KR20050111797A - 트리시클릭 인돌 유도체 및 알츠하이머병의 치료에서의그의 용도 - Google Patents

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Publication number

KR20050111797A

KR20050111797A KR1020057019979A KR20057019979A KR20050111797A KR 20050111797 A KR20050111797 A KR 20050111797A KR 1020057019979 A KR1020057019979 A KR 1020057019979A KR 20057019979 A KR20057019979 A KR 20057019979A KR 20050111797 A KR20050111797 A KR 20050111797A

Authority

KR

South Korea

Prior art keywords

alkyl

amino

cycloalkyl

methyl

mmol

Prior art date

2003-04-23

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Withdrawn

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• 238000011282 treatment Methods 0.000 title claims abstract description 18
• 208000024827 Alzheimer disease Diseases 0.000 title abstract description 11
• 229940054051 antipsychotic indole derivative Drugs 0.000 title 1
• 150000002475 indoles Chemical class 0.000 title 1
• 239000000203 mixture Substances 0.000 claims abstract description 54
• 102000013455 Amyloid beta-Peptides Human genes 0.000 claims abstract description 32
• 108010090849 Amyloid beta-Peptides Proteins 0.000 claims abstract description 32
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
• 208000037259 Amyloid Plaque Diseases 0.000 claims abstract description 17
• 201000010099 disease Diseases 0.000 claims abstract description 16
• -1 cyano, hydroxy, carboxy Chemical group 0.000 claims description 152
• 125000000217 alkyl group Chemical group 0.000 claims description 97
• 150000001875 compounds Chemical class 0.000 claims description 94
• 239000001257 hydrogen Substances 0.000 claims description 30
• 229910052739 hydrogen Inorganic materials 0.000 claims description 30
• 150000003839 salts Chemical class 0.000 claims description 28
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 22
• 125000000623 heterocyclic group Chemical group 0.000 claims description 21
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
• 125000003118 aryl group Chemical group 0.000 claims description 20
• 229910052757 nitrogen Inorganic materials 0.000 claims description 19
• 125000003545 alkoxy group Chemical group 0.000 claims description 16
• 239000012453 solvate Substances 0.000 claims description 15
• 229910052736 halogen Inorganic materials 0.000 claims description 14
• 150000002367 halogens Chemical class 0.000 claims description 14
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 13
• 125000001072 heteroaryl group Chemical group 0.000 claims description 12
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 11
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 10
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 9
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 7
• 125000003342 alkenyl group Chemical group 0.000 claims description 5
• 125000004432 carbon atom Chemical group C* 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 239000004231 Riboflavin-5-Sodium Phosphate Substances 0.000 claims description 4
• 125000001589 carboacyl group Chemical group 0.000 claims description 4
• 125000004367 cycloalkylaryl group Chemical group 0.000 claims description 4
• 125000005842 heteroatom Chemical group 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 125000000304 alkynyl group Chemical group 0.000 claims description 3
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 2
• 239000000969 carrier Substances 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 8
• 238000000034 method Methods 0.000 abstract description 31
• 102100021257 Beta-secretase 1 Human genes 0.000 abstract description 23
• 101710150192 Beta-secretase 1 Proteins 0.000 abstract description 20
• 238000002360 preparation method Methods 0.000 abstract description 11
• 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 abstract description 9
• 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 abstract description 9
• 230000002401 inhibitory effect Effects 0.000 abstract description 9
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical class NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 abstract description 3
• 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 abstract description 3
• 239000000243 solution Substances 0.000 description 109
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 64
• 150000001412 amines Chemical class 0.000 description 50
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
• 239000012074 organic phase Substances 0.000 description 42
• 239000007787 solid Substances 0.000 description 42
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 41
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 38
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
• 150000002148 esters Chemical class 0.000 description 30
• 238000000746 purification Methods 0.000 description 30
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
• 239000000460 chlorine Substances 0.000 description 27
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
• 239000002904 solvent Substances 0.000 description 21
• 239000002253 acid Substances 0.000 description 20
• 238000003818 flash chromatography Methods 0.000 description 20
• 229920006395 saturated elastomer Polymers 0.000 description 20
• 239000000741 silica gel Substances 0.000 description 20
• 229910002027 silica gel Inorganic materials 0.000 description 20
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 239000007864 aqueous solution Substances 0.000 description 18
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 16
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 15
• 150000002431 hydrogen Chemical class 0.000 description 15
• 239000002243 precursor Substances 0.000 description 15
• 229910000104 sodium hydride Inorganic materials 0.000 description 15
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• 102000004190 Enzymes Human genes 0.000 description 13
• 108090000790 Enzymes Proteins 0.000 description 13
• 229940088598 enzyme Drugs 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• 239000012267 brine Substances 0.000 description 11
• FLTDSRFNBLQAEJ-UHFFFAOYSA-N ethyl azulene-4-carboxylate Chemical compound CCOC(=O)C1=CC=CC=C2C=CC=C12 FLTDSRFNBLQAEJ-UHFFFAOYSA-N 0.000 description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
• OXERBZQPYKPVFA-UHFFFAOYSA-N methyl 7-amino-3-ethyl-1h-indole-5-carboxylate Chemical compound C1=C(C(=O)OC)C=C2C(CC)=CNC2=C1N OXERBZQPYKPVFA-UHFFFAOYSA-N 0.000 description 10
• 239000002480 mineral oil Substances 0.000 description 10
• 235000010446 mineral oil Nutrition 0.000 description 10
• 239000003921 oil Substances 0.000 description 10
• 235000019198 oils Nutrition 0.000 description 10
• 150000002924 oxiranes Chemical class 0.000 description 10
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
• 150000007513 acids Chemical class 0.000 description 9
• 239000008346 aqueous phase Substances 0.000 description 9
• 239000000872 buffer Substances 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• 238000003556 assay Methods 0.000 description 8
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 8
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
• AJBGTOYTKPVUPX-UHFFFAOYSA-N 2-(3-methoxyphenyl)-2-methylpropanoic acid Chemical compound COC1=CC=CC(C(C)(C)C(O)=O)=C1 AJBGTOYTKPVUPX-UHFFFAOYSA-N 0.000 description 7
• RZHHKJTXXXFRFY-UHFFFAOYSA-N 3-ethyl-10-oxo-1,9-diazatricyclo[6.4.1.04,13]trideca-2,4(13),5,7-tetraene-6-carboxylic acid Chemical compound C1CC(=O)NC2=CC(C(O)=O)=CC3=C2N1C=C3CC RZHHKJTXXXFRFY-UHFFFAOYSA-N 0.000 description 7
• XUTUMDWBNHJGCH-UHFFFAOYSA-N benzyl n-[2-(3-methoxyphenyl)propan-2-yl]carbamate Chemical compound COC1=CC=CC(C(C)(C)NC(=O)OCC=2C=CC=CC=2)=C1 XUTUMDWBNHJGCH-UHFFFAOYSA-N 0.000 description 7
• LZNXSMZJMKWFQR-UHFFFAOYSA-N ethyl 2-(3-methoxyphenyl)-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)C1=CC=CC(OC)=C1 LZNXSMZJMKWFQR-UHFFFAOYSA-N 0.000 description 7
• ZRVDQBPIHQYYCU-UHFFFAOYSA-N ethyl 7-amino-3-ethyl-1h-indole-5-carboxylate Chemical compound CCOC(=O)C1=CC(N)=C2NC=C(CC)C2=C1 ZRVDQBPIHQYYCU-UHFFFAOYSA-N 0.000 description 7
• 125000005843 halogen group Chemical group 0.000 description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
• 230000008569 process Effects 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• WYEUFUDFBYLDSG-RBUKOAKNSA-N tert-butyl n-[(2s,3r)-4-(cyclohexylamino)-3-hydroxy-1-phenylbutan-2-yl]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)[C@H](O)CNC1CCCCC1)C1=CC=CC=C1 WYEUFUDFBYLDSG-RBUKOAKNSA-N 0.000 description 7
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
• XJRLZIBKKHJOHI-UHFFFAOYSA-N 2-(3-methoxyphenyl)propan-2-amine Chemical compound COC1=CC=CC(C(C)(C)N)=C1 XJRLZIBKKHJOHI-UHFFFAOYSA-N 0.000 description 6
• IJHKKRQRUUQIJU-UHFFFAOYSA-N 2-(hydroxymethylidene)propanedial Chemical compound OC=C(C=O)C=O IJHKKRQRUUQIJU-UHFFFAOYSA-N 0.000 description 6
• ZKLBPUYMTHPNOQ-UHFFFAOYSA-N 5-bromothiophene-3-carbaldehyde Chemical compound BrC1=CC(C=O)=CS1 ZKLBPUYMTHPNOQ-UHFFFAOYSA-N 0.000 description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
• 238000010511 deprotection reaction Methods 0.000 description 6
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
• PQEPFVIAMNKHAV-UHFFFAOYSA-N methyl 3-ethyl-7-nitro-1h-indole-5-carboxylate Chemical compound C1=C(C(=O)OC)C=C2C(CC)=CNC2=C1[N+]([O-])=O PQEPFVIAMNKHAV-UHFFFAOYSA-N 0.000 description 6
• PRTLMEWWYBJZPN-UHFFFAOYSA-N methyl 4-amino-3-bromo-5-nitrobenzoate Chemical compound COC(=O)C1=CC(Br)=C(N)C([N+]([O-])=O)=C1 PRTLMEWWYBJZPN-UHFFFAOYSA-N 0.000 description 6
• HNTLUEZVPLRQEV-UHFFFAOYSA-N methyl 4-amino-3-nitrobenzoate Chemical compound COC(=O)C1=CC=C(N)C([N+]([O-])=O)=C1 HNTLUEZVPLRQEV-UHFFFAOYSA-N 0.000 description 6
• DAKFRSYYMIMIEF-UHFFFAOYSA-N methyl 7-(chloromethylsulfonylamino)-3-ethyl-1h-indole-5-carboxylate Chemical compound C1=C(C(=O)OC)C=C2C(CC)=CNC2=C1NS(=O)(=O)CCl DAKFRSYYMIMIEF-UHFFFAOYSA-N 0.000 description 6
• OLYZIBQKFQFKHG-UHFFFAOYSA-N methyl 7-(ethenylsulfonylamino)-3-ethyl-1h-indole-5-carboxylate Chemical compound C1=C(C(=O)OC)C=C2C(CC)=CNC2=C1NS(=O)(=O)C=C OLYZIBQKFQFKHG-UHFFFAOYSA-N 0.000 description 6
• 238000010992 reflux Methods 0.000 description 6
• OWELBZTXHNMEKC-UHFFFAOYSA-N tert-butyl n-(4,4-difluorocyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(F)(F)CC1 OWELBZTXHNMEKC-UHFFFAOYSA-N 0.000 description 6
• OITAMJBKJGSZDG-UHFFFAOYSA-N tert-butyl n-[(3-ethyl-1,2-oxazol-5-yl)methyl]carbamate Chemical compound CCC=1C=C(CNC(=O)OC(C)(C)C)ON=1 OITAMJBKJGSZDG-UHFFFAOYSA-N 0.000 description 6
• DSPYCWLYGXGJNJ-UHFFFAOYSA-N tert-butyl n-prop-2-ynylcarbamate Chemical compound CC(C)(C)OC(=O)NCC#C DSPYCWLYGXGJNJ-UHFFFAOYSA-N 0.000 description 6
• LJNOFDXDKWGSTD-UHFFFAOYSA-N (3-ethyl-1,2-oxazol-5-yl)methanamine;hydrochloride Chemical compound Cl.CCC=1C=C(CN)ON=1 LJNOFDXDKWGSTD-UHFFFAOYSA-N 0.000 description 5
• SGFFFEYHPPBPHU-UHFFFAOYSA-N 2,6-dimethylheptan-2-amine Chemical compound CC(C)CCCC(C)(C)N SGFFFEYHPPBPHU-UHFFFAOYSA-N 0.000 description 5
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• YFGTZAZAUIXTBO-VQTJNVASSA-N benzyl n-[(2r,3s)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-phenylbutyl]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)[C@H](O)CNC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 YFGTZAZAUIXTBO-VQTJNVASSA-N 0.000 description 5
• 150000001642 boronic acid derivatives Chemical class 0.000 description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
• 238000001816 cooling Methods 0.000 description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
• 235000019441 ethanol Nutrition 0.000 description 5
• XRGVKASNSSUQFM-UHFFFAOYSA-N ethyl 2-methyl-2-[3-(trifluoromethyl)phenyl]propanoate Chemical compound CCOC(=O)C(C)(C)C1=CC=CC(C(F)(F)F)=C1 XRGVKASNSSUQFM-UHFFFAOYSA-N 0.000 description 5
• VDHOIZQKJIGJKD-UHFFFAOYSA-N ethyl 3-ethyl-7-(phenylmethoxycarbonylamino)-1h-indole-5-carboxylate Chemical compound C=12NC=C(CC)C2=CC(C(=O)OCC)=CC=1NC(=O)OCC1=CC=CC=C1 VDHOIZQKJIGJKD-UHFFFAOYSA-N 0.000 description 5
• LDRHMIYQHHLQFR-UHFFFAOYSA-N ethyl 3-ethyl-7-iodo-1h-indole-5-carboxylate Chemical compound CCOC(=O)C1=CC(I)=C2NC=C(CC)C2=C1 LDRHMIYQHHLQFR-UHFFFAOYSA-N 0.000 description 5
• QSVHOENZNLGNQE-UHFFFAOYSA-N ethyl 7-(3-chloropropanoylamino)-3-ethyl-1h-indole-5-carboxylate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCl)=C2NC=C(CC)C2=C1 QSVHOENZNLGNQE-UHFFFAOYSA-N 0.000 description 5
• XBAQPGKOHQKYGR-UHFFFAOYSA-N ethyl 7-(ethenylsulfonylamino)-3-ethyl-1h-indole-5-carboxylate Chemical compound CCOC(=O)C1=CC(NS(=O)(=O)C=C)=C2NC=C(CC)C2=C1 XBAQPGKOHQKYGR-UHFFFAOYSA-N 0.000 description 5
• 239000011737 fluorine Substances 0.000 description 5
• 229910052731 fluorine Inorganic materials 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• HEAIJOGKHVIFQN-UHFFFAOYSA-N methyl 3-bromo-5-nitro-4-[(2,2,2-trifluoroacetyl)amino]benzoate Chemical compound COC(=O)C1=CC(Br)=C(NC(=O)C(F)(F)F)C([N+]([O-])=O)=C1 HEAIJOGKHVIFQN-UHFFFAOYSA-N 0.000 description 5
• HLZDNHPUDFBUTD-UHFFFAOYSA-N methyl 6-ethyl-1h-[1,2,5]thiadiazino[3,4,5-hi]indole-8-carboxylate 2,2-dioxide Chemical compound C1S(=O)(=O)NC2=CC(C(=O)OC)=CC3=C2N1C=C3CC HLZDNHPUDFBUTD-UHFFFAOYSA-N 0.000 description 5
• LYAAGWPQSQMMII-JTQLQIEISA-N tert-butyl n-[(2s)-1-(cyclohexylamino)-1-oxopropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](C)C(=O)NC1CCCCC1 LYAAGWPQSQMMII-JTQLQIEISA-N 0.000 description 5
• UAMLXEOGMPDKNK-UONOGXRCSA-N tert-butyl n-[(2s,3r)-1-(3-chlorophenyl)-3-hydroxy-4-(methylamino)butan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]([C@H](O)CNC)CC1=CC=CC(Cl)=C1 UAMLXEOGMPDKNK-UONOGXRCSA-N 0.000 description 5
• PDLATMBIYFQTOJ-QWHCGFSZSA-N tert-butyl n-[(2s,3r)-4-amino-3-hydroxy-1-phenylbutan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]([C@H](O)CN)CC1=CC=CC=C1 PDLATMBIYFQTOJ-QWHCGFSZSA-N 0.000 description 5
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 5
• LBVGHGQWYIKFMS-SLAHTUFOSA-N (2r,3s)-3-amino-1-(cyclohexylamino)-4-phenylbutan-2-ol;dihydrochloride Chemical compound Cl.Cl.C([C@H](N)[C@H](O)CNC1CCCCC1)C1=CC=CC=C1 LBVGHGQWYIKFMS-SLAHTUFOSA-N 0.000 description 4
• AZHYDIMPPBQKHX-OAMYOWMRSA-N (2r,3s)-3-amino-1-[(3-methoxyphenyl)methylamino]-4-phenylbutan-2-ol;4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.COC1=CC=CC(CNC[C@@H](O)[C@@H](N)CC=2C=CC=CC=2)=C1 AZHYDIMPPBQKHX-OAMYOWMRSA-N 0.000 description 4
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 4
• YEGWNHBRMASMGR-UHFFFAOYSA-N 2-[3-(trifluoromethyl)phenyl]propan-2-amine Chemical compound CC(C)(N)C1=CC=CC(C(F)(F)F)=C1 YEGWNHBRMASMGR-UHFFFAOYSA-N 0.000 description 4
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 4
• XJOFPJZWSSQZMN-UHFFFAOYSA-N 2-methyl-2-[3-(trifluoromethyl)phenyl]propanoic acid Chemical compound OC(=O)C(C)(C)C1=CC=CC(C(F)(F)F)=C1 XJOFPJZWSSQZMN-UHFFFAOYSA-N 0.000 description 4
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 4
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