SK3542002A3 - Pteridinones as kinase inhibitors - Google Patents

Pteridinones as kinase inhibitors Download PDF

Info

Publication number: SK3542002A3
Authority: SK; Slovakia
Prior art keywords: group; substituted; amino; mono; dialkylamino
Prior art date: 1999-09-15

Application number

SK354-2002A

Other languages

English (en)

Slovak (sk)

Inventor

William Alexander Denny

Ellen Myra Dobrusin

James Bernard Kramer

Namara Dennis Joseph Mc

Gordon William Rewcastle

Howard Daniel Hollis Showalter

Peter Laurence Toogood

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.)

1999-09-15

Filing date

2000-06-21

Publication date

2003-04-01

2000-06-21 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2003-04-01 Publication of SK3542002A3 publication Critical patent/SK3542002A3/sk

Links

229940043355 kinase inhibitor Drugs 0.000 title description 2
239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
VWXIHLCLIOQWRA-UHFFFAOYSA-N 1h-pteridin-2-one Chemical class N1=CC=NC2=NC(O)=NC=C21 VWXIHLCLIOQWRA-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 157
125000000217 alkyl group Chemical group 0.000 claims abstract description 113
125000003545 alkoxy group Chemical group 0.000 claims abstract description 77
229910052760 oxygen Inorganic materials 0.000 claims abstract description 64
229910052736 halogen Inorganic materials 0.000 claims abstract description 58
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 54
125000002837 carbocyclic group Chemical group 0.000 claims abstract description 51
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 47
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 44
150000002367 halogens Chemical class 0.000 claims abstract description 42
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 42
239000001257 hydrogen Substances 0.000 claims abstract description 39
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 32
125000005842 heteroatom Chemical group 0.000 claims abstract description 28
238000000034 method Methods 0.000 claims abstract description 27
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 23
239000001301 oxygen Substances 0.000 claims abstract description 23
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 17
125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 17
206010028980 Neoplasm Diseases 0.000 claims abstract description 16
230000002062 proliferating effect Effects 0.000 claims abstract description 12
102000003903 Cyclin-dependent kinases Human genes 0.000 claims abstract description 11
108090000266 Cyclin-dependent kinases Proteins 0.000 claims abstract description 11
108091000080 Phosphotransferase Proteins 0.000 claims abstract description 11
102000020233 phosphotransferase Human genes 0.000 claims abstract description 11
239000003102 growth factor Substances 0.000 claims abstract description 10
208000037803 restenosis Diseases 0.000 claims abstract description 10
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 8
230000001404 mediated effect Effects 0.000 claims abstract description 8
201000011510 cancer Diseases 0.000 claims abstract description 7
229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
-1 alkylaminoxy Chemical group 0.000 claims description 152
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 79
125000004663 dialkyl amino group Chemical group 0.000 claims description 74
125000003118 aryl group Chemical group 0.000 claims description 56
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 54
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 44
125000000547 substituted alkyl group Chemical group 0.000 claims description 39
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 37
150000003839 salts Chemical class 0.000 claims description 35
150000003857 carboxamides Chemical class 0.000 claims description 31
125000005843 halogen group Chemical group 0.000 claims description 31
125000004001 thioalkyl group Chemical group 0.000 claims description 26
125000004432 carbon atom Chemical group C* 0.000 claims description 25
150000001733 carboxylic acid esters Chemical class 0.000 claims description 25
150000002825 nitriles Chemical class 0.000 claims description 24
125000000304 alkynyl group Chemical group 0.000 claims description 23
125000003342 alkenyl group Chemical group 0.000 claims description 22
150000002148 esters Chemical class 0.000 claims description 22
150000001408 amides Chemical class 0.000 claims description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
LJDZFAPLPVPTBD-UHFFFAOYSA-N nitroformic acid Chemical compound OC(=O)[N+]([O-])=O LJDZFAPLPVPTBD-UHFFFAOYSA-N 0.000 claims description 21
125000004426 substituted alkynyl group Chemical group 0.000 claims description 20
125000005017 substituted alkenyl group Chemical group 0.000 claims description 19
125000004984 dialkylaminoalkoxy group Chemical group 0.000 claims description 18
125000002431 aminoalkoxy group Chemical group 0.000 claims description 17
201000010099 disease Diseases 0.000 claims description 16
125000005236 alkanoylamino group Chemical group 0.000 claims description 15
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
239000000651 prodrug Substances 0.000 claims description 15
229940002612 prodrug Drugs 0.000 claims description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 13
108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 13
125000003277 amino group Chemical group 0.000 claims description 13
125000003386 piperidinyl group Chemical group 0.000 claims description 13
125000004193 piperazinyl group Chemical group 0.000 claims description 12
125000004103 aminoalkyl group Chemical group 0.000 claims description 11
125000002757 morpholinyl group Chemical group 0.000 claims description 11
201000009030 Carcinoma Diseases 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
RGJOEKWQDUBAIZ-HDCXRZRFSA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3s)-3-hydroxy-2,2-dimethyl-4-oxo-4-[[3-oxo-3-(2-sulfanylethylamino)propyl]amino]butyl] hydrogen phosphate Chemical group O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-HDCXRZRFSA-N 0.000 claims description 9
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 9
201000001320 Atherosclerosis Diseases 0.000 claims description 8
101150073031 cdk2 gene Proteins 0.000 claims description 8
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 8
201000004681 Psoriasis Diseases 0.000 claims description 7
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 7
230000002401 inhibitory effect Effects 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
125000006540 piperadinylalkyl group Chemical group 0.000 claims description 7
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
230000004663 cell proliferation Effects 0.000 claims description 6
125000000753 cycloalkyl group Chemical group 0.000 claims description 6
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
OOIPDYWPGUHUJW-UHFFFAOYSA-N 8h-pteridin-7-one Chemical compound C1=NC=NC2=NC(O)=CN=C21 OOIPDYWPGUHUJW-UHFFFAOYSA-N 0.000 claims description 5
101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 claims description 5
241000124008 Mammalia Species 0.000 claims description 5
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 5
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
230000033115 angiogenesis Effects 0.000 claims description 5
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
239000004202 carbamide Substances 0.000 claims description 5
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 5
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
230000035755 proliferation Effects 0.000 claims description 5
208000023275 Autoimmune disease Diseases 0.000 claims description 4
125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 4
206010012689 Diabetic retinopathy Diseases 0.000 claims description 4
241000700605 Viruses Species 0.000 claims description 4
125000003418 alkyl amino alkoxy group Chemical group 0.000 claims description 4
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
241001529453 unidentified herpesvirus Species 0.000 claims description 4
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 3
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
MDECEBVDPQGMBN-UHFFFAOYSA-N 8-cyclopentyl-2-[4-[4-(2-hydroxyethyl)-3,5-dimethylpiperazin-1-yl]anilino]-5-methyl-6h-pteridin-7-one Chemical compound C1C(C)N(CCO)C(C)CN1C(C=C1)=CC=C1NC1=NC=C(N(C)CC(=O)N2C3CCCC3)C2=N1 MDECEBVDPQGMBN-UHFFFAOYSA-N 0.000 claims description 3
101150012716 CDK1 gene Proteins 0.000 claims description 3
208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 claims description 3
206010017533 Fungal infection Diseases 0.000 claims description 3
206010018364 Glomerulonephritis Diseases 0.000 claims description 3
201000005569 Gout Diseases 0.000 claims description 3
208000009329 Graft vs Host Disease Diseases 0.000 claims description 3
206010061218 Inflammation Diseases 0.000 claims description 3
208000031888 Mycoses Diseases 0.000 claims description 3
206010052779 Transplant rejections Diseases 0.000 claims description 3
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
208000036142 Viral infection Diseases 0.000 claims description 3
125000004414 alkyl thio group Chemical group 0.000 claims description 3
241001493065 dsRNA viruses Species 0.000 claims description 3
208000024908 graft versus host disease Diseases 0.000 claims description 3
230000004054 inflammatory process Effects 0.000 claims description 3
210000003734 kidney Anatomy 0.000 claims description 3
206010025135 lupus erythematosus Diseases 0.000 claims description 3
201000006417 multiple sclerosis Diseases 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
210000000056 organ Anatomy 0.000 claims description 3
239000000825 pharmaceutical preparation Substances 0.000 claims description 3
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
238000001356 surgical procedure Methods 0.000 claims description 3
PACFJVOTNZCCMS-UHFFFAOYSA-N tert-butyl n-[1-[4-[(8-cyclopentyl-7-oxopteridin-2-yl)amino]phenyl]pyrrolidin-3-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CCN1C(C=C1)=CC=C1NC1=NC=C(N=CC(=O)N2C3CCCC3)C2=N1 PACFJVOTNZCCMS-UHFFFAOYSA-N 0.000 claims description 3
125000003831 tetrazolyl group Chemical group 0.000 claims description 3
230000009385 viral infection Effects 0.000 claims description 3
HMJWPGZQVPVRJD-UHFFFAOYSA-N 2-[4-(4-acetylpiperazin-1-yl)anilino]-8-cyclopentyl-5-methyl-6h-pteridin-7-one Chemical compound C12=NC(NC=3C=CC(=CC=3)N3CCN(CC3)C(C)=O)=NC=C2N(C)CC(=O)N1C1CCCC1 HMJWPGZQVPVRJD-UHFFFAOYSA-N 0.000 claims description 2
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
YVAMJXLFGYVFNQ-UHFFFAOYSA-N 4-[[6-(2,6-dichlorophenyl)-8-methyl-7-oxopteridin-2-yl]amino]-n,n-diethylbenzamide Chemical compound C1=CC(C(=O)N(CC)CC)=CC=C1NC1=NC=C(N=C(C=2C(=CC=CC=2Cl)Cl)C(=O)N2C)C2=N1 YVAMJXLFGYVFNQ-UHFFFAOYSA-N 0.000 claims description 2
BRFNADVHVKIRKP-UHFFFAOYSA-N 4-[[6-(3,5-dichloro-2,6-dimethoxypyridin-4-yl)-8-methyl-7-oxopteridin-2-yl]amino]-n,n-diethylbenzamide Chemical compound C1=CC(C(=O)N(CC)CC)=CC=C1NC1=NC=C(N=C(C=2C(=C(OC)N=C(OC)C=2Cl)Cl)C(=O)N2C)C2=N1 BRFNADVHVKIRKP-UHFFFAOYSA-N 0.000 claims description 2
SFMVMYSZIILQHZ-UHFFFAOYSA-N 6-(3,5-dibromopyridin-4-yl)-8-methyl-2-(4-morpholin-4-ylanilino)pteridin-7-one Chemical compound N=1C=C2N=C(C=3C(=CN=CC=3Br)Br)C(=O)N(C)C2=NC=1NC(C=C1)=CC=C1N1CCOCC1 SFMVMYSZIILQHZ-UHFFFAOYSA-N 0.000 claims description 2
BKBUIGURKIBNQN-UHFFFAOYSA-N 6-(3,5-dichloropyridin-4-yl)-2-[4-[2-(diethylamino)ethoxy]anilino]-8-methylpteridin-7-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(N=C(C=2C(=CN=CC=2Cl)Cl)C(=O)N2C)C2=N1 BKBUIGURKIBNQN-UHFFFAOYSA-N 0.000 claims description 2
BZWWHOTUSNLRPR-UHFFFAOYSA-N 8-cyclopentyl-2-(4-morpholin-4-ylanilino)-5h-pteridine-6,7-dione Chemical compound N1=C2N(C3CCCC3)C(=O)C(=O)NC2=CN=C1NC(C=C1)=CC=C1N1CCOCC1 BZWWHOTUSNLRPR-UHFFFAOYSA-N 0.000 claims description 2
BYJLIXXRIFPQTH-UHFFFAOYSA-N 8-cyclopentyl-2-(4-piperazin-1-ylanilino)pteridin-7-one Chemical compound N1=C2N(C3CCCC3)C(=O)C=NC2=CN=C1NC(C=C1)=CC=C1N1CCNCC1 BYJLIXXRIFPQTH-UHFFFAOYSA-N 0.000 claims description 2
RGRBSDXLEVJXBQ-UHFFFAOYSA-N 8-cyclopentyl-5-methyl-2-(4-piperazin-1-ylanilino)-6h-pteridin-7-one Chemical compound C12=NC(NC=3C=CC(=CC=3)N3CCNCC3)=NC=C2N(C)CC(=O)N1C1CCCC1 RGRBSDXLEVJXBQ-UHFFFAOYSA-N 0.000 claims description 2
208000024172 Cardiovascular disease Diseases 0.000 claims description 2
206010057469 Vascular stenosis Diseases 0.000 claims description 2
101100273808 Xenopus laevis cdk1-b gene Proteins 0.000 claims description 2
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims description 2
230000004770 neurodegeneration Effects 0.000 claims description 2
208000015122 neurodegenerative disease Diseases 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
230000002792 vascular Effects 0.000 claims description 2
125000003396 thiol group Chemical class [H]S* 0.000 claims 22
150000001735 carboxylic acids Chemical class 0.000 claims 4
YQYPLGPPOZBEJU-UHFFFAOYSA-N acetyloxycarbamic acid Chemical class CC(=O)ONC(O)=O YQYPLGPPOZBEJU-UHFFFAOYSA-N 0.000 claims 3
125000001589 carboacyl group Chemical group 0.000 claims 3
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
125000002560 nitrile group Chemical group 0.000 claims 2
210000002460 smooth muscle Anatomy 0.000 claims 2
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 2
238000006467 substitution reaction Methods 0.000 claims 2
BPLXCAMXOVROGU-UHFFFAOYSA-N 1-tert-butyl-3-[2-(4-fluoro-3-methylanilino)-6-methylpteridin-7-yl]urea Chemical compound C1=C(F)C(C)=CC(NC=2N=C3N=C(NC(=O)NC(C)(C)C)C(C)=NC3=CN=2)=C1 BPLXCAMXOVROGU-UHFFFAOYSA-N 0.000 claims 1
IYNMEUFWCCKCDP-UHFFFAOYSA-N 2-(3-chloro-4-fluoroanilino)-8-cyclopentylpteridin-7-one Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=C(N=CC(=O)N2C3CCCC3)C2=N1 IYNMEUFWCCKCDP-UHFFFAOYSA-N 0.000 claims 1
MOSSYTVPDMVLCJ-UHFFFAOYSA-N 2-(3-chloro-4-piperazin-1-ylanilino)-8-cyclopentylpteridin-7-one Chemical compound C=1C=C(N2CCNCC2)C(Cl)=CC=1NC(N=C12)=NC=C1N=CC(=O)N2C1CCCC1 MOSSYTVPDMVLCJ-UHFFFAOYSA-N 0.000 claims 1
JFRQYWUUGCZUSX-UHFFFAOYSA-N 2-[3-chloro-4-[3-chloro-4-(trifluoromethyl)pyrrolidin-1-yl]anilino]-8-cyclopentylpteridin-7-one Chemical compound C1C(Cl)C(C(F)(F)F)CN1C(C(=C1)Cl)=CC=C1NC1=NC=C(N=CC(=O)N2C3CCCC3)C2=N1 JFRQYWUUGCZUSX-UHFFFAOYSA-N 0.000 claims 1
DDIKGEFRJASUNV-UHFFFAOYSA-N 2-[4-[2-(diethylamino)ethoxy]anilino]-6-(3,5-dimethoxyphenyl)-8-ethylpteridin-7-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(N=C(C=2C=C(OC)C=C(OC)C=2)C(=O)N2CC)C2=N1 DDIKGEFRJASUNV-UHFFFAOYSA-N 0.000 claims 1
OZMUSTCAXPHENL-UHFFFAOYSA-N 2-[4-[2-(diethylamino)ethoxy]anilino]-8-methyl-6-phenylpteridin-7-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(N=C(C=2C=CC=CC=2)C(=O)N2C)C2=N1 OZMUSTCAXPHENL-UHFFFAOYSA-N 0.000 claims 1
FXCKJOKRNXKDDL-UHFFFAOYSA-N 4-[(8-cyclopentyl-6-methyl-7-oxopteridin-2-yl)amino]benzenesulfonamide Chemical compound N1=C2N(C3CCCC3)C(=O)C(C)=NC2=CN=C1NC1=CC=C(S(N)(=O)=O)C=C1 FXCKJOKRNXKDDL-UHFFFAOYSA-N 0.000 claims 1
HNSVDKLARSSFGE-UHFFFAOYSA-N 5,8-dihydropteridine-6,7-dione Chemical compound N1=CN=C2NC(=O)C(=O)NC2=C1 HNSVDKLARSSFGE-UHFFFAOYSA-N 0.000 claims 1
QDBOEKJCIQAAQP-UHFFFAOYSA-N 5-[(8-cyclopentyl-7-oxopteridin-2-yl)amino]-2-methylisoindole-1,3-dione Chemical compound C1=C2C(=O)N(C)C(=O)C2=CC=C1NC(N=C12)=NC=C1N=CC(=O)N2C1CCCC1 QDBOEKJCIQAAQP-UHFFFAOYSA-N 0.000 claims 1
XDYSEPCCXCCKCB-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-[2-(diethylamino)ethoxy]anilino]-8-methylpteridin-7-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(N=C(C=2C(=CC=CC=2Cl)Cl)C(=O)N2C)C2=N1 XDYSEPCCXCCKCB-UHFFFAOYSA-N 0.000 claims 1
VTZRVCJFRVSILI-UHFFFAOYSA-N 6-(3,5-dichloro-2,6-dimethoxypyridin-4-yl)-2-[4-[2-(diethylamino)ethoxy]anilino]-8-methylpteridin-7-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(N=C(C=2C(=C(OC)N=C(OC)C=2Cl)Cl)C(=O)N2C)C2=N1 VTZRVCJFRVSILI-UHFFFAOYSA-N 0.000 claims 1
JTWZNNWPAFJACJ-UHFFFAOYSA-N 6-(3,5-dichloro-2,6-dimethoxypyridin-4-yl)-8-methyl-2-(4-morpholin-4-ylanilino)pteridin-7-one Chemical compound COC1=NC(OC)=C(Cl)C(C=2C(N(C)C3=NC(NC=4C=CC(=CC=4)N4CCOCC4)=NC=C3N=2)=O)=C1Cl JTWZNNWPAFJACJ-UHFFFAOYSA-N 0.000 claims 1
KGGZHEZJFLMSOJ-UHFFFAOYSA-N 6-(3,5-dichloropyridin-4-yl)-8-methyl-2-(4-morpholin-4-ylanilino)pteridin-7-one Chemical compound N=1C=C2N=C(C=3C(=CN=CC=3Cl)Cl)C(=O)N(C)C2=NC=1NC(C=C1)=CC=C1N1CCOCC1 KGGZHEZJFLMSOJ-UHFFFAOYSA-N 0.000 claims 1
ASIIYBZDAMLQSS-UHFFFAOYSA-N 6-(3,5-dimethoxyphenyl)-8-ethyl-2-(pyridin-4-ylamino)pteridin-7-one Chemical compound N=1C=C2N=C(C=3C=C(OC)C=C(OC)C=3)C(=O)N(CC)C2=NC=1NC1=CC=NC=C1 ASIIYBZDAMLQSS-UHFFFAOYSA-N 0.000 claims 1
TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 claims 1
125000001960 7 membered carbocyclic group Chemical group 0.000 claims 1
SHSRNBYIPWQSJB-UHFFFAOYSA-N 8-cyclohexyl-2-(4-fluoro-3-methylanilino)pteridin-7-one Chemical compound C1=C(F)C(C)=CC(NC=2N=C3N(C4CCCCC4)C(=O)C=NC3=CN=2)=C1 SHSRNBYIPWQSJB-UHFFFAOYSA-N 0.000 claims 1
WPKSQIGQEAHERC-UHFFFAOYSA-N 8-cyclopentyl-2-(4-fluoro-3-methylanilino)pteridin-7-one Chemical compound C1=C(F)C(C)=CC(NC=2N=C3N(C4CCCC4)C(=O)C=NC3=CN=2)=C1 WPKSQIGQEAHERC-UHFFFAOYSA-N 0.000 claims 1
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125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000005494 pyridonyl group Chemical group 0.000 description 1
OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 1
CSNFMBGHUOSBFU-UHFFFAOYSA-N pyrimidine-2,4,5-triamine Chemical compound NC1=NC=C(N)C(N)=N1 CSNFMBGHUOSBFU-UHFFFAOYSA-N 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
150000004728 pyruvic acid derivatives Chemical class 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
206010038038 rectal cancer Diseases 0.000 description 1
208000020615 rectal carcinoma Diseases 0.000 description 1
230000009467 reduction Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 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
230000007017 scission Effects 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
208000000587 small cell lung carcinoma Diseases 0.000 description 1
201000002314 small intestine cancer Diseases 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
CMZUMMUJMWNLFH-UHFFFAOYSA-N sodium metavanadate Chemical compound [Na+].[O-][V](=O)=O CMZUMMUJMWNLFH-UHFFFAOYSA-N 0.000 description 1
229940080313 sodium starch Drugs 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000007885 tablet disintegrant Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
RGAOLFMYUHHOIN-UHFFFAOYSA-N tert-butyl n-[1-(4-aminophenyl)pyrrolidin-3-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CCN1C1=CC=C(N)C=C1 RGAOLFMYUHHOIN-UHFFFAOYSA-N 0.000 description 1
230000002381 testicular Effects 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
229960004559 theobromine Drugs 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
201000002510 thyroid cancer Diseases 0.000 description 1
208000013077 thyroid gland carcinoma Diseases 0.000 description 1
208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000000699 topical 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
238000012546 transfer Methods 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
231100000588 tumorigenic Toxicity 0.000 description 1
230000000381 tumorigenic effect Effects 0.000 description 1
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
231100000402 unacceptable toxicity Toxicity 0.000 description 1
208000010576 undifferentiated carcinoma Diseases 0.000 description 1
201000005112 urinary bladder cancer Diseases 0.000 description 1
230000002485 urinary effect Effects 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011345 viscous material Substances 0.000 description 1
229910000166 zirconium phosphate Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
- C07D475/04—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
- A—HUMAN NECESSITIES
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
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- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
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- 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
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- 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

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Virology (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Molecular Biology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Diabetes (AREA)
Rheumatology (AREA)
Biomedical Technology (AREA)
Pain & Pain Management (AREA)
Ophthalmology & Optometry (AREA)
Physical Education & Sports Medicine (AREA)
Biotechnology (AREA)
Urology & Nephrology (AREA)
Hematology (AREA)
Obesity (AREA)
Endocrinology (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Emergency Medicine (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
AIDS & HIV (AREA)
Tropical Medicine & Parasitology (AREA)
Dermatology (AREA)

SK354-2002A 1999-09-15 2000-06-21 Pteridinones as kinase inhibitors SK3542002A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US15409599P	1999-09-15	1999-09-15
PCT/US2000/017037 WO2001019825A1 (fr)	1999-09-15	2000-06-21	Pteridinones utilisees comme inhibiteurs de kinases

Publications (1)

Publication Number	Publication Date
SK3542002A3 true SK3542002A3 (en)	2003-04-01

Family

ID=22549985

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK354-2002A SK3542002A3 (en)	1999-09-15	2000-06-21	Pteridinones as kinase inhibitors

Country Status (29)

Country	Link
US (2)	US7169778B2 (fr)
EP (1)	EP1409487A1 (fr)
JP (1)	JP2003509425A (fr)
KR (1)	KR20020027649A (fr)
CN (1)	CN1373763A (fr)
AP (1)	AP2002002479A0 (fr)
AU (1)	AU777468B2 (fr)
BG (1)	BG106594A (fr)
BR (1)	BR0013952A (fr)
CA (1)	CA2393896A1 (fr)
CR (1)	CR6586A (fr)
CZ (1)	CZ2002846A3 (fr)
DZ (1)	DZ3186A1 (fr)
EA (1)	EA005287B1 (fr)
EE (1)	EE200200140A (fr)
HK (1)	HK1048992A1 (fr)
HU (1)	HUP0202713A3 (fr)
IL (1)	IL148614A0 (fr)
IS (1)	IS6298A (fr)
MA (1)	MA26819A1 (fr)
MX (1)	MXPA02001108A (fr)
NO (1)	NO20021239L (fr)
NZ (1)	NZ516872A (fr)
OA (1)	OA12010A (fr)
PL (1)	PL353269A1 (fr)
SK (1)	SK3542002A3 (fr)
WO (1)	WO2001019825A1 (fr)
YU (1)	YU18502A (fr)
ZA (1)	ZA200200896B (fr)

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BRPI0413018B8 (pt)	2003-07-30	2021-05-25	Rigel Pharmaceuticals Inc	composto, e, uso de um composto
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AU777468B2 (en)	2004-10-21
CZ2002846A3 (cs)	2003-02-12
HK1048992A1 (zh)	2003-04-25
AU5629500A (en)	2001-04-17
HUP0202713A2 (hu)	2002-12-28
MA26819A1 (fr)	2004-12-20
YU18502A (sh)	2004-12-31
EA005287B1 (ru)	2004-12-30
EA200200078A1 (ru)	2002-12-26
IS6298A (is)	2002-03-13
IL148614A0 (en)	2002-09-12
NO20021239D0 (no)	2002-03-13
EE200200140A (et)	2003-04-15
US7169778B2 (en)	2007-01-30
CR6586A (es)	2004-02-02
WO2001019825A1 (fr)	2001-03-22
EP1409487A1 (fr)	2004-04-21
CN1373763A (zh)	2002-10-09
US20070049600A1 (en)	2007-03-01
DZ3186A1 (fr)	2001-03-22
NZ516872A (en)	2003-10-31
ZA200200896B (en)	2003-07-30
HUP0202713A3 (en)	2005-02-28
NO20021239L (no)	2002-03-13
JP2003509425A (ja)	2003-03-11
MXPA02001108A (es)	2002-08-20
PL353269A1 (en)	2003-11-03
US20030130286A1 (en)	2003-07-10
KR20020027649A (ko)	2002-04-13
BR0013952A (pt)	2002-05-14
AP2002002479A0 (en)	2002-06-30
CA2393896A1 (fr)	2001-03-22
BG106594A (en)	2002-12-29
OA12010A (en)	2006-04-19

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Publication	Publication Date	Title
SK3542002A3 (en)	2003-04-01	Pteridinones as kinase inhibitors
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