HRP980093A2 - Heterocyclic compounds, pharmaceutical compositions comprising same, and methods for inhibiting "beta"-amyloid peptide release and/or its synthesis by use of such compounds - Google Patents

Info

Publication number

HRP980093A2

HRP980093A2 HR08/808,236A HRP980093A HRP980093A2 HR P980093 A2 HRP980093 A2 HR P980093A2 HR P980093 A HRP980093 A HR P980093A HR P980093 A2 HRP980093 A2 HR P980093A2

Authority

HR

Croatia

Prior art keywords

group

substituted

alkyl

cycloalkyl

aryl

Prior art date

1997-02-28

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• 150000001875 compounds Chemical class 0.000 title claims description 187
• 238000000034 method Methods 0.000 title claims description 174
• 150000002391 heterocyclic compounds Chemical class 0.000 title claims description 173
• 230000015572 biosynthetic process Effects 0.000 title claims description 97
• 238000003786 synthesis reaction Methods 0.000 title claims description 95
• 230000002401 inhibitory effect Effects 0.000 title claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 9
• 108090000765 processed proteins & peptides Proteins 0.000 title description 5
• -1 Cyano, Carboxyl Chemical group 0.000 claims description 748
• 125000000217 alkyl group Chemical group 0.000 claims description 256
• 125000003118 aryl group Chemical group 0.000 claims description 236
• 125000001072 heteroaryl group Chemical group 0.000 claims description 219
• 229910052739 hydrogen Inorganic materials 0.000 claims description 199
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 196
• 239000001257 hydrogen Substances 0.000 claims description 192
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 187
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 158
• 125000003342 alkenyl group Chemical group 0.000 claims description 124
• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 112
• 125000000304 alkynyl group Chemical group 0.000 claims description 93
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 90
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 89
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 87
• 125000001424 substituent group Chemical group 0.000 claims description 87
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 85
• 125000004426 substituted alkynyl group Chemical group 0.000 claims description 83
• 229910052760 oxygen Inorganic materials 0.000 claims description 77
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 75
• 239000001301 oxygen Substances 0.000 claims description 75
• 125000003545 alkoxy group Chemical group 0.000 claims description 71
• 239000000203 mixture Substances 0.000 claims description 69
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 67
• 239000011737 fluorine Chemical group 0.000 claims description 67
• 229910052731 fluorine Chemical group 0.000 claims description 67
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 64
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 57
• 229910052717 sulfur Inorganic materials 0.000 claims description 57
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 56
• 239000011593 sulfur Substances 0.000 claims description 56
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 50
• 125000004043 oxo group Chemical group O=* 0.000 claims description 47
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 47
• 125000005309 thioalkoxy group Chemical group 0.000 claims description 44
• 125000003282 alkyl amino group Chemical class 0.000 claims description 43
• 125000004432 carbon atom Chemical group C* 0.000 claims description 41
• 125000002252 acyl group Chemical group 0.000 claims description 36
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 36
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 35
• 125000005843 halogen group Chemical group 0.000 claims description 35
• 125000000623 heterocyclic group Chemical group 0.000 claims description 34
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 33
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 32
• 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims description 31
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 30
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 30
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 30
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 30
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 30
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 30
• 125000004122 cyclic group Chemical group 0.000 claims description 29
• DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 claims description 28
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 28
• 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 27
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 27
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 27
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 26
• 239000002131 composite material Substances 0.000 claims description 26
• 229910052799 carbon Inorganic materials 0.000 claims description 24
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 24
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 22
• 229910052757 nitrogen Chemical group 0.000 claims description 22
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 21
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 21
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
• 125000004001 thioalkyl group Chemical group 0.000 claims description 21
• 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 20
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 20
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 20
• 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 20
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 20
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 20
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 19
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
• 150000003573 thiols Chemical class 0.000 claims description 17
• 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 16
• 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 16
• 125000005842 heteroatom Chemical group 0.000 claims description 16
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
• 125000003107 substituted aryl group Chemical group 0.000 claims description 15
• 101100240516 Caenorhabditis elegans nhr-10 gene Proteins 0.000 claims description 14
• 150000001733 carboxylic acid esters Chemical class 0.000 claims description 14
• 125000003277 amino group Chemical group 0.000 claims description 13
• 125000004076 pyridyl group Chemical group 0.000 claims description 12
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 11
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
• 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 11
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 10
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 10
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 10
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 10
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 10
• 125000004361 3,4,5-trifluorophenyl group Chemical group [H]C1=C(F)C(F)=C(F)C([H])=C1* 0.000 claims description 10
• 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 10
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 10
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 10
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 10
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 10
• 125000006291 3-hydroxybenzyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 10
• 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 10
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 10
• 125000005917 3-methylpentyl group Chemical group 0.000 claims description 10
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 10
• 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 10
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 10
• 125000006323 alkenyl amino group Chemical class 0.000 claims description 10
• 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 10
• 125000006378 chloropyridyl group Chemical group 0.000 claims description 10
• 125000006310 cycloalkyl amino group Chemical class 0.000 claims description 10
• 125000006379 fluoropyridyl group Chemical group 0.000 claims description 10
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 10
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 10
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 10
• 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 10
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 10
• 125000004265 thionaphthen-2-yl group Chemical group [H]C1=C(*)SC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 10
• 125000004423 acyloxy group Chemical group 0.000 claims description 9
• 238000006467 substitution reaction Methods 0.000 claims description 9
• 125000005605 benzo group Chemical group 0.000 claims description 7
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 7
• 125000000464 thioxo group Chemical group S=* 0.000 claims description 7
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 6
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 6
• CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 claims description 5
• JTJGQDDZZZKALW-UHFFFAOYSA-N 3-o-tert-butyl 5-o-methyl 5-phenyl-2-[1-(phenylmethoxycarbonylamino)ethyl]-4h-imidazole-3,5-dicarboxylate Chemical compound N=1C(C(=O)OC)(C=2C=CC=CC=2)CN(C(=O)OC(C)(C)C)C=1C(C)NC(=O)OCC1=CC=CC=C1 JTJGQDDZZZKALW-UHFFFAOYSA-N 0.000 claims description 4
• 230000001413 cellular effect Effects 0.000 claims description 4
• 230000006866 deterioration Effects 0.000 claims description 4
• JUIQOABNSLTJSW-UHFFFAOYSA-N 2-Methyl-4,5-dihydro-1,3-thiazole Chemical compound CC1=NCCS1 JUIQOABNSLTJSW-UHFFFAOYSA-N 0.000 claims description 3
• IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 claims description 3
• VMZJJMLEBNSYTG-LLTODGECSA-N ethyl 2-[(1S)-1-[[2-(3,5-difluorophenyl)acetyl]amino]ethyl]-4,5-dihydro-1,3-oxazole-5-carboxylate Chemical compound FC=1C=C(C=C(C=1)F)CC(=O)N[C@@H](C)C=1OC(CN=1)C(=O)OCC VMZJJMLEBNSYTG-LLTODGECSA-N 0.000 claims description 3
• VRGDMTDTSATYAB-UHFFFAOYSA-N methyl 2-[1-[[2-(3,5-difluorophenyl)acetyl]amino]ethyl]-5-phenyl-1,4-dihydroimidazole-5-carboxylate Chemical compound N=1C(C(=O)OC)(C=2C=CC=CC=2)CNC=1C(C)NC(=O)CC1=CC(F)=CC(F)=C1 VRGDMTDTSATYAB-UHFFFAOYSA-N 0.000 claims description 3
• WOIZKMKUGJBVMI-UHFFFAOYSA-N methyl 5-phenyl-3-[1-(phenylmethoxycarbonylamino)ethyl]-4h-imidazole-5-carboxylate Chemical compound C1=NC(C(=O)OC)(C=2C=CC=CC=2)CN1C(C)NC(=O)OCC1=CC=CC=C1 WOIZKMKUGJBVMI-UHFFFAOYSA-N 0.000 claims description 3
• 125000004301 thiazolin-2-yl group Chemical group [H]C1([H])SC(*)=NC1([H])[H] 0.000 claims description 3
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 7
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 4
• LWCQHEHMHWIMQY-UHFFFAOYSA-N FC=1C=C(C=C(C1)F)CC(=O)NC(C)C=1NCC(N1)(CC1=CC=CC=C1)C(=O)OC.C(C)(C)(C)OC(=O)N1C(=NC(C1)(CC1=CC=CC=C1)C(=O)OC)C(C)NC(CC1=CC(=CC(=C1)F)F)=O Chemical compound FC=1C=C(C=C(C1)F)CC(=O)NC(C)C=1NCC(N1)(CC1=CC=CC=C1)C(=O)OC.C(C)(C)(C)OC(=O)N1C(=NC(C1)(CC1=CC=CC=C1)C(=O)OC)C(C)NC(CC1=CC(=CC(=C1)F)F)=O LWCQHEHMHWIMQY-UHFFFAOYSA-N 0.000 claims 2
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical class C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 claims 2
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 1
• 238000006243 chemical reaction Methods 0.000 description 77
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
• 150000003951 lactams Chemical class 0.000 description 69
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 55
• 239000000243 solution Substances 0.000 description 46
• 125000004450 alkenylene group Chemical group 0.000 description 42
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 41
• 208000024827 Alzheimer disease Diseases 0.000 description 38
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
• 125000002947 alkylene group Chemical group 0.000 description 36
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
• 239000000047 product Substances 0.000 description 31
• 239000013543 active substance Substances 0.000 description 27
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
• 235000019439 ethyl acetate Nutrition 0.000 description 26
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 24
• 125000004093 cyano group Chemical group *C#N 0.000 description 22
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
• 150000001412 amines Chemical class 0.000 description 20
• 239000003153 chemical reaction reagent Substances 0.000 description 19
• 238000005481 NMR spectroscopy Methods 0.000 description 18
• 239000002585 base Substances 0.000 description 18
• 125000000266 alpha-aminoacyl group Chemical group 0.000 description 17
• 238000002360 preparation method Methods 0.000 description 17
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
• 239000000126 substance Substances 0.000 description 16
• 229940024606 amino acid Drugs 0.000 description 15
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