MXPA02007221A - Inhibidores de pirido [2,3-d)pirimidin-2,7-diamina cinasa. - Google Patents

Inhibidores de pirido [2,3-d)pirimidin-2,7-diamina cinasa.

Info

Publication number: MXPA02007221A
Authority: MX; Mexico
Prior art keywords: pyrimidin; pyrido; urea; piperazin; phenylamino
Prior art date: 2000-01-25

Application number

MXPA02007221A

Other languages

English (en)

Spanish (es)

Inventor

Ellen Myra Dobrusin

Original Assignee

Warner Lambert Co

Priority date (The priority date 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 date listed.)

2000-01-25

Filing date

2001-01-23

Publication date

2002-11-29

2001-01-23 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2002-11-29 Publication of MXPA02007221A publication Critical patent/MXPA02007221A/es

Links

QRRCMVPZJCHBLQ-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound C1=NC(N)=NC2=NC(N)=CC=C21 QRRCMVPZJCHBLQ-UHFFFAOYSA-N 0.000 title description 2
229940043355 kinase inhibitor Drugs 0.000 title 1
239000003757 phosphotransferase inhibitor Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 147
125000000217 alkyl group Chemical group 0.000 claims abstract description 72
229910052736 halogen Inorganic materials 0.000 claims abstract description 53
150000002367 halogens Chemical group 0.000 claims abstract description 53
239000001257 hydrogen Substances 0.000 claims abstract description 39
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 39
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 38
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 30
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 29
125000003118 aryl group Chemical group 0.000 claims abstract description 28
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 28
125000003342 alkenyl group Chemical group 0.000 claims abstract description 21
125000000304 alkynyl group Chemical group 0.000 claims abstract description 21
206010028980 Neoplasm Diseases 0.000 claims abstract description 18
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 16
201000011510 cancer Diseases 0.000 claims abstract description 12
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
239000003102 growth factor Substances 0.000 claims abstract description 9
230000001404 mediated effect Effects 0.000 claims abstract description 9
230000002062 proliferating effect Effects 0.000 claims abstract description 9
208000037803 restenosis Diseases 0.000 claims abstract description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
101150020251 NR13 gene Proteins 0.000 claims abstract description 4
150000002431 hydrogen Chemical class 0.000 claims abstract 21
-1 nitro, carboxy Chemical group 0.000 claims description 168
239000004202 carbamide Substances 0.000 claims description 53
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 30
125000003545 alkoxy group Chemical group 0.000 claims description 27
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
125000004663 dialkyl amino group Chemical group 0.000 claims description 24
150000003839 salts Chemical class 0.000 claims description 24
239000002253 acid Substances 0.000 claims description 23
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
229910052757 nitrogen Inorganic materials 0.000 claims description 18
102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 16
108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 16
150000001408 amides Chemical class 0.000 claims description 16
125000002837 carbocyclic group Chemical group 0.000 claims description 16
150000002148 esters Chemical class 0.000 claims description 16
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 claims description 16
102000004190 Enzymes Human genes 0.000 claims description 15
108090000790 Enzymes Proteins 0.000 claims description 15
229910052760 oxygen Inorganic materials 0.000 claims description 15
239000000651 prodrug Substances 0.000 claims description 15
229940002612 prodrug Drugs 0.000 claims description 15
101150073031 cdk2 gene Proteins 0.000 claims description 13
125000003710 aryl alkyl group Chemical group 0.000 claims description 11
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 11
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 11
230000002401 inhibitory effect Effects 0.000 claims description 11
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 10
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
208000035475 disorder Diseases 0.000 claims description 9
239000001301 oxygen Substances 0.000 claims description 9
229910052717 sulfur Inorganic materials 0.000 claims description 9
ZDQUGBAOJVAHFP-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-5-methylpyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C(C)=CC(NC(=O)NC(C)(C)C)=N2)C2=N1 ZDQUGBAOJVAHFP-UHFFFAOYSA-N 0.000 claims description 8
125000004181 carboxyalkyl group Chemical group 0.000 claims description 8
125000005842 heteroatom Chemical group 0.000 claims description 8
230000035755 proliferation Effects 0.000 claims description 8
101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 claims description 7
201000010099 disease Diseases 0.000 claims description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
VGFQMCUDJBVYIU-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)-3-chloroanilino]pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound C1CN(C(=O)C)CCN1C(C(=C1)Cl)=CC=C1NC1=NC=C(C=CC(NC(=O)NC(C)(C)C)=N2)C2=N1 VGFQMCUDJBVYIU-UHFFFAOYSA-N 0.000 claims description 6
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 6
125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 6
VWUJZWLAORFRFO-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-6-fluoropyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=C(F)C(NC(=O)NC(C)(C)C)=N2)C2=N1 VWUJZWLAORFRFO-UHFFFAOYSA-N 0.000 claims description 5
ZERHTVLLTUQOES-UHFFFAOYSA-N 1-tert-butyl-3-[2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C2=NC(NC(=O)NC(C)(C)C)=CC=C2C=NC=1NC(C=C1)=CC=C1N1CCNCC1 ZERHTVLLTUQOES-UHFFFAOYSA-N 0.000 claims description 5
201000001320 Atherosclerosis Diseases 0.000 claims description 5
201000009030 Carcinoma Diseases 0.000 claims description 5
201000004681 Psoriasis Diseases 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 claims description 5
XSDIGEOCQDHWOK-UHFFFAOYSA-N 1-[6-cyano-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]-3-cyclohexylurea Chemical compound N=1C2=NC(NC=3C=CC(=CC=3)N3CCNCC3)=NC=C2C=C(C#N)C=1NC(=O)NC1CCCCC1 XSDIGEOCQDHWOK-UHFFFAOYSA-N 0.000 claims description 4
206010006187 Breast cancer Diseases 0.000 claims description 4
208000026310 Breast neoplasm Diseases 0.000 claims description 4
230000004663 cell proliferation Effects 0.000 claims description 4
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
210000004509 vascular smooth muscle cell Anatomy 0.000 claims description 4
206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
208000032839 leukemia Diseases 0.000 claims description 3
201000005202 lung cancer Diseases 0.000 claims description 3
208000020816 lung neoplasm Diseases 0.000 claims description 3
201000001441 melanoma Diseases 0.000 claims description 3
XMINZZZOTRYZGB-UHFFFAOYSA-N 1-(2-hydroxyethyl)-3-[2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C2=NC(NC(=O)NCCO)=CC=C2C=NC=1NC(C=C1)=CC=C1N1CCNCC1 XMINZZZOTRYZGB-UHFFFAOYSA-N 0.000 claims description 2
XFILUMCRLWWGHF-UHFFFAOYSA-N 1-(2-hydroxyethyl)-3-[5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C=C2C(C)=CC(NC(=O)NCCO)=NC2=NC=1NC(C=C1)=CC=C1N1CCNCC1 XFILUMCRLWWGHF-UHFFFAOYSA-N 0.000 claims description 2
OJAWTIFCYCKDIF-UHFFFAOYSA-N 1-(2-hydroxyethyl)-3-[5-methyl-2-(pyridin-4-ylamino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C=C2C(C)=CC(NC(=O)NCCO)=NC2=NC=1NC1=CC=NC=C1 OJAWTIFCYCKDIF-UHFFFAOYSA-N 0.000 claims description 2
LWWHQXYBJDKMHB-UHFFFAOYSA-N 1-(4-hydroxycyclohexyl)-3-[2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound C1CC(O)CCC1NC(=O)NC1=CC=C(C=NC(NC=2C=CC(=CC=2)N2CCNCC2)=N2)C2=N1 LWWHQXYBJDKMHB-UHFFFAOYSA-N 0.000 claims description 2
HIDCSIGTHYPMDE-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)-3-chloroanilino]pyrido[2,3-d]pyrimidin-7-yl]-3-cyclohexylurea Chemical compound C1CN(C(=O)C)CCN1C(C(=C1)Cl)=CC=C1NC1=NC=C(C=CC(NC(=O)NC2CCCCC2)=N2)C2=N1 HIDCSIGTHYPMDE-UHFFFAOYSA-N 0.000 claims description 2
VPZMIWQERRSJMV-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)-3-chloroanilino]pyrido[2,3-d]pyrimidin-7-yl]-3-ethylurea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2C=NC=1NC(C=C1Cl)=CC=C1N1CCN(C(C)=O)CC1 VPZMIWQERRSJMV-UHFFFAOYSA-N 0.000 claims description 2
DWKOQXAXRXLTRO-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-5-methylpyrido[2,3-d]pyrimidin-7-yl]-3-(2-hydroxyethyl)urea Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C(C)=CC(NC(=O)NCCO)=N2)C2=N1 DWKOQXAXRXLTRO-UHFFFAOYSA-N 0.000 claims description 2
NSELCHMQELGYCQ-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-5-methylpyrido[2,3-d]pyrimidin-7-yl]-3-cyclohexylurea Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C(C)=CC(NC(=O)NC2CCCCC2)=N2)C2=N1 NSELCHMQELGYCQ-UHFFFAOYSA-N 0.000 claims description 2
BPMKMCMJBBHAMO-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-5-methylpyrido[2,3-d]pyrimidin-7-yl]-3-ethylurea Chemical compound N=1C2=NC(NC(=O)NCC)=CC(C)=C2C=NC=1NC(C=C1)=CC=C1N1CCN(C(C)=O)CC1 BPMKMCMJBBHAMO-UHFFFAOYSA-N 0.000 claims description 2
ROWUHEGVMUYETM-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-6-fluoropyrido[2,3-d]pyrimidin-7-yl]-3-(2-hydroxyethyl)urea Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=C(F)C(NC(=O)NCCO)=N2)C2=N1 ROWUHEGVMUYETM-UHFFFAOYSA-N 0.000 claims description 2
UUJKLLDOWWAPFC-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-6-fluoropyrido[2,3-d]pyrimidin-7-yl]-3-cyclohexylurea Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=C(F)C(NC(=O)NC2CCCCC2)=N2)C2=N1 UUJKLLDOWWAPFC-UHFFFAOYSA-N 0.000 claims description 2
BRJVIFGBXXBAAR-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]-6-fluoropyrido[2,3-d]pyrimidin-7-yl]-3-ethylurea Chemical compound N=1C=C2C=C(F)C(NC(=O)NCC)=NC2=NC=1NC(C=C1)=CC=C1N1CCN(C(C)=O)CC1 BRJVIFGBXXBAAR-UHFFFAOYSA-N 0.000 claims description 2
LPKPUNZWAHLJID-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-7-yl]-3-(2-hydroxyethyl)urea Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=CC(NC(=O)NCCO)=N2)C2=N1 LPKPUNZWAHLJID-UHFFFAOYSA-N 0.000 claims description 2
QSYGBWVAZZCIDX-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-7-yl]-3-cyclohexylurea Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=CC(NC(=O)NC2CCCCC2)=N2)C2=N1 QSYGBWVAZZCIDX-UHFFFAOYSA-N 0.000 claims description 2
MPKZVSBVKJFRCB-UHFFFAOYSA-N 1-[2-[4-(4-acetylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-7-yl]-3-ethylurea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2C=NC=1NC(C=C1)=CC=C1N1CCN(C(C)=O)CC1 MPKZVSBVKJFRCB-UHFFFAOYSA-N 0.000 claims description 2
BWORXTLBVMGUGI-UHFFFAOYSA-N 1-[6-bromo-5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]-3-cyclohexylurea Chemical compound N=1C2=NC(NC=3C=CC(=CC=3)N3CCNCC3)=NC=C2C(C)=C(Br)C=1NC(=O)NC1CCCCC1 BWORXTLBVMGUGI-UHFFFAOYSA-N 0.000 claims description 2
UXBCLFZSEPAATK-UHFFFAOYSA-N 1-[6-chloro-5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]-3-cyclohexylurea Chemical compound N=1C2=NC(NC=3C=CC(=CC=3)N3CCNCC3)=NC=C2C(C)=C(Cl)C=1NC(=O)NC1CCCCC1 UXBCLFZSEPAATK-UHFFFAOYSA-N 0.000 claims description 2
YPQGDMGZMAKMEA-UHFFFAOYSA-N 1-[6-fluoro-2-(pyridin-4-ylamino)pyrido[2,3-d]pyrimidin-7-yl]-3-(2-hydroxyethyl)urea Chemical compound N=1C=C2C=C(F)C(NC(=O)NCCO)=NC2=NC=1NC1=CC=NC=C1 YPQGDMGZMAKMEA-UHFFFAOYSA-N 0.000 claims description 2
BVMSORLIMAKEEG-UHFFFAOYSA-N 1-cyclohexyl-3-[2-(4-fluoroanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound C1=CC(F)=CC=C1NC1=NC=C(C=CC(NC(=O)NC2CCCCC2)=N2)C2=N1 BVMSORLIMAKEEG-UHFFFAOYSA-N 0.000 claims description 2
RSWODMAWDOIYSI-UHFFFAOYSA-N 1-cyclohexyl-3-[2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound C=1C=C2C=NC(NC=3C=CC(=CC=3)N3CCNCC3)=NC2=NC=1NC(=O)NC1CCCCC1 RSWODMAWDOIYSI-UHFFFAOYSA-N 0.000 claims description 2
HSXKXMHAELFQJA-UHFFFAOYSA-N 1-cyclohexyl-3-[2-(4-sulfamoylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound C1=CC(S(=O)(=O)N)=CC=C1NC1=NC=C(C=CC(NC(=O)NC2CCCCC2)=N2)C2=N1 HSXKXMHAELFQJA-UHFFFAOYSA-N 0.000 claims description 2
LNDIIIZPJOCMAU-UHFFFAOYSA-N 1-cyclohexyl-3-[6-fluoro-2-(pyridin-4-ylamino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N1=C2N=C(NC(=O)NC3CCCCC3)C(F)=CC2=CN=C1NC1=CC=NC=C1 LNDIIIZPJOCMAU-UHFFFAOYSA-N 0.000 claims description 2
ZMWBWZXAOFKNCZ-UHFFFAOYSA-N 1-cyclohexyl-3-[6-fluoro-5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C2=NC(NC=3C=CC(=CC=3)N3CCNCC3)=NC=C2C(C)=C(F)C=1NC(=O)NC1CCCCC1 ZMWBWZXAOFKNCZ-UHFFFAOYSA-N 0.000 claims description 2
BAZVIVARXKYKOK-UHFFFAOYSA-N 1-cyclohexyl-3-[6-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N1=C2N=C(NC(=O)NC3CCCCC3)C(C)=CC2=CN=C1NC(C=C1)=CC=C1N1CCNCC1 BAZVIVARXKYKOK-UHFFFAOYSA-N 0.000 claims description 2
PMFGZMVIXFORHF-UHFFFAOYSA-N 1-ethyl-3-[2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2C=NC=1NC(C=C1)=CC=C1N1CCNCC1 PMFGZMVIXFORHF-UHFFFAOYSA-N 0.000 claims description 2
OIFYXWOZMWGIJQ-UHFFFAOYSA-N 1-ethyl-3-[6-fluoro-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C=C2C=C(F)C(NC(=O)NCC)=NC2=NC=1NC(C=C1)=CC=C1N1CCNCC1 OIFYXWOZMWGIJQ-UHFFFAOYSA-N 0.000 claims description 2
PULCUZSSHSLGTG-UHFFFAOYSA-N 1-ethyl-3-[6-fluoro-2-(pyridin-4-ylamino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C=C2C=C(F)C(NC(=O)NCC)=NC2=NC=1NC1=CC=NC=C1 PULCUZSSHSLGTG-UHFFFAOYSA-N 0.000 claims description 2
VNRUZNQJRRPDRR-UHFFFAOYSA-N 1-tert-butyl-3-[2-(pyridin-4-ylamino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C2=NC(NC(=O)NC(C)(C)C)=CC=C2C=NC=1NC1=CC=NC=C1 VNRUZNQJRRPDRR-UHFFFAOYSA-N 0.000 claims description 2
UPRFABWGAFHLFH-UHFFFAOYSA-N 1-tert-butyl-3-[5-methyl-2-(pyridin-4-ylamino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C=C2C(C)=CC(NC(=O)NC(C)(C)C)=NC2=NC=1NC1=CC=NC=C1 UPRFABWGAFHLFH-UHFFFAOYSA-N 0.000 claims description 2
FTPGODXQOCTHDX-UHFFFAOYSA-N 1-tert-butyl-3-[6-fluoro-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C=C2C=C(F)C(NC(=O)NC(C)(C)C)=NC2=NC=1NC(C=C1)=CC=C1N1CCNCC1 FTPGODXQOCTHDX-UHFFFAOYSA-N 0.000 claims description 2
PBUDIXSYLRMHOQ-UHFFFAOYSA-N 1-tert-butyl-3-[6-fluoro-2-(pyridin-4-ylamino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C=C2C=C(F)C(NC(=O)NC(C)(C)C)=NC2=NC=1NC1=CC=NC=C1 PBUDIXSYLRMHOQ-UHFFFAOYSA-N 0.000 claims description 2
KNWWGBNAUNTSRV-UHFFFAOYSA-N 4-methylpiperazine-1-carboxylic acid Chemical compound CN1CCN(C(O)=O)CC1 KNWWGBNAUNTSRV-UHFFFAOYSA-N 0.000 claims description 2
241000124008 Mammalia Species 0.000 claims description 2
PGQSLDLNYLTRIQ-UHFFFAOYSA-N [5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C=C2C(C)=CC(NC(N)=O)=NC2=NC=1NC(C=C1)=CC=C1N1CCNCC1 PGQSLDLNYLTRIQ-UHFFFAOYSA-N 0.000 claims description 2
210000002464 muscle smooth vascular Anatomy 0.000 claims description 2
FRTLPVFIQJYINI-UHFFFAOYSA-N n-[2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]acetamide Chemical compound N=1C2=NC(NC(=O)C)=CC=C2C=NC=1NC(C=C1)=CC=C1N1CCNCC1 FRTLPVFIQJYINI-UHFFFAOYSA-N 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 16
MEPIXWYYOTZYNT-UHFFFAOYSA-N 1-ethyl-3-[5-methyl-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC(C)=C2C=NC=1NC(C=C1)=CC=C1N1CCNCC1 MEPIXWYYOTZYNT-UHFFFAOYSA-N 0.000 claims 2
ICZIDKIHTCFFMY-UHFFFAOYSA-N 2-N-(4-piperazin-1-ylphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound N=1C2=NC(N)=CC=C2C=NC=1NC(C=C1)=CC=C1N1CCNCC1 ICZIDKIHTCFFMY-UHFFFAOYSA-N 0.000 claims 2
102000018233 Fibroblast Growth Factor Human genes 0.000 claims 2
108050007372 Fibroblast Growth Factor Proteins 0.000 claims 2
102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims 2
108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims 2
229940126864 fibroblast growth factor Drugs 0.000 claims 2
IZPRSDVSVWVZOM-UHFFFAOYSA-N 1,1-bis(2-hydroxyethyl)-3-[2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C2=NC(NC(=O)N(CCO)CCO)=CC=C2C=NC=1NC(C=C1)=CC=C1N1CCNCC1 IZPRSDVSVWVZOM-UHFFFAOYSA-N 0.000 claims 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

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Bioinformatics & Cheminformatics (AREA)
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Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
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Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Molecular Biology (AREA)
Biochemistry (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
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Dermatology (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Enzymes And Modification Thereof (AREA)

MXPA02007221A 2000-01-25 2001-01-23 Inhibidores de pirido [2,3-d)pirimidin-2,7-diamina cinasa. MXPA02007221A (es)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US17826100P	2000-01-25	2000-01-25
PCT/IB2001/000069 WO2001055147A1 (en)	2000-01-25	2001-01-23	PYRIDO[2,3-d]PYRIMIDINE-2,7-DIAMINE KINASE INHIBITORS

Publications (1)

Publication Number	Publication Date
MXPA02007221A true MXPA02007221A (es)	2002-11-29

Family

ID=22651853

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
MXPA02007221A MXPA02007221A (es)	2000-01-25	2001-01-23	Inhibidores de pirido [2,3-d)pirimidin-2,7-diamina cinasa.

Country Status (34)

Country	Link
EP (1)	EP1254137A1 (xx)
JP (1)	JP4047010B2 (xx)
KR (1)	KR20020065939A (xx)
CN (1)	CN1395578A (xx)
AP (1)	AP2002002586A0 (xx)
AR (1)	AR030044A1 (xx)
AU (1)	AU2542501A (xx)
BG (1)	BG106850A (xx)
BR (1)	BR0107751A (xx)
CA (1)	CA2397961C (xx)
CO (1)	CO5261549A1 (xx)
CR (1)	CR6706A (xx)
CZ (1)	CZ20022475A3 (xx)
DZ (1)	DZ3266A1 (xx)
EA (1)	EA200200643A1 (xx)
EE (1)	EE200200405A (xx)
GT (1)	GT200100016A (xx)
HN (1)	HN2001000013A (xx)
HU (1)	HUP0204141A3 (xx)
IL (1)	IL150545A0 (xx)
IS (1)	IS6443A (xx)
MA (1)	MA26868A1 (xx)
MX (1)	MXPA02007221A (xx)
NO (1)	NO20023527L (xx)
OA (1)	OA12161A (xx)
PA (1)	PA8510701A1 (xx)
PE (1)	PE20011066A1 (xx)
PL (1)	PL356802A1 (xx)
SK (1)	SK10632002A3 (xx)
SV (1)	SV2002000294A (xx)
TN (1)	TNSN01014A1 (xx)
WO (1)	WO2001055147A1 (xx)
YU (1)	YU50402A (xx)
ZA (1)	ZA200205879B (xx)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7235551B2 (en)	2000-03-02	2007-06-26	Smithkline Beecham Corporation	1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases
AU2002246855B2 (en)	2000-10-23	2005-12-22	Smithkline Beecham Corporation	Novel compounds
PE20030008A1 (es) *	2001-06-19	2003-01-22	Bristol Myers Squibb Co	Inhibidores duales de pde 7 y pde 4
KR20040103972A (ko)	2002-04-19	2004-12-09	스미스클라인 비참 코포레이션	신규 화합물
HRP20050601A2 (en) *	2002-11-28	2005-10-31	Schering Ag	Chk-, pdk-, and akt-inhibitory pyrimidines, their production and use as pharmarmaceutical agents
US7157455B2 (en) *	2003-02-10	2007-01-02	Hoffmann-La Roche Inc.	4-Aminopyrimidine-5-one derivatives
TW200502236A (en)	2003-03-28	2005-01-16	Hoffmann La Roche	Novel pyrido[2,3-d]pyrimidin-7-carboxylic acid derivatives, their manufacture and use as pharmaceutical agents
FR2873118B1 (fr)	2004-07-15	2007-11-23	Sanofi Synthelabo	Derives de pyrido-pyrimidine, leur application en therapeutique
EP1794160A1 (en) *	2004-09-21	2007-06-13	F.Hoffmann-La Roche Ag	6-(2-alkyl-phenyl) - pyrido[2,3-d] pyrimidines useful as proteine kinase inhibitors
EP1865959A2 (en)	2005-03-25	2007-12-19	Glaxo Group Limited	Process for preparing pyridoý2,3-d¨pyrimidin-7-one and 3,4-dihydropyrimidoý4,5-d¨pyrimidin-2(1h)-one derivatives
EP1868612A4 (en)	2005-03-25	2010-03-24	Glaxo Group Ltd	NOVEL CONNECTIONS
TW200724142A (en)	2005-03-25	2007-07-01	Glaxo Group Ltd	Novel compounds
PE20061351A1 (es)	2005-03-25	2007-01-14	Glaxo Group Ltd	COMPUESTOS 8H-PIRIDO[2,3-d]PIRIMIDIN-7-ONA 2,4,8-TRISUSTITUIDOS COMO INHIBIDORES DE LA QUINASA CSBP/RK/p38
FR2887882B1 (fr) *	2005-07-01	2007-09-07	Sanofi Aventis Sa	Derives de pyrido[2,3-d] pyrimidine, leur preparation, leur application en therapeutique
CN101243081A (zh) *	2005-07-21	2008-08-13	霍夫曼-拉罗奇有限公司	作为PTP1B抑制剂的吡啶并[2,3-d]嘧啶-2,4-二胺化合物
ATE482958T1 (de)	2005-08-09	2010-10-15	Irm Llc	Verbindungen und zusammensetzungen als proteinkinaseinhibitoren
FR2896246B1 (fr)	2006-01-13	2008-08-15	Sanofi Aventis Sa	Derives de pyrido-pyrimidone, leur preparation, leur application en therapeutique.
EP1914234A1 (en)	2006-10-16	2008-04-23	GPC Biotech Inc.	Pyrido[2,3-d]pyrimidines and their use as kinase inhibitors
JO2985B1 (ar)	2006-12-20	2016-09-05	Takeda Pharmaceuticals Co	مثبطات كينازmapk/erk
FR2910813B1 (fr) *	2006-12-28	2009-02-06	Sanofi Aventis Sa	Nouvelle utilisation therapeutique pour le traitement des leucemies
EP2112150B1 (en)	2008-04-22	2013-10-16	Forma Therapeutics, Inc.	Improved raf inhibitors
EP2352732B1 (en) *	2008-12-01	2013-02-20	Merck Patent GmbH	2,5-DIAMINO-SUBSTITUTED PYRIDO[4, 3-d]PYRIMIDINES AS AUTOTAXIN INHIBITORS AGAINST CANCER
GB201104267D0 (en)	2011-03-14	2011-04-27	Cancer Rec Tech Ltd	Pyrrolopyridineamino derivatives
GB201216017D0 (en)	2012-09-07	2012-10-24	Cancer Rec Tech Ltd	Inhibitor compounds
GB201216018D0 (en)	2012-09-07	2012-10-24	Cancer Rec Tech Ltd	Pharmacologically active compounds
US9815847B2 (en)	2013-03-14	2017-11-14	Icahn School Of Medicine At Mount Sinai	Pyrimidine compounds as kinase inhibitors
GB201403536D0 (en)	2014-02-28	2014-04-16	Cancer Rec Tech Ltd	Inhibitor compounds
KR101671404B1 (ko) *	2014-09-02	2016-11-02	한국원자력의학원	항암 효과, 방사선 병용치료 효과 및 당뇨병 치료 효과를 갖는 피리미딘 유도체 및 이의 의학적 용도
CN107286180B (zh) *	2016-04-11	2019-07-02	上海勋和医药科技有限公司	杂代吡啶并嘧啶酮衍生物作为cdk抑制剂及其应用
GB201709840D0 (en)	2017-06-20	2017-08-02	Inst Of Cancer Research: Royal Cancer Hospital	Methods and medical uses

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL115256A0 (en) *	1994-11-14	1995-12-31	Warner Lambert Co	6-Aryl pyrido (2,3-d) pyrimidines and naphthyridines and their use
ES2146782T3 (es) *	1994-11-14	2000-08-16	Warner Lambert Co	6-aril-pirido(2,3-d)pirimidinas y naftiridinas para la inhibicion de la proliferacion celular inducida por la proteina tirosina quinasa.
US5620981A (en) *	1995-05-03	1997-04-15	Warner-Lambert Company	Pyrido [2,3-D]pyrimidines for inhibiting protein tyrosine kinase mediated cellular proliferation
DE69939168D1 (de) *	1998-05-26	2008-09-04	Warner Lambert Co	Bicyclische pyrimidine und bicyclische 3,4-dihydropyrimidine als inhibitoren der zellvermehrung

2001
- 2001-01-23 AP APAP/P/2002/002586A patent/AP2002002586A0/en unknown
- 2001-01-23 GT GT200100016A patent/GT200100016A/es unknown
- 2001-01-23 HU HU0204141A patent/HUP0204141A3/hu unknown
- 2001-01-23 OA OA1200200213A patent/OA12161A/en unknown
- 2001-01-23 BR BR0107751-1A patent/BR0107751A/pt not_active IP Right Cessation
- 2001-01-23 YU YU50402A patent/YU50402A/sh unknown
- 2001-01-23 MX MXPA02007221A patent/MXPA02007221A/es not_active Application Discontinuation
- 2001-01-23 AR ARP010100285A patent/AR030044A1/es not_active Application Discontinuation
- 2001-01-23 KR KR1020027009516A patent/KR20020065939A/ko not_active Ceased
- 2001-01-23 EE EEP200200405A patent/EE200200405A/xx unknown
- 2001-01-23 SK SK1063-2002A patent/SK10632002A3/sk not_active Application Discontinuation
- 2001-01-23 EP EP01900591A patent/EP1254137A1/en not_active Withdrawn
- 2001-01-23 DZ DZ013266A patent/DZ3266A1/fr active
- 2001-01-23 CA CA002397961A patent/CA2397961C/en not_active Expired - Fee Related
- 2001-01-23 EA EA200200643A patent/EA200200643A1/ru unknown
- 2001-01-23 IL IL15054501A patent/IL150545A0/xx unknown
- 2001-01-23 CN CN01804048A patent/CN1395578A/zh active Pending
- 2001-01-23 WO PCT/IB2001/000069 patent/WO2001055147A1/en not_active Application Discontinuation
- 2001-01-23 PL PL01356802A patent/PL356802A1/xx not_active Application Discontinuation
- 2001-01-23 PA PA20018510701A patent/PA8510701A1/es unknown
- 2001-01-23 AU AU25425/01A patent/AU2542501A/en not_active Abandoned
- 2001-01-23 PE PE2001000072A patent/PE20011066A1/es not_active Application Discontinuation
- 2001-01-23 JP JP2001561006A patent/JP4047010B2/ja not_active Expired - Fee Related
- 2001-01-23 CZ CZ20022475A patent/CZ20022475A3/cs unknown
- 2001-01-24 HN HN2001000013A patent/HN2001000013A/es unknown
- 2001-01-24 TN TNTNSN01014A patent/TNSN01014A1/fr unknown
- 2001-01-24 CO CO01005268A patent/CO5261549A1/es not_active Application Discontinuation
- 2001-01-24 SV SV2001000294A patent/SV2002000294A/es not_active Application Discontinuation
2002
- 2002-06-20 BG BG106850A patent/BG106850A/bg unknown
- 2002-06-25 IS IS6443A patent/IS6443A/is unknown
- 2002-07-17 CR CR6706A patent/CR6706A/es not_active Application Discontinuation
- 2002-07-22 MA MA26736A patent/MA26868A1/fr unknown
- 2002-07-23 ZA ZA200205879A patent/ZA200205879B/en unknown
- 2002-07-24 NO NO20023527A patent/NO20023527L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
PE20011066A1 (es)	2001-10-22
WO2001055147A1 (en)	2001-08-02
CN1395578A (zh)	2003-02-05
EP1254137A1 (en)	2002-11-06
HUP0204141A2 (hu)	2003-04-28
TNSN01014A1 (fr)	2005-11-10
SV2002000294A (es)	2002-07-16
EA200200643A1 (ru)	2002-12-26
JP4047010B2 (ja)	2008-02-13
CO5261549A1 (es)	2003-03-31
CR6706A (es)	2005-04-04
AR030044A1 (es)	2003-08-13
IS6443A (is)	2002-06-25
KR20020065939A (ko)	2002-08-14
DZ3266A1 (fr)	2001-08-02
HN2001000013A (es)	2001-06-18
NO20023527D0 (no)	2002-07-24
NO20023527L (no)	2002-09-10
PA8510701A1 (es)	2002-12-11
AP2002002586A0 (en)	2002-09-30
HUP0204141A3 (en)	2005-03-29
AU2542501A (en)	2001-08-07
BR0107751A (pt)	2002-11-12
CZ20022475A3 (cs)	2003-03-12
GT200100016A (es)	2001-10-19
EE200200405A (et)	2003-12-15
JP2003523357A (ja)	2003-08-05
PL356802A1 (en)	2004-07-12
MA26868A1 (fr)	2004-12-20
CA2397961A1 (en)	2001-08-02
YU50402A (sh)	2005-11-28
CA2397961C (en)	2008-08-26
IL150545A0 (en)	2003-02-12
OA12161A (en)	2006-05-08
BG106850A (bg)	2003-02-28
ZA200205879B (en)	2003-09-29
SK10632002A3 (sk)	2003-06-03

Publication	Publication Date	Title
MXPA02007221A (es)	2002-11-29	Inhibidores de pirido [2,3-d)pirimidin-2,7-diamina cinasa.
US7053070B2 (en)	2006-05-30	Pyrido[2,3-d]pyrimidine-2,7-diamine kinase inhibitors
CA2329703C (en)	2005-12-20	Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation
US7390805B2 (en)	2008-06-24	4-amino-6-phenyl-pyrrolo[2,3-d]pyrimidine derivatives
US20230142839A1 (en)	2023-05-11	N4-phenyl-quinazoline-4 -amine derivatives and related compounds as ErbB type I receptor tyrosine kinase inhibitors for the treatment of hyperproliferative diseases
EP0964864B1 (en)	2008-04-09	Pyrido 2,3-d pyrimidines and 4-aminopyrimidines as inhibitors of cellular proliferation
AU2007254491A1 (en)	2007-11-29	Compositions and methods for FGF receptor kinases inhibitors
SK3542002A3 (en)	2003-04-01	Pteridinones as kinase inhibitors
SK141097A3 (en)	1998-07-08	Pyrido[2,3-d]pyrimidines for inhibiting protein tyrosine kinase mediated cellular proliferation
US20040044012A1 (en)	2004-03-04	Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation
JP2008504281A (ja)	2008-02-14	タンパク質キナーゼ阻害剤としての化合物および組成物
JP2013530250A (ja)	2013-07-25	二環式ピリミジン化合物
US7323469B2 (en)	2008-01-29	7H-pyrrolo[2,3-d]pyrimidine derivatives
OA11554A (en)	2004-06-03	Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation.
EP1801112A1 (en)	2007-06-27	Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation
MXPA00010738A (en)	2001-09-07	Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation
HK1065483B (en)	2008-08-22	4-amino-6-phenyl-pyrrolo[2,3-d]pyrimidine derivatives

Legal Events

Date	Code	Title	Description
2013-09-30	FA	Abandonment or withdrawal