BG102936A - Инхибитори на протеин фарнезил трансфераза - Google Patents

Info

Publication number

BG102936A

BG102936A BG102936A BG10293698A BG102936A BG 102936 A BG102936 A BG 102936A BG 102936 A BG102936 A BG 102936A BG 10293698 A BG10293698 A BG 10293698A BG 102936 A BG102936 A BG 102936A

Authority

BG

Bulgaria

Prior art keywords

methyl

benzyl

ethyl

imidazol

carbamoyl

Prior art date

1996-05-22

Links

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• Global Dossier
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• 108010054353 p21(ras) farnesyl-protein transferase Proteins 0.000 title abstract description 9
• 239000003112 inhibitor Substances 0.000 title abstract description 6
• 239000000203 mixture Substances 0.000 claims abstract description 51
• 238000000034 method Methods 0.000 claims abstract description 41
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 40
• 208000037803 restenosis Diseases 0.000 claims abstract description 32
• 201000011510 cancer Diseases 0.000 claims abstract description 31
• 201000004681 Psoriasis Diseases 0.000 claims abstract description 17
• -1 N-pyridyl Chemical group 0.000 claims description 481
• 150000001875 compounds Chemical class 0.000 claims description 265
• 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 91
• 125000000217 alkyl group Chemical group 0.000 claims description 74
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 71
• KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims description 64
• 229910052739 hydrogen Inorganic materials 0.000 claims description 60
• 239000001257 hydrogen Substances 0.000 claims description 60
• 150000002148 esters Chemical class 0.000 claims description 42
• 150000002431 hydrogen Chemical class 0.000 claims description 33
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
• PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 claims description 25
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
• 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 21
• 150000003839 salts Chemical class 0.000 claims description 21
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
• 150000001408 amides Chemical class 0.000 claims description 18
• 229910052736 halogen Inorganic materials 0.000 claims description 17
• 150000002367 halogens Chemical class 0.000 claims description 17
• 229940002612 prodrug Drugs 0.000 claims description 17
• 239000000651 prodrug Substances 0.000 claims description 17
• 208000036142 Viral infection Diseases 0.000 claims description 16
• 230000009385 viral infection Effects 0.000 claims description 16
• 239000002253 acid Substances 0.000 claims description 14
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 13
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
• 125000001072 heteroaryl group Chemical group 0.000 claims description 8
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 7
• ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 6
• 125000003118 aryl group Chemical group 0.000 claims description 6
• 210000001072 colon Anatomy 0.000 claims description 6
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• 239000000460 chlorine Substances 0.000 claims description 5
• 229940080818 propionamide Drugs 0.000 claims description 5
• 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 4
• 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 claims description 4
• 206010005003 Bladder cancer Diseases 0.000 claims description 4
• 210000000481 breast Anatomy 0.000 claims description 4
• 229910052794 bromium Inorganic materials 0.000 claims description 4
• 201000010099 disease Diseases 0.000 claims description 4
• 210000001685 thyroid gland Anatomy 0.000 claims description 4
• YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 claims description 3
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 claims description 3
• 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 3
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
• RDXDECXODBTMOR-IZCXSWDTSA-N benzyl n-[(2s)-1-[(2-chlorophenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1Cl RDXDECXODBTMOR-IZCXSWDTSA-N 0.000 claims description 3
• OIDZVPMBRLHMFX-FZNWDQQTSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(4-methoxyphenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(OC)=CC=C1CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC(=O)NCC(C)C1=CC=CC=C1 OIDZVPMBRLHMFX-FZNWDQQTSA-N 0.000 claims description 3
• HWLKYGTXYNWEPH-NYZBEGEVSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-oxo-1-[[2-oxo-2-(2-phenylbutylamino)ethyl]-[(4-phenylmethoxyphenyl)methyl]amino]propan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(CC)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 HWLKYGTXYNWEPH-NYZBEGEVSA-N 0.000 claims description 3
• JLCNKOBKJBWEIC-UHFFFAOYSA-N benzyl n-[3-(1h-imidazol-5-yl)-1-[2-methylpropyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1NC=NC=1CC(NC(=O)OCC=1C=CC=CC=1)C(=O)N(CC(C)C)CC(=O)NCC(C)C1=CC=CC=C1 JLCNKOBKJBWEIC-UHFFFAOYSA-N 0.000 claims description 3
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
• 229910052801 chlorine Inorganic materials 0.000 claims description 3
• 208000029742 colonic neoplasm Diseases 0.000 claims description 3
• 229910052731 fluorine Inorganic materials 0.000 claims description 3
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
• DUFPCEPLPMRHOB-UHFFFAOYSA-N N-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]propanamide Chemical compound CC(CNC(=O)CNC(CC)=O)(C)C1=CC=CC=C1 DUFPCEPLPMRHOB-UHFFFAOYSA-N 0.000 claims description 2
• NQVJXBFXQFGIHU-IZCXSWDTSA-N benzyl n-[(2s)-1-[(4-bromophenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(Br)C=C1 NQVJXBFXQFGIHU-IZCXSWDTSA-N 0.000 claims description 2
• 239000011737 fluorine Substances 0.000 claims description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
• 230000001225 therapeutic effect Effects 0.000 claims 6
• 208000026310 Breast neoplasm Diseases 0.000 claims 2
• 208000024770 Thyroid neoplasm Diseases 0.000 claims 2
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 2
• KWBIXTIBYFUAGV-UHFFFAOYSA-N ethylcarbamic acid Chemical compound CCNC(O)=O KWBIXTIBYFUAGV-UHFFFAOYSA-N 0.000 claims 2
• 208000020816 lung neoplasm Diseases 0.000 claims 2
• 210000000496 pancreas Anatomy 0.000 claims 2
• 201000005112 urinary bladder cancer Diseases 0.000 claims 2
• 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 claims 1
• DMGJRELNPSPIKC-IZCXSWDTSA-N benzyl n-[(2s)-1-[(3-chlorophenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC(Cl)=C1 DMGJRELNPSPIKC-IZCXSWDTSA-N 0.000 claims 1
• SSXFUPUONWGRIP-IZCXSWDTSA-N benzyl n-[(2s)-1-[(4-chlorophenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(Cl)C=C1 SSXFUPUONWGRIP-IZCXSWDTSA-N 0.000 claims 1
• QCNOUBMNVDBZBN-IZCXSWDTSA-N benzyl n-[(2s)-1-[(4-fluorophenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(F)C=C1 QCNOUBMNVDBZBN-IZCXSWDTSA-N 0.000 claims 1
• NPVIMMQTVLPHKV-RWYGWLOXSA-N benzyl n-[(2s)-1-[[2-(2,2-diphenylethylamino)-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 NPVIMMQTVLPHKV-RWYGWLOXSA-N 0.000 claims 1
• JFRDYWFPSQJTNE-FZNWDQQTSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(3-methoxyphenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound COC1=CC=CC(CN(CC(=O)NCC(C)C=2C=CC=CC=2)C(=O)[C@H](CC=2NC=NC=2)NC(=O)OCC=2C=CC=CC=2)=C1 JFRDYWFPSQJTNE-FZNWDQQTSA-N 0.000 claims 1
• QGXVHBXRVCWIAD-NDEPHWFRSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(4-iodophenyl)methyl-[2-oxo-2-(2-phenylethylamino)ethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(I)=CC=C1CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC(=O)NCCC1=CC=CC=C1 QGXVHBXRVCWIAD-NDEPHWFRSA-N 0.000 claims 1
• LDKNRMHCDWFIOW-PMERELPUSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(4-methoxyphenyl)methyl-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(OC)=CC=C1CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(=O)NCC(C)(C)C1=CC=CC=C1 LDKNRMHCDWFIOW-PMERELPUSA-N 0.000 claims 1
• XSNSVLNJHGTYTL-NDEPHWFRSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-(pyridin-4-ylmethyl)amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=NC=C1 XSNSVLNJHGTYTL-NDEPHWFRSA-N 0.000 claims 1
• JRRUOMUYZWMQNH-VKPSHWPRSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[naphthalen-1-ylmethyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](C(=O)N(CC=1C2=CC=CC=C2C=CC=1)CC(=O)NCC(C)C=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)C1=CN=CN1 JRRUOMUYZWMQNH-VKPSHWPRSA-N 0.000 claims 1
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims 1
• 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 1
• 238000011282 treatment Methods 0.000 abstract description 6
• AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 abstract 1
• 208000015181 infectious disease Diseases 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 164
• 239000000243 solution Substances 0.000 description 95
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 86
• 239000006260 foam Substances 0.000 description 71
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 62
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 41
• ZVTWZSXLLMNMQC-UHFFFAOYSA-N 4-phenylmethoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OCC1=CC=CC=C1 ZVTWZSXLLMNMQC-UHFFFAOYSA-N 0.000 description 40
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 40
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 31
• 235000019341 magnesium sulphate Nutrition 0.000 description 31
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
• 239000012267 brine Substances 0.000 description 28
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 27
• 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 27
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
• 239000010410 layer Substances 0.000 description 24
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
• XPQIPUZPSLAZDV-UHFFFAOYSA-N 2-pyridylethylamine Chemical compound NCCC1=CC=CC=N1 XPQIPUZPSLAZDV-UHFFFAOYSA-N 0.000 description 23
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
• 108010014186 ras Proteins Proteins 0.000 description 23
• 102000016914 ras Proteins Human genes 0.000 description 23
• 239000011541 reaction mixture Substances 0.000 description 21
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
• AXORVIZLPOGIRG-UHFFFAOYSA-N β-methylphenethylamine Chemical compound NCC(C)C1=CC=CC=C1 AXORVIZLPOGIRG-UHFFFAOYSA-N 0.000 description 20
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 19
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 19
• 239000000047 product Substances 0.000 description 19
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 17
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
• 238000003818 flash chromatography Methods 0.000 description 16
• 239000007787 solid Substances 0.000 description 16
• RORCPASRNRYEDG-UHFFFAOYSA-N 2-methyl-2-phenylpropan-1-amine;hydrochloride Chemical compound Cl.NCC(C)(C)C1=CC=CC=C1 RORCPASRNRYEDG-UHFFFAOYSA-N 0.000 description 15
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
• 108090000623 proteins and genes Proteins 0.000 description 14
• 235000017557 sodium bicarbonate Nutrition 0.000 description 14
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
• 239000012044 organic layer Substances 0.000 description 13
• 235000018102 proteins Nutrition 0.000 description 13
• 102000004169 proteins and genes Human genes 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 12
• 229920001817 Agar Polymers 0.000 description 11
• 235000010419 agar Nutrition 0.000 description 11
• 239000011230 binding agent Substances 0.000 description 11
• 239000000706 filtrate Substances 0.000 description 11
• 239000008272 agar Substances 0.000 description 10
• 239000002904 solvent Substances 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• 238000006243 chemical reaction Methods 0.000 description 9
• 230000012010 growth Effects 0.000 description 9
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
• 239000003921 oil Substances 0.000 description 9
• 235000019198 oils Nutrition 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 9
• 238000012360 testing method Methods 0.000 description 9
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
• 235000019441 ethanol Nutrition 0.000 description 8
• 230000002401 inhibitory effect Effects 0.000 description 8
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