C(C=CC=1)C=1SC(C=O)=CC=1)NC(C)=O)C1=CC(F)=CC(F)=C1 TYNXZNKYQRBNEY-NCPLZGKYSA-N 0.000 claims 1
- SOIKLQNRXYQQBN-GJGLBJJNSA-N methyl 3-[[(2r,3s)-3-acetamido-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino]-3-[3-(trifluoromethyl)phenyl]propanoate Chemical compound C([C@@H]([C@H](O)CNC(CC(=O)OC)C=1C=C(C=CC=1)C(F)(F)F)NC(C)=O)C1=CC(F)=CC(F)=C1 SOIKLQNRXYQQBN-GJGLBJJNSA-N 0.000 claims 1
- AMLJWLYRONUCKO-UHFFFAOYSA-N n-(6-amino-5-iodopyridin-2-yl)acetamide Chemical compound CC(=O)NC1=CC=C(I)C(N)=N1 AMLJWLYRONUCKO-UHFFFAOYSA-N 0.000 claims 1
- PNVOXFMMAWCICZ-MDEZFMAYSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(2-prop-1-en-2-yl-9h-fluoren-9-yl)amino]butan-2-yl]acetamide Chemical compound C([C@H](NC(=O)C)[C@H](O)CNC1C2=CC(=CC=C2C2=CC=CC=C21)C(C)=C)C1=CC(F)=CC(F)=C1 PNVOXFMMAWCICZ-MDEZFMAYSA-N 0.000 claims 1
- YNRCUSIBKRXCLA-RBUKOAKNSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]acetamide Chemical compound C([C@H](NC(=O)C)[C@H](O)CNCC=1C=C(I)C=CC=1)C1=CC(F)=CC(F)=C1 YNRCUSIBKRXCLA-RBUKOAKNSA-N 0.000 claims 1
- UIFHRHVYZFLBCX-ATTQYFOMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(6-propan-2-yl-3,4-dihydro-2h-chromen-4-yl)amino]butan-2-yl]acetamide Chemical compound C([C@@H]([C@H](O)CNC1CCOC2=CC=C(C=C21)C(C)C)NC(C)=O)C1=CC(F)=CC(F)=C1 UIFHRHVYZFLBCX-ATTQYFOMSA-N 0.000 claims 1
- GIBLVACOCVLBIP-ATTQYFOMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)amino]butan-2-yl]acetamide Chemical compound C([C@@H]([C@H](O)CNC1CCCC2=CC=C(C=C21)OC)NC(C)=O)C1=CC(F)=CC(F)=C1 GIBLVACOCVLBIP-ATTQYFOMSA-N 0.000 claims 1
- XWRSCLXARRERCR-HSALFYBXSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[[(4r)-6-iodo-3,4-dihydro-2h-chromen-4-yl]amino]butan-2-yl]acetamide Chemical compound C([C@H](NC(=O)C)[C@H](O)CN[C@H]1C2=CC(I)=CC=C2OCC1)C1=CC(F)=CC(F)=C1 XWRSCLXARRERCR-HSALFYBXSA-N 0.000 claims 1
- RONVEGQPUBZTQN-LOSJGSFVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[[1-(3-propan-2-ylphenyl)cyclohexyl]amino]butan-2-yl]-2-fluoroacetamide Chemical compound CC(C)C1=CC=CC(C2(CCCCC2)NC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CF)=C1 RONVEGQPUBZTQN-LOSJGSFVSA-N 0.000 claims 1
- HLCWFSFOWQTZPY-VQTJNVASSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[[1-[3-(2-methylpropyl)-1,2-oxazol-5-yl]cyclopropyl]amino]butan-2-yl]acetamide Chemical compound O1N=C(CC(C)C)C=C1C1(NC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(C)=O)CC1 HLCWFSFOWQTZPY-VQTJNVASSA-N 0.000 claims 1
- CAQUERUPLGOZIF-IZZNHLLZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[[4-oxo-1-(3-propan-2-ylphenyl)cyclohexyl]amino]butan-2-yl]acetamide Chemical compound CC(C)C1=CC=CC(C2(CCC(=O)CC2)NC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(C)=O)=C1 CAQUERUPLGOZIF-IZZNHLLZSA-N 0.000 claims 1
- PIIOKHOQAWUAAY-NRRUETGQSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-(3,4-dihydro-2h-chromen-4-ylamino)-3-hydroxybutan-2-yl]acetamide Chemical compound C([C@H](NC(=O)C)[C@H](O)CNC1C2=CC=CC=C2OCC1)C1=CC(F)=CC(F)=C1 PIIOKHOQAWUAAY-NRRUETGQSA-N 0.000 claims 1
- BVSPJLUHPHUNHL-BJKOFHAPSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-(9h-fluoren-9-ylamino)-3-hydroxybutan-2-yl]acetamide Chemical compound C([C@H](NC(=O)C)[C@H](O)CNC1C2=CC=CC=C2C2=CC=CC=C21)C1=CC(F)=CC(F)=C1 BVSPJLUHPHUNHL-BJKOFHAPSA-N 0.000 claims 1
- DSSTULDVWVKMRA-SIGULFFNSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(2,2-dioxo-3,4-dihydro-1h-isothiochromen-4-yl)amino]-3-hydroxybutan-2-yl]acetamide Chemical compound C([C@H](NC(=O)C)[C@H](O)CNC1C2=CC=CC=C2CS(=O)(=O)C1)C1=CC(F)=CC(F)=C1 DSSTULDVWVKMRA-SIGULFFNSA-N 0.000 claims 1
- MMSHGDJMZDMBDE-QDSWCARHSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(2-ethyl-5-fluoro-9h-fluoren-9-yl)amino]-3-hydroxybutan-2-yl]acetamide Chemical compound C([C@@H]([C@H](O)CNC1C=2C(C3=C(F)C=CC=C31)=CC=C(C=2)CC)NC(C)=O)C1=CC(F)=CC(F)=C1 MMSHGDJMZDMBDE-QDSWCARHSA-N 0.000 claims 1
- FFCLAKQJARATFW-MDEZFMAYSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(2-ethyl-9-methylfluoren-9-yl)amino]-3-hydroxybutan-2-yl]acetamide Chemical compound C([C@@H]([C@H](O)CNC1(C2=CC=CC=C2C2=CC=C(C=C21)CC)C)NC(C)=O)C1=CC(F)=CC(F)=C1 FFCLAKQJARATFW-MDEZFMAYSA-N 0.000 claims 1
- KMIAWUBAUDJNHI-LEWJYISDSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(C)=O)=C1 KMIAWUBAUDJNHI-LEWJYISDSA-N 0.000 claims 1
- WZCKSIHHQWTNMW-OCESARCHSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(6-ethyl-3,4-dihydro-1h-isothiochromen-4-yl)amino]-3-hydroxybutan-2-yl]acetamide Chemical compound C([C@@H]([C@H](O)CNC1CSCC2=CC=C(C=C21)CC)NC(C)=O)C1=CC(F)=CC(F)=C1 WZCKSIHHQWTNMW-OCESARCHSA-N 0.000 claims 1
- JGTOEGONAQRUFP-YDUIRMPASA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[1-(3-ethylphenyl)butylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound C([C@@H]([C@H](O)CNC(CCC)C=1C=C(CC)C=CC=1)NC(C)=O)C1=CC(F)=CC(F)=C1 JGTOEGONAQRUFP-YDUIRMPASA-N 0.000 claims 1
- APTQIODKEXPXMX-UMIAIAFLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[2-(3-ethylphenyl)propan-2-ylamino]-3-hydroxybutan-2-yl]acetamide;hydrochloride Chemical compound Cl.CCC1=CC=CC(C(C)(C)NC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(C)=O)=C1 APTQIODKEXPXMX-UMIAIAFLSA-N 0.000 claims 1
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- 230000001953 sensory effect Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229960001407 sodium bicarbonate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960002668 sodium chloride Drugs 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229940032330 sulfuric acid Drugs 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- IBXBAKVPBSZRAX-SXNCYPNXSA-N tert-butyl n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(6-iodo-4-methyl-2,3-dihydrochromen-4-yl)amino]butan-2-yl]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)[C@H](O)CNC1(C)C2=CC(I)=CC=C2OCC1)C1=CC(F)=CC(F)=C1 IBXBAKVPBSZRAX-SXNCYPNXSA-N 0.000 description 1
- RTEJVQDVLLEQHH-KMDXXIMOSA-N tert-butyl n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[[(4s)-6-propan-2-yl-3,4-dihydro-2h-chromen-4-yl]amino]butan-2-yl]carbamate Chemical compound C([C@@H]([C@H](O)CN[C@H]1CCOC2=CC=C(C=C21)C(C)C)NC(=O)OC(C)(C)C)C1=CC(F)=CC(F)=C1 RTEJVQDVLLEQHH-KMDXXIMOSA-N 0.000 description 1
- BGEABFACPQXBIX-KMDXXIMOSA-N tert-butyl n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[[(4s)-6-propan-2-yloxy-3,4-dihydro-2h-chromen-4-yl]amino]butan-2-yl]carbamate Chemical compound C([C@@H]([C@H](O)CN[C@H]1CCOC2=CC=C(C=C21)OC(C)C)NC(=O)OC(C)(C)C)C1=CC(F)=CC(F)=C1 BGEABFACPQXBIX-KMDXXIMOSA-N 0.000 description 1
- TTXVFBIUURWQOL-KCIKGWAESA-N tert-butyl n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[[6-(2,2-dimethylpropyl)-3,4-dihydro-1h-isochromen-4-yl]amino]-3-hydroxybutan-2-yl]carbamate Chemical compound C([C@@H]([C@H](O)CNC1COCC2=CC=C(C=C21)CC(C)(C)C)NC(=O)OC(C)(C)C)C1=CC(F)=CC(F)=C1 TTXVFBIUURWQOL-KCIKGWAESA-N 0.000 description 1
- PGZNVQZFCHDJSV-NCPLZGKYSA-N tert-butyl n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[[6-(2,2-dimethylpropyl)-3,4-dihydro-2h-chromen-4-yl]amino]-3-hydroxybutan-2-yl]carbamate Chemical compound C([C@@H]([C@H](O)CNC1CCOC2=CC=C(C=C21)CC(C)(C)C)NC(=O)OC(C)(C)C)C1=CC(F)=CC(F)=C1 PGZNVQZFCHDJSV-NCPLZGKYSA-N 0.000 description 1
- MNCZFZJFVNLIBJ-QWHCGFSZSA-N tert-butyl n-[(2s,3r)-4-amino-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]([C@H](O)CN)CC1=CC(F)=CC(F)=C1 MNCZFZJFVNLIBJ-QWHCGFSZSA-N 0.000 description 1
- LJMGYUWQMIXDEA-HNNXBMFYSA-N tert-butyl n-[(4s)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2h-chromen-4-yl]carbamate Chemical compound C([C@@H](C1=C2)NC(=O)OC(C)(C)C)COC1=CC=C2B1OC(C)(C)C(C)(C)O1 LJMGYUWQMIXDEA-HNNXBMFYSA-N 0.000 description 1
- FIWIUPVUDGYINI-NSHDSACASA-N tert-butyl n-[(4s)-6-hydroxy-3,4-dihydro-2h-chromen-4-yl]carbamate Chemical compound C1=C(O)C=C2[C@@H](NC(=O)OC(C)(C)C)CCOC2=C1 FIWIUPVUDGYINI-NSHDSACASA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- DSDCDMKASWVZHI-UHFFFAOYSA-M zinc;2-methanidylpropane;bromide Chemical compound Br[Zn+].CC(C)[CH2-] DSDCDMKASWVZHI-UHFFFAOYSA-M 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/34—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
- C07C233/35—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/36—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- 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
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/10—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
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- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/72—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms
- C07C235/74—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of a saturated carbon skeleton
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- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/24—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a ring other than a six-membered aromatic ring
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/05—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
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- C07C327/00—Thiocarboxylic acids
- C07C327/20—Esters of monothiocarboxylic acids
- C07C327/30—Esters of monothiocarboxylic acids having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
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- C—CHEMISTRY; METALLURGY
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- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—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
- C07D215/16—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 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
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- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—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
- C07D215/16—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 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
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- C07D215/02—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
- C07D215/16—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 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
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
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- C07D215/16—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 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
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- C07D215/42—Nitrogen atoms attached in position 4
- C07D215/46—Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
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- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
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- C07D233/61—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
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- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
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| US7618978B2 (en) | 2004-04-22 | 2009-11-17 | Eli Lilly And Company | Amides as BACE inhibitors |
| US7585885B2 (en) | 2004-04-22 | 2009-09-08 | Eli Lilly And Company | Pyrrolidine derivatives useful as BACE inhibitors |
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| US7838676B2 (en) | 2005-11-21 | 2010-11-23 | Amgen Inc. | Beta-secretase modulators and methods of use |
| US7745484B2 (en) | 2005-11-21 | 2010-06-29 | Amgen Inc. | Beta-secretase modulators and methods of use |
| US7872009B2 (en) | 2005-11-21 | 2011-01-18 | Amgen Inc. | Beta-Secretase modulators and methods of use |
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| EP1957448A1 (en) * | 2005-11-22 | 2008-08-20 | Pfizer Products Inc. | Substituted azacycloalkanes useful for treating cns conditions |
| BRPI0719336A2 (pt) * | 2006-11-23 | 2014-02-04 | Novartis Ag | Derivados de 2-hidróxi-1,3-diaminopropano |
| TW200901991A (en) | 2007-05-25 | 2009-01-16 | Amgen Inc | Substituted hydroxyethyl amine compounds as beta-secretase modulators and methods of use |
| CA2687608C (en) | 2007-05-25 | 2013-07-02 | Amgen Inc. | Substituted hydroxyethyl amine compounds as beta-secretase modulators and methods of use |
| US7803809B2 (en) | 2008-11-12 | 2010-09-28 | Amgen Inc. | Substituted pyrano [2,3-b] pyridinamine compounds as beta-secretase modulators and methods of use |
| DE102008039083A1 (de) | 2008-08-21 | 2010-02-25 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 5-Aminopyrazole und ihre Verwendung |
| MX2011002705A (es) * | 2008-09-11 | 2011-09-09 | Amgen Inc | Compuestos con anillos espiro-triciclicos como moduladores de beta-secretasas y metodos de uso. |
| EP2504330A1 (en) | 2009-11-23 | 2012-10-03 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
| US9296698B2 (en) | 2009-11-23 | 2016-03-29 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
| CA2788363A1 (en) | 2010-01-19 | 2011-07-28 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
| ES2450568T3 (es) | 2010-03-15 | 2014-03-25 | Amgen Inc. | Compuestos espiero de amino-dihidrooxazina y amino-dihidrotiazina como moduladores de beta-secretasa y su uso médico |
| MX2012010658A (es) | 2010-03-15 | 2012-12-05 | Amgen Inc | Compuestos de anillo espiro tetraciclico como moduladores de beta-secretasa. |
| WO2012109165A1 (en) | 2011-02-07 | 2012-08-16 | Amgen Inc. | 5-amino-oxazepine and 5-amino-thiazepane compounds as beta-secretase antagonists and methods of use |
| WO2013044092A1 (en) | 2011-09-21 | 2013-03-28 | Amgen Inc. | Amino-oxazines and amino-dihydrothiazine compounds as beta-secretase modulators and methods of use |
| US9725469B2 (en) | 2012-11-15 | 2017-08-08 | Amgen, Inc. | Amino-oxazine and amino-dihydrothiazine compounds as beta-secretase modulators and methods of use |
| EP3490607A4 (en) | 2016-07-29 | 2020-04-08 | Sunovion Pharmaceuticals Inc. | COMPOUNDS AND COMPOSITIONS, AND USES THEREOF |
| SG11202000669VA (en) | 2017-08-02 | 2020-02-27 | Sunovion Pharmaceuticals Inc | Isochroman compounds and uses thereof |
| US11760701B2 (en) | 2018-02-27 | 2023-09-19 | The Research Foundation For The State University Of New Yrok | Difluoromethoxylation and trifluoromethoxylation compositions and methods for synthesizing same |
| PL243516B1 (pl) * | 2020-05-20 | 2023-09-04 | Univ Jagiellonski | Nowe pochodne 9H-fluorenu lub ich farmaceutycznie dopuszczalne sole |
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| JPS61118352A (ja) * | 1984-10-29 | 1986-06-05 | イー・アール・スクイブ・アンド・サンズ・インコーポレイテツド | アミノ酸エステルおよびアミドレニン抑制剤 |
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-
2003
- 2003-09-09 UY UY27967A patent/UY27967A1/es not_active Application Discontinuation
- 2003-09-10 MX MXPA05002695A patent/MXPA05002695A/es active IP Right Grant
- 2003-09-10 JP JP2004571986A patent/JP2006504793A/ja active Pending
- 2003-09-10 EA EA200500472A patent/EA009196B1/ru not_active IP Right Cessation
- 2003-09-10 AU AU2003267132A patent/AU2003267132A1/en not_active Abandoned
- 2003-09-10 PE PE2003000914A patent/PE20041079A1/es not_active Application Discontinuation
- 2003-09-10 GE GEAP20038737A patent/GEP20074166B/en unknown
- 2003-09-10 WO PCT/US2003/028503 patent/WO2004024081A2/en not_active Ceased
- 2003-09-10 KR KR1020057004161A patent/KR20060057520A/ko not_active Ceased
- 2003-09-10 TW TW092125081A patent/TWI336320B/zh not_active IP Right Cessation
- 2003-09-10 NZ NZ539095A patent/NZ539095A/en not_active IP Right Cessation
- 2003-09-10 UA UAA200502191A patent/UA84407C2/ru unknown
- 2003-09-10 PL PL376511A patent/PL376511A1/pl not_active Application Discontinuation
- 2003-09-10 US US10/658,959 patent/US7244725B2/en not_active Expired - Fee Related
- 2003-09-10 BR BR0314188-8A patent/BR0314188A/pt not_active IP Right Cessation
- 2003-09-10 AR ARP030103276A patent/AR043679A1/es unknown
- 2003-09-10 EP EP03749607A patent/EP1565443A4/en not_active Withdrawn
- 2003-09-10 OA OA1200500066A patent/OA12919A/en unknown
- 2003-09-10 CA CA002498248A patent/CA2498248A1/en not_active Abandoned
-
2005
- 2005-03-09 IS IS7732A patent/IS7732A/is unknown
- 2005-03-10 NO NO20051239A patent/NO20051239L/no not_active Application Discontinuation
- 2005-03-21 EC EC2005005696A patent/ECSP055696A/es unknown
- 2005-04-06 MA MA28202A patent/MA27472A1/fr unknown
-
2006
- 2006-06-06 US US11/447,789 patent/US7645780B2/en not_active Expired - Fee Related
-
2009
- 2009-11-23 US US12/624,100 patent/US20100145056A1/en not_active Abandoned
-
2010
- 2010-12-08 JP JP2010273586A patent/JP2011084568A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| PE20041079A1 (es) | 2005-02-05 |
| US20040180939A1 (en) | 2004-09-16 |
| JP2011084568A (ja) | 2011-04-28 |
| NZ539095A (en) | 2007-04-27 |
| US7244725B2 (en) | 2007-07-17 |
| EP1565443A2 (en) | 2005-08-24 |
| WO2004024081A3 (en) | 2005-06-23 |
| PL376511A1 (pl) | 2006-01-09 |
| EP1565443A4 (en) | 2007-07-18 |
| UY27967A1 (es) | 2004-05-31 |
| EA200500472A1 (ru) | 2005-10-27 |
| WO2004024081A2 (en) | 2004-03-25 |
| UA84407C2 (en) | 2008-10-27 |
| US20100145056A1 (en) | 2010-06-10 |
| TWI336320B (en) | 2011-01-21 |
| EA009196B1 (ru) | 2007-12-28 |
| TW200417534A (en) | 2004-09-16 |
| ECSP055696A (es) | 2005-07-06 |
| BR0314188A (pt) | 2005-08-09 |
| US7645780B2 (en) | 2010-01-12 |
| AU2003267132A1 (en) | 2004-04-30 |
| MA27472A1 (fr) | 2005-08-01 |
| IS7732A (is) | 2005-03-09 |
| JP2006504793A (ja) | 2006-02-09 |
| AR043679A1 (es) | 2005-08-10 |
| KR20060057520A (ko) | 2006-05-26 |
| NO20051239L (no) | 2005-06-06 |
| GEP20074166B (en) | 2007-07-25 |
| MXPA05002695A (es) | 2005-09-08 |
| CA2498248A1 (en) | 2004-03-25 |
| US20070293483A1 (en) | 2007-12-20 |
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