JP2007506746A - 抗癌剤としての５−アリールピリミジン類 - Google Patents
抗癌剤としての５−アリールピリミジン類 Download PDFInfo
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- JP2007506746A JP2007506746A JP2006528086A JP2006528086A JP2007506746A JP 2007506746 A JP2007506746 A JP 2007506746A JP 2006528086 A JP2006528086 A JP 2006528086A JP 2006528086 A JP2006528086 A JP 2006528086A JP 2007506746 A JP2007506746 A JP 2007506746A
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- JP
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- Prior art keywords
- chloro
- amine
- pyrimidin
- pharmaceutically acceptable
- acceptable salt
- 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 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 298
- 238000000034 method Methods 0.000 claims abstract description 145
- 150000003839 salts Chemical class 0.000 claims abstract description 139
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 98
- 241000124008 Mammalia Species 0.000 claims abstract description 64
- 230000036457 multidrug resistance Effects 0.000 claims abstract description 56
- 201000010099 disease Diseases 0.000 claims abstract description 41
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 41
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 28
- 230000004565 tumor cell growth Effects 0.000 claims abstract description 25
- 230000012010 growth Effects 0.000 claims abstract description 21
- 230000002265 prevention Effects 0.000 claims abstract description 21
- 230000001737 promoting effect Effects 0.000 claims abstract description 21
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 19
- 230000005764 inhibitory process Effects 0.000 claims abstract description 17
- 230000029115 microtubule polymerization Effects 0.000 claims abstract description 12
- -1 cyano, hydroxy Chemical group 0.000 claims description 251
- 102000004243 Tubulin Human genes 0.000 claims description 83
- 108090000704 Tubulin Proteins 0.000 claims description 83
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 80
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 79
- 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 75
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 56
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 51
- 102000029749 Microtubule Human genes 0.000 claims description 46
- 108091022875 Microtubule Proteins 0.000 claims description 46
- 229910052794 bromium Inorganic materials 0.000 claims description 45
- 229910052801 chlorine Inorganic materials 0.000 claims description 45
- 229910052731 fluorine Inorganic materials 0.000 claims description 44
- 210000004688 microtubule Anatomy 0.000 claims description 44
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 40
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 40
- 229910052799 carbon Inorganic materials 0.000 claims description 37
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 36
- 150000001412 amines Chemical class 0.000 claims description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 125000006413 ring segment Chemical group 0.000 claims description 33
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
- MCLITRXWHZUNCQ-UHFFFAOYSA-N methylcyanamide Chemical compound CNC#N MCLITRXWHZUNCQ-UHFFFAOYSA-N 0.000 claims description 29
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 24
- 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 22
- 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
- 229910052760 oxygen Inorganic materials 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 18
- 125000002485 formyl group Chemical group [H]C(*)=O 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
- 230000000087 stabilizing effect Effects 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 16
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 150000001540 azides Chemical class 0.000 claims description 13
- 239000002585 base Substances 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 230000004663 cell proliferation Effects 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 11
- 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 10
- 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
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- AAVPJMAUGKOJNP-UHFFFAOYSA-N 6-chloro-2-(1h-pyrrol-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=2NC=CC=2)N=C1NCC(F)(F)F AAVPJMAUGKOJNP-UHFFFAOYSA-N 0.000 claims description 7
- LILWNAIAPCBLHU-UHFFFAOYSA-N 6-chloro-2-imidazol-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=NC=C2)N=C1NCC(F)(F)F LILWNAIAPCBLHU-UHFFFAOYSA-N 0.000 claims description 7
- 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 7
- 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 7
- 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 7
- 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 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
- 239000000010 aprotic solvent Substances 0.000 claims description 7
- 229940127089 cytotoxic agent Drugs 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
- ADGOHMZGCSFAOQ-UHFFFAOYSA-N 6-chloro-2-(4-methylpyridin-2-yl)-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound CC1=CC=NC(C=2N=C(NCC(F)(F)F)C(=C(Cl)N=2)C=2C(=CC(F)=CC=2F)F)=C1 ADGOHMZGCSFAOQ-UHFFFAOYSA-N 0.000 claims description 6
- LNCPZOZLBVKFPW-UHFFFAOYSA-N 6-chloro-2-(5-nitropyridin-2-yl)-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound N1=CC([N+](=O)[O-])=CC=C1C1=NC(Cl)=C(C=2C(=CC(F)=CC=2F)F)C(NCC(F)(F)F)=N1 LNCPZOZLBVKFPW-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
- 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
- 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 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
- XCWLPLOUCMTHFI-UHFFFAOYSA-N [4-chloro-5-[4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl]-6-(1,1,1-trifluoropropan-2-ylamino)pyrimidin-2-yl]methylcyanamide Chemical compound FC(F)(F)C(C)NC1=NC(CNC#N)=NC(Cl)=C1C1=C(F)C=C(OCCCN(C)C)C=C1F XCWLPLOUCMTHFI-UHFFFAOYSA-N 0.000 claims description 6
- 239000003513 alkali Substances 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
- 150000008044 alkali metal hydroxides Chemical group 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
- 239000008194 pharmaceutical composition Substances 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
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 5
- NTFWSBHKPIJJFO-UHFFFAOYSA-N methyl(methylamino)cyanamide Chemical compound C(#N)N(NC)C NTFWSBHKPIJJFO-UHFFFAOYSA-N 0.000 claims description 5
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 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 4
- 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 4
- 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 class 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 4
- 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 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 229910052727 yttrium Inorganic materials 0.000 claims description 4
- 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 3
- 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 3
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 230000008029 eradication Effects 0.000 claims description 3
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 3
- FZZMTSNZRBFGGU-UHFFFAOYSA-N 2-chloro-7-fluoroquinazolin-4-amine Chemical compound FC1=CC=C2C(N)=NC(Cl)=NC2=C1 FZZMTSNZRBFGGU-UHFFFAOYSA-N 0.000 claims 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 claims 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 60
- 201000011510 cancer Diseases 0.000 abstract description 23
- 230000001568 sexual effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 46
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- 210000004027 cell Anatomy 0.000 description 42
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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
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- 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
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- Chemical & Material Sciences (AREA)
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- 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)
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| US50548703P | 2003-09-24 | 2003-09-24 | |
| PCT/US2004/030682 WO2005030216A1 (en) | 2003-09-24 | 2004-09-17 | 5-arylpyrimidines as anticancer agents |
Publications (2)
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| JP2007506746A true JP2007506746A (ja) | 2007-03-22 |
| JP2007506746A5 JP2007506746A5 (enExample) | 2007-10-25 |
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| JP2006528086A Withdrawn JP2007506746A (ja) | 2003-09-24 | 2004-09-17 | 抗癌剤としての５−アリールピリミジン類 |
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| JP (1) | JP2007506746A (enExample) |
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| 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) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008528535A (ja) * | 2005-01-31 | 2008-07-31 | ビーエーエスエフ ソシエタス・ヨーロピア | 治療における置換５−フェニルピリミジンｉ |
| WO2021085540A1 (ja) * | 2019-11-01 | 2021-05-06 | ユニマテック株式会社 | 含フッ素ピリミジン化合物およびその製造方法 |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
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
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008528535A (ja) * | 2005-01-31 | 2008-07-31 | ビーエーエスエフ ソシエタス・ヨーロピア | 治療における置換５−フェニルピリミジンｉ |
| WO2021085540A1 (ja) * | 2019-11-01 | 2021-05-06 | ユニマテック株式会社 | 含フッ素ピリミジン化合物およびその製造方法 |
| JPWO2021085540A1 (enExample) * | 2019-11-01 | 2021-05-06 | ||
| JP7109684B2 (ja) | 2019-11-01 | 2022-07-29 | ユニマテック株式会社 | 含フッ素ピリミジン化合物およびその製造方法 |
| US12371422B2 (en) | 2019-11-01 | 2025-07-29 | Unimatec Co., Ltd. | Fluorine-containing pyrimidine compound and manufacturing method for same |
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 |
| WO2005030216A1 (en) | 2005-04-07 |
| GT200400188A (es) | 2005-05-02 |
| PE20050470A1 (es) | 2005-10-03 |
| KR20060089215A (ko) | 2006-08-08 |
| 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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