KR20060089215A - 항암제로서의 5-아릴피리미딘 - Google Patents
항암제로서의 5-아릴피리미딘 Download PDFInfo
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- KR20060089215A KR20060089215A KR1020067005903A KR20067005903A KR20060089215A KR 20060089215 A KR20060089215 A KR 20060089215A KR 1020067005903 A KR1020067005903 A KR 1020067005903A KR 20067005903 A KR20067005903 A KR 20067005903A KR 20060089215 A KR20060089215 A KR 20060089215A
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- KR
- South Korea
- Prior art keywords
- chloro
- pyrimidin
- amine
- compound
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000002246 antineoplastic agent Substances 0.000 title claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 302
- 150000003839 salts Chemical class 0.000 claims abstract description 136
- 238000000034 method Methods 0.000 claims abstract description 98
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 72
- 241000124008 Mammalia Species 0.000 claims abstract description 62
- 230000036457 multidrug resistance Effects 0.000 claims abstract description 58
- 230000012010 growth Effects 0.000 claims abstract description 34
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 25
- 201000010099 disease Diseases 0.000 claims abstract description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 24
- 230000001737 promoting effect Effects 0.000 claims abstract description 19
- -1 cyano, hydroxy Chemical group 0.000 claims description 235
- 102000004243 Tubulin Human genes 0.000 claims description 91
- 108090000704 Tubulin Proteins 0.000 claims description 91
- 229910052739 hydrogen Inorganic materials 0.000 claims description 76
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 51
- 102000029749 Microtubule Human genes 0.000 claims description 48
- 108091022875 Microtubule Proteins 0.000 claims description 48
- 210000004688 microtubule Anatomy 0.000 claims description 46
- 229910052801 chlorine Inorganic materials 0.000 claims description 45
- 229910052731 fluorine Inorganic materials 0.000 claims description 44
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 43
- 229910052794 bromium Inorganic materials 0.000 claims description 42
- 229910052799 carbon Inorganic materials 0.000 claims description 37
- 150000001412 amines Chemical class 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 31
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 31
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 29
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- 125000006413 ring segment Chemical group 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 20
- MQLACMBJVPINKE-UHFFFAOYSA-N 10-[(3-hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one Chemical compound C1=C(O)C(OC)=CC=C1C=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MQLACMBJVPINKE-UHFFFAOYSA-N 0.000 claims description 19
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 18
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 18
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 18
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 18
- 125000002541 furyl group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 16
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 16
- 239000002585 base Substances 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 230000000087 stabilizing effect Effects 0.000 claims description 15
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 238000006116 polymerization reaction Methods 0.000 claims description 12
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- ODURFEQFDLNVNA-UHFFFAOYSA-N [4-chloro-6-(2,2,2-trifluoroethylamino)-5-(2,4,6-trifluorophenyl)pyrimidin-2-yl]-methylcyanamide Chemical compound FC(F)(F)CNC1=NC(N(C#N)C)=NC(Cl)=C1C1=C(F)C=C(F)C=C1F ODURFEQFDLNVNA-UHFFFAOYSA-N 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- VKAOCYPNKOPRSE-UHFFFAOYSA-N 3-[4-(4-chloro-6-cycloheptyl-2-pyrazin-2-ylpyrimidin-5-yl)-3,5-difluorophenoxy]-n-methylpropan-1-amine Chemical compound FC1=CC(OCCCNC)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=NC=2)N=C1C1CCCCCC1 VKAOCYPNKOPRSE-UHFFFAOYSA-N 0.000 claims description 9
- CBWLEMXYPINBTA-NSHDSACASA-N 6-chloro-5-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-2-pyrazin-2-yl-n-[(2s)-1,1,1-trifluoropropan-2-yl]pyrimidin-4-amine Chemical compound FC1=CC(OCCCNC)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=NC=2)N=C1N[C@@H](C)C(F)(F)F CBWLEMXYPINBTA-NSHDSACASA-N 0.000 claims description 9
- QIHITHOIUNZULD-UHFFFAOYSA-N 6-chloro-5-[4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl]-2-imidazol-1-yl-n-(2,2,2-trifluoroethyl)pyrimidin-4-amine Chemical compound FC1=CC(OCCCN(C)C)=CC(F)=C1C1=C(Cl)N=C(N2C=NC=C2)N=C1NCC(F)(F)F QIHITHOIUNZULD-UHFFFAOYSA-N 0.000 claims description 9
- 229910052727 yttrium Inorganic materials 0.000 claims description 9
- LDESLYKWJNFLSX-UHFFFAOYSA-N 6-chloro-5-[4-[2-(dimethylamino)ethoxy]-2,6-difluorophenyl]-2-pyrazin-2-yl-n-(2,2,2-trifluoroethyl)pyrimidin-4-amine Chemical compound FC1=CC(OCCN(C)C)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=NC=2)N=C1NCC(F)(F)F LDESLYKWJNFLSX-UHFFFAOYSA-N 0.000 claims description 8
- HXJHMTCVYUBCGI-UHFFFAOYSA-N 6-chloro-5-[4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl]-2-pyrazin-2-yl-n-(2,2,2-trifluoroethyl)pyrimidin-4-amine Chemical compound FC1=CC(OCCCN(C)C)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=NC=2)N=C1NCC(F)(F)F HXJHMTCVYUBCGI-UHFFFAOYSA-N 0.000 claims description 8
- DDOWVXUYVOTAEQ-UHFFFAOYSA-N 6-chloro-5-[4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl]-2-quinolin-2-yl-n-(2,2,2-trifluoroethyl)pyrimidin-4-amine Chemical compound FC1=CC(OCCCN(C)C)=CC(F)=C1C1=C(Cl)N=C(C=2N=C3C=CC=CC3=CC=2)N=C1NCC(F)(F)F DDOWVXUYVOTAEQ-UHFFFAOYSA-N 0.000 claims description 8
- ZIHOWUDDUIKPMZ-UHFFFAOYSA-N 6-chloro-5-[4-[4-(dimethylamino)butoxy]-2,6-difluorophenyl]-2-pyrazin-2-yl-n-(2,2,2-trifluoroethyl)pyrimidin-4-amine Chemical compound FC1=CC(OCCCCN(C)C)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=NC=2)N=C1NCC(F)(F)F ZIHOWUDDUIKPMZ-UHFFFAOYSA-N 0.000 claims description 8
- MNKMDNZSTSFIFY-UHFFFAOYSA-N CN(C)CCCOC(C=C1F)=CC(F)=C1C1=C(NCC(F)(F)F)N=C(CNC#N)N=C1Cl Chemical compound CN(C)CCCOC(C=C1F)=CC(F)=C1C1=C(NCC(F)(F)F)N=C(CNC#N)N=C1Cl MNKMDNZSTSFIFY-UHFFFAOYSA-N 0.000 claims description 8
- MQQNODRQFDMVEW-UHFFFAOYSA-N [4-chloro-5-[4-[4-(dimethylamino)butoxy]-2,6-difluorophenyl]-6-(2,2,2-trifluoroethylamino)pyrimidin-2-yl]-methylcyanamide Chemical compound FC1=CC(OCCCCN(C)C)=CC(F)=C1C1=C(Cl)N=C(N(C)C#N)N=C1NCC(F)(F)F MQQNODRQFDMVEW-UHFFFAOYSA-N 0.000 claims description 8
- 125000003368 amide group Chemical group 0.000 claims description 8
- 229940127089 cytotoxic agent Drugs 0.000 claims description 8
- CBWLEMXYPINBTA-UHFFFAOYSA-N 6-chloro-5-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-2-pyrazin-2-yl-n-(1,1,1-trifluoropropan-2-yl)pyrimidin-4-amine Chemical compound FC1=CC(OCCCNC)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=NC=2)N=C1NC(C)C(F)(F)F CBWLEMXYPINBTA-UHFFFAOYSA-N 0.000 claims description 7
- SXRPINFLPQMOJG-LBPRGKRZSA-N 6-chloro-5-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-2-pyridin-2-yl-n-[(2s)-1,1,1-trifluoropropan-2-yl]pyrimidin-4-amine Chemical compound FC1=CC(OCCCNC)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=CC=2)N=C1N[C@@H](C)C(F)(F)F SXRPINFLPQMOJG-LBPRGKRZSA-N 0.000 claims description 7
- GBKOAMQVMBTXRG-UHFFFAOYSA-N 6-chloro-5-[4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl]-2-n-methyl-4-n-(2,2,2-trifluoroethyl)pyrimidine-2,4-diamine Chemical compound FC(F)(F)CNC1=NC(NC)=NC(Cl)=C1C1=C(F)C=C(OCCCN(C)C)C=C1F GBKOAMQVMBTXRG-UHFFFAOYSA-N 0.000 claims description 7
- NAYVKTCBVLDANS-UHFFFAOYSA-N CN(C)CCOC(C=C1F)=CC(F)=C1C1=C(NCC(F)(F)F)N=C(CNC#N)N=C1Cl Chemical compound CN(C)CCOC(C=C1F)=CC(F)=C1C1=C(NCC(F)(F)F)N=C(CNC#N)N=C1Cl NAYVKTCBVLDANS-UHFFFAOYSA-N 0.000 claims description 7
- CKWQLHOKWJDKEX-NSHDSACASA-N [4-chloro-5-[4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl]-6-[[(2s)-1,1,1-trifluoropropan-2-yl]amino]pyrimidin-2-yl]-methylcyanamide Chemical compound FC(F)(F)[C@H](C)NC1=NC(N(C)C#N)=NC(Cl)=C1C1=C(F)C=C(OCCCN(C)C)C=C1F CKWQLHOKWJDKEX-NSHDSACASA-N 0.000 claims description 7
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- FGDWZLMPZYDLKE-UHFFFAOYSA-N 6-chloro-2-(1-methylimidazol-2-yl)-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound CN1C=CN=C1C1=NC(Cl)=C(C=2C(=CC(F)=CC=2F)F)C(NCC(F)(F)F)=N1 FGDWZLMPZYDLKE-UHFFFAOYSA-N 0.000 claims description 6
- ILYCKCZXFXHRMJ-UHFFFAOYSA-N 6-chloro-2-(furan-2-yl)-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(C=2OC=CC=2)N=C1NCC(F)(F)F ILYCKCZXFXHRMJ-UHFFFAOYSA-N 0.000 claims description 6
- QBYHZMDVKBPHAA-UHFFFAOYSA-N 6-chloro-2-isoquinolin-1-yl-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(C=2C3=CC=CC=C3C=CN=2)N=C1NCC(F)(F)F QBYHZMDVKBPHAA-UHFFFAOYSA-N 0.000 claims description 6
- GNJIOXWXWUUCQZ-UHFFFAOYSA-N 6-chloro-2-isoquinolin-3-yl-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC3=CC=CC=C3C=2)N=C1NCC(F)(F)F GNJIOXWXWUUCQZ-UHFFFAOYSA-N 0.000 claims description 6
- RFSSBTBRSZAIBG-UHFFFAOYSA-N 6-chloro-2-pyrazin-2-yl-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=NC=2)N=C1NCC(F)(F)F RFSSBTBRSZAIBG-UHFFFAOYSA-N 0.000 claims description 6
- PYOACZADEZQCJS-UHFFFAOYSA-N 6-chloro-2-pyridin-2-yl-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=CC=2)N=C1NCC(F)(F)F PYOACZADEZQCJS-UHFFFAOYSA-N 0.000 claims description 6
- ODKBOKAYDWNIFV-UHFFFAOYSA-N 6-chloro-2-pyridin-3-yl-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(C=2C=NC=CC=2)N=C1NCC(F)(F)F ODKBOKAYDWNIFV-UHFFFAOYSA-N 0.000 claims description 6
- IOOKTIUCSYUVRN-UHFFFAOYSA-N 6-chloro-2-pyridin-4-yl-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(C=2C=CN=CC=2)N=C1NCC(F)(F)F IOOKTIUCSYUVRN-UHFFFAOYSA-N 0.000 claims description 6
- BIKBKLCRFOIENH-UHFFFAOYSA-N 6-chloro-2-pyrimidin-2-yl-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=CN=2)N=C1NCC(F)(F)F BIKBKLCRFOIENH-UHFFFAOYSA-N 0.000 claims description 6
- ZDOGRDYQRDOYPT-UHFFFAOYSA-N 6-chloro-2-quinolin-2-yl-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(C=2N=C3C=CC=CC3=CC=2)N=C1NCC(F)(F)F ZDOGRDYQRDOYPT-UHFFFAOYSA-N 0.000 claims description 6
- JPNHKLURIKULOR-UHFFFAOYSA-N 6-chloro-2-thiophen-2-yl-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(C=2SC=CC=2)N=C1NCC(F)(F)F JPNHKLURIKULOR-UHFFFAOYSA-N 0.000 claims description 6
- CBWLEMXYPINBTA-LLVKDONJSA-N 6-chloro-5-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-2-pyrazin-2-yl-n-[(2r)-1,1,1-trifluoropropan-2-yl]pyrimidin-4-amine Chemical compound FC1=CC(OCCCNC)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=NC=2)N=C1N[C@H](C)C(F)(F)F CBWLEMXYPINBTA-LLVKDONJSA-N 0.000 claims description 6
- SXRPINFLPQMOJG-UHFFFAOYSA-N 6-chloro-5-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-2-pyridin-2-yl-n-(1,1,1-trifluoropropan-2-yl)pyrimidin-4-amine Chemical compound FC1=CC(OCCCNC)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=CC=2)N=C1NC(C)C(F)(F)F SXRPINFLPQMOJG-UHFFFAOYSA-N 0.000 claims description 6
- SXRPINFLPQMOJG-GFCCVEGCSA-N 6-chloro-5-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-2-pyridin-2-yl-n-[(2r)-1,1,1-trifluoropropan-2-yl]pyrimidin-4-amine Chemical compound FC1=CC(OCCCNC)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=CC=2)N=C1N[C@H](C)C(F)(F)F SXRPINFLPQMOJG-GFCCVEGCSA-N 0.000 claims description 6
- CMRXBBZWPSTMEC-UHFFFAOYSA-N 6-chloro-5-[4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl]-2-pyrimidin-2-yl-n-(2,2,2-trifluoroethyl)pyrimidin-4-amine Chemical compound FC1=CC(OCCCN(C)C)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=CN=2)N=C1NCC(F)(F)F CMRXBBZWPSTMEC-UHFFFAOYSA-N 0.000 claims description 6
- CKWQLHOKWJDKEX-LLVKDONJSA-N [4-chloro-5-[4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl]-6-[[(2r)-1,1,1-trifluoropropan-2-yl]amino]pyrimidin-2-yl]-methylcyanamide Chemical compound FC(F)(F)[C@@H](C)NC1=NC(N(C)C#N)=NC(Cl)=C1C1=C(F)C=C(OCCCN(C)C)C=C1F CKWQLHOKWJDKEX-LLVKDONJSA-N 0.000 claims description 6
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 6
- 150000008041 alkali metal carbonates Chemical class 0.000 claims description 6
- 239000000010 aprotic solvent Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- JOGZZTFIGKYTSV-UHFFFAOYSA-N ethylcyanamide Chemical compound CCNC#N JOGZZTFIGKYTSV-UHFFFAOYSA-N 0.000 claims description 6
- 150000004678 hydrides Chemical class 0.000 claims description 6
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 6
- USZDFOPAUAEWBC-UHFFFAOYSA-N 6-chloro-2-pyrazin-2-yl-5-(2,4,6-trifluorophenyl)-n-(1,1,1-trifluoropropan-2-yl)pyrimidin-4-amine Chemical compound FC(F)(F)C(C)NC1=NC(C=2N=CC=NC=2)=NC(Cl)=C1C1=C(F)C=C(F)C=C1F USZDFOPAUAEWBC-UHFFFAOYSA-N 0.000 claims description 5
- KNFWEQCTFQIEMA-UHFFFAOYSA-N 6-chloro-2-pyridin-2-yl-5-(2,4,6-trifluorophenyl)-n-(1,1,1-trifluoropropan-2-yl)pyrimidin-4-amine Chemical compound FC(F)(F)C(C)NC1=NC(C=2N=CC=CC=2)=NC(Cl)=C1C1=C(F)C=C(F)C=C1F KNFWEQCTFQIEMA-UHFFFAOYSA-N 0.000 claims description 5
- YDUXGZDCHMEEGU-UHFFFAOYSA-N 6-chloro-2-pyrrol-1-yl-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(N2C=CC=C2)N=C1NCC(F)(F)F YDUXGZDCHMEEGU-UHFFFAOYSA-N 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 5
- 150000008044 alkali metal hydroxides Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- USCQBKSUWCKHKG-UHFFFAOYSA-N 2-(5-azidopyridin-2-yl)-6-chloro-5-[4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl]-n-(2,2,2-trifluoroethyl)pyrimidin-4-amine Chemical compound FC1=CC(OCCCN(C)C)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC(=CC=2)N=[N+]=[N-])N=C1NCC(F)(F)F USCQBKSUWCKHKG-UHFFFAOYSA-N 0.000 claims description 2
- ZXUDPCQCQFLPJR-UHFFFAOYSA-N [4-chloro-5-[4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl]-6-(2,2,2-trifluoroethylamino)pyrimidin-2-yl]-methylcyanamide Chemical compound FC1=CC(OCCCN(C)C)=CC(F)=C1C1=C(Cl)N=C(N(C)C#N)N=C1NCC(F)(F)F ZXUDPCQCQFLPJR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- 239000011574 phosphorus Substances 0.000 claims description 2
- MCLITRXWHZUNCQ-UHFFFAOYSA-N methylcyanamide Chemical compound CNC#N MCLITRXWHZUNCQ-UHFFFAOYSA-N 0.000 claims 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 claims 1
- 230000008029 eradication Effects 0.000 claims 1
- 230000009036 growth inhibition Effects 0.000 claims 1
- 150000003018 phosphorus compounds Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 74
- 201000011510 cancer Diseases 0.000 abstract description 23
- 238000011282 treatment Methods 0.000 abstract description 22
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50548703P | 2003-09-24 | 2003-09-24 | |
| US60/505,487 | 2003-09-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20060089215A true KR20060089215A (ko) | 2006-08-08 |
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| KR1020067005903A Withdrawn KR20060089215A (ko) | 2003-09-24 | 2004-09-17 | 항암제로서의 5-아릴피리미딘 |
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| EP (1) | EP1663241B1 (enExample) |
| JP (1) | JP2007506746A (enExample) |
| KR (1) | KR20060089215A (enExample) |
| CN (1) | CN1871009A (enExample) |
| AR (1) | AR045811A1 (enExample) |
| AT (1) | ATE432077T1 (enExample) |
| AU (1) | AU2004275733A1 (enExample) |
| BR (1) | BRPI0414736A (enExample) |
| CA (1) | CA2539235A1 (enExample) |
| CO (1) | CO5690592A2 (enExample) |
| DE (1) | DE602004021269D1 (enExample) |
| EC (1) | ECSP066457A (enExample) |
| GT (1) | GT200400188A (enExample) |
| IL (1) | IL174305A0 (enExample) |
| MX (1) | MXPA06003207A (enExample) |
| NO (1) | NO20061319L (enExample) |
| PA (1) | PA8613201A1 (enExample) |
| PE (1) | PE20050470A1 (enExample) |
| RU (1) | RU2006107578A (enExample) |
| SA (1) | SA04250303A (enExample) |
| TW (1) | TW200512198A (enExample) |
| WO (1) | WO2005030216A1 (enExample) |
| ZA (1) | ZA200602386B (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
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| TW200637556A (en) * | 2005-01-31 | 2006-11-01 | Basf Ag | Substituted 5-phenyl pyrimidines I in therapy |
| EP1891052A1 (en) * | 2005-06-13 | 2008-02-27 | Wyeth | Tubulin inhibitor and process for its preparation |
| CN101193884A (zh) | 2005-06-13 | 2008-06-04 | 惠氏公司 | 微管蛋白抑制剂和其制备方法 |
| US20110201496A1 (en) * | 2006-03-27 | 2011-08-18 | Joachim Rheinheimer | Substituted 5-Hetaryl-4-Aminopyrimidines |
| CL2007002231A1 (es) * | 2006-08-02 | 2008-04-11 | Basf Ag | Uso de compuestos derivados de 5-(het) arilpirimidina para combatir hongos daninos; compuestos derivados de 5-(het) arilpirimidina; agente fungicida; y agente farmaceutico. |
| AR064852A1 (es) * | 2007-01-11 | 2009-04-29 | Basf Ag | Pirimidinas sustituidas en posicion 2 |
| WO2009007187A1 (de) * | 2007-07-09 | 2009-01-15 | Basf Se | Substituierte 5-hetarylpyrimidine |
| PE20140502A1 (es) | 2011-04-22 | 2014-05-02 | Signal Pharm Llc | Pirimidinas sustituidas de diaminocarboxamida y diaminocarbonitrilo, composiciones de las mismas y metodos de tratamiento con las mismas |
| WO2014047257A2 (en) | 2012-09-19 | 2014-03-27 | The Trustees Of The University Of Pennsylvania | Heterocyclic compounds and their use for the treatment of neurodegenerative tauopathies |
| NZ715903A (en) | 2014-01-30 | 2017-06-30 | Signal Pharm Llc | Solid forms of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide, compositions thereof and methods of their use |
| BR112017012795A2 (pt) | 2014-12-16 | 2018-01-02 | Signal Pharmaceuticals, Llc | Formulações de 2-(terc-butilamino)-4-((1r,3r,4r)-3- hidroxi-4-metilciclo-hexilamino)-pirimidina-5- carboxamida |
| JP6903577B2 (ja) | 2014-12-16 | 2021-07-14 | シグナル ファーマシューティカルズ，エルエルシー | 皮膚におけるｃ−Ｊｕｎ Ｎ末端キナーゼの阻害の測定方法 |
| CA2975260C (en) | 2015-01-29 | 2024-05-21 | Signal Pharmaceuticals Llc | Isotopologues of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide |
| MX2018001004A (es) | 2015-07-24 | 2018-06-07 | Celgene Corp | Metodos de sintesis de clorhidrato de (1r,2r,5r)-5-amino-2-metilci clohexanol e intermedios utiles en este. |
| WO2019169111A1 (en) | 2018-03-02 | 2019-09-06 | The Trustees Of The University Of Pennsylvania | [1,2,4]triazolo[1,5-a]pyrimidine compounds and use in stabilizing microtubules |
| EP4052759A4 (en) * | 2019-11-01 | 2023-12-20 | Unimatec Co., Ltd. | FLUORINE-CONTAINING PYRIMIDINE COMPOUND AND METHOD FOR THE PRODUCTION THEREOF |
| TW202132285A (zh) * | 2019-11-13 | 2021-09-01 | 美商愛彼特生物製藥股份有限公司 | 經取代異吲哚啉基2,2’-聯嘧啶基化合物、其類似物及使用其之方法 |
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| US88096A (en) * | 1869-03-23 | t h a y e r | ||
| US116429A (en) * | 1871-06-27 | Improvement in dial-telegraph apparatus | ||
| US61889A (en) * | 1867-02-05 | Improvement in animal teaps | ||
| US69242A (en) * | 1867-09-24 | Calvin pepper | ||
| US147744A (en) * | 1874-02-24 | Improvement in locomotive-furnaces | ||
| GB9700664D0 (en) | 1997-01-14 | 1997-03-05 | British Tech Group | Anti-cancer agents |
| US6117876A (en) | 1997-04-14 | 2000-09-12 | American Cyanamid Company | Fungicidal trifluorophenyl-triazolopyrimidines |
| AU3536699A (en) | 1998-04-27 | 1999-11-16 | Ihara Chemical Industry Co. Ltd. | 3-arylphenyl sulfide derivatives and insecticides and miticides |
| US5986135A (en) | 1998-09-25 | 1999-11-16 | American Cyanamid Company | Fungicidal trifluoromethylalkylamino-triazolopyrimidines |
| US6156925A (en) | 1998-09-25 | 2000-12-05 | American Cyanamid Company | Process for the preparation of halogenated phenylmaloates |
| AU778913B2 (en) * | 2000-06-13 | 2004-12-23 | Basf Aktiengesellschaft | Fungicidal 5-phenyl substituted 2-(cyanoamino) pyrimidines |
| US6670362B2 (en) | 2000-09-20 | 2003-12-30 | Pfizer Inc. | Pyridazine endothelin antagonists |
| WO2002074753A2 (de) | 2001-03-15 | 2002-09-26 | Basf Aktiengesellschaft | 5-phenylpyrimidine, verfahren und zwischenprodukte zu ihrer herstellung und ihre verwendung zur bekaempfung von schadpilzen |
| DE60204509T2 (de) | 2001-04-20 | 2006-03-16 | Ciba Speciality Chemicals Holding Inc. | 4-Amino-2-(2-pyridinyl)pyrimidine als mikrobizide Wirksubstanzen |
| CN1312134C (zh) | 2001-11-19 | 2007-04-25 | 巴斯福股份公司 | 5－苯基嘧啶化合物、包含它们的组合物、其制备方法及其用途 |
| ATE428705T1 (de) | 2002-02-21 | 2009-05-15 | Basf Se | 2-(2-pyridyl)-5-phenyl-6-aminopyrimidine, verfahren und zwischenprodukte zu ihrer herstellung und ihre verwendung zur bekämpfung von schadpilzen |
| CN1642422A (zh) | 2002-03-15 | 2005-07-20 | 西巴特殊化学品控股有限公司 | 4－氨基嘧啶及其在表面抗菌处理中的应用 |
| PT2316831E (pt) | 2002-11-21 | 2013-06-06 | Novartis Ag | 2-(morfolin-4-il)pirimidinas como inibidores da fosfatidilinositol (pi) quinase e a sua utilização no tratamento do cancro |
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2004
- 2004-09-17 MX MXPA06003207A patent/MXPA06003207A/es unknown
- 2004-09-17 CA CA002539235A patent/CA2539235A1/en not_active Abandoned
- 2004-09-17 CN CNA200480031581XA patent/CN1871009A/zh active Pending
- 2004-09-17 KR KR1020067005903A patent/KR20060089215A/ko not_active Withdrawn
- 2004-09-17 RU RU2006107578/04A patent/RU2006107578A/ru not_active Application Discontinuation
- 2004-09-17 WO PCT/US2004/030682 patent/WO2005030216A1/en not_active Ceased
- 2004-09-17 EP EP04784529A patent/EP1663241B1/en not_active Expired - Lifetime
- 2004-09-17 BR BRPI0414736-7A patent/BRPI0414736A/pt not_active IP Right Cessation
- 2004-09-17 JP JP2006528086A patent/JP2007506746A/ja not_active Withdrawn
- 2004-09-17 AT AT04784529T patent/ATE432077T1/de not_active IP Right Cessation
- 2004-09-17 AU AU2004275733A patent/AU2004275733A1/en not_active Withdrawn
- 2004-09-17 DE DE602004021269T patent/DE602004021269D1/de not_active Expired - Fee Related
- 2004-09-21 TW TW093128501A patent/TW200512198A/zh unknown
- 2004-09-22 SA SA04250303A patent/SA04250303A/ar unknown
- 2004-09-22 PE PE2004000922A patent/PE20050470A1/es not_active Application Discontinuation
- 2004-09-23 GT GT200400188A patent/GT200400188A/es unknown
- 2004-09-23 AR ARP040103441A patent/AR045811A1/es not_active Application Discontinuation
- 2004-09-24 PA PA20048613201A patent/PA8613201A1/es unknown
- 2004-09-24 US US10/950,375 patent/US7524849B2/en not_active Expired - Fee Related
-
2006
- 2006-03-13 IL IL174305A patent/IL174305A0/en unknown
- 2006-03-23 NO NO20061319A patent/NO20061319L/no not_active Application Discontinuation
- 2006-03-23 ZA ZA200602386A patent/ZA200602386B/xx unknown
- 2006-03-24 EC EC2006006457A patent/ECSP066457A/es unknown
- 2006-04-21 CO CO06038135A patent/CO5690592A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1663241B1 (en) | 2009-05-27 |
| AR045811A1 (es) | 2005-11-16 |
| US20050075357A1 (en) | 2005-04-07 |
| PA8613201A1 (es) | 2005-11-25 |
| BRPI0414736A (pt) | 2006-11-21 |
| TW200512198A (en) | 2005-04-01 |
| ECSP066457A (es) | 2006-09-18 |
| RU2006107578A (ru) | 2007-10-27 |
| CN1871009A (zh) | 2006-11-29 |
| EP1663241A1 (en) | 2006-06-07 |
| SA04250303A (ar) | 2005-12-03 |
| JP2007506746A (ja) | 2007-03-22 |
| WO2005030216A1 (en) | 2005-04-07 |
| GT200400188A (es) | 2005-05-02 |
| PE20050470A1 (es) | 2005-10-03 |
| ZA200602386B (en) | 2009-03-25 |
| CO5690592A2 (es) | 2006-10-31 |
| DE602004021269D1 (de) | 2009-07-09 |
| MXPA06003207A (es) | 2006-06-23 |
| US7524849B2 (en) | 2009-04-28 |
| NO20061319L (no) | 2006-04-20 |
| CA2539235A1 (en) | 2005-04-07 |
| IL174305A0 (en) | 2008-02-09 |
| AU2004275733A1 (en) | 2005-04-07 |
| ATE432077T1 (de) | 2009-06-15 |
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Legal Events
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| PA0105 | International application |
Patent event date: 20060324 Patent event code: PA01051R01D Comment text: International Patent Application |
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| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |