SK398A3 - Pyrrolopyrimidines and processes for the preparation thereof - Google Patents

Info

Publication number

SK398A3

SK398A3 SK3-98A SK398A SK398A3 SK 398 A3 SK398 A3 SK 398A3 SK 398 A SK398 A SK 398A SK 398 A3 SK398 A3 SK 398A3

Authority

SK

Slovakia

Prior art keywords

group

lower alkyl

carbamoyl

phenyl

pyrrolo

Prior art date

1995-07-06

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims description 58
• 238000002360 preparation method Methods 0.000 title claims description 36
• 230000008569 process Effects 0.000 title claims description 17
• 150000004944 pyrrolopyrimidines Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 224
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 18
• JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical class N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 claims abstract description 6
• 125000000217 alkyl group Chemical group 0.000 claims description 495
• -1 cyano, amino Chemical group 0.000 claims description 234
• 229910052757 nitrogen Inorganic materials 0.000 claims description 183
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 181
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 114
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 112
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 94
• 150000003839 salts Chemical class 0.000 claims description 85
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 83
• 125000003282 alkyl amino group Chemical group 0.000 claims description 78
• 125000003277 amino group Chemical group 0.000 claims description 71
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 65
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 65
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 63
• 125000003545 alkoxy group Chemical group 0.000 claims description 61
• 125000005843 halogen group Chemical group 0.000 claims description 61
• 125000004423 acyloxy group Chemical group 0.000 claims description 59
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 54
• 125000004432 carbon atom Chemical group C* 0.000 claims description 51
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 50
• 125000006239 protecting group Chemical group 0.000 claims description 47
• 125000001424 substituent group Chemical group 0.000 claims description 39
• 229910052739 hydrogen Inorganic materials 0.000 claims description 38
• 229910052736 halogen Inorganic materials 0.000 claims description 37
• 150000002367 halogens Chemical class 0.000 claims description 33
• 125000001624 naphthyl group Chemical group 0.000 claims description 29
• 239000001257 hydrogen Substances 0.000 claims description 28
• 125000004076 pyridyl group Chemical group 0.000 claims description 27
• 125000002252 acyl group Chemical group 0.000 claims description 25
• 125000000524 functional group Chemical group 0.000 claims description 25
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 24
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
• 239000002253 acid Substances 0.000 claims description 22
• 125000003342 alkenyl group Chemical group 0.000 claims description 21
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 17
• 125000004193 piperazinyl group Chemical group 0.000 claims description 15
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 14
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 12
• 230000001681 protective effect Effects 0.000 claims description 12
• 150000001412 amines Chemical class 0.000 claims description 11
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
• JLYIDLKBGFXUTE-UHFFFAOYSA-N ethyl 4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidine-6-carboxylate Chemical compound N1=CN=C2NC(C(=O)OCC)=CC2=C1NC1=CC=CC(Cl)=C1 JLYIDLKBGFXUTE-UHFFFAOYSA-N 0.000 claims description 10
• 241001465754 Metazoa Species 0.000 claims description 9
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
• 150000004943 pyrrolo[2,3-d]pyrimidines Chemical class 0.000 claims description 8
• 201000011510 cancer Diseases 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• YOAQRPAYMXTKQI-UHFFFAOYSA-N 4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid Chemical compound N1=CN=C2NC(C(=O)O)=CC2=C1NC1=CC=CC(Cl)=C1 YOAQRPAYMXTKQI-UHFFFAOYSA-N 0.000 claims description 6
• 125000004429 atom Chemical group 0.000 claims description 6
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 6
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
• WTGCGBNMDUJBEX-UHFFFAOYSA-N 4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 WTGCGBNMDUJBEX-UHFFFAOYSA-N 0.000 claims description 5
• FLBNYSVQCAAWOC-UHFFFAOYSA-N ethyl 4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 FLBNYSVQCAAWOC-UHFFFAOYSA-N 0.000 claims description 5
• 150000003512 tertiary amines Chemical class 0.000 claims description 5
• KWAKLZADYVJMGC-UHFFFAOYSA-N 4-[4-(3-chloroanilino)-5-[(dimethylamino)methyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol Chemical compound C=12C(CN(C)C)=C(C=3C=CC(O)=CC=3)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 KWAKLZADYVJMGC-UHFFFAOYSA-N 0.000 claims description 4
• UZDFIMXOVIIKQO-UHFFFAOYSA-N 6-(4-aminophenyl)-n-(3-chlorophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(N)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 UZDFIMXOVIIKQO-UHFFFAOYSA-N 0.000 claims description 4
• UPDHEPFPHMXRKP-UHFFFAOYSA-N [4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]methanol Chemical compound N1=CN=C2NC(CO)=CC2=C1NC1=CC=CC(Cl)=C1 UPDHEPFPHMXRKP-UHFFFAOYSA-N 0.000 claims description 4
• 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 4
• 239000012024 dehydrating agents‎ Substances 0.000 claims description 4
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
• SIVRSPUOZPNICK-UHFFFAOYSA-N n-(3-chlorophenyl)-6-[(dimethylamino)methyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N1=CN=C2NC(CN(C)C)=CC2=C1NC1=CC=CC(Cl)=C1 SIVRSPUOZPNICK-UHFFFAOYSA-N 0.000 claims description 4
• ONUUZBLFKUZPCU-UHFFFAOYSA-N n-(3-chlorophenyl)-6-pyridin-2-yl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C=C(NC=3N=CN=2)C=2N=CC=CC=2)=C1 ONUUZBLFKUZPCU-UHFFFAOYSA-N 0.000 claims description 4
• RFOKKVGXGZFMQU-OAHLLOKOSA-N n-[4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]propanamide Chemical compound C1=CC(NC(=O)CC)=CC=C1C(NC1=NC=N2)=CC1=C2N[C@H](C)C1=CC=CC=C1 RFOKKVGXGZFMQU-OAHLLOKOSA-N 0.000 claims description 4
• 150000003233 pyrroles Chemical class 0.000 claims description 4
• JJJQHTCJNMSSJV-UHFFFAOYSA-N pyrrolo[2,3-d]pyrimidin-4-one Chemical class O=C1N=CN=C2N=CC=C12 JJJQHTCJNMSSJV-UHFFFAOYSA-N 0.000 claims description 4
• BYYLPECJKOEHBV-UHFFFAOYSA-N 4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde Chemical compound ClC1=CC=CC(NC=2C=3C=C(C=O)NC=3N=CN=2)=C1 BYYLPECJKOEHBV-UHFFFAOYSA-N 0.000 claims description 3
• HRRSTGSFDNCRBK-UHFFFAOYSA-N 4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=CN=C2NC(C(=O)N)=CC2=C1NC1=CC=CC(Cl)=C1 HRRSTGSFDNCRBK-UHFFFAOYSA-N 0.000 claims description 3
• YFOPRDNSBLGPMI-UHFFFAOYSA-N 4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol Chemical compound C1=CC(O)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 YFOPRDNSBLGPMI-UHFFFAOYSA-N 0.000 claims description 3
• 241000282412 Homo Species 0.000 claims description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
• KXVFXQNQBCHBKL-UHFFFAOYSA-N n-(3-chlorophenyl)-5-methyl-6-pyridin-2-yl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=12C(C)=C(C=3N=CC=CC=3)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 KXVFXQNQBCHBKL-UHFFFAOYSA-N 0.000 claims description 3
• DHSPAWKUZSBXHS-UHFFFAOYSA-N n-(3-chlorophenyl)-6-(4-nitrophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 DHSPAWKUZSBXHS-UHFFFAOYSA-N 0.000 claims description 3
• ZPPJQVOJGAAFFM-MRXNPFEDSA-N 2,2-dimethyl-n-[3-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]propanamide Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=CC(NC(=O)C(C)(C)C)=C1 ZPPJQVOJGAAFFM-MRXNPFEDSA-N 0.000 claims description 2
• QWTLRAWOLQZKFX-MRXNPFEDSA-N 2,2-dimethyl-n-[4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]propanamide Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(NC(=O)C(C)(C)C)C=C1 QWTLRAWOLQZKFX-MRXNPFEDSA-N 0.000 claims description 2
• VEBRIZYASKCCKZ-UHFFFAOYSA-N 2-[3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenoxy]acetamide Chemical compound NC(=O)COC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 VEBRIZYASKCCKZ-UHFFFAOYSA-N 0.000 claims description 2
• AHBMPRJMHUNHRS-UHFFFAOYSA-N 2-[4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenoxy]acetamide Chemical compound C1=CC(OCC(=O)N)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 AHBMPRJMHUNHRS-UHFFFAOYSA-N 0.000 claims description 2
• GYFHQWOKLLBICP-UHFFFAOYSA-N 2-[4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenoxy]acetic acid Chemical compound C1=CC(OCC(=O)O)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 GYFHQWOKLLBICP-UHFFFAOYSA-N 0.000 claims description 2
• SUEXSSUXWXXPNN-MRXNPFEDSA-N 2-methyl-n-[3-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]propanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C=2NC3=NC=NC(N[C@H](C)C=4C=CC=CC=4)=C3C=2)=C1 SUEXSSUXWXXPNN-MRXNPFEDSA-N 0.000 claims description 2
• QEMJSPGYFNYBPQ-UHFFFAOYSA-N 2-methylpropyl 4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]benzoate Chemical compound C1=CC(C(=O)OCC(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 QEMJSPGYFNYBPQ-UHFFFAOYSA-N 0.000 claims description 2
• RZRXPHUZFBUQFN-UHFFFAOYSA-N 3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 RZRXPHUZFBUQFN-UHFFFAOYSA-N 0.000 claims description 2
• IVXPKMHNZJSHQA-UHFFFAOYSA-N 4-(3-chloroanilino)-5-methyl-7h-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde Chemical compound C=12C(C)=C(C=O)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 IVXPKMHNZJSHQA-UHFFFAOYSA-N 0.000 claims description 2
• VIYAUNPLBAEUSN-UHFFFAOYSA-N 4-(3-chloroanilino)-5-methyl-7h-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid Chemical compound C=12C(C)=C(C(O)=O)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 VIYAUNPLBAEUSN-UHFFFAOYSA-N 0.000 claims description 2
• LNWOKFXJMDSXCT-UHFFFAOYSA-N 4-(3-chloroanilino)-6-methyl-7h-pyrrolo[2,3-d]pyrimidine-5-carbaldehyde Chemical compound C=12C(C=O)=C(C)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 LNWOKFXJMDSXCT-UHFFFAOYSA-N 0.000 claims description 2
• FBMVGKKWZJCOEZ-UHFFFAOYSA-N 4-(3-chloroanilino)-6-methyl-7h-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid Chemical compound C=12C(C(O)=O)=C(C)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 FBMVGKKWZJCOEZ-UHFFFAOYSA-N 0.000 claims description 2
• DKRKYQJAGJAZRT-UHFFFAOYSA-N 4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidine-6-carbonitrile Chemical compound ClC1=CC=CC(NC=2C=3C=C(NC=3N=CN=2)C#N)=C1 DKRKYQJAGJAZRT-UHFFFAOYSA-N 0.000 claims description 2
• QYVBDLWIXVYDDY-UHFFFAOYSA-N 4-(3-chloroanilino)-n-(3-methylbutyl)-7h-pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=CN=C2NC(C(=O)NCCC(C)C)=CC2=C1NC1=CC=CC(Cl)=C1 QYVBDLWIXVYDDY-UHFFFAOYSA-N 0.000 claims description 2
• HTUAWMQFTGNRIW-UHFFFAOYSA-N 4-(3-chloroanilino)-n-methyl-7h-pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=CN=C2NC(C(=O)NC)=CC2=C1NC1=CC=CC(Cl)=C1 HTUAWMQFTGNRIW-UHFFFAOYSA-N 0.000 claims description 2
• ZATTZEUEAMCUQY-UHFFFAOYSA-N 4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-diethylbenzamide Chemical compound C1=CC(C(=O)N(CC)CC)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 ZATTZEUEAMCUQY-UHFFFAOYSA-N 0.000 claims description 2
• ZILMYGJFUYGNHX-UHFFFAOYSA-N 4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]-n,n-dimethylbenzamide Chemical compound C1=CC(C(=O)N(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 ZILMYGJFUYGNHX-UHFFFAOYSA-N 0.000 claims description 2
• XRYJULCDUUATMC-CYBMUJFWSA-N 4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(O)C=C1 XRYJULCDUUATMC-CYBMUJFWSA-N 0.000 claims description 2
• KWPPCQGFDDELRR-SNVBAGLBSA-N 4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde Chemical compound C1([C@H](NC=2C=3C=C(C=O)NC=3N=CN=2)C)=CC=CC=C1 KWPPCQGFDDELRR-SNVBAGLBSA-N 0.000 claims description 2
• TVNJDLRYYVDKJX-SNVBAGLBSA-N 4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidine-6-carbonitrile Chemical compound C1([C@H](NC=2C=3C=C(NC=3N=CN=2)C#N)C)=CC=CC=C1 TVNJDLRYYVDKJX-SNVBAGLBSA-N 0.000 claims description 2
• YBUPNHZFCNMZET-GFCCVEGCSA-N 5,6-dimethyl-n-[(1r)-1-phenylethyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1([C@H](NC=2C=3C(C)=C(C)NC=3N=CN=2)C)=CC=CC=C1 YBUPNHZFCNMZET-GFCCVEGCSA-N 0.000 claims description 2
• YBUPNHZFCNMZET-LBPRGKRZSA-N 5,6-dimethyl-n-[(1s)-1-phenylethyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1([C@@H](NC=2C=3C(C)=C(C)NC=3N=CN=2)C)=CC=CC=C1 YBUPNHZFCNMZET-LBPRGKRZSA-N 0.000 claims description 2
• HKHFMNRHSUUBJE-UHFFFAOYSA-N 6-(1-benzylpyridin-1-ium-2-yl)-n-(3-chlorophenyl)-5-methyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine;bromide Chemical compound [Br-].C=12C(C)=C(C=3[N+](=CC=CC=3)CC=3C=CC=CC=3)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 HKHFMNRHSUUBJE-UHFFFAOYSA-N 0.000 claims description 2
• KFNHYCUETQTMIC-UHFFFAOYSA-N 6-(3-aminophenyl)-n-(3-chlorophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound NC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 KFNHYCUETQTMIC-UHFFFAOYSA-N 0.000 claims description 2
• OVWSZWFGFGIFNR-CYBMUJFWSA-N 6-(3-aminophenyl)-n-[(1r)-1-phenylethyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=CC(N)=C1 OVWSZWFGFGIFNR-CYBMUJFWSA-N 0.000 claims description 2
• GCFYJDAFLTYJQQ-UHFFFAOYSA-N 6-(4-aminophenyl)-n-(3-chloro-4-fluorophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(N)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=C(F)C(Cl)=C1 GCFYJDAFLTYJQQ-UHFFFAOYSA-N 0.000 claims description 2
• HBEXKMFNANAKRL-UHFFFAOYSA-N 6-(4-aminophenyl)-n-(3-methylphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CC1=CC=CC(NC=2C=3C=C(NC=3N=CN=2)C=2C=CC(N)=CC=2)=C1 HBEXKMFNANAKRL-UHFFFAOYSA-N 0.000 claims description 2
• SRSAKUNDUJJZAN-CYBMUJFWSA-N 6-(4-aminophenyl)-n-[(1r)-1-phenylethyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(N)C=C1 SRSAKUNDUJJZAN-CYBMUJFWSA-N 0.000 claims description 2
• SRSAKUNDUJJZAN-ZDUSSCGKSA-N 6-(4-aminophenyl)-n-[(1s)-1-phenylethyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(N)C=C1 SRSAKUNDUJJZAN-ZDUSSCGKSA-N 0.000 claims description 2
• YILGPGFTIGZEMT-UHFFFAOYSA-N 6-(4-aminophenyl)-n-[(3-chlorophenyl)methyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(N)=CC=C1C(NC1=NC=N2)=CC1=C2NCC1=CC=CC(Cl)=C1 YILGPGFTIGZEMT-UHFFFAOYSA-N 0.000 claims description 2
• NQGFVQYELMDSEE-UHFFFAOYSA-N 6-(4-aminophenyl)-n-benzyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(N)=CC=C1C(NC1=NC=N2)=CC1=C2NCC1=CC=CC=C1 NQGFVQYELMDSEE-UHFFFAOYSA-N 0.000 claims description 2
• RSJMXGTWBRPXFK-UHFFFAOYSA-N 6-(aminomethyl)-n-(3-chlorophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N1=CN=C2NC(CN)=CC2=C1NC1=CC=CC(Cl)=C1 RSJMXGTWBRPXFK-UHFFFAOYSA-N 0.000 claims description 2
• OSIXZWGGFJMMGB-SNVBAGLBSA-N 6-(aminomethyl)-n-[(1r)-1-phenylethyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1([C@H](NC=2C=3C=C(CN)NC=3N=CN=2)C)=CC=CC=C1 OSIXZWGGFJMMGB-SNVBAGLBSA-N 0.000 claims description 2
• OZEGDEJMJWEICF-QGZVFWFLSA-N 6-[4-(diethylamino)phenyl]-n-[(1r)-1-phenylethyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(N(CC)CC)=CC=C1C(NC1=NC=N2)=CC1=C2N[C@H](C)C1=CC=CC=C1 OZEGDEJMJWEICF-QGZVFWFLSA-N 0.000 claims description 2
• GHHFHFMUMPSSLA-UHFFFAOYSA-N N-(3-chlorophenyl)-6-(4-phenylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC=1C=C(NC=2C3=C(N=CN=2)NC(=C3)C2=CC=C(C=C2)C2=CC=CC=C2)C=CC=1 GHHFHFMUMPSSLA-UHFFFAOYSA-N 0.000 claims description 2
• XORWUZZYYBVNGK-UHFFFAOYSA-N [4-(3-chloroanilino)-5-methyl-7h-pyrrolo[2,3-d]pyrimidin-6-yl]methanol Chemical compound C=12C(C)=C(CO)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 XORWUZZYYBVNGK-UHFFFAOYSA-N 0.000 claims description 2
• KQOYPTNWBVSLFP-UHFFFAOYSA-N [4-(3-chloroanilino)-6-methyl-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanol Chemical compound C=12C(CO)=C(C)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 KQOYPTNWBVSLFP-UHFFFAOYSA-N 0.000 claims description 2
• 150000001448 anilines Chemical class 0.000 claims description 2
• BSPSSCYOVCVCPZ-UHFFFAOYSA-N benzyl 2-[4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenoxy]acetate Chemical compound ClC1=CC=CC(NC=2C=3C=C(NC=3N=CN=2)C=2C=CC(OCC(=O)OCC=3C=CC=CC=3)=CC=2)=C1 BSPSSCYOVCVCPZ-UHFFFAOYSA-N 0.000 claims description 2
• LECHBUCPHKVJDO-UHFFFAOYSA-N ethyl 3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 LECHBUCPHKVJDO-UHFFFAOYSA-N 0.000 claims description 2
• COOAQHCSEIASLA-OAQYLSRUSA-N methyl (1r)-1-[[2-amino-6-(4-aminophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]methyl]cyclohexa-2,4-diene-1-carboxylate Chemical compound N=1C(N)=NC=2NC(C=3C=CC(N)=CC=3)=CC=2C=1C[C@]1(C(=O)OC)CC=CC=C1 COOAQHCSEIASLA-OAQYLSRUSA-N 0.000 claims description 2
• COOAQHCSEIASLA-NRFANRHFSA-N methyl (1s)-1-[[2-amino-6-(4-aminophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]methyl]cyclohexa-2,4-diene-1-carboxylate Chemical compound N=1C(N)=NC=2NC(C=3C=CC(N)=CC=3)=CC=2C=1C[C@@]1(C(=O)OC)CC=CC=C1 COOAQHCSEIASLA-NRFANRHFSA-N 0.000 claims description 2
• JMCVZMUNIHKBQR-UHFFFAOYSA-N methyl 2-[3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenoxy]acetate Chemical compound COC(=O)COC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 JMCVZMUNIHKBQR-UHFFFAOYSA-N 0.000 claims description 2
• XIYBXBOOMUTAAW-UHFFFAOYSA-N methyl 2-[4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OC)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 XIYBXBOOMUTAAW-UHFFFAOYSA-N 0.000 claims description 2
• DQEDUHZVZFCPNR-UHFFFAOYSA-N methyl 4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 DQEDUHZVZFCPNR-UHFFFAOYSA-N 0.000 claims description 2
• QOLAJPKWYZODDL-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-5-methyl-6-pyridin-2-yl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=12C(C)=C(C=3N=CC=CC=3)NC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 QOLAJPKWYZODDL-UHFFFAOYSA-N 0.000 claims description 2
• PKDOFPOVUJYXGS-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-pyridin-2-yl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=C1C=C(C=1N=CC=CC=1)N2 PKDOFPOVUJYXGS-UHFFFAOYSA-N 0.000 claims description 2
• LKLOGPADZDRICC-UHFFFAOYSA-N n-(3-chlorophenyl)-5-[(dimethylamino)methyl]-6-phenyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=12C(CN(C)C)=C(C=3C=CC=CC=3)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 LKLOGPADZDRICC-UHFFFAOYSA-N 0.000 claims description 2
• MNFSCBWPDZBHFU-UHFFFAOYSA-N n-(3-chlorophenyl)-5-[(dimethylamino)methyl]-6-pyridin-2-yl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=12C(CN(C)C)=C(C=3N=CC=CC=3)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 MNFSCBWPDZBHFU-UHFFFAOYSA-N 0.000 claims description 2
• ZYVNWPUNWKXMAI-UHFFFAOYSA-N n-(3-chlorophenyl)-6-(methoxymethyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N1=CN=C2NC(COC)=CC2=C1NC1=CC=CC(Cl)=C1 ZYVNWPUNWKXMAI-UHFFFAOYSA-N 0.000 claims description 2
• QBUVNTKTFHFJQO-UHFFFAOYSA-N n-(3-chlorophenyl)-6-(piperazin-1-ylmethyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C=C(CN4CCNCC4)NC=3N=CN=2)=C1 QBUVNTKTFHFJQO-UHFFFAOYSA-N 0.000 claims description 2
• AGSWLWOVDOZUQF-UHFFFAOYSA-N n-(3-chlorophenyl)-6-[3-(dimethylamino)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CN(C)C1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 AGSWLWOVDOZUQF-UHFFFAOYSA-N 0.000 claims description 2
• BWKIKAJTKWXBHR-UHFFFAOYSA-N n-(3-chlorophenyl)-6-[4-(dimethylamino)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(N(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 BWKIKAJTKWXBHR-UHFFFAOYSA-N 0.000 claims description 2
• HGWSNRCTGXESSV-UHFFFAOYSA-N n-(3-chlorophenyl)-6-[4-(ethylamino)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(NCC)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 HGWSNRCTGXESSV-UHFFFAOYSA-N 0.000 claims description 2
• HRRXDMWJPSVMFK-UHFFFAOYSA-N n-(3-chlorophenyl)-6-naphthalen-2-yl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C=C(NC=3N=CN=2)C=2C=C3C=CC=CC3=CC=2)=C1 HRRXDMWJPSVMFK-UHFFFAOYSA-N 0.000 claims description 2
• BCLXVHJHHBULCV-UHFFFAOYSA-N n-(3-chlorophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C=CNC=3N=CN=2)=C1 BCLXVHJHHBULCV-UHFFFAOYSA-N 0.000 claims description 2
• DTNMTOMHMKSMGS-UHFFFAOYSA-N n-(3-chlorophenyl)-9h-pyrido[2,3]pyrrolo[2,4-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C4=CC=CN=C4NC=3N=CN=2)=C1 DTNMTOMHMKSMGS-UHFFFAOYSA-N 0.000 claims description 2
• ZPFUVKUMPHXXAI-CQSZACIVSA-N n-[(1r)-1-phenylethyl]-6-(piperazin-1-ylmethyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2CN1CCNCC1 ZPFUVKUMPHXXAI-CQSZACIVSA-N 0.000 claims description 2
• GDQXIFMWBNDZHY-UHFFFAOYSA-N n-[3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-2-methylpropanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 GDQXIFMWBNDZHY-UHFFFAOYSA-N 0.000 claims description 2
• CFGHZGPMVNPLOH-UHFFFAOYSA-N n-[3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 CFGHZGPMVNPLOH-UHFFFAOYSA-N 0.000 claims description 2
• WDYCLGNCBYRZGO-CQSZACIVSA-N n-[3-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]acetamide Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=CC(NC(C)=O)=C1 WDYCLGNCBYRZGO-CQSZACIVSA-N 0.000 claims description 2
• GOVANMMKAZSZDV-OAHLLOKOSA-N n-[3-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]propanamide Chemical compound CCC(=O)NC1=CC=CC(C=2NC3=NC=NC(N[C@H](C)C=4C=CC=CC=4)=C3C=2)=C1 GOVANMMKAZSZDV-OAHLLOKOSA-N 0.000 claims description 2
• NOZSFOBLVYJJRV-UHFFFAOYSA-N n-[4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-2,2-dimethylpropanamide Chemical compound C1=CC(NC(=O)C(C)(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 NOZSFOBLVYJJRV-UHFFFAOYSA-N 0.000 claims description 2
• DXZDXJBFPMSDLT-UHFFFAOYSA-N n-[4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-3-methylbutanamide Chemical compound C1=CC(NC(=O)CC(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 DXZDXJBFPMSDLT-UHFFFAOYSA-N 0.000 claims description 2
• VUHIWJQXEJGBGV-UHFFFAOYSA-N n-[4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]propanamide Chemical compound C1=CC(NC(=O)CC)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 VUHIWJQXEJGBGV-UHFFFAOYSA-N 0.000 claims description 2
• MBJIUVXHGKAMMX-CQSZACIVSA-N n-[4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]acetamide Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(NC(C)=O)C=C1 MBJIUVXHGKAMMX-CQSZACIVSA-N 0.000 claims description 2
• PGTNANTWNTYJNR-UHFFFAOYSA-N n-benzyl-4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound ClC1=CC=CC(NC=2C=3C=C(NC=3N=CN=2)C(=O)NCC=2C=CC=CC=2)=C1 PGTNANTWNTYJNR-UHFFFAOYSA-N 0.000 claims description 2
• NAUFEHNAGJNAPG-SNVBAGLBSA-N n-methyl-4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C1([C@@H](C)NC2=C3C=C(NC3=NC=N2)C(=O)NC)=CC=CC=C1 NAUFEHNAGJNAPG-SNVBAGLBSA-N 0.000 claims description 2
• OEKGIPDDTYGUGD-UHFFFAOYSA-N n-tert-butyl-4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=CN=C2NC(C(=O)NC(C)(C)C)=CC2=C1NC1=CC=CC(Cl)=C1 OEKGIPDDTYGUGD-UHFFFAOYSA-N 0.000 claims description 2
• RFLAVHHYEHEFAA-UHFFFAOYSA-N propan-2-yl 4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]benzoate Chemical compound C1=CC(C(=O)OC(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 RFLAVHHYEHEFAA-UHFFFAOYSA-N 0.000 claims description 2
• IBRLTAAEOLMURX-UHFFFAOYSA-N propyl 4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]benzoate Chemical compound C1=CC(C(=O)OCCC)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 IBRLTAAEOLMURX-UHFFFAOYSA-N 0.000 claims description 2
• 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 claims description 2
• 150000003230 pyrimidines Chemical class 0.000 claims description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 6
• 238000002512 chemotherapy Methods 0.000 claims 2
• XLFTWOBDSIGCSU-UHFFFAOYSA-N 2-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol Chemical compound OC1=CC=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 XLFTWOBDSIGCSU-UHFFFAOYSA-N 0.000 claims 1
• STYSVCBDICPKCL-UHFFFAOYSA-N 3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol Chemical compound OC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 STYSVCBDICPKCL-UHFFFAOYSA-N 0.000 claims 1
• QENYERPATNBODW-UHFFFAOYSA-N 4-[4-(3-chloroanilino)-5-methyl-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol Chemical compound C=12C(C)=C(C=3C=CC(O)=CC=3)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 QENYERPATNBODW-UHFFFAOYSA-N 0.000 claims 1
• PKPUUHRVTLUSRY-UHFFFAOYSA-N 4-[4-[(3-methylphenyl)methyl]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]aniline Chemical compound CC1=CC=CC(CC=2C=3C=C(NC=3N=CN=2)C=2C=CC(N)=CC=2)=C1 PKPUUHRVTLUSRY-UHFFFAOYSA-N 0.000 claims 1
• JUIGWJFLRFPMJH-UHFFFAOYSA-N 6-[4-(ethylamino)phenyl]-n-(1-phenylethyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(NCC)=CC=C1C(NC1=NC=N2)=CC1=C2NC(C)C1=CC=CC=C1 JUIGWJFLRFPMJH-UHFFFAOYSA-N 0.000 claims 1
• 125000001589 carboacyl group Chemical group 0.000 claims 1
• OXGSEKLRSYJZFX-UHFFFAOYSA-N n-(3-chlorophenyl)-6-[3-(ethylamino)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CCNC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 OXGSEKLRSYJZFX-UHFFFAOYSA-N 0.000 claims 1
• TYPWJEJPDZAMPB-UHFFFAOYSA-N n-[3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]propanamide Chemical compound CCC(=O)NC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 TYPWJEJPDZAMPB-UHFFFAOYSA-N 0.000 claims 1
• YATLKRCBIRXWCR-UHFFFAOYSA-N n-[4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-2-methylpropanamide Chemical compound C1=CC(NC(=O)C(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 YATLKRCBIRXWCR-UHFFFAOYSA-N 0.000 claims 1
• SWWFXMGJQPPKRW-UHFFFAOYSA-N n-benzyl-5,6-dimethyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=12C(C)=C(C)NC2=NC=NC=1NCC1=CC=CC=C1 SWWFXMGJQPPKRW-UHFFFAOYSA-N 0.000 claims 1
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 abstract description 10
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 abstract description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
• 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 abstract description 5
• 201000010099 disease Diseases 0.000 abstract description 5
• 230000003463 hyperproliferative effect Effects 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 132
• 150000003254 radicals Chemical class 0.000 description 88
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 87
• 239000000203 mixture Substances 0.000 description 84
• 239000000047 product Substances 0.000 description 82
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 75
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 70
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 66
• 235000002639 sodium chloride Nutrition 0.000 description 59
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
• 239000000243 solution Substances 0.000 description 57
• 239000011541 reaction mixture Substances 0.000 description 52
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 48
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 41
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
• 238000001704 evaporation Methods 0.000 description 34
• 230000008020 evaporation Effects 0.000 description 34
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 34
• 239000000725 suspension Substances 0.000 description 33
• 239000007858 starting material Substances 0.000 description 32
• 238000006243 chemical reaction Methods 0.000 description 30
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 28
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 28
• 239000004480 active ingredient Substances 0.000 description 23
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 22
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 20
• 239000013078 crystal Substances 0.000 description 20
• 238000004128 high performance liquid chromatography Methods 0.000 description 20
• 239000002904 solvent Substances 0.000 description 20
• 238000009835 boiling Methods 0.000 description 18
• 239000012074 organic phase Substances 0.000 description 18
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 17
• 235000019253 formic acid Nutrition 0.000 description 17
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
• 239000012267 brine Substances 0.000 description 16
• 210000004027 cell Anatomy 0.000 description 16
• 238000003756 stirring Methods 0.000 description 16
• PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 15
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• 239000012298 atmosphere Substances 0.000 description 15
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
• 235000014113 dietary fatty acids Nutrition 0.000 description 14
• 239000000194 fatty acid Substances 0.000 description 14
• 229930195729 fatty acid Natural products 0.000 description 14
• 239000005457 ice water Substances 0.000 description 14
• 239000000741 silica gel Substances 0.000 description 13
• 229910002027 silica gel Inorganic materials 0.000 description 13
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 12
• 239000007868 Raney catalyst Substances 0.000 description 12
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 12
• 229910000564 Raney nickel Inorganic materials 0.000 description 12
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 12
• 229910052801 chlorine Inorganic materials 0.000 description 12
• 239000012043 crude product Substances 0.000 description 12
• GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 12
• 239000000706 filtrate Substances 0.000 description 12
• 239000007789 gas Substances 0.000 description 12
• 239000007787 solid Substances 0.000 description 12
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• 239000008346 aqueous phase Substances 0.000 description 10
• 125000003118 aryl group Chemical group 0.000 description 10
• 229920001223 polyethylene glycol Polymers 0.000 description 10
• 238000006722 reduction reaction Methods 0.000 description 10
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• 125000001309 chloro group Chemical group Cl* 0.000 description 9
• 238000001816 cooling Methods 0.000 description 9
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 9
• 150000002828 nitro derivatives Chemical class 0.000 description 9
• 230000009467 reduction Effects 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• 238000012360 testing method Methods 0.000 description 9
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
• 108091000080 Phosphotransferase Proteins 0.000 description 8
• 229910052786 argon Inorganic materials 0.000 description 8
• 230000002401 inhibitory effect Effects 0.000 description 8
• 239000000543 intermediate Substances 0.000 description 8
• 102000020233 phosphotransferase Human genes 0.000 description 8
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 8
• 102000001301 EGF receptor Human genes 0.000 description 7
• 108060006698 EGF receptor Proteins 0.000 description 7
• 102000009024 Epidermal Growth Factor Human genes 0.000 description 7
• 101800003838 Epidermal growth factor Proteins 0.000 description 7
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 7
• 102000001253 Protein Kinase Human genes 0.000 description 7
• 150000007513 acids Chemical class 0.000 description 7
• 229940116977 epidermal growth factor Drugs 0.000 description 7
• VOHFLYOSVGWQOS-UHFFFAOYSA-N ethyl 3-amino-3-iminopropanoate;hydrochloride Chemical compound Cl.CCOC(=O)CC(N)=N VOHFLYOSVGWQOS-UHFFFAOYSA-N 0.000 description 7
• 230000005764 inhibitory process Effects 0.000 description 7
• 108060006633 protein kinase Proteins 0.000 description 7
• 238000005406 washing Methods 0.000 description 7
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• 239000002202 Polyethylene glycol Substances 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 238000002425 crystallisation Methods 0.000 description 6
• 230000008025 crystallization Effects 0.000 description 6
• 230000000694 effects Effects 0.000 description 6
• 239000003995 emulsifying agent Substances 0.000 description 6
• 230000007717 exclusion Effects 0.000 description 6
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 6
• 150000002431 hydrogen Chemical group 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 239000002674 ointment Substances 0.000 description 6
• 229920006395 saturated elastomer Polymers 0.000 description 6
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
• 238000004809 thin layer chromatography Methods 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 5
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 5
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
• 229920002472 Starch Polymers 0.000 description 5
• 239000000654 additive Substances 0.000 description 5
• 238000006136 alcoholysis reaction Methods 0.000 description 5
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• 239000000460 chlorine Substances 0.000 description 5
• 239000007903 gelatin capsule Substances 0.000 description 5
• 230000012010 growth Effects 0.000 description 5
• 229930195733 hydrocarbon Natural products 0.000 description 5
• 150000002430 hydrocarbons Chemical class 0.000 description 5
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
• 235000019341 magnesium sulphate Nutrition 0.000 description 5
• 238000002156 mixing Methods 0.000 description 5
• 239000012299 nitrogen atmosphere Substances 0.000 description 5
• 239000003921 oil Substances 0.000 description 5
• 235000019198 oils Nutrition 0.000 description 5
• 239000000546 pharmaceutical excipient Substances 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 238000003797 solvolysis reaction Methods 0.000 description 5
• 239000000600 sorbitol Substances 0.000 description 5
• 239000000454 talc Substances 0.000 description 5
• 229910052623 talc Inorganic materials 0.000 description 5
• 235000012222 talc Nutrition 0.000 description 5
• FJMVUBXZUXYVBL-UHFFFAOYSA-M 1-benzyl-2-bromopyridin-1-ium;bromide Chemical compound [Br-].BrC1=CC=CC=[N+]1CC1=CC=CC=C1 FJMVUBXZUXYVBL-UHFFFAOYSA-M 0.000 description 4
• 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 4
• HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 4
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
• 241000208199 Buxus sempervirens Species 0.000 description 4
• 238000005684 Liebig rearrangement reaction Methods 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• 239000005662 Paraffin oil Substances 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 150000001298 alcohols Chemical class 0.000 description 4
• 239000012300 argon atmosphere Substances 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• 235000010233 benzoic acid Nutrition 0.000 description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 229910052794 bromium Inorganic materials 0.000 description 4
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 4
• 239000001768 carboxy methyl cellulose Substances 0.000 description 4
• 239000006071 cream Substances 0.000 description 4
• 150000004292 cyclic ethers Chemical class 0.000 description 4
• POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 239000008298 dragée Substances 0.000 description 4
• 150000002191 fatty alcohols Chemical class 0.000 description 4
• 238000011049 filling Methods 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 125000005456 glyceride group Chemical group 0.000 description 4
• 150000008282 halocarbons Chemical class 0.000 description 4
• 125000000623 heterocyclic group Chemical group 0.000 description 4
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
• 239000012442 inert solvent Substances 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• XOWGESNQLHDSON-UHFFFAOYSA-N n-(3-chlorophenyl)-9h-pyrimido[4,5-b]indol-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C4=CC=CC=C4NC=3N=CN=2)=C1 XOWGESNQLHDSON-UHFFFAOYSA-N 0.000 description 4
• GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 4
• 238000007911 parenteral administration Methods 0.000 description 4
• WQEPLUUGTLDZJY-UHFFFAOYSA-N pentadecanoic acid Chemical compound CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 4
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 239000003381 stabilizer Substances 0.000 description 4
• 150000005846 sugar alcohols Polymers 0.000 description 4
• 238000003786 synthesis reaction Methods 0.000 description 4
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
• 238000001665 trituration Methods 0.000 description 4
• 238000010626 work up procedure Methods 0.000 description 4
• NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
• UUGVARUTGQCQHQ-UHFFFAOYSA-N 4-chloro-6-(4-methoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C1=CC(OC)=CC=C1C1=CC2=C(Cl)N=CN=C2N1 UUGVARUTGQCQHQ-UHFFFAOYSA-N 0.000 description 3
• QSQGUTKNTCCWKO-UHFFFAOYSA-N 6-pyridin-2-yl-1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound C=1C=2C(O)=NC=NC=2NC=1C1=CC=CC=N1 QSQGUTKNTCCWKO-UHFFFAOYSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 239000005711 Benzoic acid Substances 0.000 description 3
• 102100030011 Endoribonuclease Human genes 0.000 description 3
• 101710199605 Endoribonuclease Proteins 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 3
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
• 239000004264 Petrolatum Substances 0.000 description 3
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 3
• 101710113029 Serine/threonine-protein kinase Proteins 0.000 description 3
• 229910004298 SiO 2 Inorganic materials 0.000 description 3
• 235000021355 Stearic acid Nutrition 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
• 150000001335 aliphatic alkanes Chemical class 0.000 description 3
• 125000006242 amine protecting group Chemical group 0.000 description 3
• 229910021529 ammonia Inorganic materials 0.000 description 3
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
• 150000001721 carbon Chemical group 0.000 description 3
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 3
• 229960000541 cetyl alcohol Drugs 0.000 description 3
• 239000003610 charcoal Substances 0.000 description 3
• 239000007795 chemical reaction product Substances 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
• 238000000576 coating method Methods 0.000 description 3
• 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 3
• 239000006185 dispersion Substances 0.000 description 3
• 239000003480 eluent Substances 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 3
• BMVGJDTURCUCNP-UHFFFAOYSA-N ethyl 4-chloro-7h-pyrrolo[2,3-d]pyrimidine-6-carboxylate Chemical compound N1=CN=C2NC(C(=O)OCC)=CC2=C1Cl BMVGJDTURCUCNP-UHFFFAOYSA-N 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 238000010438 heat treatment Methods 0.000 description 3
• 210000005260 human cell Anatomy 0.000 description 3
• 238000005984 hydrogenation reaction Methods 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 229910052500 inorganic mineral Inorganic materials 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 239000000314 lubricant Substances 0.000 description 3
• 210000004962 mammalian cell Anatomy 0.000 description 3
• 238000004949 mass spectrometry Methods 0.000 description 3
• 235000010755 mineral Nutrition 0.000 description 3
• 239000011707 mineral Substances 0.000 description 3
• 150000007522 mineralic acids Chemical class 0.000 description 3
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 239000002245 particle Substances 0.000 description 3
• 229940066842 petrolatum Drugs 0.000 description 3
• 235000019271 petrolatum Nutrition 0.000 description 3
• 239000002953 phosphate buffered saline Substances 0.000 description 3
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 238000001953 recrystallisation Methods 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 230000019491 signal transduction Effects 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 239000007901 soft capsule Substances 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 239000008117 stearic acid Substances 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
• 230000004614 tumor growth Effects 0.000 description 3
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 3
• KAKZBPTYRLMSJV-UHFFFAOYSA-N vinyl-ethylene Natural products C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 3
• 238000005303 weighing Methods 0.000 description 3
• 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
• RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
• OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 2
• PFSDNRSZTVQQOJ-UHFFFAOYSA-N 2-amino-5-(1-benzylpyridin-1-ium-2-yl)-4-methyl-1h-pyrrole-3-carbonitrile;bromide Chemical compound [Br-].N#CC1=C(N)NC(C=2[N+](=CC=CC=2)CC=2C=CC=CC=2)=C1C PFSDNRSZTVQQOJ-UHFFFAOYSA-N 0.000 description 2
• IOOHBIFQNQQUFI-UHFFFAOYSA-N 2-bromo-1-(3-methoxyphenyl)ethanone Chemical compound COC1=CC=CC(C(=O)CBr)=C1 IOOHBIFQNQQUFI-UHFFFAOYSA-N 0.000 description 2
• SJSOFNCYXJUNBT-UHFFFAOYSA-N 3,4,5-trimethoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC(OC)=C1OC SJSOFNCYXJUNBT-UHFFFAOYSA-N 0.000 description 2
• QHJJSLUZWHFHTK-UHFFFAOYSA-N 3-amino-3-azaniumylidenepropanoate Chemical compound NC(=N)CC(O)=O QHJJSLUZWHFHTK-UHFFFAOYSA-N 0.000 description 2
• YSEMCVGMNUUNRK-UHFFFAOYSA-N 3-chloro-4-fluoroaniline Chemical compound NC1=CC=C(F)C(Cl)=C1 YSEMCVGMNUUNRK-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• KISILDQSFGBNPG-UHFFFAOYSA-N 4-[4-(3-chloroanilino)-5-methyl-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol;hydrobromide Chemical compound Br.C=12C(C)=C(C=3C=CC(O)=CC=3)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 KISILDQSFGBNPG-UHFFFAOYSA-N 0.000 description 2
• WMYMREUTXVUMJL-UHFFFAOYSA-N 4-chloro-6-(2-methoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidine Chemical compound COC1=CC=CC=C1C1=CC2=C(Cl)N=CN=C2N1 WMYMREUTXVUMJL-UHFFFAOYSA-N 0.000 description 2
• SSWAQKJRCGLPFV-UHFFFAOYSA-N 4-chloro-6-(3-methoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidine Chemical compound COC1=CC=CC(C=2NC3=NC=NC(Cl)=C3C=2)=C1 SSWAQKJRCGLPFV-UHFFFAOYSA-N 0.000 description 2
• CTGKOXVYPPTORX-UHFFFAOYSA-N 4-chloro-6-(4-methoxyphenyl)-5-methyl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C1=CC(OC)=CC=C1C1=C(C)C2=C(Cl)N=CN=C2N1 CTGKOXVYPPTORX-UHFFFAOYSA-N 0.000 description 2
• UIDMSVGNGNXGET-UHFFFAOYSA-N 4-chloro-6-(4-nitrophenyl)-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=CC2=C(Cl)N=CN=C2N1 UIDMSVGNGNXGET-UHFFFAOYSA-N 0.000 description 2
• BIRCPJMMGKFDFK-UHFFFAOYSA-N 4-chloro-6-(4-phenylphenyl)-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C=1C=2C(Cl)=NC=NC=2NC=1C(C=C1)=CC=C1C1=CC=CC=C1 BIRCPJMMGKFDFK-UHFFFAOYSA-N 0.000 description 2
• GOKKERDAMCCYGR-UHFFFAOYSA-N 4-chloro-6-naphthalen-2-yl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C1=CC=CC2=CC(C=3NC=4N=CN=C(C=4C=3)Cl)=CC=C21 GOKKERDAMCCYGR-UHFFFAOYSA-N 0.000 description 2
• AGLAPJLLGQYKAH-UHFFFAOYSA-N 4-chloro-6-phenyl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C=1C=2C(Cl)=NC=NC=2NC=1C1=CC=CC=C1 AGLAPJLLGQYKAH-UHFFFAOYSA-N 0.000 description 2
• JOQKUNXMSSFLBX-UHFFFAOYSA-N 4-chloro-6-pyridin-2-yl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C=1C=2C(Cl)=NC=NC=2NC=1C1=CC=CC=N1 JOQKUNXMSSFLBX-UHFFFAOYSA-N 0.000 description 2
• HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
• AOZPOAPGPDEDJI-UHFFFAOYSA-O 6-(1-benzylpyridin-1-ium-2-yl)-4-chloro-5-methyl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1C2=NC=NC(Cl)=C2C(C)=C1C1=CC=CC=[N+]1CC1=CC=CC=C1 AOZPOAPGPDEDJI-UHFFFAOYSA-O 0.000 description 2
• UDRRJKACDZHQDQ-UHFFFAOYSA-O 6-(1-benzylpyridin-1-ium-2-yl)-5-methyl-1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound N1C2=NC=NC(O)=C2C(C)=C1C1=CC=CC=[N+]1CC1=CC=CC=C1 UDRRJKACDZHQDQ-UHFFFAOYSA-O 0.000 description 2
• JYJYWMUEFVRDCO-UHFFFAOYSA-N 6-(2-methoxyphenyl)-1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound COC1=CC=CC=C1C1=CC2=C(O)N=CN=C2N1 JYJYWMUEFVRDCO-UHFFFAOYSA-N 0.000 description 2
• AWTJSTYWTOXEAB-UHFFFAOYSA-N 6-(3-methoxyphenyl)-1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound COC1=CC=CC(C=2NC3=NC=NC(O)=C3C=2)=C1 AWTJSTYWTOXEAB-UHFFFAOYSA-N 0.000 description 2
• WXLDAMGBNHAYSE-UHFFFAOYSA-N 6-(4-methoxyphenyl)-1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CC2=C(O)N=CN=C2N1 WXLDAMGBNHAYSE-UHFFFAOYSA-N 0.000 description 2
• AWFOZCHHTUUXAI-UHFFFAOYSA-N 6-(4-nitrophenyl)-1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound C=1C=2C(O)=NC=NC=2NC=1C1=CC=C([N+]([O-])=O)C=C1 AWFOZCHHTUUXAI-UHFFFAOYSA-N 0.000 description 2
• DQINSOHBTWYJFL-UHFFFAOYSA-N 6-(4-phenylphenyl)-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1(=CC=C(C=C1)C1=CC=CC=C1)C1=CC2=C(N=CN=C2O)N1 DQINSOHBTWYJFL-UHFFFAOYSA-N 0.000 description 2
• SMRZRICUXPUNRK-UHFFFAOYSA-N 6-naphthalen-2-yl-1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC=CC2=CC(C=3NC=4N=CN=C(C=4C=3)O)=CC=C21 SMRZRICUXPUNRK-UHFFFAOYSA-N 0.000 description 2
• GAMJQSLUWWEVCN-UHFFFAOYSA-N 6-phenyl-1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound C=1C=2C(O)=NC=NC=2NC=1C1=CC=CC=C1 GAMJQSLUWWEVCN-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
• KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
• 238000006418 Brown reaction Methods 0.000 description 2
• 102000029330 CSK Tyrosine-Protein Kinase Human genes 0.000 description 2
• 108010069682 CSK Tyrosine-Protein Kinase Proteins 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
• 229940126062 Compound A Drugs 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• 229920002307 Dextran Polymers 0.000 description 2
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
• 238000002965 ELISA Methods 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
• 229930195725 Mannitol Natural products 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
• OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 description 2
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
• 235000021314 Palmitic acid Nutrition 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
• 239000004698 Polyethylene Substances 0.000 description 2
• 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
• 108090000315 Protein Kinase C Proteins 0.000 description 2
• 102000003923 Protein Kinase C Human genes 0.000 description 2
• 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 2
• 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 102000038012 SFKs Human genes 0.000 description 2
• 108091008118 SFKs Proteins 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
• XQAXGZLFSSPBMK-UHFFFAOYSA-M [7-(dimethylamino)phenothiazin-3-ylidene]-dimethylazanium;chloride;trihydrate Chemical compound O.O.O.[Cl-].C1=CC(=[N+](C)C)C=C2SC3=CC(N(C)C)=CC=C3N=C21 XQAXGZLFSSPBMK-UHFFFAOYSA-M 0.000 description 2
• WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
• 229910052783 alkali metal Inorganic materials 0.000 description 2
• 150000003863 ammonium salts Chemical class 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 235000006708 antioxidants Nutrition 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 150000005840 aryl radicals Chemical class 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 229960005070 ascorbic acid Drugs 0.000 description 2
• 239000011668 ascorbic acid Substances 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 150000001735 carboxylic acids Chemical class 0.000 description 2
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 239000004359 castor oil Substances 0.000 description 2
• 235000019438 castor oil Nutrition 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• 238000009833 condensation Methods 0.000 description 2
• 230000005494 condensation Effects 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 125000000753 cycloalkyl group Chemical group 0.000 description 2
• UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 description 2
• YEWDOWIBJZTOCM-UHFFFAOYSA-N diethyl 5-amino-1h-pyrrole-2,4-dicarboxylate Chemical compound CCOC(=O)C1=CC(C(=O)OCC)=C(N)N1 YEWDOWIBJZTOCM-UHFFFAOYSA-N 0.000 description 2
• FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 description 2
• 230000029087 digestion Effects 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 229940113088 dimethylacetamide Drugs 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 150000002009 diols Chemical class 0.000 description 2
• YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
• 238000004090 dissolution Methods 0.000 description 2
• UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 2
• 239000003814 drug Substances 0.000 description 2
• ZQPPMHVWECSIRJ-MDZDMXLPSA-N elaidic acid Chemical compound CCCCCCCC\C=C\CCCCCCCC(O)=O ZQPPMHVWECSIRJ-MDZDMXLPSA-N 0.000 description 2
• 238000002451 electron ionisation mass spectrometry Methods 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 239000003623 enhancer Substances 0.000 description 2
• 210000002919 epithelial cell Anatomy 0.000 description 2
• 150000002170 ethers Chemical class 0.000 description 2
• ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 2
• DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 2
• WYOIODVYTKHXFC-UHFFFAOYSA-N ethyl 2-amino-5-(2-methoxyphenyl)-1h-pyrrole-3-carboxylate Chemical compound N1C(N)=C(C(=O)OCC)C=C1C1=CC=CC=C1OC WYOIODVYTKHXFC-UHFFFAOYSA-N 0.000 description 2
• PFANZDRAGVIABF-UHFFFAOYSA-N ethyl 2-amino-5-(3-methoxyphenyl)-1h-pyrrole-3-carboxylate Chemical compound N1C(N)=C(C(=O)OCC)C=C1C1=CC=CC(OC)=C1 PFANZDRAGVIABF-UHFFFAOYSA-N 0.000 description 2
• MAGIZELSVUYGDI-UHFFFAOYSA-N ethyl 2-amino-5-(4-methoxyphenyl)-1h-pyrrole-3-carboxylate Chemical compound N1C(N)=C(C(=O)OCC)C=C1C1=CC=C(OC)C=C1 MAGIZELSVUYGDI-UHFFFAOYSA-N 0.000 description 2
• HAXXOPWEDLHULE-UHFFFAOYSA-N ethyl 2-amino-5-(4-nitrophenyl)-1h-pyrrole-3-carboxylate Chemical compound N1C(N)=C(C(=O)OCC)C=C1C1=CC=C([N+]([O-])=O)C=C1 HAXXOPWEDLHULE-UHFFFAOYSA-N 0.000 description 2
• VVSMJELQIIQVJI-UHFFFAOYSA-N ethyl 2-amino-5-(4-phenylphenyl)-1h-pyrrole-3-carboxylate Chemical compound N1C(N)=C(C(=O)OCC)C=C1C1=CC=C(C=2C=CC=CC=2)C=C1 VVSMJELQIIQVJI-UHFFFAOYSA-N 0.000 description 2
• JLGCEKWLNWQGNE-UHFFFAOYSA-N ethyl 2-amino-5-naphthalen-2-yl-1h-pyrrole-3-carboxylate Chemical compound N1C(N)=C(C(=O)OCC)C=C1C1=CC=C(C=CC=C2)C2=C1 JLGCEKWLNWQGNE-UHFFFAOYSA-N 0.000 description 2
• LLHVZRPIASAWJO-UHFFFAOYSA-N ethyl 4-(4-chloro-7h-pyrrolo[2,3-d]pyrimidin-6-yl)benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C1=CC2=C(Cl)N=CN=C2N1 LLHVZRPIASAWJO-UHFFFAOYSA-N 0.000 description 2
• CSEXQMHRRUWZKC-UHFFFAOYSA-N ethyl 4-(4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-6-yl)benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C1=CC2=C(O)N=CN=C2N1 CSEXQMHRRUWZKC-UHFFFAOYSA-N 0.000 description 2
• JGUCDXJQDNRICX-LLVKDONJSA-N ethyl 4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidine-6-carboxylate Chemical compound C1([C@@H](C)NC2=C3C=C(NC3=NC=N2)C(=O)OCC)=CC=CC=C1 JGUCDXJQDNRICX-LLVKDONJSA-N 0.000 description 2
• RSJUPDUDZRGVRW-UHFFFAOYSA-N ethyl 4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidine-6-carboxylate Chemical compound N1C=NC(=O)C2=C1NC(C(=O)OCC)=C2 RSJUPDUDZRGVRW-UHFFFAOYSA-N 0.000 description 2
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 238000003818 flash chromatography Methods 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• KEMQGTRYUADPNZ-UHFFFAOYSA-N heptadecanoic acid Chemical compound CCCCCCCCCCCCCCCCC(O)=O KEMQGTRYUADPNZ-UHFFFAOYSA-N 0.000 description 2
• UKJFVOWPUXSBOM-UHFFFAOYSA-N hexane;oxolane Chemical compound C1CCOC1.CCCCCC UKJFVOWPUXSBOM-UHFFFAOYSA-N 0.000 description 2
• QKGYJVXSKCDGOK-UHFFFAOYSA-N hexane;propan-2-ol Chemical compound CC(C)O.CCCCCC QKGYJVXSKCDGOK-UHFFFAOYSA-N 0.000 description 2
• 239000003906 humectant Substances 0.000 description 2
• 238000007327 hydrogenolysis reaction Methods 0.000 description 2
• VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 229910052740 iodine Chemical group 0.000 description 2
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 2
• TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
• 229960000907 methylthioninium chloride Drugs 0.000 description 2
• WLSUPJHXRMFNST-UHFFFAOYSA-N n-(3-chlorophenyl)-6-(2-methoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound COC1=CC=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 WLSUPJHXRMFNST-UHFFFAOYSA-N 0.000 description 2
• DIMZJZIUDYHGON-UHFFFAOYSA-N n-(3-chlorophenyl)-6-(4-methoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 DIMZJZIUDYHGON-UHFFFAOYSA-N 0.000 description 2
• IDXBUYOYBRRRRB-UHFFFAOYSA-N n-(3-chlorophenyl)-6-phenyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C=C(NC=3N=CN=2)C=2C=CC=CC=2)=C1 IDXBUYOYBRRRRB-UHFFFAOYSA-N 0.000 description 2
• YPFMMHFXVQVPGO-UHFFFAOYSA-N n-butyl-4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=CN=C2NC(C(=O)NCCCC)=CC2=C1NC1=CC=CC(Cl)=C1 YPFMMHFXVQVPGO-UHFFFAOYSA-N 0.000 description 2
• GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 2
• 230000007935 neutral effect Effects 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• BDJRBEYXGGNYIS-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 239000012188 paraffin wax Substances 0.000 description 2
• 239000002304 perfume Substances 0.000 description 2
• 210000001428 peripheral nervous system Anatomy 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
• XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
• WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
• 229920000573 polyethylene Polymers 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 238000006268 reductive amination reaction Methods 0.000 description 2
• 230000026267 regulation of growth Effects 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
• 239000011492 sheep wool Substances 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• 159000000000 sodium salts Chemical class 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000004408 titanium dioxide Substances 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• SZHOJFHSIKHZHA-UHFFFAOYSA-N tridecanoic acid Chemical compound CCCCCCCCCCCCC(O)=O SZHOJFHSIKHZHA-UHFFFAOYSA-N 0.000 description 2
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
• 230000001228 trophic effect Effects 0.000 description 2
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
• 229940100445 wheat starch Drugs 0.000 description 2
• RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• ZLCOWUKVVFVVKA-WDSKDSINSA-N (2r)-3-[[(2r)-2-acetamido-2-carboxyethyl]disulfanyl]-2-aminopropanoic acid Chemical compound CC(=O)N[C@H](C(O)=O)CSSC[C@H](N)C(O)=O ZLCOWUKVVFVVKA-WDSKDSINSA-N 0.000 description 1
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• AFENDNXGAFYKQO-VKHMYHEASA-N (S)-2-hydroxybutyric acid Chemical compound CC[C@H](O)C(O)=O AFENDNXGAFYKQO-VKHMYHEASA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
• XTEGVFVZDVNBPF-UHFFFAOYSA-N 1,5-naphthalene disulfonic acid Natural products C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 description 1
• GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 description 1
• MSGAWNVGFAVEGP-UHFFFAOYSA-N 1-benzyl-n-(3-chlorophenyl)pyrimido[4,5-b]indol-4-amine Chemical compound ClC1=CC=CC(NC2=C3C4=CC=CC=C4N=C3N(CC=3C=CC=CC=3)C=N2)=C1 MSGAWNVGFAVEGP-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• FTQJOVOINUHYIV-UHFFFAOYSA-N 2,6-dimethyl-1h-pyridin-2-amine Chemical compound CC1=CC=CC(C)(N)N1 FTQJOVOINUHYIV-UHFFFAOYSA-N 0.000 description 1
• NXRGKFVQYZGDIY-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1.CC1=CC=CC(C)=N1 NXRGKFVQYZGDIY-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• UXYFZUWAZMLQNN-UHFFFAOYSA-N 2-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol;hydrobromide Chemical compound Br.OC1=CC=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 UXYFZUWAZMLQNN-UHFFFAOYSA-N 0.000 description 1
• XKKFLDQPHGDREE-UHFFFAOYSA-N 2-amino-1-benzyl-4,5,6,7-tetrahydroindole-3-carbonitrile Chemical compound NC1=C(C#N)C=2CCCCC=2N1CC1=CC=CC=C1 XKKFLDQPHGDREE-UHFFFAOYSA-N 0.000 description 1
• GKNCPTLOPRDYMH-UHFFFAOYSA-N 2-bromo-1-(2-methoxyphenyl)ethanone Chemical compound COC1=CC=CC=C1C(=O)CBr GKNCPTLOPRDYMH-UHFFFAOYSA-N 0.000 description 1
• XQJAHBHCLXUGEP-UHFFFAOYSA-N 2-bromo-1-(4-methoxyphenyl)ethanone Chemical compound COC1=CC=C(C(=O)CBr)C=C1 XQJAHBHCLXUGEP-UHFFFAOYSA-N 0.000 description 1
• MBUPVGIGAMCMBT-UHFFFAOYSA-N 2-bromo-1-(4-nitrophenyl)ethanone Chemical compound [O-][N+](=O)C1=CC=C(C(=O)CBr)C=C1 MBUPVGIGAMCMBT-UHFFFAOYSA-N 0.000 description 1
• YHXHHGDUANVQHE-UHFFFAOYSA-N 2-bromo-1-naphthalen-2-ylethanone Chemical compound C1=CC=CC2=CC(C(=O)CBr)=CC=C21 YHXHHGDUANVQHE-UHFFFAOYSA-N 0.000 description 1
• ODZTXUXIYGJLMC-UHFFFAOYSA-N 2-hydroxycyclohexan-1-one Chemical compound OC1CCCCC1=O ODZTXUXIYGJLMC-UHFFFAOYSA-N 0.000 description 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• YRNDGUSDBCARGC-UHFFFAOYSA-N 2-methoxyacetophenone Chemical compound COCC(=O)C1=CC=CC=C1 YRNDGUSDBCARGC-UHFFFAOYSA-N 0.000 description 1
• JAMSOXVEIZFPBF-MRXNPFEDSA-N 2-methyl-n-[4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]propanamide Chemical compound C1=CC(NC(=O)C(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2N[C@H](C)C1=CC=CC=C1 JAMSOXVEIZFPBF-MRXNPFEDSA-N 0.000 description 1
• DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
• PKRSYEPBQPFNRB-UHFFFAOYSA-N 2-phenoxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OC1=CC=CC=C1 PKRSYEPBQPFNRB-UHFFFAOYSA-N 0.000 description 1
• WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• JZIBVTUXIVIFGC-UHFFFAOYSA-N 2H-pyrrole Chemical compound C1C=CC=N1 JZIBVTUXIVIFGC-UHFFFAOYSA-N 0.000 description 1
• IWPZKOJSYQZABD-UHFFFAOYSA-N 3,4,5-trimethoxybenzoic acid Natural products COC1=CC(OC)=CC(C(O)=O)=C1 IWPZKOJSYQZABD-UHFFFAOYSA-N 0.000 description 1
• ZBUSMOYNEJMRCC-UHFFFAOYSA-N 3-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol;hydrobromide Chemical compound Br.OC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 ZBUSMOYNEJMRCC-UHFFFAOYSA-N 0.000 description 1
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
• JDQDSEVNMTYMOC-UHFFFAOYSA-N 3-methylbenzenesulfonic acid Chemical compound CC1=CC=CC(S(O)(=O)=O)=C1 JDQDSEVNMTYMOC-UHFFFAOYSA-N 0.000 description 1
• OSJPPGNTCRNQQC-UHFFFAOYSA-N 3-phosphoglyceric acid Chemical compound OC(=O)C(O)COP(O)(O)=O OSJPPGNTCRNQQC-UHFFFAOYSA-N 0.000 description 1
• ICTHGQKQYABWMV-UHFFFAOYSA-N 4-(2,2-dimethylpropyl)phenol Chemical compound CC(C)(C)CC1=CC=C(O)C=C1 ICTHGQKQYABWMV-UHFFFAOYSA-N 0.000 description 1
• 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 1
• DVKHNTDLXNHOQD-UHFFFAOYSA-N 4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol;hydrobromide Chemical compound Br.C1=CC(O)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 DVKHNTDLXNHOQD-UHFFFAOYSA-N 0.000 description 1
• IQNYCLWUBSTSKY-SECBINFHSA-N 4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C1([C@H](NC=2C=3C=C(NC=3N=CN=2)C(N)=O)C)=CC=CC=C1 IQNYCLWUBSTSKY-SECBINFHSA-N 0.000 description 1
• WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
• BPTCCCTWWAUJRK-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=CN2 BPTCCCTWWAUJRK-UHFFFAOYSA-N 0.000 description 1
• BYADTXRINBQQHX-UHFFFAOYSA-N 4-chloro-9h-pyrido[2,3]pyrrolo[2,4-d]pyrimidine Chemical compound N1C2=NC=CC=C2C2=C1N=CN=C2Cl BYADTXRINBQQHX-UHFFFAOYSA-N 0.000 description 1
• 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
• UXNMROXAXKRCEC-UHFFFAOYSA-N 5-(anilinomethyl)-n-(3-chlorophenyl)-6-methyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=12C(CNC=3C=CC=CC=3)=C(C)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 UXNMROXAXKRCEC-UHFFFAOYSA-N 0.000 description 1
• RZMJLBHHJPRYKJ-UHFFFAOYSA-N 5-(anilinomethyl)-n-(3-chlorophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C(CNC=4C=CC=CC=4)=CNC=3N=CN=2)=C1 RZMJLBHHJPRYKJ-UHFFFAOYSA-N 0.000 description 1
• ACZQUYSPTJDIRG-UHFFFAOYSA-N 6-(4-aminophenyl)-n-[(3-methylphenyl)methyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CC1=CC=CC(CNC=2C=3C=C(NC=3N=CN=2)C=2C=CC(N)=CC=2)=C1 ACZQUYSPTJDIRG-UHFFFAOYSA-N 0.000 description 1
• LQXHLZBLYDZGEY-UHFFFAOYSA-N 6-(4-methoxyphenyl)-5-methyl-1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC(OC)=CC=C1C1=C(C)C2=C(O)N=CN=C2N1 LQXHLZBLYDZGEY-UHFFFAOYSA-N 0.000 description 1
• DGXVGHDUNRFLDB-CQSZACIVSA-N 6-(4-methoxyphenyl)-n-[(1r)-1-phenylethyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1C(NC1=NC=N2)=CC1=C2N[C@H](C)C1=CC=CC=C1 DGXVGHDUNRFLDB-CQSZACIVSA-N 0.000 description 1
• RHWWAIDIUZKYKK-UHFFFAOYSA-N 6-(bromomethyl)-n-(3-chlorophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C=C(CBr)NC=3N=CN=2)=C1 RHWWAIDIUZKYKK-UHFFFAOYSA-N 0.000 description 1
• GGDWKXPIGAHORY-GFCCVEGCSA-N 6-[(dimethylamino)methyl]-n-[(1r)-1-phenylethyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1([C@H](NC=2C=3C=C(CN(C)C)NC=3N=CN=2)C)=CC=CC=C1 GGDWKXPIGAHORY-GFCCVEGCSA-N 0.000 description 1
• GNVWZEIUTBVYLZ-UHFFFAOYSA-N 6-[4-(dimethylamino)phenyl]-n-(1-phenylethyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=1C=CC=CC=1C(C)NC(C=1C=2)=NC=NC=1NC=2C1=CC=C(N(C)C)C=C1 GNVWZEIUTBVYLZ-UHFFFAOYSA-N 0.000 description 1
• XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 235000019489 Almond oil Nutrition 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 238000011729 BALB/c nude mouse Methods 0.000 description 1
• 229910015900 BF3 Inorganic materials 0.000 description 1
• 235000021357 Behenic acid Nutrition 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• XHIYZRASNJPMIO-UHFFFAOYSA-N BrCC(=O)C1=CC=C(C=C1)C1=CC=CC=C1.BrCC(=O)C1=CC=C(C=C1)C1=CC=CC=C1 Chemical compound BrCC(=O)C1=CC=C(C=C1)C1=CC=CC=C1.BrCC(=O)C1=CC=C(C=C1)C1=CC=CC=C1 XHIYZRASNJPMIO-UHFFFAOYSA-N 0.000 description 1
• DPUOLQHDNGRHBS-UHFFFAOYSA-N Brassidinsaeure Natural products CCCCCCCCC=CCCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-UHFFFAOYSA-N 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 244000060011 Cocos nucifera Species 0.000 description 1
• 235000013162 Cocos nucifera Nutrition 0.000 description 1
• XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• URXZXNYJPAJJOQ-UHFFFAOYSA-N Erucic acid Natural products CCCCCCC=CCCCCCCCCCCCC(O)=O URXZXNYJPAJJOQ-UHFFFAOYSA-N 0.000 description 1
• KIWBPDUYBMNFTB-UHFFFAOYSA-N Ethyl hydrogen sulfate Chemical compound CCOS(O)(=O)=O KIWBPDUYBMNFTB-UHFFFAOYSA-N 0.000 description 1
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
• 108091008794 FGF receptors Proteins 0.000 description 1
• 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 1
• KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical class F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical group [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
• DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
• DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• 102100026720 Interferon beta Human genes 0.000 description 1
• 108090000467 Interferon-beta Proteins 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 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
• 239000004166 Lanolin Substances 0.000 description 1
• 239000005639 Lauric acid Substances 0.000 description 1
• 239000002841 Lewis acid Substances 0.000 description 1
• 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
• SVYKKECYCPFKGB-UHFFFAOYSA-N N,N-dimethylcyclohexylamine Chemical compound CN(C)C1CCCCC1 SVYKKECYCPFKGB-UHFFFAOYSA-N 0.000 description 1
• HXFOXFJUNFFYMO-BYPYZUCNSA-N N-alpha-acetyl-L-asparagine Chemical compound CC(=O)N[C@H](C(O)=O)CC(N)=O HXFOXFJUNFFYMO-BYPYZUCNSA-N 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
• 208000003788 Neoplasm Micrometastasis Diseases 0.000 description 1
• 208000034179 Neoplasms, Glandular and Epithelial Diseases 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• 108700020796 Oncogene Proteins 0.000 description 1
• 108091008606 PDGF receptors Proteins 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 239000004721 Polyphenylene oxide Substances 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
• 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
• 229940123924 Protein kinase C inhibitor Drugs 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 1
• 108091005682 Receptor kinases Proteins 0.000 description 1
• 108010077895 Sarcosine Proteins 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 102000004584 Somatomedin Receptors Human genes 0.000 description 1
• 108010017622 Somatomedin Receptors Proteins 0.000 description 1
• NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 229930006000 Sucrose Natural products 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
• 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
• XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
• 108091008605 VEGF receptors Proteins 0.000 description 1
• NLPUTBDZNNXHCO-CGHBYZBKSA-N Val(5)-angiotensin II Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 NLPUTBDZNNXHCO-CGHBYZBKSA-N 0.000 description 1
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
• 229930003427 Vitamin E Natural products 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• FGUZFFWTBWJBIL-XWVZOOPGSA-N [(1r)-1-[(2s,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)O[C@H](CO)[C@H]1OC[C@H](O)[C@H]1O FGUZFFWTBWJBIL-XWVZOOPGSA-N 0.000 description 1
• SMEGJBVQLJJKKX-HOTMZDKISA-N [(2R,3S,4S,5R,6R)-5-acetyloxy-3,4,6-trihydroxyoxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@@H](O1)O)OC(=O)C)O)O SMEGJBVQLJJKKX-HOTMZDKISA-N 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 229940081735 acetylcellulose Drugs 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 125000004442 acylamino group Chemical group 0.000 description 1
• JIMXXGFJRDUSRO-UHFFFAOYSA-N adamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC2CC1(C(=O)O)C3 JIMXXGFJRDUSRO-UHFFFAOYSA-N 0.000 description 1
• 239000001361 adipic acid Substances 0.000 description 1
• 235000011037 adipic acid Nutrition 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
• IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 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
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 125000005103 alkyl silyl group Chemical group 0.000 description 1
• OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
• 125000005336 allyloxy group Chemical group 0.000 description 1
• 239000008168 almond oil Substances 0.000 description 1
• OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 235000001014 amino acid Nutrition 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 229960004909 aminosalicylic acid Drugs 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 229940046836 anti-estrogen Drugs 0.000 description 1
• 230000001833 anti-estrogenic effect Effects 0.000 description 1
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
• 239000010477 apricot oil Substances 0.000 description 1
• 239000003886 aromatase inhibitor Substances 0.000 description 1
• 229940046844 aromatase inhibitors Drugs 0.000 description 1
• 150000001491 aromatic compounds Chemical class 0.000 description 1
• 239000003849 aromatic solvent Substances 0.000 description 1
• 125000003435 aroyl group Chemical group 0.000 description 1
• 125000005101 aryl methoxy carbonyl group Chemical group 0.000 description 1
• 125000005110 aryl thio group Chemical group 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 229940116226 behenic acid Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 150000001559 benzoic acids Chemical class 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 239000011648 beta-carotene Substances 0.000 description 1
• 235000013734 beta-carotene Nutrition 0.000 description 1
• TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
• 229960002747 betacarotene Drugs 0.000 description 1
• 235000013361 beverage Nutrition 0.000 description 1
• 125000006267 biphenyl group Chemical group 0.000 description 1
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000032823 cell division Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 230000010307 cell transformation Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• HNEGQIOMVPPMNR-IHWYPQMZSA-N citraconic acid Chemical compound OC(=O)C(/C)=C\C(O)=O HNEGQIOMVPPMNR-IHWYPQMZSA-N 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 235000008504 concentrate Nutrition 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 229940099112 cornstarch Drugs 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 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 1
• HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
• 239000000824 cytostatic agent Substances 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 239000002274 desiccant Substances 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 239000003599 detergent Substances 0.000 description 1
• 229950006137 dexfosfoserine Drugs 0.000 description 1
• MUVJLUQRPOPLEQ-UHFFFAOYSA-M di(ethylidene)azanium;iodide Chemical compound [I-].CC=[N+]=CC MUVJLUQRPOPLEQ-UHFFFAOYSA-M 0.000 description 1
• 235000019700 dicalcium phosphate Nutrition 0.000 description 1
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
• NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
• WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
• 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
• ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• GRWZHXKQBITJKP-UHFFFAOYSA-L dithionite(2-) Chemical compound [O-]S(=O)S([O-])=O GRWZHXKQBITJKP-UHFFFAOYSA-L 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
• LLRANSBEYQZKFY-UHFFFAOYSA-N dodecanoic acid;propane-1,2-diol Chemical compound CC(O)CO.CCCCCCCCCCCC(O)=O LLRANSBEYQZKFY-UHFFFAOYSA-N 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 239000002532 enzyme inhibitor Substances 0.000 description 1
• DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 0.000 description 1
• VVDUZZGYBOWDSQ-UHFFFAOYSA-M eschenmoser's salt Chemical compound [I-].C[N+](C)=C VVDUZZGYBOWDSQ-UHFFFAOYSA-M 0.000 description 1
• 239000000328 estrogen antagonist Substances 0.000 description 1
• GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 1
• IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
• ZRSDQBKGDNPFLT-UHFFFAOYSA-N ethanol;oxolane Chemical compound CCO.C1CCOC1 ZRSDQBKGDNPFLT-UHFFFAOYSA-N 0.000 description 1
• XTLNYNMNUCLWEZ-UHFFFAOYSA-N ethanol;propan-2-one Chemical compound CCO.CC(C)=O XTLNYNMNUCLWEZ-UHFFFAOYSA-N 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
• MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
• CHDFNIZLAAFFPX-UHFFFAOYSA-N ethoxyethane;oxolane Chemical compound CCOCC.C1CCOC1 CHDFNIZLAAFFPX-UHFFFAOYSA-N 0.000 description 1
• FPIQZBQZKBKLEI-UHFFFAOYSA-N ethyl 1-[[2-chloroethyl(nitroso)carbamoyl]amino]cyclohexane-1-carboxylate Chemical compound ClCCN(N=O)C(=O)NC1(C(=O)OCC)CCCCC1 FPIQZBQZKBKLEI-UHFFFAOYSA-N 0.000 description 1
• XKJUSNOUOLSNJN-UHFFFAOYSA-N ethyl 2-amino-1h-pyrrole-3-carboxylate Chemical compound CCOC(=O)C=1C=CNC=1N XKJUSNOUOLSNJN-UHFFFAOYSA-N 0.000 description 1
• FBEUGWGZZFGLNB-UHFFFAOYSA-N ethyl 2-amino-5-(1-benzylpyridin-1-ium-2-yl)-1h-pyrrole-3-carboxylate;bromide Chemical compound [Br-].N1C(N)=C(C(=O)OCC)C=C1C1=CC=CC=[N+]1CC1=CC=CC=C1 FBEUGWGZZFGLNB-UHFFFAOYSA-N 0.000 description 1
• TZMRHCCWFFHZLP-UHFFFAOYSA-N ethyl 2-amino-5-(3-ethoxycarbonylphenyl)-1h-pyrrole-3-carboxylate Chemical compound N1C(N)=C(C(=O)OCC)C=C1C1=CC=CC(C(=O)OCC)=C1 TZMRHCCWFFHZLP-UHFFFAOYSA-N 0.000 description 1
• ONENVWRGVMDXJN-UHFFFAOYSA-N ethyl 2-amino-5-(4-ethoxycarbonylphenyl)-1h-pyrrole-3-carboxylate Chemical compound N1C(N)=C(C(=O)OCC)C=C1C1=CC=C(C(=O)OCC)C=C1 ONENVWRGVMDXJN-UHFFFAOYSA-N 0.000 description 1
• LRPAKNYVOAOQGG-UHFFFAOYSA-N ethyl 2-amino-5-phenyl-1h-pyrrole-3-carboxylate Chemical compound N1C(N)=C(C(=O)OCC)C=C1C1=CC=CC=C1 LRPAKNYVOAOQGG-UHFFFAOYSA-N 0.000 description 1
• GWDKTZHFCFZFQI-UHFFFAOYSA-N ethyl 3-(4-chloro-7h-pyrrolo[2,3-d]pyrimidin-6-yl)benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2NC3=NC=NC(Cl)=C3C=2)=C1 GWDKTZHFCFZFQI-UHFFFAOYSA-N 0.000 description 1
• ZMZYRZTVZRTYLY-UHFFFAOYSA-N ethyl 3-(4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-6-yl)benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2NC3=NC=NC(O)=C3C=2)=C1 ZMZYRZTVZRTYLY-UHFFFAOYSA-N 0.000 description 1
• VICYTAYPKBLQFB-UHFFFAOYSA-N ethyl 3-bromo-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CBr VICYTAYPKBLQFB-UHFFFAOYSA-N 0.000 description 1
• MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 1
• WHQLQYRFIHPMNA-UHFFFAOYSA-N ethyl acetate;oxolane Chemical compound C1CCOC1.CCOC(C)=O WHQLQYRFIHPMNA-UHFFFAOYSA-N 0.000 description 1
• VMPIPCOGRWYUDT-UHFFFAOYSA-N ethyl acetate;oxolane;hydrate Chemical compound O.C1CCOC1.CCOC(C)=O VMPIPCOGRWYUDT-UHFFFAOYSA-N 0.000 description 1
• OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-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
• SIVVHUQWDOGLJN-UHFFFAOYSA-N ethylsulfamic acid Chemical compound CCNS(O)(=O)=O SIVVHUQWDOGLJN-UHFFFAOYSA-N 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 238000010265 fast atom bombardment Methods 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 239000010685 fatty oil Substances 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 238000005187 foaming Methods 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 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
• 238000005227 gel permeation chromatography Methods 0.000 description 1
• 239000012213 gelatinous substance Substances 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 229940097043 glucuronic acid Drugs 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• UHUSDOQQWJGJQS-UHFFFAOYSA-N glycerol 1,2-dioctadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCCCC UHUSDOQQWJGJQS-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 244000144993 groups of animals Species 0.000 description 1
• 239000003630 growth substance Substances 0.000 description 1
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
• MOTRZVVGCFFABN-UHFFFAOYSA-N hexane;2-propan-2-yloxypropane Chemical compound CCCCCC.CC(C)OC(C)C MOTRZVVGCFFABN-UHFFFAOYSA-N 0.000 description 1
• GGQOPZKTDHXXON-UHFFFAOYSA-N hexane;methanol Chemical compound OC.CCCCCC GGQOPZKTDHXXON-UHFFFAOYSA-N 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 230000000887 hydrating effect Effects 0.000 description 1
• 239000010512 hydrogenated peanut oil Substances 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
• 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
• 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 208000026278 immune system disease Diseases 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 239000003978 infusion fluid Substances 0.000 description 1
• 239000002198 insoluble material Substances 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 238000004255 ion exchange chromatography Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• BMFVGAAISNGQNM-UHFFFAOYSA-N isopentylamine Chemical compound CC(C)CCN BMFVGAAISNGQNM-UHFFFAOYSA-N 0.000 description 1
• XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
• 210000002510 keratinocyte Anatomy 0.000 description 1
• 150000003951 lactams Chemical group 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 235000019388 lanolin Nutrition 0.000 description 1
• 229940039717 lanolin Drugs 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 150000007517 lewis acids Chemical class 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 235000014666 liquid concentrate Nutrition 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 150000004668 long chain fatty acids Chemical class 0.000 description 1
• 238000012792 lyophilization process Methods 0.000 description 1
• QXUAFCKBYYPTPQ-ZWKAXHIPSA-L magnesium (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(2R,3S,4R,5R)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol octadecanoate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O QXUAFCKBYYPTPQ-ZWKAXHIPSA-L 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 239000000155 melt Substances 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 239000002184 metal Chemical class 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 229910044991 metal oxide Inorganic materials 0.000 description 1
• 150000004706 metal oxides Chemical class 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• JZMJDSHXVKJFKW-UHFFFAOYSA-N methyl sulfate Chemical compound COS(O)(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-N 0.000 description 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 229960002900 methylcellulose Drugs 0.000 description 1
• MYMDOKBFMTVEGE-UHFFFAOYSA-N methylsulfamic acid Chemical compound CNS(O)(=O)=O MYMDOKBFMTVEGE-UHFFFAOYSA-N 0.000 description 1
• 230000003641 microbiacidal effect Effects 0.000 description 1
• 229940124561 microbicide Drugs 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• JWEJFZOBSUTUAD-UHFFFAOYSA-N n-(3-chlorophenyl)-6-(3-methoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound COC1=CC=CC(C=2NC3=NC=NC(NC=4C=C(Cl)C=CC=4)=C3C=2)=C1 JWEJFZOBSUTUAD-UHFFFAOYSA-N 0.000 description 1
• GTKVVNIPANLAHN-UHFFFAOYSA-N n-(3-chlorophenyl)-6-(4-methoxyphenyl)-5-methyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1C1=C(C)C2=C(NC=3C=C(Cl)C=CC=3)N=CN=C2N1 GTKVVNIPANLAHN-UHFFFAOYSA-N 0.000 description 1
• CMSUFJFFMVZJTI-UHFFFAOYSA-N n-(3-chlorophenyl)-6-[4-(2-methylpropylamino)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(NCC(C)C)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 CMSUFJFFMVZJTI-UHFFFAOYSA-N 0.000 description 1
• MWXVWRAPMYEJOF-UHFFFAOYSA-N n-(3-chlorophenyl)-6-pyridin-2-yl-7h-pyrrolo[2,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.ClC1=CC=CC(NC=2C=3C=C(NC=3N=CN=2)C=2N=CC=CC=2)=C1 MWXVWRAPMYEJOF-UHFFFAOYSA-N 0.000 description 1
• IWGZZXIHUTZVBV-UHFFFAOYSA-N n-(3-chlorophenyl)-9h-pyrimido[4,5-b]indol-4-amine;hydrochloride Chemical compound Cl.ClC1=CC=CC(NC=2C=3C4=CC=CC=C4NC=3N=CN=2)=C1 IWGZZXIHUTZVBV-UHFFFAOYSA-N 0.000 description 1
• UZLGAFFKTLBDIB-UHFFFAOYSA-N n-[4-[4-(3-chloroanilino)-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1C(NC1=NC=N2)=CC1=C2NC1=CC=CC(Cl)=C1 UZLGAFFKTLBDIB-UHFFFAOYSA-N 0.000 description 1
• GEKBGSALZDJBEL-UHFFFAOYSA-N n-benzyl-5,6-dimethyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.C=12C(C)=C(C)NC2=NC=NC=1NCC1=CC=CC=C1 GEKBGSALZDJBEL-UHFFFAOYSA-N 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
• 230000003472 neutralizing effect Effects 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 150000002829 nitrogen Chemical class 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 238000010899 nucleation Methods 0.000 description 1
• 230000000269 nucleophilic effect Effects 0.000 description 1
• YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical class CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 238000005580 one pot reaction Methods 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 239000003791 organic solvent mixture Substances 0.000 description 1
• 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• BHIIWXJHALLFBD-UHFFFAOYSA-N oxolane;propan-2-ol Chemical compound CC(C)O.C1CCOC1 BHIIWXJHALLFBD-UHFFFAOYSA-N 0.000 description 1
• 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
• 230000020477 pH reduction Effects 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 150000003009 phosphonic acids Chemical class 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
• 238000006303 photolysis reaction Methods 0.000 description 1
• 230000015843 photosynthesis, light reaction Effects 0.000 description 1
• XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
• 239000000049 pigment Substances 0.000 description 1
• 239000004014 plasticizer Substances 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920000768 polyamine Polymers 0.000 description 1
• 229920000570 polyether Polymers 0.000 description 1
• 229920000223 polyglycerol Polymers 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 229920000137 polyphosphoric acid Polymers 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 229920000053 polysorbate 80 Polymers 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 229940116317 potato starch Drugs 0.000 description 1
• 235000014483 powder concentrate Nutrition 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000003881 protein kinase C inhibitor Substances 0.000 description 1
• 239000003909 protein kinase inhibitor Substances 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• DXVAQZJPPDWTNY-UHFFFAOYSA-N pyrrolo[3,2-d]pyrimidin-2-one Chemical compound O=C1N=CC2=NC=CC2=N1 DXVAQZJPPDWTNY-UHFFFAOYSA-N 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 229940100486 rice starch Drugs 0.000 description 1
• 238000002390 rotary evaporation Methods 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 235000003441 saturated fatty acids Nutrition 0.000 description 1
• 150000004671 saturated fatty acids Chemical class 0.000 description 1
• 239000012047 saturated solution Substances 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 230000008054 signal transmission Effects 0.000 description 1
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 235000015424 sodium Nutrition 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 229940080236 sodium cetyl sulfate Drugs 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• RZWQDAUIUBVCDD-UHFFFAOYSA-M sodium;benzenethiolate Chemical compound [Na+].[S-]C1=CC=CC=C1 RZWQDAUIUBVCDD-UHFFFAOYSA-M 0.000 description 1
• GGHPAKFFUZUEKL-UHFFFAOYSA-M sodium;hexadecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCCCOS([O-])(=O)=O GGHPAKFFUZUEKL-UHFFFAOYSA-M 0.000 description 1
• NWZBFJYXRGSRGD-UHFFFAOYSA-M sodium;octadecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCCCCCOS([O-])(=O)=O NWZBFJYXRGSRGD-UHFFFAOYSA-M 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 238000000638 solvent extraction Methods 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 229940057429 sorbitan isostearate Drugs 0.000 description 1
• 229940035044 sorbitan monolaurate Drugs 0.000 description 1
• 229950004959 sorbitan oleate Drugs 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid group Chemical class S(N)(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
• 150000003460 sulfonic acids Chemical class 0.000 description 1
• 239000002511 suppository base Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 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 description 1
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
• 125000004149 thio group Chemical group *S* 0.000 description 1
• RSPCKAHMRANGJZ-UHFFFAOYSA-N thiohydroxylamine Chemical group SN RSPCKAHMRANGJZ-UHFFFAOYSA-N 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 150000007944 thiolates Chemical class 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• 229940078499 tricalcium phosphate Drugs 0.000 description 1
• 235000019731 tricalcium phosphate Nutrition 0.000 description 1
• 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
• ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
• 150000004072 triols Chemical class 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
• 230000004565 tumor cell growth Effects 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 238000010518 undesired secondary reaction Methods 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 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
• 239000001993 wax Substances 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 239000011787 zinc oxide Substances 0.000 description 1
• OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1