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
- Publication number
- 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
- Authority
- JP
- Japan
- 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.)
- Withdrawn
Links
- 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
- 229930012538 Paclitaxel Natural products 0.000 description 46
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 46
- 229960001592 paclitaxel Drugs 0.000 description 46
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 46
- 210000004027 cell Anatomy 0.000 description 42
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 36
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 34
- 239000007787 solid Substances 0.000 description 27
- 230000000694 effects Effects 0.000 description 26
- 239000003814 drug Substances 0.000 description 24
- 229960001338 colchicine Drugs 0.000 description 23
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 229940079593 drug Drugs 0.000 description 21
- 230000000144 pharmacologic effect Effects 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- 235000008504 concentrate Nutrition 0.000 description 19
- 239000012141 concentrate Substances 0.000 description 19
- 239000003795 chemical substances by application Substances 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 18
- 235000019341 magnesium sulphate Nutrition 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 17
- 230000027455 binding Effects 0.000 description 17
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 17
- 229960004528 vincristine Drugs 0.000 description 17
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 17
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 16
- 241000699670 Mus sp. Species 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000012312 sodium hydride Substances 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 12
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 12
- 238000010998 test method Methods 0.000 description 12
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 12
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 11
- 229940123237 Taxane Drugs 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 11
- 238000006116 polymerization reaction Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 239000011780 sodium chloride Substances 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 239000003981 vehicle Substances 0.000 description 10
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 description 10
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
- 108010078791 Carrier Proteins Proteins 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 0 C*c1nc(C)nc(N(*)[C@@](*)I)c1* Chemical compound C*c1nc(C)nc(N(*)[C@@](*)I)c1* 0.000 description 8
- 206010009944 Colon cancer Diseases 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 238000002835 absorbance Methods 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 229960003668 docetaxel Drugs 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 239000002480 mineral oil Substances 0.000 description 8
- 235000010446 mineral oil Nutrition 0.000 description 8
- 241000863480 Vinca Species 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 230000001988 toxicity Effects 0.000 description 7
- 231100000419 toxicity Toxicity 0.000 description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- XKMLYUALXHKNFT-UUOKFMHZSA-N Guanosine-5'-triphosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XKMLYUALXHKNFT-UUOKFMHZSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 208000029742 colonic neoplasm Diseases 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- FCVKLVNLBIBCCU-UHFFFAOYSA-N hydron;pyrazine-2-carboximidamide;chloride Chemical compound Cl.NC(=N)C1=CN=CC=N1 FCVKLVNLBIBCCU-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- XKMLYUALXHKNFT-UHFFFAOYSA-N rGTP Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O XKMLYUALXHKNFT-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 6
- TURWXBQPPKQQIC-UHFFFAOYSA-N 4-[4-(4-oxobutylamino)butylamino]butanal Chemical compound O=CCCCNCCCCNCCCC=O TURWXBQPPKQQIC-UHFFFAOYSA-N 0.000 description 5
- 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 description 5
- 201000009030 Carcinoma Diseases 0.000 description 5
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 230000001472 cytotoxic effect Effects 0.000 description 5
- 230000002140 halogenating effect Effects 0.000 description 5
- 208000032839 leukemia Diseases 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 5
- 229960003048 vinblastine Drugs 0.000 description 5
- 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
- KRGXWTOLFOPIKV-UHFFFAOYSA-N 3-(methylamino)propan-1-ol Chemical compound CNCCCO KRGXWTOLFOPIKV-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- 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 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-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
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 229960004679 doxorubicin Drugs 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 201000001441 melanoma Diseases 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000002287 radioligand Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 3
- YFNHCZXWVMBHAC-UHFFFAOYSA-N 2-(5-aminopyridin-2-yl)-6-chloro-n-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine Chemical compound N1=CC(N)=CC=C1C1=NC(Cl)=C(C=2C(=CC(F)=CC=2F)F)C(NCC(F)(F)F)=N1 YFNHCZXWVMBHAC-UHFFFAOYSA-N 0.000 description 3
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 3
- PYSGFFTXMUWEOT-UHFFFAOYSA-N 3-(dimethylamino)propan-1-ol Chemical compound CN(C)CCCO PYSGFFTXMUWEOT-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- AVMZTTMEKCSZEV-UHFFFAOYSA-N 6-cycloheptyl-2-pyrazin-2-yl-5-(2,4,6-trifluorophenyl)-1h-pyrimidin-4-one Chemical compound FC=1C=C(F)C=C(F)C=1C=1C(O)=NC(C=2N=CC=NC=2)=NC=1C1CCCCCC1 AVMZTTMEKCSZEV-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 102100021339 Multidrug resistance-associated protein 1 Human genes 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical group [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 208000036815 beta tubulin Diseases 0.000 description 3
- 210000004556 brain Anatomy 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
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 230000002275 effect on microtubule Effects 0.000 description 3
- SZWVYJLZOMWPLJ-UHFFFAOYSA-N ethyl 3-cycloheptyl-3-oxo-2-(2,4,6-trifluorophenyl)propanoate Chemical compound FC=1C=C(F)C=C(F)C=1C(C(=O)OCC)C(=O)C1CCCCCC1 SZWVYJLZOMWPLJ-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 208000005017 glioblastoma Diseases 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 3
- 239000000391 magnesium silicate Substances 0.000 description 3
- 229910052919 magnesium silicate Inorganic materials 0.000 description 3
- 235000019792 magnesium silicate Nutrition 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 231100000782 microtubule inhibitor Toxicity 0.000 description 3
- 108010066052 multidrug resistance-associated protein 1 Proteins 0.000 description 3
- 229930014626 natural product Natural products 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 150000003512 tertiary amines Chemical class 0.000 description 3
- NBKZGRPRTQELKX-UHFFFAOYSA-N (2-methylpropan-2-yl)oxymethanone Chemical compound CC(C)(C)O[C]=O NBKZGRPRTQELKX-UHFFFAOYSA-N 0.000 description 2
- VLVCERQEOKPRTG-DKWTVANSSA-N (2s)-1,1,1-trifluoropropan-2-amine;hydrochloride Chemical compound Cl.C[C@H](N)C(F)(F)F VLVCERQEOKPRTG-DKWTVANSSA-N 0.000 description 2
- RHUYHJGZWVXEHW-UHFFFAOYSA-N 1,1-Dimethyhydrazine Chemical compound CN(C)N RHUYHJGZWVXEHW-UHFFFAOYSA-N 0.000 description 2
- VUHMRVLSRIYKKU-UHFFFAOYSA-N 1-methylimidazole-2-carbonitrile Chemical compound CN1C=CN=C1C#N VUHMRVLSRIYKKU-UHFFFAOYSA-N 0.000 description 2
- WJQAKFRHCZWOKB-UHFFFAOYSA-N 1-methylimidazole-2-carboximidamide;hydrochloride Chemical compound Cl.CN1C=CN=C1C(N)=N WJQAKFRHCZWOKB-UHFFFAOYSA-N 0.000 description 2
- ZLCUYPLENIBECZ-UHFFFAOYSA-N 2,4,6-trichloro-5-(2,4,6-trifluorophenyl)pyrimidine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(Cl)N=C1Cl ZLCUYPLENIBECZ-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- XJULAXDLPMEOEL-UHFFFAOYSA-N 4,6-dichloro-2-imidazol-1-yl-5-(2,4,6-trifluorophenyl)pyrimidine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(N2C=NC=C2)N=C1Cl XJULAXDLPMEOEL-UHFFFAOYSA-N 0.000 description 2
- RAZDJZZSHLZQFL-UHFFFAOYSA-N 4-hydroxy-2-pyrazin-2-yl-5-(2,4,6-trifluorophenyl)-1h-pyrimidin-6-one Chemical compound OC1=NC(C=2N=CC=NC=2)=NC(O)=C1C1=C(F)C=C(F)C=C1F RAZDJZZSHLZQFL-UHFFFAOYSA-N 0.000 description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 2
- FRUHHVIOSKAPJF-UHFFFAOYSA-N 5,7-dichloro-6-(2,4,6-trifluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N2N=CN=C2N=C1Cl FRUHHVIOSKAPJF-UHFFFAOYSA-N 0.000 description 2
- YZDHDHMJKCKESU-UHFFFAOYSA-N 5-nitropyridine-2-carbonitrile Chemical compound [O-][N+](=O)C1=CC=C(C#N)N=C1 YZDHDHMJKCKESU-UHFFFAOYSA-N 0.000 description 2
- YWLXLRUDGLRYDR-ZHPRIASZSA-N 5beta,20-epoxy-1,7beta,10beta,13alpha-tetrahydroxy-9-oxotax-11-ene-2alpha,4alpha-diyl 4-acetate 2-benzoate Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](O)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 YWLXLRUDGLRYDR-ZHPRIASZSA-N 0.000 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- GFZIFIOUTHTQDI-UHFFFAOYSA-N 6-hydroxy-5-(2,4,6-trifluorophenyl)-1h-pyrimidine-2,4-dione Chemical compound OC1=NC(O)=NC(O)=C1C1=C(F)C=C(F)C=C1F GFZIFIOUTHTQDI-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- VZFUCHSFHOYXIS-UHFFFAOYSA-N Cycloheptanecarboxylic acid Chemical compound OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 238000000719 MTS assay Methods 0.000 description 2
- 231100000070 MTS assay Toxicity 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 241001116500 Taxus Species 0.000 description 2
- 241001116498 Taxus baccata Species 0.000 description 2
- 241000015728 Taxus canadensis Species 0.000 description 2
- 229940122803 Vinca alkaloid Drugs 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229940009456 adriamycin Drugs 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 239000007958 cherry flavor Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000009137 competitive binding Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- PMSVVUSIPKHUMT-UHFFFAOYSA-N cyanopyrazine Chemical compound N#CC1=CN=CC=N1 PMSVVUSIPKHUMT-UHFFFAOYSA-N 0.000 description 2
- CIYPNZYEUZQIHN-UHFFFAOYSA-N cycloheptanecarbonyl chloride Chemical compound ClC(=O)C1CCCCCC1 CIYPNZYEUZQIHN-UHFFFAOYSA-N 0.000 description 2
- 210000004292 cytoskeleton Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 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 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 101150042537 dld1 gene Proteins 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- YNRBMAMRMQJKBW-UHFFFAOYSA-N ethyl 2-(2,4,6-trifluorophenyl)acetate Chemical compound CCOC(=O)CC1=C(F)C=C(F)C=C1F YNRBMAMRMQJKBW-UHFFFAOYSA-N 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000000417 fungicide Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- 239000000833 heterodimer Substances 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 201000010982 kidney cancer Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 2
- 229960001156 mitoxantrone Drugs 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000008389 polyethoxylated castor oil Substances 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 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
- 238000012546 transfer Methods 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 238000002424 x-ray crystallography Methods 0.000 description 2
- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 description 1
- VLVCERQEOKPRTG-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-amine;hydrochloride Chemical compound Cl.CC(N)C(F)(F)F VLVCERQEOKPRTG-UHFFFAOYSA-N 0.000 description 1
- SUZOCIFIGKCISE-UHFFFAOYSA-N 1-(dimethylamino)propan-1-ol Chemical compound CCC(O)N(C)C SUZOCIFIGKCISE-UHFFFAOYSA-N 0.000 description 1
- YDZONKXUTROEFD-UHFFFAOYSA-N 1-methylimidazole-2-carbaldehyde;1-methylimidazole-2-carbonitrile Chemical compound CN1C=CN=C1C=O.CN1C=CN=C1C#N YDZONKXUTROEFD-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-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
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- USWINTIHFQKJTR-UHFFFAOYSA-N 3-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2C=C(S(O)(=O)=O)C(O)=CC2=C1 USWINTIHFQKJTR-UHFFFAOYSA-N 0.000 description 1
- SAWHIQMQGZZGTO-UHFFFAOYSA-N 4,6-dichloro-2-pyrazin-2-yl-5-(2,4,6-trifluorophenyl)pyrimidine Chemical compound FC1=CC(F)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=NC=2)N=C1Cl SAWHIQMQGZZGTO-UHFFFAOYSA-N 0.000 description 1
- APRZHQXAAWPYHS-UHFFFAOYSA-N 4-[5-[3-(carboxymethoxy)phenyl]-3-(4,5-dimethyl-1,3-thiazol-2-yl)tetrazol-3-ium-2-yl]benzenesulfonate Chemical compound S1C(C)=C(C)N=C1[N+]1=NC(C=2C=C(OCC(O)=O)C=CC=2)=NN1C1=CC=C(S([O-])(=O)=O)C=C1 APRZHQXAAWPYHS-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- BBRKHARXDYTRSK-UHFFFAOYSA-N 5-chloro-3-methyl-n-(2,2,2-trifluoroethyl)-6-(2,4,6-trifluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-imine Chemical compound CN1C=NN(C2=NCC(F)(F)F)C1=NC(Cl)=C2C1=C(F)C=C(F)C=C1F BBRKHARXDYTRSK-UHFFFAOYSA-N 0.000 description 1
- LVXOXXGCJHYEOS-UHFFFAOYSA-N 5-phenylpyrimidine Chemical class C1=CC=CC=C1C1=CN=CN=C1 LVXOXXGCJHYEOS-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- USZDFOPAUAEWBC-ZETCQYMHSA-N 6-chloro-2-pyrazin-2-yl-5-(2,4,6-trifluorophenyl)-n-[(2s)-1,1,1-trifluoropropan-2-yl]pyrimidin-4-amine Chemical class FC(F)(F)[C@H](C)NC1=NC(C=2N=CC=NC=2)=NC(Cl)=C1C1=C(F)C=C(F)C=C1F USZDFOPAUAEWBC-ZETCQYMHSA-N 0.000 description 1
- CBESMOQBSQZIGA-UHFFFAOYSA-N 6-chloro-2-pyrazol-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(N2N=CC=C2)N=C1NCC(F)(F)F CBESMOQBSQZIGA-UHFFFAOYSA-N 0.000 description 1
- KNFWEQCTFQIEMA-QMMMGPOBSA-N 6-chloro-2-pyridin-2-yl-5-(2,4,6-trifluorophenyl)-n-[(2s)-1,1,1-trifluoropropan-2-yl]pyrimidin-4-amine Chemical compound FC(F)(F)[C@H](C)NC1=NC(C=2N=CC=CC=2)=NC(Cl)=C1C1=C(F)C=C(F)C=C1F KNFWEQCTFQIEMA-QMMMGPOBSA-N 0.000 description 1
- BQBWWPYFTQKHAM-MERQFXBCSA-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;hydrochloride Chemical compound Cl.FC1=CC(OCCCNC)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=NC=2)N=C1N[C@@H](C)C(F)(F)F BQBWWPYFTQKHAM-MERQFXBCSA-N 0.000 description 1
- 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 description 1
- PTRAIIDKBOAEBD-YDALLXLXSA-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;hydron;chloride Chemical compound Cl.FC1=CC(OCCCNC)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=CC=2)N=C1N[C@@H](C)C(F)(F)F PTRAIIDKBOAEBD-YDALLXLXSA-N 0.000 description 1
- OLXAKYXIDWGSGT-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;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.FC(F)(F)CNC1=NC(NC)=NC(Cl)=C1C1=C(F)C=C(OCCCN(C)C)C=C1F OLXAKYXIDWGSGT-UHFFFAOYSA-N 0.000 description 1
- GCCIANUIXPDKRK-UHFFFAOYSA-N 6-chloro-5-[4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl]-2-pyrazin-2-yl-n-(2,2,2-trifluoroethyl)pyrimidin-4-amine;hydrochloride Chemical compound Cl.FC1=CC(OCCCN(C)C)=CC(F)=C1C1=C(Cl)N=C(C=2N=CC=NC=2)N=C1NCC(F)(F)F GCCIANUIXPDKRK-UHFFFAOYSA-N 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
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- AAFQCCGAJTXQRE-UHFFFAOYSA-N C(#N)NCC1=NC=CC=N1 Chemical compound C(#N)NCC1=NC=CC=N1 AAFQCCGAJTXQRE-UHFFFAOYSA-N 0.000 description 1
- HHEBKNOWWBMJOL-UHFFFAOYSA-N CC(C)N(C)C#N Chemical compound CC(C)N(C)C#N HHEBKNOWWBMJOL-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 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 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- 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 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
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 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
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 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
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108091077621 MAPRE family Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108090000301 Membrane transport proteins Proteins 0.000 description 1
- 102000003939 Membrane transport proteins Human genes 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229940122255 Microtubule inhibitor Drugs 0.000 description 1
- 102000014842 Multidrug resistance proteins Human genes 0.000 description 1
- 108050005144 Multidrug resistance proteins Proteins 0.000 description 1
- 241000238367 Mya arenaria Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 241001116495 Taxaceae Species 0.000 description 1
- 241000202349 Taxus brevifolia Species 0.000 description 1
- 235000009065 Taxus cuspidata Nutrition 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- XCWLPLOUCMTHFI-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(CNC#N)=NC(Cl)=C1C1=C(F)C=C(OCCCN(C)C)C=C1F XCWLPLOUCMTHFI-NSHDSACASA-N 0.000 description 1
- JHCLBLFHSPBZQU-MERQFXBCSA-N [4-chloro-5-[4-[3-(dimethylamino)propoxy]-2,6-difluorophenyl]-6-[[(2s)-1,1,1-trifluoropropan-2-yl]amino]pyrimidin-2-yl]methylcyanamide;hydrochloride Chemical compound Cl.FC(F)(F)[C@H](C)NC1=NC(CNC#N)=NC(Cl)=C1C1=C(F)C=C(OCCCN(C)C)C=C1F JHCLBLFHSPBZQU-MERQFXBCSA-N 0.000 description 1
- IVTAIPZURLELLV-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(CNC#N)N=C1NCC(F)(F)F IVTAIPZURLELLV-UHFFFAOYSA-N 0.000 description 1
- HDRRAMINWIWTNU-PRJDIBJQSA-N [[(5r)-5-(2-amino-6-oxo-3h-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1CCC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HDRRAMINWIWTNU-PRJDIBJQSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 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
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 230000009876 antimalignant effect Effects 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 208000012999 benign epithelial neoplasm Diseases 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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 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
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- VCCISIBKCNTCLR-UHFFFAOYSA-N diethyl 2-(2,4,6-trifluorophenyl)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)C1=C(F)C=C(F)C=C1F VCCISIBKCNTCLR-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229930004069 diterpene Natural products 0.000 description 1
- 150000004141 diterpene derivatives Chemical class 0.000 description 1
- 229950007919 egtazic acid Drugs 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005917 in vivo anti-tumor Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 210000003734 kidney Anatomy 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
- 210000000867 larynx Anatomy 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- FODOUIXGKGNSMR-UHFFFAOYSA-L magnesium;2-oxidooxycarbonylbenzoate;hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[O-]OC(=O)C1=CC=CC=C1C([O-])=O FODOUIXGKGNSMR-UHFFFAOYSA-L 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229940074355 nitric acid Drugs 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 235000020004 porter Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- DRYYOLGDWVJUCL-UHFFFAOYSA-N pyrimidin-2-ylcyanamide Chemical class N#CNC1=NC=CC=N1 DRYYOLGDWVJUCL-UHFFFAOYSA-N 0.000 description 1
- XXHGDLJQCZLECB-UHFFFAOYSA-N pyrimidin-4-amine;hydrochloride Chemical compound Cl.NC1=CC=NC=N1 XXHGDLJQCZLECB-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 229940032330 sulfuric acid Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DVOBHVDPGRBJCG-UHFFFAOYSA-N tert-butyl n-[3-[4-(6-cycloheptyl-4-oxo-2-pyrazin-2-yl-1h-pyrimidin-5-yl)-3,5-difluorophenoxy]propyl]-n-methylcarbamate Chemical compound FC1=CC(OCCCN(C)C(=O)OC(C)(C)C)=CC(F)=C1C1=C(O)N=C(C=2N=CC=NC=2)N=C1C1CCCCCC1 DVOBHVDPGRBJCG-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- NTADARNNAPPIBY-UHFFFAOYSA-N triazolo[1,5-a]pyrimidin-7-amine Chemical compound NC1=CC=NC2=CN=NN12 NTADARNNAPPIBY-UHFFFAOYSA-N 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
Classifications
-
- 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)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Hematology (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 | |
| PCT/US2004/030682 WO2005030216A1 (en) | 2003-09-24 | 2004-09-17 | 5-arylpyrimidines as anticancer agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007506746A true JP2007506746A (ja) | 2007-03-22 |
| JP2007506746A5 JP2007506746A5 (enExample) | 2007-10-25 |
Family
ID=34393022
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| 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 |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US7524849B2 (enExample) |
| 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) |
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 |
| JPWO2021085540A1 (enExample) * | 2019-11-01 | 2021-05-06 |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| JP2008543838A (ja) * | 2005-06-13 | 2008-12-04 | ワイス | チューブリンインヒビターおよびその調製のためのプロセス |
| EP2001298A2 (de) * | 2006-03-27 | 2008-12-17 | Basf Se | Substituierte 5-hetaryl-4-aminopyrimidine |
| 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. |
| WO2008084081A2 (en) * | 2007-01-11 | 2008-07-17 | Basf Se | 2-substituted 5-phenylpyrimidines for the treatment of proliferative disorders |
| WO2009007187A1 (de) * | 2007-07-09 | 2009-01-15 | Basf Se | Substituierte 5-hetarylpyrimidine |
| TWI548621B (zh) | 2011-04-22 | 2016-09-11 | 標誌製藥公司 | 經取代之二胺基甲醯胺及二胺基甲腈嘧啶、其組合物、及以該等治療之方法 |
| EP3219207A1 (en) * | 2012-09-19 | 2017-09-20 | 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 |
| EP3712134B1 (en) | 2014-12-16 | 2023-11-29 | Signal Pharmaceuticals, LLC | Salts of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methycyclohexylamino)-pyrimidine-5-carboxamide |
| US9513297B2 (en) | 2014-12-16 | 2016-12-06 | Signal Pharmaceuticals, Llc | Methods for measurement of inhibition of c-Jun N-terminal kinase in skin |
| EP3250557B1 (en) | 2015-01-29 | 2024-11-20 | Signal Pharmaceuticals, LLC | Isotopologues of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide |
| EP3325432B1 (en) | 2015-07-24 | 2020-09-02 | Celgene Corporation | Methods of synthesis of (1r,2r,5r)-5-amino-2-methylcyclohexanol hydrochloride and intermediates useful therein |
| 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 |
|---|---|---|---|---|
| US116429A (en) * | 1871-06-27 | Improvement in dial-telegraph apparatus | ||
| US69242A (en) * | 1867-09-24 | Calvin pepper | ||
| US61889A (en) * | 1867-02-05 | Improvement in animal teaps | ||
| US88096A (en) * | 1869-03-23 | t h a y e r | ||
| 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 |
| US6156925A (en) | 1998-09-25 | 2000-12-05 | American Cyanamid Company | Process for the preparation of halogenated phenylmaloates |
| US5986135A (en) | 1998-09-25 | 1999-11-16 | American Cyanamid Company | Fungicidal trifluoromethylalkylamino-triazolopyrimidines |
| PL362551A1 (en) * | 2000-06-13 | 2004-11-02 | Basf Aktiengesellschaft | Fungicidal 5-phenyl substituted 2-(cyanoamino) pyrimidines |
| US6670362B2 (en) | 2000-09-20 | 2003-12-30 | Pfizer Inc. | Pyridazine endothelin antagonists |
| SK11422003A3 (sk) * | 2001-03-15 | 2004-04-06 | Basf Aktiengesellschaft | 5-Fenylpyrimidíny, spôsoby a medziprodukty na ich prípravu a ich použitie pri ničení škodlivých húb |
| ATE297390T1 (de) | 2001-04-20 | 2005-06-15 | Ciba Sc Holding Ag | 4-amino-2-(2-pyridinyl)pyrimidine als mikrobizide wirksubstanzen |
| JP4450625B2 (ja) | 2001-11-19 | 2010-04-14 | ビーエーエスエフ ソシエタス・ヨーロピア | ５−フェニルピリミジン類、その製造方法、これらを含む組成物及びこれらの使用 |
| EP1504001B1 (de) | 2002-02-21 | 2009-04-15 | Basf Se | 2-(2-pyridyl)-5-phenyl-6-aminopyrimidine, verfahren und zwischenprodukte zu ihrer herstellung und ihre verwendung zur bekämpfung von schadpilzen |
| AU2003214110A1 (en) | 2002-03-15 | 2003-09-29 | Ciba Specialty Chemicals Holding Inc. | 4-aminopyrimidines and their use for the antimicrobial treatment of surfaces |
| DK2316831T3 (da) | 2002-11-21 | 2013-06-10 | Novartis Ag | 2-(Morpholin-4-yl)pyrimidiner som phosphotidylinositol (PI)-3-kinaseinhibitorer samt deres anvendelse ved behandling af cancer |
-
2004
- 2004-09-17 JP JP2006528086A patent/JP2007506746A/ja not_active Withdrawn
- 2004-09-17 DE DE602004021269T patent/DE602004021269D1/de not_active Expired - Fee Related
- 2004-09-17 MX MXPA06003207A patent/MXPA06003207A/es unknown
- 2004-09-17 RU RU2006107578/04A patent/RU2006107578A/ru not_active Application Discontinuation
- 2004-09-17 KR KR1020067005903A patent/KR20060089215A/ko not_active Withdrawn
- 2004-09-17 AT AT04784529T patent/ATE432077T1/de not_active IP Right Cessation
- 2004-09-17 CN CNA200480031581XA patent/CN1871009A/zh active Pending
- 2004-09-17 AU AU2004275733A patent/AU2004275733A1/en not_active Withdrawn
- 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 CA CA002539235A patent/CA2539235A1/en not_active Abandoned
- 2004-09-17 WO PCT/US2004/030682 patent/WO2005030216A1/en not_active Ceased
- 2004-09-21 TW TW093128501A patent/TW200512198A/zh unknown
- 2004-09-22 PE PE2004000922A patent/PE20050470A1/es not_active Application Discontinuation
- 2004-09-22 SA SA04250303A patent/SA04250303A/ar unknown
- 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 ZA ZA200602386A patent/ZA200602386B/xx unknown
- 2006-03-23 NO NO20061319A patent/NO20061319L/no not_active Application Discontinuation
- 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 |
| JPWO2021085540A1 (enExample) * | 2019-11-01 | 2021-05-06 | ||
| 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 |
| 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 |
|---|---|
| MXPA06003207A (es) | 2006-06-23 |
| KR20060089215A (ko) | 2006-08-08 |
| IL174305A0 (en) | 2008-02-09 |
| CA2539235A1 (en) | 2005-04-07 |
| ZA200602386B (en) | 2009-03-25 |
| WO2005030216A1 (en) | 2005-04-07 |
| DE602004021269D1 (de) | 2009-07-09 |
| EP1663241A1 (en) | 2006-06-07 |
| CN1871009A (zh) | 2006-11-29 |
| RU2006107578A (ru) | 2007-10-27 |
| US7524849B2 (en) | 2009-04-28 |
| SA04250303A (ar) | 2005-12-03 |
| EP1663241B1 (en) | 2009-05-27 |
| AR045811A1 (es) | 2005-11-16 |
| TW200512198A (en) | 2005-04-01 |
| PE20050470A1 (es) | 2005-10-03 |
| NO20061319L (no) | 2006-04-20 |
| ECSP066457A (es) | 2006-09-18 |
| CO5690592A2 (es) | 2006-10-31 |
| US20050075357A1 (en) | 2005-04-07 |
| ATE432077T1 (de) | 2009-06-15 |
| BRPI0414736A (pt) | 2006-11-21 |
| GT200400188A (es) | 2005-05-02 |
| PA8613201A1 (es) | 2005-11-25 |
| AU2004275733A1 (en) | 2005-04-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7524849B2 (en) | 5-arylpyrimidines as anticancer agents | |
| US7030118B2 (en) | Pyrrolotriazinone compounds and their use to treat diseases | |
| US20100068197A1 (en) | Pharmaceutical compounds as inhibitors of cell proliferation and the use thereof | |
| JP2021050231A (ja) | 結晶性ｆｇｆｒ４阻害剤化合物およびその使用 | |
| EP1680425B1 (en) | 6- [(substituted)phenyl] triazolopyrimidines as anticancer agents | |
| US11787812B2 (en) | Substituted pyrazolo[4,3-d]pyrimidines and imidazo[5,1 -f][1,2,4]triazines as androgen receptor and phosphodiesterase dual inhibitors | |
| AU2018337138A1 (en) | 2-substituted pyrazole amino-4-substituted amino-5-pyrimidine formamide compound, composition, and application thereof | |
| US7915266B2 (en) | 6-aryl-7-halo-imidazo[1,2-a]pyrimidines as anticancer agents | |
| WO2017070135A1 (en) | Prodrugs of 2-(4-(3-((4-amino-7-cyano-imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperaz in-1-yl)propanamide derivatives as ck2 inhibitors for the treatment of cancer | |
| CN101370813A (zh) | 用作抗癌药物的6-[(取代的)苯基]三唑并嘧啶类的二聚体和加合物 | |
| HK1090374B (en) | 6- [(substituted)phenyl] triazolopyrimidines as anticancer agents | |
| HK40033932B (en) | 2-substituted pyrazole amino-4-substituted amino-5-pyrimidine formamide compound, composition, and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070905 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070905 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20091015 |