HRP20040069A2 - N-(3-amino-2-hydroxy-propyl) substituted alkylamide compounds - Google Patents
N-(3-amino-2-hydroxy-propyl) substituted alkylamide compoundsInfo
- Publication number
- HRP20040069A2 HRP20040069A2 HR20040069A HRP20040069A HRP20040069A2 HR P20040069 A2 HRP20040069 A2 HR P20040069A2 HR 20040069 A HR20040069 A HR 20040069A HR P20040069 A HRP20040069 A HR P20040069A HR P20040069 A2 HRP20040069 A2 HR P20040069A2
- Authority
- HR
- Croatia
- Prior art keywords
- amino
- difluorobenzyl
- alkyl
- hydroxypropyl
- ethylbenzyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 297
- -1 -C1-C3 alkoxy Chemical group 0.000 claims description 312
- 229910052736 halogen Inorganic materials 0.000 claims description 182
- 150000002367 halogens Chemical class 0.000 claims description 178
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 169
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 145
- 238000000034 method Methods 0.000 claims description 121
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 107
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 89
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 87
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 87
- 125000003118 aryl group Chemical group 0.000 claims description 62
- 208000024827 Alzheimer disease Diseases 0.000 claims description 48
- 125000000623 heterocyclic group Chemical group 0.000 claims description 48
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 47
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 45
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 45
- 125000001072 heteroaryl group Chemical group 0.000 claims description 45
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 40
- 201000010099 disease Diseases 0.000 claims description 37
- 238000002360 preparation method Methods 0.000 claims description 37
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 35
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 29
- 206010012289 Dementia Diseases 0.000 claims description 29
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 28
- 230000002265 prevention Effects 0.000 claims description 26
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 24
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 22
- 208000010877 cognitive disease Diseases 0.000 claims description 22
- 208000027061 mild cognitive impairment Diseases 0.000 claims description 22
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 18
- 125000000304 alkynyl group Chemical group 0.000 claims description 16
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 15
- 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 15
- 230000003412 degenerative effect Effects 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 13
- 201000010374 Down Syndrome Diseases 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 238000011161 development Methods 0.000 claims description 12
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 9
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 210000004558 lewy body Anatomy 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- FBHAXPHZFVWFHO-ZDGKEXRSSA-N 2-(4-butyl-2,3-dioxopiperazin-1-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide;hydrochloride Chemical compound Cl.O=C1C(=O)N(CCCC)CCN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 FBHAXPHZFVWFHO-ZDGKEXRSSA-N 0.000 claims description 5
- 208000018282 ACys amyloidosis Diseases 0.000 claims description 5
- 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 claims description 5
- 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 claims description 5
- 206010044688 Trisomy 21 Diseases 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
- UVGLQSINWJOBPO-KZDWWKKTSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-ethyl-2,3-dioxopiperazin-1-yl)acetamide;hydrochloride Chemical group Cl.O=C1C(=O)N(CC)CCN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 UVGLQSINWJOBPO-KZDWWKKTSA-N 0.000 claims description 4
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 4
- QGRYNVQJIHOJIA-RWSKJCERSA-N (2s)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[4-(2-methoxyethyl)piperidin-1-yl]-4-methylsulfanylbutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)[C@H](CCSC)N2CCC(CCOC)CC2)=C1 QGRYNVQJIHOJIA-RWSKJCERSA-N 0.000 claims description 3
- VEGTUHAXDHISOE-OWHBQTKESA-N (2s)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[4-(2-methoxyethyl)piperidin-1-yl]hexanamide Chemical compound N1([C@@H](CCCC)C(=O)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@H](O)CNCC=2C=C(CC)C=CC=2)CCC(CCOC)CC1 VEGTUHAXDHISOE-OWHBQTKESA-N 0.000 claims description 3
- HRSUOWAZQMXCID-RWSKJCERSA-N (2s)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[4-(ethoxymethyl)piperidin-1-yl]-4-methylsulfanylbutanamide Chemical compound C1CC(COCC)CCN1[C@@H](CCSC)C(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 HRSUOWAZQMXCID-RWSKJCERSA-N 0.000 claims description 3
- WLOIMDOVNZNYQS-OWHBQTKESA-N (2s)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[4-(ethoxymethyl)piperidin-1-yl]hexanamide Chemical compound N1([C@@H](CCCC)C(=O)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@H](O)CNCC=2C=C(CC)C=CC=2)CCC(COCC)CC1 WLOIMDOVNZNYQS-OWHBQTKESA-N 0.000 claims description 3
- AICFTYJRCILKMG-RWSKJCERSA-N (2s)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[4-(ethoxymethyl)piperidin-1-yl]pentanamide Chemical compound N1([C@@H](CCC)C(=O)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@H](O)CNCC=2C=C(CC)C=CC=2)CCC(COCC)CC1 AICFTYJRCILKMG-RWSKJCERSA-N 0.000 claims description 3
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 3
- 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
- IHPWKBXPLCIWLU-WUFINQPMSA-N 2-(1-butyl-2-oxopyridin-4-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound O=C1N(CCCC)C=CC(CC(=O)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@H](O)CNCC=2C=C(CC)C=CC=2)=C1 IHPWKBXPLCIWLU-WUFINQPMSA-N 0.000 claims description 3
- SCTJTPVJLZSHFL-YFISABEZSA-N 2-(4-butyl-2,3-dioxopiperazin-1-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]hexanamide Chemical compound N([C@@H](CC=1C=C(F)C=C(F)C=1)[C@H](O)CNCC=1C=C(CC)C=CC=1)C(=O)C(CCCC)N1CCN(CCCC)C(=O)C1=O SCTJTPVJLZSHFL-YFISABEZSA-N 0.000 claims description 3
- YHCSKLPNABJYSZ-IZZNHLLZSA-N 2-(4-butyl-2,5-dioxopiperazin-1-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)CC(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 YHCSKLPNABJYSZ-IZZNHLLZSA-N 0.000 claims description 3
- 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 3
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 3
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 3
- 238000007913 intrathecal administration Methods 0.000 claims description 3
- HRSUOWAZQMXCID-GAGJGVLVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[4-(ethoxymethyl)piperidin-1-yl]-4-methylsulfanylbutanamide Chemical compound C1CC(COCC)CCN1C(CCSC)C(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 HRSUOWAZQMXCID-GAGJGVLVSA-N 0.000 claims description 3
- WLOIMDOVNZNYQS-HRFHJXJKSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[4-(ethoxymethyl)piperidin-1-yl]hexanamide Chemical compound N([C@@H](CC=1C=C(F)C=C(F)C=1)[C@H](O)CNCC=1C=C(CC)C=CC=1)C(=O)C(CCCC)N1CCC(COCC)CC1 WLOIMDOVNZNYQS-HRFHJXJKSA-N 0.000 claims description 3
- AICFTYJRCILKMG-GAGJGVLVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[4-(ethoxymethyl)piperidin-1-yl]pentanamide Chemical compound N([C@@H](CC=1C=C(F)C=C(F)C=1)[C@H](O)CNCC=1C=C(CC)C=CC=1)C(=O)C(CCC)N1CCC(COCC)CC1 AICFTYJRCILKMG-GAGJGVLVSA-N 0.000 claims description 3
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 3
- PVIXQGJDWURPGC-RWSKJCERSA-N (2s)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[4-(2-methoxyethyl)piperidin-1-yl]pentanamide Chemical compound N1([C@@H](CCC)C(=O)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@H](O)CNCC=2C=C(CC)C=CC=2)CCC(CCOC)CC1 PVIXQGJDWURPGC-RWSKJCERSA-N 0.000 claims description 2
- 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 claims description 2
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims description 2
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 claims description 2
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 2
- 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 2
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 2
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- RHOHWDBPUZEAFC-JSZYHFPGSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3-oxo-4-propylcyclohexyl)acetamide Chemical compound C1C(=O)C(CCC)CCC1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 RHOHWDBPUZEAFC-JSZYHFPGSA-N 0.000 claims description 2
- 125000004303 thiolan-2-yl group Chemical group [H]C1([H])SC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000006482 3-iodobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(I)=C1[H])C([H])([H])* 0.000 claims 19
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims 10
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims 5
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims 4
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 3
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims 3
- IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 claims 3
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 2
- ALBYIUDWACNRRB-UHFFFAOYSA-N hexanamide Chemical compound CCCCCC(N)=O ALBYIUDWACNRRB-UHFFFAOYSA-N 0.000 claims 2
- RFWAVSLBDJSFQL-IZZNHLLZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-methoxyphenyl)methylamino]butan-2-yl]-3-phenylpropanamide Chemical compound COC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC=2C=CC=CC=2)=C1 RFWAVSLBDJSFQL-IZZNHLLZSA-N 0.000 claims 2
- AQOMFTROEFZAJP-RRPNLBNLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2,3-dioxo-4-pentylpiperazin-1-yl)acetamide Chemical compound O=C1C(=O)N(CCCCC)CCN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 AQOMFTROEFZAJP-RRPNLBNLSA-N 0.000 claims 2
- WQDNVQDPJXNWOF-XAGDYJCDSA-N (2r)-1-acetyl-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-phenylpyrrolidine-2-carboxamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)[C@]2(N(CCC2)C(C)=O)C=2C=CC=CC=2)=C1 WQDNVQDPJXNWOF-XAGDYJCDSA-N 0.000 claims 1
- IEPRDSVSOZHXMV-AOLGGSBGSA-N (2r)-2-(4-butyl-3-oxopiperazin-1-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]propanamide Chemical compound C1C(=O)N(CCCC)CCN1[C@H](C)C(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 IEPRDSVSOZHXMV-AOLGGSBGSA-N 0.000 claims 1
- QOZBACZSRVCTQQ-SSBOKUKZSA-N (2r)-n-acetyl-2-amino-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-phenylpropanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)N(C(C)=O)C(=O)[C@H](N)CC=2C=CC=CC=2)=C1 QOZBACZSRVCTQQ-SSBOKUKZSA-N 0.000 claims 1
- KTSSLTMWODXCNS-RWSKJCERSA-N (2s)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-methylsulfanyl-2-(4-propoxypiperidin-1-yl)butanamide Chemical compound C1CC(OCCC)CCN1[C@@H](CCSC)C(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 KTSSLTMWODXCNS-RWSKJCERSA-N 0.000 claims 1
- KFCAOUOFJWGASP-YTCPBCGMSA-N (2s)-n-acetyl-2-amino-3-(4-chlorophenyl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)N(C(C)=O)C(=O)[C@@H](N)CC=2C=CC(Cl)=CC=2)=C1 KFCAOUOFJWGASP-YTCPBCGMSA-N 0.000 claims 1
- NDZQZKYFRVOIMS-WKFRDEQSSA-N (z)-n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-phenyl-3-pyridin-4-ylprop-2-enamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)C(=C/C=1C=CN=CC=1)\C=1C=CC=CC=1)NCC1=CC=CC(I)=C1 NDZQZKYFRVOIMS-WKFRDEQSSA-N 0.000 claims 1
- KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 claims 1
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 claims 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- LTCDDKSLFGVWJY-RRPNLBNLSA-N 2-(1-benzofuran-2-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-methylpropanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(C)(C)C=2OC3=CC=CC=C3C=2)=C1 LTCDDKSLFGVWJY-RRPNLBNLSA-N 0.000 claims 1
- MOKKLECACKPZQL-RRPNLBNLSA-N 2-(1-benzothiophen-4-yl)-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(=O)CC=2C=3C=CSC=3C=CC=2)=C1 MOKKLECACKPZQL-RRPNLBNLSA-N 0.000 claims 1
- QBDLNXUVTUKURZ-BJKOFHAPSA-N 2-(2-acetamido-1,3-thiazol-4-yl)-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(=O)CC=2N=C(NC(C)=O)SC=2)=C1 QBDLNXUVTUKURZ-BJKOFHAPSA-N 0.000 claims 1
- OBYHCHFCLNBFNT-IZZNHLLZSA-N 2-(4-butyl-2,3-dioxopiperazin-1-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound O=C1C(=O)N(CCCC)CCN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 OBYHCHFCLNBFNT-IZZNHLLZSA-N 0.000 claims 1
- FIRXDYIBVYNHAD-GAGJGVLVSA-N 2-(4-butyl-2,3-dioxopiperazin-1-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[[1-(3-ethylphenyl)cyclopropyl]amino]-3-hydroxybutan-2-yl]hexanamide Chemical compound N([C@@H](CC=1C=C(F)C=C(F)C=1)[C@H](O)CNC1(CC1)C=1C=C(CC)C=CC=1)C(=O)C(CCCC)N1CCN(CCCC)C(=O)C1=O FIRXDYIBVYNHAD-GAGJGVLVSA-N 0.000 claims 1
- BRNVVTQLBLHFIT-LOSJGSFVSA-N 2-(4-butyl-3-oxopiperazin-1-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)CCN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 BRNVVTQLBLHFIT-LOSJGSFVSA-N 0.000 claims 1
- VQJSTAQRTDOGCN-BJKOFHAPSA-N 2-(4-chloro-2-oxo-1,3-benzothiazol-3-yl)-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(=O)CN2C(SC3=CC=CC(Cl)=C32)=O)=C1 VQJSTAQRTDOGCN-BJKOFHAPSA-N 0.000 claims 1
- OBVAGCRIYNEYNZ-LOSJGSFVSA-N 2-(5-acetylthiophen-2-yl)-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(=O)CC=2SC(=CC=2)C(C)=O)=C1 OBVAGCRIYNEYNZ-LOSJGSFVSA-N 0.000 claims 1
- SJIHWBBEBNVBPY-BQLUWKOISA-N 2-(benzotriazol-1-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]hexanamide Chemical compound C([C@H](NC(=O)C(CCCC)N1C2=CC=CC=C2N=N1)[C@H](O)CNCC=1C=C(CC)C=CC=1)C1=CC(F)=CC(F)=C1 SJIHWBBEBNVBPY-BQLUWKOISA-N 0.000 claims 1
- YUSOMNGIKJYEGL-RSTHSURTSA-N 2-(benzotriazol-2-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]butanamide Chemical compound C([C@H](NC(=O)C(CC)N1N=C2C=CC=CC2=N1)[C@H](O)CNCC=1C=C(CC)C=CC=1)C1=CC(F)=CC(F)=C1 YUSOMNGIKJYEGL-RSTHSURTSA-N 0.000 claims 1
- RPVWQRLFQRCIPW-JIMJEQGWSA-N 2-[(3r)-3,4-diethyl-2,5-dioxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound O=C1[C@@H](CC)N(CC)C(=O)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 RPVWQRLFQRCIPW-JIMJEQGWSA-N 0.000 claims 1
- DHRJYJDKVWUEFM-DSNGMDLFSA-N 2-[(3r)-3,4-diethyl-5-oxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]acetamide Chemical compound C1C(=O)N(CC)[C@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 DHRJYJDKVWUEFM-DSNGMDLFSA-N 0.000 claims 1
- MXADDKSADWWTNP-WTNLLYQRSA-N 2-[(3r)-4-butyl-2,5-dioxo-3-propan-2-ylpiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)[C@H](C(C)C)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 MXADDKSADWWTNP-WTNLLYQRSA-N 0.000 claims 1
- BBKUBZNJZWLIFO-UPRLRBBYSA-N 2-[(3r)-4-butyl-3-ethyl-2,5-dioxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)[C@H](CC)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 BBKUBZNJZWLIFO-UPRLRBBYSA-N 0.000 claims 1
- QLBBYTXBMZODSJ-KWXIBIRDSA-N 2-[(3r)-4-butyl-3-ethyl-5-oxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)[C@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 QLBBYTXBMZODSJ-KWXIBIRDSA-N 0.000 claims 1
- OQLLJGJKJCEWSX-JAMKYWPSSA-N 2-[(3r)-4-butyl-3-methyl-2,5-dioxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)[C@H](C)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 OQLLJGJKJCEWSX-JAMKYWPSSA-N 0.000 claims 1
- HPXWBWXFUWJXTE-JSRBVGTNSA-N 2-[(3r)-4-butyl-3-methyl-5-oxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)[C@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 HPXWBWXFUWJXTE-JSRBVGTNSA-N 0.000 claims 1
- RPVWQRLFQRCIPW-KKUQBAQOSA-N 2-[(3s)-3,4-diethyl-2,5-dioxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound O=C1[C@H](CC)N(CC)C(=O)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 RPVWQRLFQRCIPW-KKUQBAQOSA-N 0.000 claims 1
- DHRJYJDKVWUEFM-CCDWMCETSA-N 2-[(3s)-3,4-diethyl-5-oxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]acetamide Chemical compound C1C(=O)N(CC)[C@@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 DHRJYJDKVWUEFM-CCDWMCETSA-N 0.000 claims 1
- MXADDKSADWWTNP-QXIHQKPUSA-N 2-[(3s)-4-butyl-2,5-dioxo-3-propan-2-ylpiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)[C@@H](C(C)C)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 MXADDKSADWWTNP-QXIHQKPUSA-N 0.000 claims 1
- BBKUBZNJZWLIFO-HZFUHODCSA-N 2-[(3s)-4-butyl-3-ethyl-2,5-dioxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)[C@@H](CC)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 BBKUBZNJZWLIFO-HZFUHODCSA-N 0.000 claims 1
- QLBBYTXBMZODSJ-GMQQYTKMSA-N 2-[(3s)-4-butyl-3-ethyl-5-oxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)[C@@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 QLBBYTXBMZODSJ-GMQQYTKMSA-N 0.000 claims 1
- OQLLJGJKJCEWSX-SQMFLSJESA-N 2-[(3s)-4-butyl-3-methyl-2,5-dioxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)[C@@H](C)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 OQLLJGJKJCEWSX-SQMFLSJESA-N 0.000 claims 1
- HPXWBWXFUWJXTE-RRWZXMNXSA-N 2-[(3s)-4-butyl-3-methyl-5-oxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)[C@@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 HPXWBWXFUWJXTE-RRWZXMNXSA-N 0.000 claims 1
- HOPWPVZGRUXMMN-OZNIXHKMSA-N 2-[(5R)-4-butyl-5-ethyl-2,3-dioxopiperazin-1-yl]-N-[(2S,3R)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound C(CCC)N1C(C(N(C[C@H]1CC)CC(=O)N[C@H]([C@@H](CNCC1=CC(=CC=C1)CC)O)CC1=CC(=CC(=C1)F)F)=O)=O HOPWPVZGRUXMMN-OZNIXHKMSA-N 0.000 claims 1
- QHGSSYNRNOHEJF-UODIDJSMSA-N 2-[(5r)-4,5-diethyl-2,3-dioxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound O=C1C(=O)N(CC)[C@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 QHGSSYNRNOHEJF-UODIDJSMSA-N 0.000 claims 1
- PMIIMSZALCGEDS-YTCPBCGMSA-N 2-[(5r)-4-butyl-2,3-dioxo-5-propan-2-ylpiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound O=C1C(=O)N(CCCC)[C@H](C(C)C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 PMIIMSZALCGEDS-YTCPBCGMSA-N 0.000 claims 1
- VLMVXXGBXNECKS-HZFUHODCSA-N 2-[(5r)-4-butyl-3-oxo-5-propan-2-ylpiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)[C@H](C(C)C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 VLMVXXGBXNECKS-HZFUHODCSA-N 0.000 claims 1
- WXIRLNYZWMRTLO-JAMKYWPSSA-N 2-[(5r)-4-butyl-5-methyl-2,3-dioxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound O=C1C(=O)N(CCCC)[C@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 WXIRLNYZWMRTLO-JAMKYWPSSA-N 0.000 claims 1
- QHGSSYNRNOHEJF-KKUQBAQOSA-N 2-[(5s)-4,5-diethyl-2,3-dioxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound O=C1C(=O)N(CC)[C@@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 QHGSSYNRNOHEJF-KKUQBAQOSA-N 0.000 claims 1
- PMIIMSZALCGEDS-ZGIBFIJWSA-N 2-[(5s)-4-butyl-2,3-dioxo-5-propan-2-ylpiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound O=C1C(=O)N(CCCC)[C@@H](C(C)C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 PMIIMSZALCGEDS-ZGIBFIJWSA-N 0.000 claims 1
- HOPWPVZGRUXMMN-HZFUHODCSA-N 2-[(5s)-4-butyl-5-ethyl-2,3-dioxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound O=C1C(=O)N(CCCC)[C@@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 HOPWPVZGRUXMMN-HZFUHODCSA-N 0.000 claims 1
- WXIRLNYZWMRTLO-SQMFLSJESA-N 2-[(5s)-4-butyl-5-methyl-2,3-dioxopiperazin-1-yl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound O=C1C(=O)N(CCCC)[C@@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 WXIRLNYZWMRTLO-SQMFLSJESA-N 0.000 claims 1
- CXIHQTCBRLEZSS-LOSJGSFVSA-N 2-[3-(2-amino-2-oxoethoxy)phenyl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]acetamide Chemical compound NC(=O)COC1=CC=CC(CC(=O)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@H](O)CNCC=2C=C(I)C=CC=2)=C1 CXIHQTCBRLEZSS-LOSJGSFVSA-N 0.000 claims 1
- IFUGLFUNJBEMAB-XXXHFSMGSA-N 2-[3-chloro-4-(3-oxo-1h-isoindol-2-yl)phenyl]-n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]propanamide Chemical compound C([C@H](NC(=O)C(C)C=1C=C(Cl)C(N2C(C3=CC=CC=C3C2)=O)=CC=1)[C@H](O)CNCC=1C=C(I)C=CC=1)C1=CC(F)=CC(F)=C1 IFUGLFUNJBEMAB-XXXHFSMGSA-N 0.000 claims 1
- FZODZTKZGASQOW-XDFJSJKPSA-N 2-[4-[4-[[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]amino]-4-oxobutanoyl]phenyl]benzamide Chemical compound NC(=O)C1=CC=CC=C1C1=CC=C(C(=O)CCC(=O)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@H](O)CNCC=2C=C(I)C=CC=2)C=C1 FZODZTKZGASQOW-XDFJSJKPSA-N 0.000 claims 1
- VLEDWVDVEUMKNR-LOSJGSFVSA-N 2-[5-(1,3-benzodioxol-5-yl)tetrazol-2-yl]-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(=O)CN2N=C(N=N2)C=2C=C3OCOC3=CC=2)=C1 VLEDWVDVEUMKNR-LOSJGSFVSA-N 0.000 claims 1
- BKMFUDSBPLDSOL-WRTWKEETSA-N 2-acetamido-2-(benzotriazol-1-yl)-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(=O)C(NC(C)=O)N2C3=CC=CC=C3N=N2)=C1 BKMFUDSBPLDSOL-WRTWKEETSA-N 0.000 claims 1
- GCENEARYFCUEGK-MOCYAETESA-N 2-cyano-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-(3,4-dimethoxyphenyl)-2-methylpropanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(C)(CC=2C=C(OC)C(OC)=CC=2)C#N)=C1 GCENEARYFCUEGK-MOCYAETESA-N 0.000 claims 1
- FKCQILINHLDHMQ-IZZNHLLZSA-N 3-(1,3-benzodioxol-5-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC=2C=C3OCOC3=CC=2)=C1 FKCQILINHLDHMQ-IZZNHLLZSA-N 0.000 claims 1
- UYUUTMCICWHWHB-AJRFNQODSA-N 3-(1,3-benzothiazol-2-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-methoxypropanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC(OC)C=2SC3=CC=CC=C3N=2)=C1 UYUUTMCICWHWHB-AJRFNQODSA-N 0.000 claims 1
- RNQDSZOHFGNXEA-WUFINQPMSA-N 3-(1-butylpyrazol-4-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]propanamide Chemical compound C1=NN(CCCC)C=C1CCC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 RNQDSZOHFGNXEA-WUFINQPMSA-N 0.000 claims 1
- RNKQDQDVKDPTTI-DRXLFZDCSA-N 3-(1h-benzimidazol-2-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-hydroxypropanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC(O)C=2NC3=CC=CC=C3N=2)=C1 RNKQDQDVKDPTTI-DRXLFZDCSA-N 0.000 claims 1
- DFRJLXSYWSJKNJ-WHWDJVTISA-N 3-(2-chlorophenyl)-2-cyano-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(CC=2C(=CC=CC=2)Cl)C#N)=C1 DFRJLXSYWSJKNJ-WHWDJVTISA-N 0.000 claims 1
- PKGSVCWQUGQZCA-XZOQPEGZSA-N 3-(3-chloro-1,2-oxazol-5-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC=2ON=C(Cl)C=2)=C1 PKGSVCWQUGQZCA-XZOQPEGZSA-N 0.000 claims 1
- 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 claims 1
- OZJBYRRHACYIRW-RRPNLBNLSA-N 4-(1,3-benzodioxol-5-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]butanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCCC=2C=C3OCOC3=CC=2)=C1 OZJBYRRHACYIRW-RRPNLBNLSA-N 0.000 claims 1
- WYPIGFFEZOVUPD-RRPNLBNLSA-N 4-(1,3-benzothiazol-2-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]butanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCCC=2SC3=CC=CC=C3N=2)=C1 WYPIGFFEZOVUPD-RRPNLBNLSA-N 0.000 claims 1
- WNUFDZQVOLLKLC-XTEPFMGCSA-N 4-(1-benzofuran-2-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2OC3=CC=CC=C3C=2)=C1 WNUFDZQVOLLKLC-XTEPFMGCSA-N 0.000 claims 1
- QWZXPCIONIFHNI-XDFJSJKPSA-N 4-(2-acetamido-4,5-dimethylphenyl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C(=CC(C)=C(C)C=2)NC(C)=O)=C1 QWZXPCIONIFHNI-XDFJSJKPSA-N 0.000 claims 1
- OQYRVFRMLUMPCM-XTEPFMGCSA-N 4-(3,4-dichlorophenyl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=C(Cl)C(Cl)=CC=2)=C1 OQYRVFRMLUMPCM-XTEPFMGCSA-N 0.000 claims 1
- NSMQRJGPEKNTSK-XTEPFMGCSA-N 4-(3,4-difluorophenyl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=C(F)C(F)=CC=2)=C1 NSMQRJGPEKNTSK-XTEPFMGCSA-N 0.000 claims 1
- HUEHQNWQCXQHMM-LBNVMWSVSA-N 4-(4-chloro-2-hydroxyphenyl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C(=CC(Cl)=CC=2)O)=C1 HUEHQNWQCXQHMM-LBNVMWSVSA-N 0.000 claims 1
- WBMBKJDJBKFAFT-AHKZPQOWSA-N 4-(4-fluorophenyl)-n-[(2s,3r)-3-hydroxy-4-[(3-methoxyphenyl)methylamino]-1-phenylbutan-2-yl]-4-oxobutanamide Chemical compound COC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)CCC(=O)C=2C=CC(F)=CC=2)=C1 WBMBKJDJBKFAFT-AHKZPQOWSA-N 0.000 claims 1
- FLOSOFQGVKXMDG-XDFJSJKPSA-N 4-dibenzofuran-2-yl-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=C3C4=CC=CC=C4OC3=CC=2)=C1 FLOSOFQGVKXMDG-XDFJSJKPSA-N 0.000 claims 1
- OWVUOGHUVNAIJY-XZOQPEGZSA-N CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2N3C(O)=CC(C)=NC3=NN=2)=C1 Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2N3C(O)=CC(C)=NC3=NN=2)=C1 OWVUOGHUVNAIJY-XZOQPEGZSA-N 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
- OISLXOJXWGOOOW-PRIWKQAOSA-N n'-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-phenyl-n,n-dipropylpentanediamide Chemical compound C([C@H](NC(=O)CCC(C(=O)N(CCC)CCC)C=1C=CC=CC=1)[C@H](O)CNCC=1C=C(CC)C=CC=1)C1=CC(F)=CC(F)=C1 OISLXOJXWGOOOW-PRIWKQAOSA-N 0.000 claims 1
- PHAUHNUYRBTKOI-DLUPVDQLSA-N n-[(2r,3s)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)methyl]-3-heptan-4-ylsulfonylpropanamide Chemical compound N([C@H](CC=1C=C(F)C=C(F)C=1)[C@@H](O)CNCC=1C=C(CC)C=CC=1)C(=O)C(CS(=O)(=O)C(CCC)CCC)CN1C(=O)NC(C)(C)C1=O PHAUHNUYRBTKOI-DLUPVDQLSA-N 0.000 claims 1
- ARTFSXVGODRDSA-HHBYWCROSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-(1-hydroxypropan-2-ylamino)butan-2-yl]-2-(4-propan-2-ylphenyl)acetamide Chemical compound C1=CC(C(C)C)=CC=C1CC(=O)N[C@H]([C@H](O)CNC(C)CO)CC1=CC(F)=CC(F)=C1 ARTFSXVGODRDSA-HHBYWCROSA-N 0.000 claims 1
- PLQKRXRETFVIJX-JDGCJKAJSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-(1-hydroxypropan-2-ylamino)butan-2-yl]-3-phenylpropanamide Chemical compound C([C@@H]([C@H](O)CNC(CO)C)NC(=O)CCC=1C=CC=CC=1)C1=CC(F)=CC(F)=C1 PLQKRXRETFVIJX-JDGCJKAJSA-N 0.000 claims 1
- WTSRRGSQONPYOD-FDPJYKKHSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-(1-methoxypropan-2-ylamino)butan-2-yl]-2-(4-propan-2-ylphenyl)acetamide Chemical compound C([C@@H]([C@H](O)CNC(C)COC)NC(=O)CC=1C=CC(=CC=1)C(C)C)C1=CC(F)=CC(F)=C1 WTSRRGSQONPYOD-FDPJYKKHSA-N 0.000 claims 1
- HGVHOLBOZMEBNG-APFNHRKESA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-(1-methoxypropan-2-ylamino)butan-2-yl]-3-phenylpropanamide Chemical compound C([C@@H]([C@H](O)CNC(C)COC)NC(=O)CCC=1C=CC=CC=1)C1=CC(F)=CC(F)=C1 HGVHOLBOZMEBNG-APFNHRKESA-N 0.000 claims 1
- ZQSGLTYFOOCRCH-BJKOFHAPSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-(pyridin-2-ylmethylamino)butan-2-yl]-3-phenylpropanamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CCC=1C=CC=CC=1)NCC1=CC=CC=N1 ZQSGLTYFOOCRCH-BJKOFHAPSA-N 0.000 claims 1
- JLPNDKJVRNVSGW-CVWZLOPKSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-(2,3-dihydro-1h-inden-5-yl)butanamide Chemical compound C([C@H](NC(=O)C(CC)C=1C=C2CCCC2=CC=1)[C@H](O)CNCC=1C=C(I)C=CC=1)C1=CC(F)=CC(F)=C1 JLPNDKJVRNVSGW-CVWZLOPKSA-N 0.000 claims 1
- RQLLSPSNAXUKMO-LEWJYISDSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-(3-oxopiperazin-1-yl)acetamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CN1CC(=O)NCC1)NCC1=CC=CC(I)=C1 RQLLSPSNAXUKMO-LEWJYISDSA-N 0.000 claims 1
- WZRKCTPYVDYNLX-LOSJGSFVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-(4-methylsulfanylphenyl)acetamide Chemical compound C1=CC(SC)=CC=C1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 WZRKCTPYVDYNLX-LOSJGSFVSA-N 0.000 claims 1
- SJUUTWAZEJUFTH-XZWHSSHBSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-(4-phenoxyphenyl)acetamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CC=1C=CC(OC=2C=CC=CC=2)=CC=1)NCC1=CC=CC(I)=C1 SJUUTWAZEJUFTH-XZWHSSHBSA-N 0.000 claims 1
- XBKRCJHAKNCOHP-IOWSJCHKSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-(4-phenylmethoxyphenyl)acetamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CC=1C=CC(OCC=2C=CC=CC=2)=CC=1)NCC1=CC=CC(I)=C1 XBKRCJHAKNCOHP-IOWSJCHKSA-N 0.000 claims 1
- ZHHKYYANBXCRNG-RRPNLBNLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-(4-propan-2-ylphenyl)acetamide Chemical compound C1=CC(C(C)C)=CC=C1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 ZHHKYYANBXCRNG-RRPNLBNLSA-N 0.000 claims 1
- ZVKJPZBBDLYMQI-GDRMZMBQSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-(methanesulfonamido)-4-phenylbutanamide Chemical compound N([C@@H](CC=1C=C(F)C=C(F)C=1)[C@H](O)CNCC=1C=C(I)C=CC=1)C(=O)C(NS(=O)(=O)C)CCC1=CC=CC=C1 ZVKJPZBBDLYMQI-GDRMZMBQSA-N 0.000 claims 1
- TYEDPIIPMBHUFW-UZFJHSOTSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[(3r)-3,4-dimethyl-5-oxopiperazin-1-yl]acetamide Chemical compound C1C(=O)N(C)[C@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 TYEDPIIPMBHUFW-UZFJHSOTSA-N 0.000 claims 1
- LSMRBEZWZKWOLK-TZRRMPRUSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[(3r)-3-ethyl-4-methyl-5-oxopiperazin-1-yl]acetamide Chemical compound C1C(=O)N(C)[C@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 LSMRBEZWZKWOLK-TZRRMPRUSA-N 0.000 claims 1
- YPPODLPAFBBCFH-UODIDJSMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[(3r)-3-ethyl-5-oxo-4-propylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CCC)[C@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 YPPODLPAFBBCFH-UODIDJSMSA-N 0.000 claims 1
- NPZRULVAHNYGJG-AYCKEJKLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[(3r)-3-methyl-5-oxo-4-propylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CCC)[C@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 NPZRULVAHNYGJG-AYCKEJKLSA-N 0.000 claims 1
- OHBMNKFENUHQLL-GAZXMLTASA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[(3r)-4-ethyl-3-methyl-5-oxopiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CC)[C@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 OHBMNKFENUHQLL-GAZXMLTASA-N 0.000 claims 1
- TYEDPIIPMBHUFW-IRBZQWRBSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[(3s)-3,4-dimethyl-5-oxopiperazin-1-yl]acetamide Chemical compound C1C(=O)N(C)[C@@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 TYEDPIIPMBHUFW-IRBZQWRBSA-N 0.000 claims 1
- LSMRBEZWZKWOLK-KMDXXIMOSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[(3s)-3-ethyl-4-methyl-5-oxopiperazin-1-yl]acetamide Chemical compound C1C(=O)N(C)[C@@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 LSMRBEZWZKWOLK-KMDXXIMOSA-N 0.000 claims 1
- YPPODLPAFBBCFH-KKUQBAQOSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[(3s)-3-ethyl-5-oxo-4-propylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CCC)[C@@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 YPPODLPAFBBCFH-KKUQBAQOSA-N 0.000 claims 1
- NPZRULVAHNYGJG-RIEVBORMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[(3s)-3-methyl-5-oxo-4-propylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CCC)[C@@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 NPZRULVAHNYGJG-RIEVBORMSA-N 0.000 claims 1
- OHBMNKFENUHQLL-YRUKQIKQSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[(3s)-4-ethyl-3-methyl-5-oxopiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CC)[C@@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 OHBMNKFENUHQLL-YRUKQIKQSA-N 0.000 claims 1
- AYYNJRCVLREOTD-GMQQYTKMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[(5r)-3-oxo-5-propan-2-yl-4-propylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CCC)[C@H](C(C)C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 AYYNJRCVLREOTD-GMQQYTKMSA-N 0.000 claims 1
- AYYNJRCVLREOTD-OYUWMTPXSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[(5s)-3-oxo-5-propan-2-yl-4-propylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CCC)[C@@H](C(C)C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 AYYNJRCVLREOTD-OYUWMTPXSA-N 0.000 claims 1
- IKGWFOIXTIABFI-XZAYMCHPSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[4-(2-methylprop-1-enyl)phenyl]propanamide Chemical compound C([C@H](NC(=O)C(C)C=1C=CC(C=C(C)C)=CC=1)[C@H](O)CNCC=1C=C(I)C=CC=1)C1=CC(F)=CC(F)=C1 IKGWFOIXTIABFI-XZAYMCHPSA-N 0.000 claims 1
- BTIJDXJWYKCWPF-RRPNLBNLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-[4-(2-oxopyrrolidin-1-yl)phenyl]acetamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CC=1C=CC(=CC=1)N1C(CCC1)=O)NCC1=CC=CC(I)=C1 BTIJDXJWYKCWPF-RRPNLBNLSA-N 0.000 claims 1
- PALLVNHTXBJCSB-TZFXDJNOSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-2-methyl-2-(2-methyl-2,3-dihydro-1-benzofuran-5-yl)propanamide Chemical compound C([C@H](NC(=O)C(C)(C)C=1C=C2CC(OC2=CC=1)C)[C@H](O)CNCC=1C=C(I)C=CC=1)C1=CC(F)=CC(F)=C1 PALLVNHTXBJCSB-TZFXDJNOSA-N 0.000 claims 1
- DVFOCBNDKACSBJ-JHOUSYSJSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-3-(2,4-dimethyl-6-phenylmethoxyphenyl)-3-methylbutanamide Chemical compound C=1C(C)=CC(C)=C(C(C)(C)CC(=O)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@H](O)CNCC=2C=C(I)C=CC=2)C=1OCC1=CC=CC=C1 DVFOCBNDKACSBJ-JHOUSYSJSA-N 0.000 claims 1
- YOSOGSJKLGVLJG-LOSJGSFVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-3-(2-fluorophenyl)propanamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CCC=1C(=CC=CC=1)F)NCC1=CC=CC(I)=C1 YOSOGSJKLGVLJG-LOSJGSFVSA-N 0.000 claims 1
- JBLLBGNAPMWKPP-BCAKTTGJSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-3-hydroxy-4-phenoxy-3-phenylbutanamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CC(O)(COC=1C=CC=CC=1)C=1C=CC=CC=1)NCC1=CC=CC(I)=C1 JBLLBGNAPMWKPP-BCAKTTGJSA-N 0.000 claims 1
- UGRCWIQGBBEJSG-AHKZPQOWSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-3-indol-1-ylpropanamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CCN1C2=CC=CC=C2C=C1)NCC1=CC=CC(I)=C1 UGRCWIQGBBEJSG-AHKZPQOWSA-N 0.000 claims 1
- FQUGLJSHBZNRQC-DBUNYZNWSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-4-(2,3-dihydro-1h-inden-1-yl)butanamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CCCC1C2=CC=CC=C2CC1)NCC1=CC=CC(I)=C1 FQUGLJSHBZNRQC-DBUNYZNWSA-N 0.000 claims 1
- ITTKGCQWUMMLLR-XTEPFMGCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-4-(2,4-dimethylphenyl)-4-oxobutanamide Chemical compound CC1=CC(C)=CC=C1C(=O)CCC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 ITTKGCQWUMMLLR-XTEPFMGCSA-N 0.000 claims 1
- MTUNROCUZGDWMJ-AJQTZOPKSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-4-(4-phenoxyphenyl)butanamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CCCC=1C=CC(OC=2C=CC=CC=2)=CC=1)NCC1=CC=CC(I)=C1 MTUNROCUZGDWMJ-AJQTZOPKSA-N 0.000 claims 1
- QPLCPIMRAGTYCF-AHKZPQOWSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-4-(7-methoxy-2,3-dihydro-1-benzofuran-4-yl)-4-oxobutanamide Chemical compound C([C@H](NC(=O)CCC(=O)C1=CC=C(C=2OCCC=21)OC)[C@H](O)CNCC=1C=C(I)C=CC=1)C1=CC(F)=CC(F)=C1 QPLCPIMRAGTYCF-AHKZPQOWSA-N 0.000 claims 1
- LYBLLYKEKGIKIT-AHKZPQOWSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-4-[2-(methanesulfonamido)phenyl]-4-oxobutanamide Chemical compound CS(=O)(=O)NC1=CC=CC=C1C(=O)CCC(=O)N[C@H]([C@H](O)CNCC=1C=C(I)C=CC=1)CC1=CC(F)=CC(F)=C1 LYBLLYKEKGIKIT-AHKZPQOWSA-N 0.000 claims 1
- KNVKHVDEAVTNTK-UKILVPOCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-iodophenyl)methylamino]butan-2-yl]-4-oxo-4-pyridin-2-ylbutanamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CCC(=O)C=1N=CC=CC=1)NCC1=CC=CC(I)=C1 KNVKHVDEAVTNTK-UKILVPOCSA-N 0.000 claims 1
- SCCVOJLPXVZYIP-IZZNHLLZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-methoxyphenyl)methylamino]butan-2-yl]-2-(4-methylsulfanylphenyl)acetamide Chemical compound COC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=CC(SC)=CC=2)=C1 SCCVOJLPXVZYIP-IZZNHLLZSA-N 0.000 claims 1
- XDCNNAPXXIWTJD-WUFINQPMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(3-methoxyphenyl)methylamino]butan-2-yl]-2-(4-propan-2-ylphenyl)acetamide Chemical compound COC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=CC(=CC=2)C(C)C)=C1 XDCNNAPXXIWTJD-WUFINQPMSA-N 0.000 claims 1
- UYAYNWPWMNAGQG-IZZNHLLZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(4-methylphenyl)methylamino]butan-2-yl]-2-(4-methylsulfanylphenyl)acetamide Chemical compound C1=CC(SC)=CC=C1CC(=O)N[C@H]([C@H](O)CNCC=1C=CC(C)=CC=1)CC1=CC(F)=CC(F)=C1 UYAYNWPWMNAGQG-IZZNHLLZSA-N 0.000 claims 1
- WINXDERVYAISEF-WUFINQPMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(4-methylphenyl)methylamino]butan-2-yl]-2-(4-propan-2-ylphenyl)acetamide Chemical compound C1=CC(C(C)C)=CC=C1CC(=O)N[C@H]([C@H](O)CNCC=1C=CC(C)=CC=1)CC1=CC(F)=CC(F)=C1 WINXDERVYAISEF-WUFINQPMSA-N 0.000 claims 1
- OBKWKDOSZPDMPO-XZOQPEGZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-(furan-2-ylmethylamino)-3-hydroxybutan-2-yl]-2-(4-methylsulfanylphenyl)acetamide Chemical compound C1=CC(SC)=CC=C1CC(=O)N[C@H]([C@H](O)CNCC=1OC=CC=1)CC1=CC(F)=CC(F)=C1 OBKWKDOSZPDMPO-XZOQPEGZSA-N 0.000 claims 1
- XSPGXIOIRKSJOT-UKILVPOCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-(furan-2-ylmethylamino)-3-hydroxybutan-2-yl]-3-indol-1-ylpropanamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CCN1C2=CC=CC=C2C=C1)NCC1=CC=CO1 XSPGXIOIRKSJOT-UKILVPOCSA-N 0.000 claims 1
- PXLACKIHLRDIAY-XZOQPEGZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-(furan-2-ylmethylamino)-3-hydroxybutan-2-yl]-3-phenylpropanamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CCC=1C=CC=CC=1)NCC1=CC=CO1 PXLACKIHLRDIAY-XZOQPEGZSA-N 0.000 claims 1
- NRZNQAWMOQTISO-ZJWHSJSFSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(1,1-dioxothiolan-3-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC2CS(=O)(=O)CC2)=C1 NRZNQAWMOQTISO-ZJWHSJSFSA-N 0.000 claims 1
- CFUYAJOVIXQVOS-XZOQPEGZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(1,3-dimethyl-2,6-dioxopurin-7-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C=3C(=O)N(C)C(=O)N(C)C=3N=C2)=C1 CFUYAJOVIXQVOS-XZOQPEGZSA-N 0.000 claims 1
- GJTDUMXWQOUDQU-XZOQPEGZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(1,3-dimethyl-2,6-dioxopurin-9-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C3=C(C(N(C)C(=O)N3C)=O)N=C2)=C1 GJTDUMXWQOUDQU-XZOQPEGZSA-N 0.000 claims 1
- WMUOBGVYRUCCAL-YOFGRZFMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(1,3-dioxo-3a,4,5,6,7,7a-hexahydroisoindol-2-yl)butanamide Chemical compound C([C@H](NC(=O)C(N1C(C2CCCCC2C1=O)=O)CC)[C@H](O)CNCC=1C=C(CC)C=CC=1)C1=CC(F)=CC(F)=C1 WMUOBGVYRUCCAL-YOFGRZFMSA-N 0.000 claims 1
- XHNJOEJSLLGVRL-IZZNHLLZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(1,3-dioxoisoindol-2-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C(C3=CC=CC=C3C2=O)=O)=C1 XHNJOEJSLLGVRL-IZZNHLLZSA-N 0.000 claims 1
- RDOBZCWUKSKYAS-TZFXDJNOSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(1,3-dioxoisoindol-2-yl)propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(C)N2C(C3=CC=CC=C3C2=O)=O)=C1 RDOBZCWUKSKYAS-TZFXDJNOSA-N 0.000 claims 1
- WYFGDROVXJZPEC-LITSAYRRSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(1-methyl-3-methylsulfanylindol-2-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2N(C3=CC=CC=C3C=2SC)C)=C1 WYFGDROVXJZPEC-LITSAYRRSA-N 0.000 claims 1
- FVNCPDKYZJCTHO-XTEPFMGCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(1-methylindol-3-yl)-2-oxoacetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(=O)C=2C3=CC=CC=C3N(C)C=2)=C1 FVNCPDKYZJCTHO-XTEPFMGCSA-N 0.000 claims 1
- JKRSICNSCDWVLU-LOSJGSFVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2,3-dioxo-4-propylpiperazin-1-yl)acetamide Chemical compound O=C1C(=O)N(CCC)CCN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 JKRSICNSCDWVLU-LOSJGSFVSA-N 0.000 claims 1
- JACZKYBYOOQOML-FCHUYYIVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2,4-dioxo-1h-pyrimidin-6-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2N=C(O)N=C(O)C=2)=C1 JACZKYBYOOQOML-FCHUYYIVSA-N 0.000 claims 1
- DQCGJOLDCRLHOF-RRPNLBNLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2,5-dioxo-4-pentylpiperazin-1-yl)acetamide Chemical compound C1C(=O)N(CCCCC)CC(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 DQCGJOLDCRLHOF-RRPNLBNLSA-N 0.000 claims 1
- YGPZWTSPKJOALP-LOSJGSFVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2,5-dioxo-4-propylpiperazin-1-yl)acetamide Chemical compound C1C(=O)N(CCC)CC(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 YGPZWTSPKJOALP-LOSJGSFVSA-N 0.000 claims 1
- NWWOODNWRARERN-LBNVMWSVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2-ethyl-[1,2,4]triazolo[1,5-a]benzimidazol-4-yl)acetamide Chemical compound C([C@H](NC(=O)CN1C2=NC(=NN2C2=CC=CC=C21)CC)[C@H](O)CNCC=1C=C(CC)C=CC=1)C1=CC(F)=CC(F)=C1 NWWOODNWRARERN-LBNVMWSVSA-N 0.000 claims 1
- VHZYVVNENHOXGE-AHKZPQOWSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2-methyl-1,3-benzoxazol-5-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=C3N=C(C)OC3=CC=2)=C1 VHZYVVNENHOXGE-AHKZPQOWSA-N 0.000 claims 1
- KNFLFJKHYBGAPP-ICNJSSKSSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2-methyl-2,3-dihydro-1-benzofuran-5-yl)propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(C)C=2C=C3CC(C)OC3=CC=2)=C1 KNFLFJKHYBGAPP-ICNJSSKSSA-N 0.000 claims 1
- KSMBSFXMEYQAAC-IZZNHLLZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2-oxo-1,3-dihydrobenzimidazol-5-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=C3NC(=O)NC3=CC=2)=C1 KSMBSFXMEYQAAC-IZZNHLLZSA-N 0.000 claims 1
- IBBAKECVQMEAKC-UKILVPOCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2-oxo-3h-1,3-benzoxazol-5-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=C3NC(=O)OC3=CC=2)=C1 IBBAKECVQMEAKC-UKILVPOCSA-N 0.000 claims 1
- DUIVHYZOBMKSRJ-RRPNLBNLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2-pyridin-2-yl-1,3-thiazol-4-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2N=C(SC=2)C=2N=CC=CC=2)=C1 DUIVHYZOBMKSRJ-RRPNLBNLSA-N 0.000 claims 1
- RTCQCEFDWFZCFE-MFMCTBQISA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2-pyridin-4-yl-1,3-benzoxazol-5-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=C3N=C(OC3=CC=2)C=2C=CN=CC=2)=C1 RTCQCEFDWFZCFE-MFMCTBQISA-N 0.000 claims 1
- DKDQFAMLHRVATP-UKILVPOCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2-sulfanylidene-1,3-benzothiazol-3-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C(SC3=CC=CC=C32)=S)=C1 DKDQFAMLHRVATP-UKILVPOCSA-N 0.000 claims 1
- FDMNFSOBPQKMRN-FCHUYYIVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(2-sulfanylidene-3h-1,3-thiazol-4-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2NC(=S)SC=2)=C1 FDMNFSOBPQKMRN-FCHUYYIVSA-N 0.000 claims 1
- BCOKYOAJHXWOLD-WUFINQPMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3,5-dimethoxyphenyl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=C(OC)C=C(OC)C=2)=C1 BCOKYOAJHXWOLD-WUFINQPMSA-N 0.000 claims 1
- XJROQCOXMYRLDR-RRPNLBNLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3,5-dioxo-4-pentylpiperazin-1-yl)acetamide Chemical compound C1C(=O)N(CCCCC)C(=O)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 XJROQCOXMYRLDR-RRPNLBNLSA-N 0.000 claims 1
- TVEBEURWSZHIRT-LOSJGSFVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3,5-dioxo-4-propylpiperazin-1-yl)acetamide Chemical compound C1C(=O)N(CCC)C(=O)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 TVEBEURWSZHIRT-LOSJGSFVSA-N 0.000 claims 1
- LKQQXVKYMWNGCK-WUFINQPMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3-fluoro-4-propoxyphenyl)acetamide Chemical compound C1=C(F)C(OCCC)=CC=C1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 LKQQXVKYMWNGCK-WUFINQPMSA-N 0.000 claims 1
- LDBBZIOZSFLYKQ-AZGAKELHSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3-hydroxy-4-methoxyphenyl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=C(O)C(OC)=CC=2)=C1 LDBBZIOZSFLYKQ-AZGAKELHSA-N 0.000 claims 1
- WIOUUHGMUJOWHF-AHKZPQOWSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3-hydroxy-4-methylphenyl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=C(O)C(C)=CC=2)=C1 WIOUUHGMUJOWHF-AHKZPQOWSA-N 0.000 claims 1
- IWWFLXZZVQSQDC-IZZNHLLZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3-hydroxyphenyl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=C(O)C=CC=2)=C1 IWWFLXZZVQSQDC-IZZNHLLZSA-N 0.000 claims 1
- VDCFCPBMJOWALR-WUFINQPMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3-methoxy-4-propoxyphenyl)acetamide Chemical compound C1=C(OC)C(OCCC)=CC=C1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 VDCFCPBMJOWALR-WUFINQPMSA-N 0.000 claims 1
- LUEDSVDOVGVZNE-RPLLCQBOSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3-methyl-2-oxobenzimidazol-1-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C(N(C)C3=CC=CC=C32)=O)=C1 LUEDSVDOVGVZNE-RPLLCQBOSA-N 0.000 claims 1
- VBOCKBWUABESSB-LOSJGSFVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3-oxo-1,2-benzothiazol-2-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C(C3=CC=CC=C3S2)=O)=C1 VBOCKBWUABESSB-LOSJGSFVSA-N 0.000 claims 1
- LGXWTXSFQOGLNZ-GDRMZMBQSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3-oxo-1,2-dihydroisoindol-1-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC2C3=CC=CC=C3C(=O)N2)=C1 LGXWTXSFQOGLNZ-GDRMZMBQSA-N 0.000 claims 1
- OMVCNODXOABMMW-QBJKRIGYSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3-oxocyclohexyl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC2CC(=O)CCC2)=C1 OMVCNODXOABMMW-QBJKRIGYSA-N 0.000 claims 1
- WXBAQUMUTSCVIA-XZOQPEGZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3-oxopiperazin-1-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2CC(=O)NCC2)=C1 WXBAQUMUTSCVIA-XZOQPEGZSA-N 0.000 claims 1
- ZPULBZWTBSFRCU-IZZNHLLZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(3-thiophen-2-ylpyrazol-1-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2N=C(C=C2)C=2SC=CC=2)=C1 ZPULBZWTBSFRCU-IZZNHLLZSA-N 0.000 claims 1
- MEBKPRJEFJNILX-WUFINQPMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-ethoxyphenyl)acetamide Chemical compound C1=CC(OCC)=CC=C1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 MEBKPRJEFJNILX-WUFINQPMSA-N 0.000 claims 1
- GYKQQJSPNWIPCS-BJKOFHAPSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-ethyl-2,3-dioxopiperazin-1-yl)acetamide Chemical compound O=C1C(=O)N(CC)CCN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 GYKQQJSPNWIPCS-BJKOFHAPSA-N 0.000 claims 1
- QVQAHSAKMOQSJB-BJKOFHAPSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-ethyl-2,5-dioxopiperazin-1-yl)acetamide Chemical compound C1C(=O)N(CC)CC(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 QVQAHSAKMOQSJB-BJKOFHAPSA-N 0.000 claims 1
- ONUFHWSAYXBGTB-BJKOFHAPSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-ethyl-3,5-dioxopiperazin-1-yl)acetamide Chemical compound C1C(=O)N(CC)C(=O)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 ONUFHWSAYXBGTB-BJKOFHAPSA-N 0.000 claims 1
- ITWVJEBCALXYRP-VQTJNVASSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-hydroxy-2-oxo-3h-1,3-thiazol-5-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC2=C(N=C(O)S2)O)=C1 ITWVJEBCALXYRP-VQTJNVASSA-N 0.000 claims 1
- RPVLQUMHSPLWCF-AZGAKELHSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-hydroxy-3-methoxyphenyl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=C(OC)C(O)=CC=2)=C1 RPVLQUMHSPLWCF-AZGAKELHSA-N 0.000 claims 1
- OISMKKZJDQSCBI-XZOQPEGZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-methyl-2,3-dioxopiperazin-1-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C(C(=O)N(C)CC2)=O)=C1 OISMKKZJDQSCBI-XZOQPEGZSA-N 0.000 claims 1
- NALVVDHKVYKFKB-XZOQPEGZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-methyl-2,5-dioxopiperazin-1-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C(CN(C)C(=O)C2)=O)=C1 NALVVDHKVYKFKB-XZOQPEGZSA-N 0.000 claims 1
- SEZWKZNZQNYRQY-XZOQPEGZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-methyl-3,5-dioxopiperazin-1-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2CC(=O)N(C)C(=O)C2)=C1 SEZWKZNZQNYRQY-XZOQPEGZSA-N 0.000 claims 1
- FHJJQWSEJNRHKL-XZWHSSHBSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-morpholin-4-ylphenyl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=CC(=CC=2)N2CCOCC2)=C1 FHJJQWSEJNRHKL-XZWHSSHBSA-N 0.000 claims 1
- IIWZDRJGLBOKJX-OOGWQVLDSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-pyrrol-1-ylphenyl)propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(C)C=2C=CC(=CC=2)N2C=CC=C2)=C1 IIWZDRJGLBOKJX-OOGWQVLDSA-N 0.000 claims 1
- FKWJPSJOIWZHSL-NCPLZGKYSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(5,6-dimethyl-2,4-dioxo-1h-pyridin-3-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC2C(C(C)=C(C)NC2=O)=O)=C1 FKWJPSJOIWZHSL-NCPLZGKYSA-N 0.000 claims 1
- CAYGMIXTWVXLLB-LOSJGSFVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC2=NN3C(C)=CC(C)=NC3=N2)=C1 CAYGMIXTWVXLLB-LOSJGSFVSA-N 0.000 claims 1
- QSIIAEDZEQGVQP-RRPNLBNLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(5-methyl-1,3-dioxoisoindol-2-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C(C3=CC(C)=CC=C3C2=O)=O)=C1 QSIIAEDZEQGVQP-RRPNLBNLSA-N 0.000 claims 1
- HSFGZEBBHJLDJA-LOSJGSFVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(5-pyridin-2-yltetrazol-2-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2N=C(N=N2)C=2N=CC=CC=2)=C1 HSFGZEBBHJLDJA-LOSJGSFVSA-N 0.000 claims 1
- VOPRXVDBGUFPRM-BJKOFHAPSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(5-pyrrolidin-1-yltetrazol-2-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2N=C(N=N2)N2CCCC2)=C1 VOPRXVDBGUFPRM-BJKOFHAPSA-N 0.000 claims 1
- JCONWJVBKVDXRX-URLMMPGGSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(6-oxo-3-phenylpyridazin-1-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C(C=CC(=N2)C=2C=CC=CC=2)=O)=C1 JCONWJVBKVDXRX-URLMMPGGSA-N 0.000 claims 1
- BOSOHHLSRHJGQE-PVTPYKNESA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3r)-2,5-dioxo-3-propan-2-yl-4-propylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CCC)[C@H](C(C)C)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 BOSOHHLSRHJGQE-PVTPYKNESA-N 0.000 claims 1
- VIDQAILATQWGSB-GAZXMLTASA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3r)-3,4-dimethyl-2,5-dioxopiperazin-1-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C([C@@H](C)N(C)C(=O)C2)=O)=C1 VIDQAILATQWGSB-GAZXMLTASA-N 0.000 claims 1
- XROANSYVQAESTN-OYUWMTPXSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3r)-3-ethyl-2,5-dioxo-4-propylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CCC)[C@H](CC)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 XROANSYVQAESTN-OYUWMTPXSA-N 0.000 claims 1
- JBPZZEXQNOTMOD-ISJGIBHGSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3r)-3-ethyl-4-methyl-2,5-dioxopiperazin-1-yl]acetamide Chemical compound O=C1[C@@H](CC)N(C)C(=O)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 JBPZZEXQNOTMOD-ISJGIBHGSA-N 0.000 claims 1
- PMESUNIJPCUQIE-JSRBVGTNSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3r)-3-methyl-2,5-dioxo-4-propylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CCC)[C@H](C)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 PMESUNIJPCUQIE-JSRBVGTNSA-N 0.000 claims 1
- VVDRDUJPQQEMNZ-IWVFXYMLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3r)-4-ethyl-2,5-dioxo-3-propan-2-ylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CC)[C@H](C(C)C)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 VVDRDUJPQQEMNZ-IWVFXYMLSA-N 0.000 claims 1
- GACLYHGFFCUHAX-BXTSTYNKSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3r)-4-methyl-2,5-dioxo-3-propan-2-ylpiperazin-1-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C([C@@H](C(C)C)N(C)C(=O)C2)=O)=C1 GACLYHGFFCUHAX-BXTSTYNKSA-N 0.000 claims 1
- BOSOHHLSRHJGQE-DURBRWELSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3s)-2,5-dioxo-3-propan-2-yl-4-propylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CCC)[C@@H](C(C)C)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 BOSOHHLSRHJGQE-DURBRWELSA-N 0.000 claims 1
- VIDQAILATQWGSB-YRUKQIKQSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3s)-3,4-dimethyl-2,5-dioxopiperazin-1-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C([C@H](C)N(C)C(=O)C2)=O)=C1 VIDQAILATQWGSB-YRUKQIKQSA-N 0.000 claims 1
- XROANSYVQAESTN-GMQQYTKMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3s)-3-ethyl-2,5-dioxo-4-propylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CCC)[C@@H](CC)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 XROANSYVQAESTN-GMQQYTKMSA-N 0.000 claims 1
- JBPZZEXQNOTMOD-CCDWMCETSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3s)-3-ethyl-4-methyl-2,5-dioxopiperazin-1-yl]acetamide Chemical compound O=C1[C@H](CC)N(C)C(=O)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 JBPZZEXQNOTMOD-CCDWMCETSA-N 0.000 claims 1
- PMESUNIJPCUQIE-RRWZXMNXSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3s)-3-methyl-2,5-dioxo-4-propylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CCC)[C@@H](C)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 PMESUNIJPCUQIE-RRWZXMNXSA-N 0.000 claims 1
- VVDRDUJPQQEMNZ-HFASVGIHSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3s)-4-ethyl-2,5-dioxo-3-propan-2-ylpiperazin-1-yl]acetamide Chemical compound C1C(=O)N(CC)[C@@H](C(C)C)C(=O)N1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 VVDRDUJPQQEMNZ-HFASVGIHSA-N 0.000 claims 1
- GACLYHGFFCUHAX-OARDWFSCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(3s)-4-methyl-2,5-dioxo-3-propan-2-ylpiperazin-1-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C([C@H](C(C)C)N(C)C(=O)C2)=O)=C1 GACLYHGFFCUHAX-OARDWFSCSA-N 0.000 claims 1
- PHAUHNUYRBTKOI-KQNYMCNKSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)methyl]-3-heptan-4-ylsulfonylpropanamide Chemical compound N([C@@H](CC=1C=C(F)C=C(F)C=1)[C@H](O)CNCC=1C=C(CC)C=CC=1)C(=O)C(CS(=O)(=O)C(CCC)CCC)CN1C(=O)NC(C)(C)C1=O PHAUHNUYRBTKOI-KQNYMCNKSA-N 0.000 claims 1
- AUXBGLXURPBRGQ-MDEZFMAYSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]-2-phenylacetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(SC=2N(C=NN=2)C)C=2C=CC=CC=2)=C1 AUXBGLXURPBRGQ-MDEZFMAYSA-N 0.000 claims 1
- SEWRQSBJGNEBHG-GAZXMLTASA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5r)-4,5-dimethyl-2,3-dioxopiperazin-1-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C(C(=O)N(C)[C@H](C)C2)=O)=C1 SEWRQSBJGNEBHG-GAZXMLTASA-N 0.000 claims 1
- BXPKGFOUOKBLSP-GMQQYTKMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5r)-4-ethyl-2,3-dioxo-5-propan-2-ylpiperazin-1-yl]acetamide Chemical compound O=C1C(=O)N(CC)[C@H](C(C)C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 BXPKGFOUOKBLSP-GMQQYTKMSA-N 0.000 claims 1
- NJVUQIIZIIBWEN-AYCKEJKLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5r)-4-ethyl-5-methyl-2,3-dioxopiperazin-1-yl]acetamide Chemical compound O=C1C(=O)N(CC)[C@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 NJVUQIIZIIBWEN-AYCKEJKLSA-N 0.000 claims 1
- KEWSEMAXQMCHHD-KKUQBAQOSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5r)-4-methyl-2,3-dioxo-5-propan-2-ylpiperazin-1-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C(C(=O)N(C)[C@H](C(C)C)C2)=O)=C1 KEWSEMAXQMCHHD-KKUQBAQOSA-N 0.000 claims 1
- MLZHNHJUFCIILR-KWXIBIRDSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5r)-5-ethyl-2,3-dioxo-4-propylpiperazin-1-yl]acetamide Chemical compound O=C1C(=O)N(CCC)[C@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 MLZHNHJUFCIILR-KWXIBIRDSA-N 0.000 claims 1
- FCANOOYQJWLJEB-DSNGMDLFSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5r)-5-ethyl-4-methyl-2,3-dioxopiperazin-1-yl]acetamide Chemical compound O=C1C(=O)N(C)[C@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 FCANOOYQJWLJEB-DSNGMDLFSA-N 0.000 claims 1
- MNDHWDROTZLRAH-JSRBVGTNSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5r)-5-methyl-2,3-dioxo-4-propylpiperazin-1-yl]acetamide Chemical compound O=C1C(=O)N(CCC)[C@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 MNDHWDROTZLRAH-JSRBVGTNSA-N 0.000 claims 1
- WKIZWRWSDJIBBT-UPRLRBBYSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5s)-2,3-dioxo-5-propan-2-yl-4-propylpiperazin-1-yl]acetamide Chemical compound O=C1C(=O)N(CCC)[C@@H](C(C)C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 WKIZWRWSDJIBBT-UPRLRBBYSA-N 0.000 claims 1
- SEWRQSBJGNEBHG-YRUKQIKQSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5s)-4,5-dimethyl-2,3-dioxopiperazin-1-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C(C(=O)N(C)[C@@H](C)C2)=O)=C1 SEWRQSBJGNEBHG-YRUKQIKQSA-N 0.000 claims 1
- BXPKGFOUOKBLSP-OYUWMTPXSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5s)-4-ethyl-2,3-dioxo-5-propan-2-ylpiperazin-1-yl]acetamide Chemical compound O=C1C(=O)N(CC)[C@@H](C(C)C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 BXPKGFOUOKBLSP-OYUWMTPXSA-N 0.000 claims 1
- NJVUQIIZIIBWEN-RIEVBORMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5s)-4-ethyl-5-methyl-2,3-dioxopiperazin-1-yl]acetamide Chemical compound O=C1C(=O)N(CC)[C@@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 NJVUQIIZIIBWEN-RIEVBORMSA-N 0.000 claims 1
- KEWSEMAXQMCHHD-JIMJEQGWSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5s)-4-methyl-2,3-dioxo-5-propan-2-ylpiperazin-1-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C(C(=O)N(C)[C@@H](C(C)C)C2)=O)=C1 KEWSEMAXQMCHHD-JIMJEQGWSA-N 0.000 claims 1
- MLZHNHJUFCIILR-GMQQYTKMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5s)-5-ethyl-2,3-dioxo-4-propylpiperazin-1-yl]acetamide Chemical compound O=C1C(=O)N(CCC)[C@@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 MLZHNHJUFCIILR-GMQQYTKMSA-N 0.000 claims 1
- FCANOOYQJWLJEB-CCDWMCETSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5s)-5-ethyl-4-methyl-2,3-dioxopiperazin-1-yl]acetamide Chemical compound O=C1C(=O)N(C)[C@@H](CC)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 FCANOOYQJWLJEB-CCDWMCETSA-N 0.000 claims 1
- MNDHWDROTZLRAH-RRWZXMNXSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[(5s)-5-methyl-2,3-dioxo-4-propylpiperazin-1-yl]acetamide Chemical compound O=C1C(=O)N(CCC)[C@@H](C)CN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 MNDHWDROTZLRAH-RRWZXMNXSA-N 0.000 claims 1
- WUPZZNODUAYZJE-XDFJSJKPSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[1-methyl-5-(4-methylbenzoyl)pyrrol-2-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2N(C(C(=O)C=3C=CC(C)=CC=3)=CC=2)C)=C1 WUPZZNODUAYZJE-XDFJSJKPSA-N 0.000 claims 1
- DNNLKQPNJGUYPL-BJKOFHAPSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[2-(1h-imidazol-2-yl)imidazol-1-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2C(=NC=C2)C=2NC=CN=2)=C1 DNNLKQPNJGUYPL-BJKOFHAPSA-N 0.000 claims 1
- FKBBOQKVBLVMEC-IGYGKHONSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[2-(4-fluorophenyl)-1,3-benzoxazol-5-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=C3N=C(OC3=CC=2)C=2C=CC(F)=CC=2)=C1 FKBBOQKVBLVMEC-IGYGKHONSA-N 0.000 claims 1
- WAYQDPMMJIAYEG-XZWHSSHBSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[2-(dipropylamino)pyridin-4-yl]acetamide Chemical compound C1=NC(N(CCC)CCC)=CC(CC(=O)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@H](O)CNCC=2C=C(CC)C=CC=2)=C1 WAYQDPMMJIAYEG-XZWHSSHBSA-N 0.000 claims 1
- OVSZWTUMLZSOPA-IZZNHLLZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[4-(2-methylpropyl)-3,5-dioxopiperazin-1-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2CC(=O)N(CC(C)C)C(=O)C2)=C1 OVSZWTUMLZSOPA-IZZNHLLZSA-N 0.000 claims 1
- KTKADUVEVKOUBV-RRPNLBNLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-[5-(4-methylphenyl)tetrazol-2-yl]acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CN2N=C(N=N2)C=2C=CC(C)=CC=2)=C1 KTKADUVEVKOUBV-RRPNLBNLSA-N 0.000 claims 1
- OXDSAMGMQVNTBJ-IJYUDYEVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-hydroxy-2-phenyl-2-thiophen-2-ylacetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(O)(C=2SC=CC=2)C=2C=CC=CC=2)=C1 OXDSAMGMQVNTBJ-IJYUDYEVSA-N 0.000 claims 1
- INFSBRMJSMEWLF-DEWJTGPOSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-hydroxy-4-oxo-4-thiophen-2-ylbutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(O)CC(=O)C=2SC=CC=2)=C1 INFSBRMJSMEWLF-DEWJTGPOSA-N 0.000 claims 1
- ZHSHFTNZIDRYOC-VCYMZNSASA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-hydroxy-4-oxo-4-thiophen-3-ylbutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(O)CC(=O)C2=CSC=C2)=C1 ZHSHFTNZIDRYOC-VCYMZNSASA-N 0.000 claims 1
- XNFCVLMJRZYRMF-XZOQPEGZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-methyl-2-(1,2,4-triazol-1-yl)propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(C)(C)N2N=CN=C2)=C1 XNFCVLMJRZYRMF-XZOQPEGZSA-N 0.000 claims 1
- AIXOVNZPVVSGBF-WUFINQPMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-methyl-2-(3-oxo-1h-isoindol-2-yl)propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(C)(C)N2C(C3=CC=CC=C3C2)=O)=C1 AIXOVNZPVVSGBF-WUFINQPMSA-N 0.000 claims 1
- YWYPBDRDAZBCPZ-AJRFNQODSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-phenyl-2-(1h-1,2,4-triazol-5-ylsulfanyl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(SC=2NC=NN=2)C=2C=CC=CC=2)=C1 YWYPBDRDAZBCPZ-AJRFNQODSA-N 0.000 claims 1
- KEGLLVLLGZFQFV-IZZNHLLZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-phenylacetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2C=CC=CC=2)=C1 KEGLLVLLGZFQFV-IZZNHLLZSA-N 0.000 claims 1
- QDOXAFWXNFWOHL-BJKOFHAPSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-thiophen-2-ylacetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC=2SC=CC=2)=C1 QDOXAFWXNFWOHL-BJKOFHAPSA-N 0.000 claims 1
- ZGLZHUPXAUXXNC-RRPNLBNLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-(1,3-dioxoisoindol-2-yl)propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCN2C(C3=CC=CC=C3C2=O)=O)=C1 ZGLZHUPXAUXXNC-RRPNLBNLSA-N 0.000 claims 1
- ADKKQVLUFTYVRJ-AZGAKELHSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-(2-oxo-1,3-benzoxazol-3-yl)propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCN2C(OC3=CC=CC=C32)=O)=C1 ADKKQVLUFTYVRJ-AZGAKELHSA-N 0.000 claims 1
- UTXSBWHZHPIVFN-RRPNLBNLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-(2-oxo-4h-1,3-benzoxazin-3-yl)propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCN2C(OC3=CC=CC=C3C2)=O)=C1 UTXSBWHZHPIVFN-RRPNLBNLSA-N 0.000 claims 1
- QZBKCXLCAFVEMT-AHKZPQOWSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-(3-oxo-2,1-benzothiazol-1-yl)propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCN2C3=CC=CC=C3C(=O)S2)=C1 QZBKCXLCAFVEMT-AHKZPQOWSA-N 0.000 claims 1
- GRXWPXVNEIWAIE-IZZNHLLZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC=2ON=C(N=2)C=2N=CC=CC=2)=C1 GRXWPXVNEIWAIE-IZZNHLLZSA-N 0.000 claims 1
- OCHSMMDQIQQFJW-XBCLTQTASA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-(methylcarbamoylamino)-3-thiophen-3-ylpropanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC(NC(=O)NC)C2=CSC=C2)=C1 OCHSMMDQIQQFJW-XBCLTQTASA-N 0.000 claims 1
- XTBMZKWEJRYJMN-CVWZLOPKSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-[(2-methoxyacetyl)amino]-3-phenylpropanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CC(NC(=O)COC)C=2C=CC=CC=2)=C1 XTBMZKWEJRYJMN-CVWZLOPKSA-N 0.000 claims 1
- IJJRTNUESMBYKR-LOSJGSFVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-[2-oxo-5-(trifluoromethyl)pyridin-1-yl]propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCN2C(C=CC(=C2)C(F)(F)F)=O)=C1 IJJRTNUESMBYKR-LOSJGSFVSA-N 0.000 claims 1
- NNLRGJUGKFTRET-WUFINQPMSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-[4-(methanesulfonamido)phenyl]propanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC=2C=CC(NS(C)(=O)=O)=CC=2)=C1 NNLRGJUGKFTRET-WUFINQPMSA-N 0.000 claims 1
- IKKKAKZMFNIYNX-RRPNLBNLSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-3-phenylpropanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC=2C=CC=CC=2)=C1 IKKKAKZMFNIYNX-RRPNLBNLSA-N 0.000 claims 1
- WSAMRKAFXYVKDZ-RSTHSURTSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(1,3-dioxoisoindol-2-yl)-2-hydroxybutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)C(O)CCN2C(C3=CC=CC=C3C2=O)=O)=C1 WSAMRKAFXYVKDZ-RSTHSURTSA-N 0.000 claims 1
- DYOXRCOIXHRHTG-MFMCTBQISA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(1h-indol-3-yl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C3=CC=CC=C3NC=2)=C1 DYOXRCOIXHRHTG-MFMCTBQISA-N 0.000 claims 1
- FNELGEISRMOJJA-XTEPFMGCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=C3OCCOC3=CC=2)=C1 FNELGEISRMOJJA-XTEPFMGCSA-N 0.000 claims 1
- HIYDMSWAENZRKQ-LMSSTIIKSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(2,3-dihydroindol-1-yl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)N2C3=CC=CC=C3CC2)=C1 HIYDMSWAENZRKQ-LMSSTIIKSA-N 0.000 claims 1
- OARDCEYBPQYQAI-LITSAYRRSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(2-hydroxy-5-methylphenyl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C(=CC=C(C)C=2)O)=C1 OARDCEYBPQYQAI-LITSAYRRSA-N 0.000 claims 1
- QWAATTNOUQTSRT-AHKZPQOWSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(2-oxo-1,3-benzoxazol-3-yl)butanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCCN2C(OC3=CC=CC=C32)=O)=C1 QWAATTNOUQTSRT-AHKZPQOWSA-N 0.000 claims 1
- HPWVLYIIXXLQOT-LMSSTIIKSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(3,4-dihydro-2h-1,5-benzodioxepin-7-yl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=C3OCCCOC3=CC=2)=C1 HPWVLYIIXXLQOT-LMSSTIIKSA-N 0.000 claims 1
- QJEQRGYGBPUPCL-MFMCTBQISA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(3,4-dihydro-2h-chromen-6-yl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=C3CCCOC3=CC=2)=C1 QJEQRGYGBPUPCL-MFMCTBQISA-N 0.000 claims 1
- DMIHWNPXBMUXCD-XTEPFMGCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(3-fluoro-4-methoxyphenyl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=C(F)C(OC)=CC=2)=C1 DMIHWNPXBMUXCD-XTEPFMGCSA-N 0.000 claims 1
- DIOVSHFOFBOOCR-XTEPFMGCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(3-hydroxyphenyl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=C(O)C=CC=2)=C1 DIOVSHFOFBOOCR-XTEPFMGCSA-N 0.000 claims 1
- MAEQGHYRIPUPCU-LMSSTIIKSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(3-methoxyphenyl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=C(OC)C=CC=2)=C1 MAEQGHYRIPUPCU-LMSSTIIKSA-N 0.000 claims 1
- GZAWUHHIVGZCCU-XTEPFMGCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(4-hydroxyphenyl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=CC(O)=CC=2)=C1 GZAWUHHIVGZCCU-XTEPFMGCSA-N 0.000 claims 1
- VWVAIONVTYBZTC-UZNNEEJFSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(4-methoxy-3-phenylphenyl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=C(C(OC)=CC=2)C=2C=CC=CC=2)=C1 VWVAIONVTYBZTC-UZNNEEJFSA-N 0.000 claims 1
- RSOPHNNFZDETTH-LMSSTIIKSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(4-methoxyphenyl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=CC(OC)=CC=2)=C1 RSOPHNNFZDETTH-LMSSTIIKSA-N 0.000 claims 1
- YZDZKAVUCWOKJG-LMSSTIIKSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(4-methylphenyl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=CC(C)=CC=2)=C1 YZDZKAVUCWOKJG-LMSSTIIKSA-N 0.000 claims 1
- SNHNKADDZBPXMJ-AHKZPQOWSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(5-methyl-1h-pyrrol-2-yl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2NC(C)=CC=2)=C1 SNHNKADDZBPXMJ-AHKZPQOWSA-N 0.000 claims 1
- WTNRNBGVYLEQGV-XTEPFMGCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(7-methoxy-1-benzofuran-2-yl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2OC3=C(OC)C=CC=C3C=2)=C1 WTNRNBGVYLEQGV-XTEPFMGCSA-N 0.000 claims 1
- FKDOBRQNCCFWPA-UKILVPOCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-(furan-2-yl)-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2OC=CC=2)=C1 FKDOBRQNCCFWPA-UKILVPOCSA-N 0.000 claims 1
- GDIURLOXFRATHZ-LMSSTIIKSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-[4-(methanesulfonamido)phenyl]-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=CC(NS(C)(=O)=O)=CC=2)=C1 GDIURLOXFRATHZ-LMSSTIIKSA-N 0.000 claims 1
- ODFMPXYBCPXDGF-LOSJGSFVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-imidazol-1-ylbutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCCN2C=NC=C2)=C1 ODFMPXYBCPXDGF-LOSJGSFVSA-N 0.000 claims 1
- VLRJRRSGCAGPTM-LOSJGSFVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-morpholin-4-yl-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)N2CCOCC2)=C1 VLRJRRSGCAGPTM-LOSJGSFVSA-N 0.000 claims 1
- PJMUBBYUMOFZME-XDFJSJKPSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-naphthalen-2-yl-4-oxobutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=C3C=CC=CC3=CC=2)=C1 PJMUBBYUMOFZME-XDFJSJKPSA-N 0.000 claims 1
- ZNCNKPIPBZFWSI-XTEPFMGCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-oxo-4-phenylbutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2C=CC=CC=2)=C1 ZNCNKPIPBZFWSI-XTEPFMGCSA-N 0.000 claims 1
- AKASXGCNOXLVLM-UKILVPOCSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-4-oxo-4-thiophen-2-ylbutanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCC(=O)C=2SC=CC=2)=C1 AKASXGCNOXLVLM-UKILVPOCSA-N 0.000 claims 1
- HUMZIZXBJKQJRP-IZZNHLLZSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-5-pyrazol-1-ylpentanamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=C(F)C=C(F)C=2)NC(=O)CCCCN2N=CC=C2)=C1 HUMZIZXBJKQJRP-IZZNHLLZSA-N 0.000 claims 1
- MLWNNNRMBMFXQN-FCHUYYIVSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[2-(1,3-dioxolan-2-yl)ethylamino]-3-hydroxybutan-2-yl]-2-(4-methylsulfanylphenyl)acetamide Chemical compound C1=CC(SC)=CC=C1CC(=O)N[C@H]([C@H](O)CNCCC1OCCO1)CC1=CC(F)=CC(F)=C1 MLWNNNRMBMFXQN-FCHUYYIVSA-N 0.000 claims 1
- DHEZLUTVWMVTPG-BJKOFHAPSA-N n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[2-(1,3-dioxolan-2-yl)ethylamino]-3-hydroxybutan-2-yl]-2-(4-propan-2-ylphenyl)acetamide Chemical compound C1=CC(C(C)C)=CC=C1CC(=O)N[C@H]([C@H](O)CNCCC1OCCO1)CC1=CC(F)=CC(F)=C1 DHEZLUTVWMVTPG-BJKOFHAPSA-N 0.000 claims 1
- IDMQQCWUPOAYDS-MSIWLXHVSA-N n-[(2s,3r)-3-hydroxy-1-phenyl-4-(1-phenylethylamino)butan-2-yl]-3-phenylbutanamide Chemical compound C([C@H](NC(=O)CC(C)C=1C=CC=CC=1)[C@H](O)CNC(C)C=1C=CC=CC=1)C1=CC=CC=C1 IDMQQCWUPOAYDS-MSIWLXHVSA-N 0.000 claims 1
- NDAPWOQKYOXBTI-OCGTUMIYSA-N n-[(2s,3r)-3-hydroxy-4-(4-methylpentan-2-ylamino)-1-phenylbutan-2-yl]-2-phenylbutanamide Chemical compound C([C@H](NC(=O)C(CC)C=1C=CC=CC=1)[C@H](O)CNC(C)CC(C)C)C1=CC=CC=C1 NDAPWOQKYOXBTI-OCGTUMIYSA-N 0.000 claims 1
- QKTUVPZKBCEIFC-JNNLDFGZSA-N n-[(2s,3r)-3-hydroxy-4-(4-methylpentan-2-ylamino)-1-phenylbutan-2-yl]-3-phenylbutanamide Chemical compound C([C@@H]([C@H](O)CNC(C)CC(C)C)NC(=O)CC(C)C=1C=CC=CC=1)C1=CC=CC=C1 QKTUVPZKBCEIFC-JNNLDFGZSA-N 0.000 claims 1
- QUEVDRSGMHFNJR-YDUIRMPASA-N n-[(2s,3r)-3-hydroxy-4-(pentan-3-ylamino)-1-phenylbutan-2-yl]-2-phenylbutanamide Chemical compound C([C@@H]([C@H](O)CNC(CC)CC)NC(=O)C(CC)C=1C=CC=CC=1)C1=CC=CC=C1 QUEVDRSGMHFNJR-YDUIRMPASA-N 0.000 claims 1
- YWPJZDVYCWVKGU-ZJWHSJSFSA-N n-[(2s,3r)-3-hydroxy-4-(pentan-3-ylamino)-1-phenylbutan-2-yl]-3-phenylbutanamide Chemical compound C([C@@H]([C@H](O)CNC(CC)CC)NC(=O)CC(C)C=1C=CC=CC=1)C1=CC=CC=C1 YWPJZDVYCWVKGU-ZJWHSJSFSA-N 0.000 claims 1
- KEXCCUIBDSZDKN-WUFINQPMSA-N n-[(2s,3r)-3-hydroxy-4-[(3-methoxyphenyl)methylamino]-1-phenylbutan-2-yl]-2-(4-propan-2-ylphenyl)acetamide Chemical compound COC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)CC=2C=CC(=CC=2)C(C)C)=C1 KEXCCUIBDSZDKN-WUFINQPMSA-N 0.000 claims 1
- QNQPZQJFPMUJDU-YVJUOPSFSA-N n-[(2s,3r)-4-(3,3-dimethylbutan-2-ylamino)-3-hydroxy-1-phenylbutan-2-yl]-3-phenylbutanamide Chemical compound C([C@H](NC(=O)CC(C)C=1C=CC=CC=1)[C@H](O)CNC(C)C(C)(C)C)C1=CC=CC=C1 QNQPZQJFPMUJDU-YVJUOPSFSA-N 0.000 claims 1
- CLHKPWNBJKJJHC-LOSJGSFVSA-N n-[(2s,3r)-4-(benzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]-2-(4-methylsulfanylphenyl)acetamide Chemical compound C1=CC(SC)=CC=C1CC(=O)N[C@H]([C@H](O)CNCC=1C=CC=CC=1)CC1=CC(F)=CC(F)=C1 CLHKPWNBJKJJHC-LOSJGSFVSA-N 0.000 claims 1
- WKWOSUFMQGWBAG-RRPNLBNLSA-N n-[(2s,3r)-4-(benzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]-2-(4-propan-2-ylphenyl)acetamide Chemical compound C1=CC(C(C)C)=CC=C1CC(=O)N[C@H]([C@H](O)CNCC=1C=CC=CC=1)CC1=CC(F)=CC(F)=C1 WKWOSUFMQGWBAG-RRPNLBNLSA-N 0.000 claims 1
- XSNBRIKFYBCUDW-AHKZPQOWSA-N n-[(2s,3r)-4-(benzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]-3-indol-1-ylpropanamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CCN1C2=CC=CC=C2C=C1)NCC1=CC=CC=C1 XSNBRIKFYBCUDW-AHKZPQOWSA-N 0.000 claims 1
- NWPCOURPAQETHE-LOSJGSFVSA-N n-[(2s,3r)-4-(benzylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]-3-phenylpropanamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CCC=1C=CC=CC=1)NCC1=CC=CC=C1 NWPCOURPAQETHE-LOSJGSFVSA-N 0.000 claims 1
- XCXSCCWPDKGSLN-FCHUYYIVSA-N n-[(2s,3r)-4-(butylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]-2-(4-methylsulfanylphenyl)acetamide Chemical compound C([C@@H]([C@H](O)CNCCCC)NC(=O)CC=1C=CC(SC)=CC=1)C1=CC(F)=CC(F)=C1 XCXSCCWPDKGSLN-FCHUYYIVSA-N 0.000 claims 1
- SFLCUQVFUGBRQA-BJKOFHAPSA-N n-[(2s,3r)-4-(butylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]-2-(4-propan-2-ylphenyl)acetamide Chemical compound C([C@@H]([C@H](O)CNCCCC)NC(=O)CC=1C=CC(=CC=1)C(C)C)C1=CC(F)=CC(F)=C1 SFLCUQVFUGBRQA-BJKOFHAPSA-N 0.000 claims 1
- OCGKMKZCOYGDDG-LADGPHEKSA-N n-[(2s,3r)-4-(cyclopropylmethylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]-3-indol-1-ylpropanamide Chemical compound C([C@@H](O)[C@H](CC=1C=C(F)C=C(F)C=1)NC(=O)CCN1C2=CC=CC=C2C=C1)NCC1CC1 OCGKMKZCOYGDDG-LADGPHEKSA-N 0.000 claims 1
- SXRPLAWYDLYCMK-ULSNANLUSA-N n-[(2s,3r)-4-[(2,3-dimethylcyclohexyl)amino]-3-hydroxy-1-phenylbutan-2-yl]-3-phenylbutanamide Chemical compound C([C@H](NC(=O)CC(C)C=1C=CC=CC=1)[C@H](O)CNC1C(C(C)CCC1)C)C1=CC=CC=C1 SXRPLAWYDLYCMK-ULSNANLUSA-N 0.000 claims 1
- UITVNTHVFRYCOT-XZOQPEGZSA-N n-[(2s,3r)-4-[(3-ethylphenyl)methylamino]-3-hydroxy-1-phenylbutan-2-yl]-2-(3-oxopiperazin-1-yl)acetamide Chemical compound CCC1=CC=CC(CNC[C@@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)CN2CC(=O)NCC2)=C1 UITVNTHVFRYCOT-XZOQPEGZSA-N 0.000 claims 1
- RASRNIZENQSXPD-NCPLZGKYSA-N n-[(2s,3r)-4-[[3-(dimethylamino)-2,2-dimethylpropyl]amino]-3-hydroxy-1-phenylbutan-2-yl]-2-phenylbutanamide Chemical compound C([C@H](NC(=O)C(CC)C=1C=CC=CC=1)[C@H](O)CNCC(C)(C)CN(C)C)C1=CC=CC=C1 RASRNIZENQSXPD-NCPLZGKYSA-N 0.000 claims 1
- XAZXLAPSTOQGPM-DYCCLRLQSA-N n-[(2s,3r)-4-[[3-(dimethylamino)-2,2-dimethylpropyl]amino]-3-hydroxy-1-phenylbutan-2-yl]-3-phenylbutanamide Chemical compound C([C@H](NC(=O)CC(C)C=1C=CC=CC=1)[C@H](O)CNCC(C)(C)CN(C)C)C1=CC=CC=C1 XAZXLAPSTOQGPM-DYCCLRLQSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 104
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 100
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 98
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 92
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 90
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 90
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 90
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 89
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 79
- 239000000243 solution Substances 0.000 description 61
- 238000003776 cleavage reaction Methods 0.000 description 59
- 230000007017 scission Effects 0.000 description 59
- 230000000694 effects Effects 0.000 description 57
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 55
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- 230000015572 biosynthetic process Effects 0.000 description 54
- 238000009472 formulation Methods 0.000 description 51
- 239000000758 substrate Substances 0.000 description 50
- 239000003112 inhibitor Substances 0.000 description 48
- 239000000047 product Substances 0.000 description 48
- 150000001412 amines Chemical class 0.000 description 47
- 238000006243 chemical reaction Methods 0.000 description 46
- 230000002401 inhibitory effect Effects 0.000 description 45
- 239000002253 acid Substances 0.000 description 41
- 150000001413 amino acids Chemical class 0.000 description 37
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
- 238000012360 testing method Methods 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 235000019439 ethyl acetate Nutrition 0.000 description 33
- 102000004190 Enzymes Human genes 0.000 description 32
- 108090000790 Enzymes Proteins 0.000 description 32
- 229940088598 enzyme Drugs 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- 239000007787 solid Substances 0.000 description 31
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 29
- 235000001014 amino acid Nutrition 0.000 description 29
- 239000002904 solvent Substances 0.000 description 29
- 101001017818 Homo sapiens ATP-dependent translocase ABCB1 Proteins 0.000 description 28
- 210000004027 cell Anatomy 0.000 description 28
- 108090000765 processed proteins & peptides Proteins 0.000 description 28
- 125000006239 protecting group Chemical group 0.000 description 28
- 238000003786 synthesis reaction Methods 0.000 description 27
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 26
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 26
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 25
- 241001465754 Metazoa Species 0.000 description 22
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 22
- 230000000875 corresponding effect Effects 0.000 description 22
- 238000003556 assay Methods 0.000 description 21
- 235000019441 ethanol Nutrition 0.000 description 21
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 20
- 210000004556 brain Anatomy 0.000 description 20
- 230000002829 reductive effect Effects 0.000 description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- 239000002585 base Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 17
- 239000012442 inert solvent Substances 0.000 description 17
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 16
- 208000037259 Amyloid Plaque Diseases 0.000 description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 150000004820 halides Chemical class 0.000 description 16
- 238000011534 incubation Methods 0.000 description 16
- 230000005764 inhibitory process Effects 0.000 description 16
- 150000002825 nitriles Chemical class 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 15
- 230000008569 process Effects 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- 229910052938 sodium sulfate Inorganic materials 0.000 description 15
- 235000011152 sodium sulphate Nutrition 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 14
- 150000002148 esters Chemical class 0.000 description 14
- 230000035772 mutation Effects 0.000 description 14
- JTHRRMFZHSDGNJ-UHFFFAOYSA-N piperazine-2,3-dione Chemical compound O=C1NCCNC1=O JTHRRMFZHSDGNJ-UHFFFAOYSA-N 0.000 description 14
- 239000012267 brine Substances 0.000 description 13
- 238000001514 detection method Methods 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 239000007832 Na2SO4 Substances 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 12
- 238000005520 cutting process Methods 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 229910052783 alkali metal Inorganic materials 0.000 description 11
- 125000003277 amino group Chemical group 0.000 description 11
- 239000002775 capsule Substances 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 150000001350 alkyl halides Chemical class 0.000 description 10
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 10
- 210000004899 c-terminal region Anatomy 0.000 description 10
- 230000018109 developmental process Effects 0.000 description 10
- 230000002255 enzymatic effect Effects 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 210000005013 brain tissue Anatomy 0.000 description 9
- 238000003018 immunoassay Methods 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 102000004196 processed proteins & peptides Human genes 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 150000001340 alkali metals Chemical class 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 229910052763 palladium Inorganic materials 0.000 description 8
- 238000012545 processing Methods 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 7
- 102100021257 Beta-secretase 1 Human genes 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 7
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 230000002378 acidificating effect Effects 0.000 description 7
- 230000002490 cerebral effect Effects 0.000 description 7
- 239000007822 coupling agent Substances 0.000 description 7
- 150000002118 epoxides Chemical class 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 102000037865 fusion proteins Human genes 0.000 description 7
- 108020001507 fusion proteins Proteins 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- VGIRNWJSIRVFRT-UHFFFAOYSA-N 2',7'-difluorofluorescein Chemical compound OC(=O)C1=CC=CC=C1C1=C2C=C(F)C(=O)C=C2OC2=CC(O)=C(F)C=C21 VGIRNWJSIRVFRT-UHFFFAOYSA-N 0.000 description 6
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical group NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 206010002022 amyloidosis Diseases 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 230000001149 cognitive effect Effects 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 210000002784 stomach Anatomy 0.000 description 6
- 230000009261 transgenic effect Effects 0.000 description 6
- 230000002792 vascular Effects 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 5
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 5
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 5
- 208000032843 Hemorrhage Diseases 0.000 description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
- 208000018737 Parkinson disease Diseases 0.000 description 5
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 5
- 229910000085 borane Inorganic materials 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 230000001054 cortical effect Effects 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 230000007850 degeneration Effects 0.000 description 5
- 150000005690 diesters Chemical class 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 239000011133 lead Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 210000002569 neuron Anatomy 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- DQLGIONSPPKALA-UHFFFAOYSA-N phenylazanium;phenoxide Chemical compound NC1=CC=CC=C1.OC1=CC=CC=C1 DQLGIONSPPKALA-UHFFFAOYSA-N 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 230000000306 recurrent effect Effects 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- SPXOTSHWBDUUMT-UHFFFAOYSA-M 4-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=C(S([O-])(=O)=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-M 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 239000007821 HATU Substances 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 4
- 102000001708 Protein Isoforms Human genes 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 description 4
- 125000005219 aminonitrile group Chemical group 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 229960002685 biotin Drugs 0.000 description 4
- 235000020958 biotin Nutrition 0.000 description 4
- 239000011616 biotin Substances 0.000 description 4
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 4
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 150000004292 cyclic ethers Chemical class 0.000 description 4
- 150000001983 dialkylethers Chemical class 0.000 description 4
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 150000003840 hydrochlorides Chemical class 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 125000004043 oxo group Chemical group O=* 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000000750 progressive effect Effects 0.000 description 4
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- 206010059245 Angiopathy Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 101710150192 Beta-secretase 1 Proteins 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 201000011240 Frontotemporal dementia Diseases 0.000 description 3
- 239000007836 KH2PO4 Substances 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 125000003158 alcohol group Chemical group 0.000 description 3
- 230000001476 alcoholic effect Effects 0.000 description 3
- 230000007131 anti Alzheimer effect Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- BYALLXJNHJRTOE-UHFFFAOYSA-N benzyl n-[3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl]-n-[(4-ethylphenyl)methyl]carbamate Chemical compound C1=CC(CC)=CC=C1CN(C(=O)OCC=1C=CC=CC=1)CC(O)C(N)CC1=CC(F)=CC(F)=C1 BYALLXJNHJRTOE-UHFFFAOYSA-N 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 3
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 230000019771 cognition Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000006911 enzymatic reaction Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 3
- 235000019796 monopotassium phosphate Nutrition 0.000 description 3
- 230000018791 negative regulation of catalytic activity Effects 0.000 description 3
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 3
- 239000010502 orange oil Substances 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 108010091748 peptide A Proteins 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 3
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000010703 silicon Substances 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 3
- 229960001685 tacrine Drugs 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 238000000844 transformation Methods 0.000 description 3
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 3
- NWPYNELTAPDGKW-OWHBQTKESA-N (2s)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-propoxypiperidin-1-yl)hexanamide Chemical compound N1([C@@H](CCCC)C(=O)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@H](O)CNCC=2C=C(CC)C=CC=2)CCC(OCCC)CC1 NWPYNELTAPDGKW-OWHBQTKESA-N 0.000 description 2
- KJAOJSDKSGQSKR-RWSKJCERSA-N (2s)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]-2-(4-propoxypiperidin-1-yl)pentanamide Chemical compound C1CC(OCCC)CCN1[C@@H](CCC)C(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 KJAOJSDKSGQSKR-RWSKJCERSA-N 0.000 description 2
- NAXPENUDVQOAED-OWHBQTKESA-N (2s)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[[1-(3-ethylphenyl)cyclopropyl]amino]-3-hydroxybutan-2-yl]-2-[4-(ethoxymethyl)piperidin-1-yl]-4-methylsulfanylbutanamide Chemical compound C1CC(COCC)CCN1[C@@H](CCSC)C(=O)N[C@H]([C@H](O)CNC1(CC1)C=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 NAXPENUDVQOAED-OWHBQTKESA-N 0.000 description 2
- SMLFLYNLKBTIJK-OWHBQTKESA-N (2s)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[[1-(3-ethylphenyl)cyclopropyl]amino]-3-hydroxybutan-2-yl]-2-[4-(ethoxymethyl)piperidin-1-yl]pentanamide Chemical compound N1([C@@H](CCC)C(=O)N[C@@H](CC=2C=C(F)C=C(F)C=2)[C@H](O)CNC2(CC2)C=2C=C(CC)C=CC=2)CCC(COCC)CC1 SMLFLYNLKBTIJK-OWHBQTKESA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- RDJUHLUBPADHNP-UHFFFAOYSA-N 1,2,3,5-tetrahydroxybenzene Chemical compound OC1=CC(O)=C(O)C(O)=C1 RDJUHLUBPADHNP-UHFFFAOYSA-N 0.000 description 2
- OEFVHHVZPVGMEI-LPRJAOSGSA-N 2-(1-butyl-2-oxopiperidin-4-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound C1C(=O)N(CCCC)CCC1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 OEFVHHVZPVGMEI-LPRJAOSGSA-N 0.000 description 2
- RYTWPAUCABOYJP-UHFFFAOYSA-N 2-(3-oxocyclohexyl)acetic acid Chemical compound OC(=O)CC1CCCC(=O)C1 RYTWPAUCABOYJP-UHFFFAOYSA-N 0.000 description 2
- KKBWPKYMEPSPBF-RRPNLBNLSA-N 2-(4-butyl-2-oxopiperazin-1-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide Chemical compound O=C1CN(CCCC)CCN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 KKBWPKYMEPSPBF-RRPNLBNLSA-N 0.000 description 2
- COJRODWYXMTGDP-MBUXBYMASA-N 2-(4-butyl-3-oxopiperazin-1-yl)-n-[(2s,3r)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]acetamide;dihydrochloride Chemical compound Cl.Cl.C1C(=O)N(CCCC)CCN1CC(=O)N[C@H]([C@H](O)CNCC=1C=C(CC)C=CC=1)CC1=CC(F)=CC(F)=C1 COJRODWYXMTGDP-MBUXBYMASA-N 0.000 description 2
- YCTJEUZFFVLCOV-UHFFFAOYSA-N 2-bromo-3-iodo-4-methylbenzenesulfonyl chloride Chemical compound IC=1C(=C(S(=O)(=O)Cl)C=CC=1C)Br YCTJEUZFFVLCOV-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 2
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 208000031124 Dementia Alzheimer type Diseases 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- SSLIBLGVKYPVPA-UHFFFAOYSA-N N#[C-].C1=CC=NC=C1 Chemical compound N#[C-].C1=CC=NC=C1 SSLIBLGVKYPVPA-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 101710121244 Putative Xaa-Pro aminopeptidase Proteins 0.000 description 2
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000006180 TBST buffer Substances 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 101710081951 Xaa-Pro aminopeptidase 1 Proteins 0.000 description 2
- 101710081950 Xaa-Pro aminopeptidase 2 Proteins 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 150000001371 alpha-amino acids Chemical class 0.000 description 2
- 235000008206 alpha-amino acids Nutrition 0.000 description 2
- 150000003862 amino acid derivatives Chemical class 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 108091007737 beta-secretases Proteins 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- JPOXNPPZZKNXOV-UHFFFAOYSA-N bromochloromethane Chemical compound ClCBr JPOXNPPZZKNXOV-UHFFFAOYSA-N 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 238000000423 cell based assay Methods 0.000 description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 239000012470 diluted sample Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- XWAIAVWHZJNZQQ-UHFFFAOYSA-N donepezil hydrochloride Chemical compound [H+].[Cl-].O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 XWAIAVWHZJNZQQ-UHFFFAOYSA-N 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000010265 fast atom bombardment Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 238000002875 fluorescence polarization Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- QLBLDBLRERSWBA-UHFFFAOYSA-N hexanamide Chemical compound [CH2]CCCCC(N)=O QLBLDBLRERSWBA-UHFFFAOYSA-N 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229940097496 nasal spray Drugs 0.000 description 2
- 239000007922 nasal spray Substances 0.000 description 2
- 239000003076 neurotropic agent Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000001301 oxygen Chemical group 0.000 description 2
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
- 230000002110 toxicologic effect Effects 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- 125000006728 (C1-C6) alkynyl group Chemical group 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- 125000004747 1,1-dimethylethoxycarbonyl group Chemical group CC(C)(OC(=O)*)C 0.000 description 1
- VDMKJSJJXQDICL-ZXVJYWQYSA-N 1,7-dipyridin-3-ylheptan-4-yl (2s)-1-[2-oxo-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O.COC1=C(OC)C(OC)=CC(C(=O)C(=O)N2[C@@H](CCCC2)C(=O)OC(CCCC=2C=NC=CC=2)CCCC=2C=NC=CC=2)=C1 VDMKJSJJXQDICL-ZXVJYWQYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- IMHCHHYIRSOEPG-UHFFFAOYSA-N 1-butyl-4-methylpyridin-2-one Chemical compound CCCCN1C=CC(C)=CC1=O IMHCHHYIRSOEPG-UHFFFAOYSA-N 0.000 description 1
- JUDAJBQHQJFGTH-UHFFFAOYSA-N 1-butylpiperazin-2-one Chemical compound CCCCN1CCNCC1=O JUDAJBQHQJFGTH-UHFFFAOYSA-N 0.000 description 1
- ZBEKOEYCWKIMGU-UHFFFAOYSA-N 1-ethylpiperazine-2,3-dione Chemical compound CCN1CCNC(=O)C1=O ZBEKOEYCWKIMGU-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- CJWCIUDXTVHAIJ-UHFFFAOYSA-N 2-(1-butyl-2-oxopiperidin-4-yl)acetic acid Chemical compound CCCCN1CCC(CC(O)=O)CC1=O CJWCIUDXTVHAIJ-UHFFFAOYSA-N 0.000 description 1
- ZKOYVVTUAUXQTF-UHFFFAOYSA-N 2-(1-butyl-2-oxopyridin-4-yl)acetic acid Chemical compound CCCCN1C=CC(CC(O)=O)=CC1=O ZKOYVVTUAUXQTF-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- CXZMQLQAMRIYJE-UHFFFAOYSA-N 2-(4-butyl-2,3-dioxopiperazin-1-yl)acetic acid Chemical compound CCCCN1CCN(CC(O)=O)C(=O)C1=O CXZMQLQAMRIYJE-UHFFFAOYSA-N 0.000 description 1
- CWMVFOSETYRVLU-UHFFFAOYSA-N 2-(4-ethyl-2,3-dioxopiperazin-1-yl)acetic acid Chemical compound CCN1CCN(CC(O)=O)C(=O)C1=O CWMVFOSETYRVLU-UHFFFAOYSA-N 0.000 description 1
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
- 229940058020 2-amino-2-methyl-1-propanol Drugs 0.000 description 1
- LSZMVESSGLHDJE-UHFFFAOYSA-N 2-bromo-4-methylpyridine Chemical compound CC1=CC=NC(Br)=C1 LSZMVESSGLHDJE-UHFFFAOYSA-N 0.000 description 1
- LRLQQERNMXHASR-UHFFFAOYSA-N 2-diphenylphosphanylpropan-2-yl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)(C)P(C=1C=CC=CC=1)C1=CC=CC=C1 LRLQQERNMXHASR-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- WNRGWPVJGDABME-UHFFFAOYSA-N 3,5-Dimethoxyaniline Chemical compound COC1=CC(N)=CC(OC)=C1 WNRGWPVJGDABME-UHFFFAOYSA-N 0.000 description 1
- 125000006288 3,5-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(C([H])=C1F)C([H])([H])* 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- VGUWZCUCNQXGBU-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-nitro-1h-indole Chemical compound C1CN(C)CCN1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 VGUWZCUCNQXGBU-UHFFFAOYSA-N 0.000 description 1
- NGKHHLLMCCQDNI-UHFFFAOYSA-N 3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylphenyl)methylamino]butan-2-ol Chemical compound CCC1=CC=CC(CNCC(O)C(N)CC=2C=C(F)C=C(F)C=2)=C1 NGKHHLLMCCQDNI-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 125000005925 3-methylpentyloxy group Chemical group 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- GVCLNACSYKYUHP-UHFFFAOYSA-N 4-amino-7-(2-hydroxyethoxymethyl)pyrrolo[2,3-d]pyrimidine-5-carbothioamide Chemical compound C1=NC(N)=C2C(C(=S)N)=CN(COCCO)C2=N1 GVCLNACSYKYUHP-UHFFFAOYSA-N 0.000 description 1
- MFOGNLYNVZWVTA-UHFFFAOYSA-N 6-propylcyclohex-2-en-1-one Chemical compound CCCC1CCC=CC1=O MFOGNLYNVZWVTA-UHFFFAOYSA-N 0.000 description 1
- NJIAKNWTIVDSDA-FQEVSTJZSA-N 7-[4-(1-methylsulfonylpiperidin-4-yl)phenyl]-n-[[(2s)-morpholin-2-yl]methyl]pyrido[3,4-b]pyrazin-5-amine Chemical compound C1CN(S(=O)(=O)C)CCC1C1=CC=C(C=2N=C(NC[C@H]3OCCNC3)C3=NC=CN=C3C=2)C=C1 NJIAKNWTIVDSDA-FQEVSTJZSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 1
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 101150058765 BACE1 gene Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- JQJPBYFTQAANLE-UHFFFAOYSA-N Butyl nitrite Chemical compound CCCCON=O JQJPBYFTQAANLE-UHFFFAOYSA-N 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 208000011359 Chromosome disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 1
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N Di-tert-butyl dicarbonate Substances CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 101000823051 Homo sapiens Amyloid-beta precursor protein Proteins 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000009668 Neurobehavioral Manifestations Diseases 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
- YJDYDFNKCBANTM-QCWCSKBGSA-N SDZ PSC 833 Chemical compound C\C=C\C[C@@H](C)C(=O)[C@@H]1N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@H](C(C)C)NC1=O YJDYDFNKCBANTM-QCWCSKBGSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 229920004896 Triton X-405 Polymers 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- DRBWRJPFNOBNIO-KOLCDFICSA-N [(2r)-1-[(2r)-2-(pyridine-4-carbonylamino)propanoyl]pyrrolidin-2-yl]boronic acid Chemical compound N([C@H](C)C(=O)N1[C@@H](CCC1)B(O)O)C(=O)C1=CC=NC=C1 DRBWRJPFNOBNIO-KOLCDFICSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 1
- 230000009102 absorption Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001251 acridines Chemical class 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 108010064397 amyloid beta-protein (1-40) Proteins 0.000 description 1
- 230000003942 amyloidogenic effect Effects 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 229940027998 antiseptic and disinfectant acridine derivative Drugs 0.000 description 1
- 229940039856 aricept Drugs 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- XSOWLKOBBDGOBD-UHFFFAOYSA-N benzyl 2-(2,5-dioxopiperazin-1-yl)acetate Chemical compound C=1C=CC=CC=1COC(=O)CN1CC(=O)NCC1=O XSOWLKOBBDGOBD-UHFFFAOYSA-N 0.000 description 1
- QHGALGYLNFMGAF-UHFFFAOYSA-N benzyl 2-(4-butyl-2,5-dioxopiperazin-1-yl)acetate Chemical compound C1C(=O)N(CCCC)CC(=O)N1CC(=O)OCC1=CC=CC=C1 QHGALGYLNFMGAF-UHFFFAOYSA-N 0.000 description 1
- FJTYXUYOMOHQSJ-UHFFFAOYSA-N benzyl 2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]-(2-oxo-2-phenylmethoxyethyl)amino]acetate Chemical compound C=1C=CC=CC=1COC(=O)CN(C(=O)CNC(=O)OC(C)(C)C)CC(=O)OCC1=CC=CC=C1 FJTYXUYOMOHQSJ-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 125000001743 benzylic group Chemical group 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- TUDWMIUPYRKEFN-UHFFFAOYSA-N bromoiodomethane Chemical compound BrCI TUDWMIUPYRKEFN-UHFFFAOYSA-N 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- HJZVHUQSQGITAM-UHFFFAOYSA-N butanamide Chemical compound CC[CH]C(N)=O HJZVHUQSQGITAM-UHFFFAOYSA-N 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 238000000114 cell free in vitro assay Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
- PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 description 1
- 208000024971 chromosomal disease Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- IKOAYBMYVQZXPV-UHFFFAOYSA-N diethyl 2-(3-oxocyclohexyl)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)C1CCCC(=O)C1 IKOAYBMYVQZXPV-UHFFFAOYSA-N 0.000 description 1
- 125000005992 dihydrobenzisothiazinyl group Chemical group 0.000 description 1
- 125000005993 dihydrobenzisoxazinyl group Chemical group 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 125000005051 dihydropyrazinyl group Chemical group N1(CC=NC=C1)* 0.000 description 1
- 125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 description 1
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- 125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 description 1
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 1
- 125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 description 1
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- DEKPYXUDJRABNK-UHFFFAOYSA-N dimethyl 5-aminobenzene-1,3-dicarboxylate Chemical compound COC(=O)C1=CC(N)=CC(C(=O)OC)=C1 DEKPYXUDJRABNK-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Natural products O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 1
- 229960003135 donepezil hydrochloride Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 229940108366 exelon Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- FGIVSGPRGVABAB-UHFFFAOYSA-N fluoren-9-ylmethyl hydrogen carbonate Chemical compound C1=CC=C2C(COC(=O)O)C3=CC=CC=C3C2=C1 FGIVSGPRGVABAB-UHFFFAOYSA-N 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000008369 fruit flavor Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000003540 gamma secretase inhibitor Substances 0.000 description 1
- 108091007739 gamma-secretases Proteins 0.000 description 1
- 102000038383 gamma-secretases Human genes 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 229930184727 ginkgolide Natural products 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000011141 high resolution liquid chromatography Methods 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 239000004030 hiv protease inhibitor Substances 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000036046 immunoreaction Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000005994 isobenzotetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005995 isobenzotetrahydrothienyl group Chemical group 0.000 description 1
- 125000005990 isobenzothienyl group Chemical group 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- 125000003151 isocoumarinyl group Chemical group C1(=O)OC(=CC2=CC=CC=C12)* 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- GAIWVDWTECBESF-VKHMYHEASA-N methyl (2s)-2-(trifluoromethylsulfonyloxy)propanoate Chemical group COC(=O)[C@H](C)OS(=O)(=O)C(F)(F)F GAIWVDWTECBESF-VKHMYHEASA-N 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- DFPGBRPWDZFIPP-UHFFFAOYSA-N n'-butylethane-1,2-diamine Chemical compound CCCCNCCN DFPGBRPWDZFIPP-UHFFFAOYSA-N 0.000 description 1
- IHCHOVVAJBADAH-UHFFFAOYSA-N n-[2-hydroxy-4-(1h-pyrazol-4-yl)phenyl]-6-methoxy-3,4-dihydro-2h-chromene-3-carboxamide Chemical compound C1C2=CC(OC)=CC=C2OCC1C(=O)NC(C(=C1)O)=CC=C1C=1C=NNC=1 IHCHOVVAJBADAH-UHFFFAOYSA-N 0.000 description 1
- OSFCMRGOZNQUSW-UHFFFAOYSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-5-methoxy-9-oxo-10h-acridine-4-carboxamide Chemical compound N1C2=C(OC)C=CC=C2C(=O)C2=C1C(C(=O)NC1=CC=C(C=C1)CCN1CCC=3C=C(C(=CC=3C1)OC)OC)=CC=C2 OSFCMRGOZNQUSW-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000000508 neurotrophic effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- ZBRJXVVKPBZPAN-UHFFFAOYSA-L nickel(2+);triphenylphosphane;dichloride Chemical compound [Cl-].[Cl-].[Ni+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 ZBRJXVVKPBZPAN-UHFFFAOYSA-L 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 150000002912 oxalic acid derivatives Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 150000007965 phenolic acids Chemical class 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000005544 phthalimido group Chemical group 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 1
- CYJAWBVQRMVFEO-UHFFFAOYSA-N piperazine-2,6-dione Chemical compound O=C1CNCC(=O)N1 CYJAWBVQRMVFEO-UHFFFAOYSA-N 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000002745 poly(ortho ester) Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- MICLTPPSCUXHJT-UHFFFAOYSA-M potassium;4-[3-(6-oxo-3h-purin-9-yl)propanoylamino]benzoate Chemical compound [K+].C1=CC(C(=O)[O-])=CC=C1NC(=O)CCN1C(NC=NC2=O)=C2N=C1 MICLTPPSCUXHJT-UHFFFAOYSA-M 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000004620 quinolinyl-N-oxide group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
- 229960000311 ritonavir Drugs 0.000 description 1
- 229960004136 rivastigmine Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- FCMLWBBLOASUSO-UHFFFAOYSA-N tert-butyl 3-oxopiperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNC(=O)C1 FCMLWBBLOASUSO-UHFFFAOYSA-N 0.000 description 1
- RPUZXWSOBBYZMJ-UHFFFAOYSA-N tert-butyl n-[1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]carbamate Chemical compound CCC1=CC=CC(CNCC(O)C(CC=2C=C(F)C=C(F)C=2)NC(=O)OC(C)(C)C)=C1 RPUZXWSOBBYZMJ-UHFFFAOYSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000011820 transgenic animal model Methods 0.000 description 1
- 238000012301 transgenic model Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229950010938 valspodar Drugs 0.000 description 1
- 108010082372 valspodar Proteins 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- IHOVFYSQUDPMCN-QKUIIBHLSA-N zosuquidar Chemical compound C([C@H](COC=1C2=CC=CN=C2C=CC=1)O)N(CC1)CCN1C1C2=CC=CC=C2C2C(F)(F)C2C2=CC=CC=C12 IHOVFYSQUDPMCN-QKUIIBHLSA-N 0.000 description 1
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
Classifications
-
- 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
- C07C233/40—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 an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
-
- 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07C235/18—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 at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides
- C07C235/20—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 at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07C235/32—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 containing six-membered aromatic rings
- C07C235/34—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 containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/41—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by carboxyl groups, other than cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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
- C07C311/06—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 carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
-
- 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
-
- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/32—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/325—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
- C07D207/327—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D211/76—Oxygen atoms attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/24—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/24—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
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D233/64—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 substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/16—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
- C07D235/26—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/14—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
- C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/16—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
- C07D249/18—Benzotriazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D263/57—Aryl or substituted aryl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles 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 in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
- C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/34—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles 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 in position 2
- C07D277/70—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/81—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/28—Radicals substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D321/00—Heterocyclic compounds containing rings having two oxygen atoms as the only ring hetero atoms, not provided for by groups C07D317/00 - C07D319/00
- C07D321/02—Seven-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyridine Compounds (AREA)
- Furan Compounds (AREA)
- Indole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Pyrane Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US30452501P | 2001-07-11 | 2001-07-11 | |
US30875601P | 2001-07-30 | 2001-07-30 | |
US34141601P | 2001-12-17 | 2001-12-17 | |
US34134101P | 2001-12-17 | 2001-12-17 | |
US38057401P | 2001-12-21 | 2001-12-21 | |
US34487201P | 2001-12-21 | 2001-12-21 | |
PCT/US2002/022255 WO2003006423A1 (en) | 2001-07-11 | 2002-07-11 | N-(3-amino-2-hydroxy-propyl) substituted alkylamide compounds |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20040069A2 true HRP20040069A2 (en) | 2005-02-28 |
Family
ID=27559660
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20040069A HRP20040069A2 (en) | 2001-07-11 | 2004-01-23 | N-(3-amino-2-hydroxy-propyl) substituted alkylamide compounds |
Country Status (27)
Country | Link |
---|---|
US (2) | US7589094B2 (ja) |
EP (1) | EP1409450B1 (ja) |
JP (1) | JP4278511B2 (ja) |
KR (1) | KR20040063110A (ja) |
CN (1) | CN101068772A (ja) |
AP (1) | AP2004002952A0 (ja) |
AT (1) | ATE451348T1 (ja) |
AU (1) | AU2002320490B2 (ja) |
BR (1) | BR0211119A (ja) |
CA (1) | CA2453503A1 (ja) |
CO (1) | CO5560553A2 (ja) |
DE (1) | DE60234696D1 (ja) |
EA (1) | EA200400162A1 (ja) |
GE (1) | GEP20074221B (ja) |
HR (1) | HRP20040069A2 (ja) |
IL (1) | IL159808A0 (ja) |
IS (1) | IS7109A (ja) |
MA (1) | MA27132A1 (ja) |
MX (1) | MXPA04000334A (ja) |
NO (1) | NO20040139L (ja) |
NZ (1) | NZ530646A (ja) |
OA (1) | OA12698A (ja) |
PL (1) | PL368052A1 (ja) |
RS (1) | RS13004A (ja) |
TN (1) | TNSN04017A1 (ja) |
WO (1) | WO2003006423A1 (ja) |
ZA (1) | ZA200400243B (ja) |
Families Citing this family (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
OA12698A (en) * | 2001-07-11 | 2006-06-22 | Elan Pharm Inc | N-(3-amino-2-hydroxy-propyl)substituted alkylamidecompounds. |
BR0214736A (pt) * | 2001-12-06 | 2004-11-23 | Elan Pharm Inc | Composto e seus sais farmaceuticamente aceitáveis, composição farmacêutica e método de tratar seres humanos ou animais que sofrem de doenças ou condições |
BR0314071A (pt) * | 2002-09-06 | 2005-07-05 | Pharmacia & Upjohn Co Llc | Derivados de pró-droga de 1,3-diamino-2-hidroxipropano |
UY27967A1 (es) * | 2002-09-10 | 2004-05-31 | Pfizer | Acetil 2-hindroxi-1,3-diaminoalcanos |
US7351738B2 (en) * | 2002-11-27 | 2008-04-01 | Elan Pharmaceuticals, Inc. | Substituted ureas and carbamates |
CL2004000848A1 (es) * | 2003-04-21 | 2005-01-28 | Elan Pharmaceuticals Inc Pharm | Compuestos derivados de fenacil-2-hidroxi-3-diaminoalcanos, inhibidores de la enzima betasecretasa, utiles para preparar un medicamento para tratar alzheimer, sindrome de down, hemorragia cerebral hereditaria con amiloidosis de tipo holandes, y otras |
MXPA05011150A (es) * | 2003-04-21 | 2005-12-14 | Elan Pharm Inc | 2-hidroxi-3-diaminoalcanos de benzamida. |
EP1729755A1 (en) * | 2004-01-21 | 2006-12-13 | Elan Pharmaceuticals, Inc. | Methods of treatment of amyloidosis using aspartyl-protease inihibitors |
JP2007528400A (ja) * | 2004-03-09 | 2007-10-11 | エラン ファーマシューティカルズ,インコーポレイテッド | 置換ヒドロキシエチルアミン系のアスパラギン酸プロテアーゼ阻害薬 |
EP1735293A2 (en) * | 2004-03-09 | 2006-12-27 | Elan Pharmaceuticals, Inc. | Substituted hydroxyethylamine aspartyl protease inhibitors |
EP1734942A1 (en) * | 2004-03-09 | 2006-12-27 | Elan Pharmaceuticals, Inc. | Substituted urea and carbamate, phenacyl-2-hydroxy-3-diaminoalkane, and benzamide-2-hydroxy-3-diaminoalkane aspartyl-protease inhibitors |
EP1773756A2 (en) | 2004-07-09 | 2007-04-18 | Elan Pharmaceuticals, Inc. | Oxime derivative substituted hydroxyethylamine aspartyl protease inhibitors |
CA2581023A1 (en) | 2004-09-21 | 2006-03-30 | Pfizer Products Inc. | N-methyl hydroxyethylamine useful in treating cns conditions |
JP2008513433A (ja) * | 2004-09-21 | 2008-05-01 | ファイザー・プロダクツ・インク | 中枢神経系の症状の治療において有用なn−エチルヒドロキシエチルアミン |
JP5067968B2 (ja) | 2004-10-07 | 2012-11-07 | ビテ ファーマシューティカルズ, インコーポレイテッド | ジアミノアルカンアスパラギン酸プロテアーゼ阻害剤 |
KR20080015079A (ko) | 2005-04-08 | 2008-02-18 | 코멘티스, 인코포레이티드 | 베타 세크레타제 활성을 억제하는 화합물 및 이것의 사용방법 |
EP1871420A4 (en) * | 2005-04-15 | 2010-09-22 | Univ North Carolina | PROCESS FOR ENABLING CELL SURVIVAL VIA NEUROTROPHINE MIMETICS |
WO2007047305A1 (en) | 2005-10-12 | 2007-04-26 | Elan Pharmaceuticals, Inc. | Methods of treating amyloidosis using cyclopropyl derivative aspartyl protease inhibitors |
TWI411607B (zh) | 2005-11-14 | 2013-10-11 | Vitae Pharmaceuticals Inc | 天門冬胺酸蛋白酶抑制劑 |
JP5274258B2 (ja) | 2005-11-21 | 2013-08-28 | アムジエン・インコーポレーテツド | β−セクレターゼ調節物質及び使用方法 |
US7838676B2 (en) | 2005-11-21 | 2010-11-23 | 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 |
TWI610684B (zh) | 2005-12-22 | 2018-01-11 | 海卓勒生物科學公司 | 用於調節trpa1功能之化合物 |
WO2007117557A2 (en) * | 2006-04-05 | 2007-10-18 | Vitae Pharmaceuticals, Inc. | Diaminopropanol renin inhibitors |
CL2007002689A1 (es) | 2006-09-18 | 2008-04-18 | Vitae Pharmaceuticals Inc | Compuestos derivados de piperidin-1-carboxamida, inhibidores de la renina; compuestos intermediarios; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como hipertension, insuficiencia cardiaca, fibrosis cardiaca, entre otras. |
AU2008215948A1 (en) | 2007-02-12 | 2008-08-21 | Merck & Co., Inc. | Piperazine derivatives for treatment of AD and related conditions |
MX2009012608A (es) | 2007-05-25 | 2009-12-07 | Amgen Inc | Compuestos de hidroxietil amina substituidos como moduladores de beta-secretasa y metodos de uso. |
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 |
EP2291181B9 (en) | 2008-04-18 | 2013-09-11 | University College Dublin National University Of Ireland, Dublin | Captodiamine for the treatment of depression symptoms |
JP2012519703A (ja) * | 2009-03-06 | 2012-08-30 | ザ ユニバーシティ オブ ノース カロライナ アット チャペル ヒル | ニューロトロフィン・ミメティック及びその使用 |
AR077692A1 (es) | 2009-08-06 | 2011-09-14 | Vitae Pharmaceuticals Inc | Sales de 2-((r)-(3-clorofenil) ((r)-1-((s) -2-(metilamino)-3-((r)-tetrahidro-2h-piran-3-il) propilcarbamoil) piperidin -3-il) metoxi) etilcarbamato de metilo |
IN2012DN05142A (ja) | 2009-11-12 | 2015-10-23 | Pharma Trophix Inc | |
US10273219B2 (en) | 2009-11-12 | 2019-04-30 | Pharmatrophix, Inc. | Crystalline forms of neurotrophin mimetic compounds and their salts |
EP2504315A1 (en) | 2009-11-23 | 2012-10-03 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
US8822485B2 (en) | 2009-11-23 | 2014-09-02 | 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 |
WO2014009872A1 (en) | 2012-07-09 | 2014-01-16 | Lupin Limited | Tetrahydroquinazolinone derivatives as parp inhibitors |
WO2014100734A1 (en) | 2012-12-21 | 2014-06-26 | Epizyme, Inc. | Prmt5 inhibitors and uses thereof |
JP2016505000A (ja) | 2012-12-21 | 2016-02-18 | エピザイム,インコーポレイティド | Prmt5阻害剤およびその使用 |
JP2016511744A (ja) * | 2012-12-21 | 2016-04-21 | エピザイム,インコーポレイティド | Prmt5を阻害する方法 |
US9745291B2 (en) | 2012-12-21 | 2017-08-29 | Epizyme, Inc. | PRMT5 inhibitors containing a dihydro- or tetrahydroisoquinoline and uses thereof |
CA2899363A1 (en) | 2012-12-21 | 2014-06-26 | Epizyme, Inc. | Prmt5 inhibitors and uses thereof |
DK2935222T3 (en) | 2012-12-21 | 2019-01-07 | Epizyme Inc | PRMT5 INHIBITORS AND APPLICATIONS THEREOF |
EP3177288A4 (en) | 2014-08-04 | 2018-04-04 | Epizyme, Inc. | Prmt5 inhibitors and uses thereof |
CN111763181A (zh) * | 2019-04-02 | 2020-10-13 | 重庆大学 | 一种制备含共轭二烯酮片段的苯并磺内酰胺类季碳氨基酸衍生物的合成方法 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS61236770A (ja) * | 1985-04-15 | 1986-10-22 | Kissei Pharmaceut Co Ltd | 新規なアミノ酸誘導体 |
CA1297631C (en) * | 1985-12-23 | 1992-03-17 | Sesha I. Natarajan | Ureido renin inhibitors |
US5559256A (en) * | 1992-07-20 | 1996-09-24 | E. R. Squibb & Sons, Inc. | Aminediol protease inhibitors |
JP2002513412A (ja) * | 1997-04-14 | 2002-05-08 | シーオーアール セラピューティクス インコーポレイテッド | 選択的Xa因子阻害剤 |
PE20020276A1 (es) * | 2000-06-30 | 2002-04-06 | Elan Pharm Inc | COMPUESTOS DE AMINA SUSTITUIDA COMO INHIBIDORES DE ß-SECRETASA PARA EL TRATAMIENTO DE ALZHEIMER |
US20030109559A1 (en) * | 2001-07-11 | 2003-06-12 | Andrea Gailunas | N-(3-amino-2-hydroxy-propyl)substituted alkylamide compounds |
OA12698A (en) * | 2001-07-11 | 2006-06-22 | Elan Pharm Inc | N-(3-amino-2-hydroxy-propyl)substituted alkylamidecompounds. |
IL161881A0 (en) * | 2001-11-08 | 2005-11-20 | Upjohn Co | N,N'-substituted-1,3-diamino-2-hydroxypropane derivatives |
-
2002
- 2002-07-11 OA OA1200400006A patent/OA12698A/en unknown
- 2002-07-11 CN CNA028177460A patent/CN101068772A/zh active Pending
- 2002-07-11 WO PCT/US2002/022255 patent/WO2003006423A1/en active Application Filing
- 2002-07-11 MX MXPA04000334A patent/MXPA04000334A/es active IP Right Grant
- 2002-07-11 EP EP02750011A patent/EP1409450B1/en not_active Expired - Lifetime
- 2002-07-11 KR KR10-2004-7000501A patent/KR20040063110A/ko not_active Application Discontinuation
- 2002-07-11 PL PL02368052A patent/PL368052A1/xx not_active Application Discontinuation
- 2002-07-11 IL IL15980802A patent/IL159808A0/xx unknown
- 2002-07-11 AT AT02750011T patent/ATE451348T1/de not_active IP Right Cessation
- 2002-07-11 NZ NZ530646A patent/NZ530646A/en unknown
- 2002-07-11 RS YU13004A patent/RS13004A/sr unknown
- 2002-07-11 GE GE5452A patent/GEP20074221B/en unknown
- 2002-07-11 EA EA200400162A patent/EA200400162A1/ru unknown
- 2002-07-11 AU AU2002320490A patent/AU2002320490B2/en not_active Ceased
- 2002-07-11 AP APAP/P/2004/002952A patent/AP2004002952A0/en unknown
- 2002-07-11 CA CA002453503A patent/CA2453503A1/en not_active Abandoned
- 2002-07-11 BR BR0211119-5A patent/BR0211119A/pt not_active IP Right Cessation
- 2002-07-11 JP JP2003512195A patent/JP4278511B2/ja not_active Expired - Fee Related
- 2002-07-11 DE DE60234696T patent/DE60234696D1/de not_active Expired - Lifetime
-
2004
- 2004-01-12 IS IS7109A patent/IS7109A/is unknown
- 2004-01-12 NO NO20040139A patent/NO20040139L/no not_active Application Discontinuation
- 2004-01-13 ZA ZA2004/00243A patent/ZA200400243B/en unknown
- 2004-01-23 TN TNP2004000017A patent/TNSN04017A1/en unknown
- 2004-01-23 HR HR20040069A patent/HRP20040069A2/hr not_active Application Discontinuation
- 2004-02-04 MA MA27510A patent/MA27132A1/fr unknown
- 2004-02-10 CO CO04010956A patent/CO5560553A2/es not_active Application Discontinuation
-
2005
- 2005-12-07 US US11/296,669 patent/US7589094B2/en not_active Expired - Fee Related
-
2009
- 2009-09-02 US US12/552,412 patent/US20100048590A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
DE60234696D1 (de) | 2010-01-21 |
WO2003006423A1 (en) | 2003-01-23 |
MA27132A1 (fr) | 2005-01-03 |
CN101068772A (zh) | 2007-11-07 |
US20100048590A1 (en) | 2010-02-25 |
ZA200400243B (en) | 2005-02-23 |
PL368052A1 (en) | 2005-03-21 |
EP1409450A1 (en) | 2004-04-21 |
BR0211119A (pt) | 2005-12-13 |
AU2002320490B2 (en) | 2008-10-02 |
US20060194817A1 (en) | 2006-08-31 |
CA2453503A1 (en) | 2003-01-23 |
IS7109A (is) | 2004-01-12 |
EP1409450B1 (en) | 2009-12-09 |
NZ530646A (en) | 2008-01-31 |
EA200400162A1 (ru) | 2005-06-30 |
RS13004A (en) | 2006-10-27 |
GEP20074221B (en) | 2007-10-25 |
JP4278511B2 (ja) | 2009-06-17 |
OA12698A (en) | 2006-06-22 |
KR20040063110A (ko) | 2004-07-12 |
MXPA04000334A (es) | 2004-09-28 |
ATE451348T1 (de) | 2009-12-15 |
US7589094B2 (en) | 2009-09-15 |
AP2004002952A0 (en) | 2004-03-31 |
TNSN04017A1 (en) | 2006-06-01 |
JP2005504737A (ja) | 2005-02-17 |
IL159808A0 (en) | 2004-06-20 |
CO5560553A2 (es) | 2005-09-30 |
NO20040139L (no) | 2004-02-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7589094B2 (en) | N- (3-amino-2-hydroxy-propyl) substituted alkylamide compounds | |
US7358264B2 (en) | Statine derivatives for the treatment of Alzheimer's disease | |
US7067507B2 (en) | Macrocycles useful in the treatment of Alzheimer's disease | |
AU2002320490A1 (en) | N-(3-amino-2-hydroxy-propyl) substituted alkylamide compounds | |
US20080207696A1 (en) | Phenacyl 2-Hydroxy-3-Diaminoalkanes | |
US20050032848A1 (en) | Benzamide 2-hydroxy-3-diaminoalkanes | |
US7067542B2 (en) | Diaminediols for the treatment of Alzheimer's disease | |
US20060100196A1 (en) | Substituted amines for the treatment of alzheimer's disease | |
US20030109559A1 (en) | N-(3-amino-2-hydroxy-propyl)substituted alkylamide compounds | |
ES2261699T3 (es) | Macrociclos utiles en el tratamiento de la enfermedad de alzheimer. | |
US7262208B2 (en) | Hydroxypropyl amides for the treatment of Alzheimer's disease | |
US7566730B2 (en) | Substituted aminoethers for the treatment of Alzheimer's disease | |
JP2004534771A (ja) | アザヒドロキシル化エチルアミン化合物 | |
US20070225374A1 (en) | Hydroxypropyl Amides for the Treatment of Alzheimer's Disease |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A1OB | Publication of a patent application | ||
AIPI | Request for the grant of a patent on the basis of a substantive examination of a patent application | ||
ODRP | Renewal fee for the maintenance of a patent |
Payment date: 20060704 Year of fee payment: 5 |
|
OBST | Application withdrawn |