UA76760C2 - Піролопіримідини як інгібітори протеїнкінази - Google Patents

Піролопіримідини як інгібітори протеїнкінази Download PDF

Info

Publication number: UA76760C2
Authority: UA; Ukraine
Prior art keywords: alkyl; compound according; compound; aryl; substituted
Prior art date: 2001-06-23

Application number

UA2004010502A

Other languages

English (en)

Russian (ru)

Ukrainian (uk)

Inventor

Пол Джозеф Кокс

Тахір Надім Маджид

Тахир Надим Маджид

Шеллі Амендола

Стефані Даніель Депре

Кріс Едлін

Крис Эдлин

Брайан Леслі Педгріфт

Брайан Лесли Педгрифт

Френк Халлі

Фрэнк Халли

Майкл Едвардз

Майкл Эдвардз

Бернар Бодуен

Лейн МакФарлан Маклей

Девіс Джон Алдос

Original Assignee

Авентіс Фармасьютікалз Інк.

Авентис Фармасьютикалз Инк.

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.)

2001-06-23

Filing date

2002-06-21

Publication date

2006-09-15

2002-06-21 Application filed by Авентіс Фармасьютікалз Інк., Авентис Фармасьютикалз Инк. filed Critical Авентіс Фармасьютікалз Інк.

2006-09-15 Publication of UA76760C2 publication Critical patent/UA76760C2/uk

Links

229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title description 3
239000003909 protein kinase inhibitor Substances 0.000 title description 3
DDWJFSYHYPDQEL-UHFFFAOYSA-N pyrimidine;1h-pyrrole Chemical class C=1C=CNC=1.C1=CN=CN=C1 DDWJFSYHYPDQEL-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 243
238000000034 method Methods 0.000 claims abstract description 64
150000003839 salts Chemical class 0.000 claims abstract description 50
239000000203 mixture Substances 0.000 claims abstract description 33
239000002253 acid Substances 0.000 claims abstract description 31
239000000651 prodrug Substances 0.000 claims abstract description 16
229940002612 prodrug Drugs 0.000 claims abstract description 16
239000012453 solvate Substances 0.000 claims abstract description 14
125000000217 alkyl group Chemical group 0.000 claims description 71
-1 cyclic acetal Chemical class 0.000 claims description 70
125000003118 aryl group Chemical group 0.000 claims description 38
125000001072 heteroaryl group Chemical group 0.000 claims description 32
229910052739 hydrogen Inorganic materials 0.000 claims description 26
125000000753 cycloalkyl group Chemical group 0.000 claims description 25
239000001257 hydrogen Substances 0.000 claims description 25
125000001041 indolyl group Chemical group 0.000 claims description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
125000003342 alkenyl group Chemical group 0.000 claims description 17
229910052736 halogen Inorganic materials 0.000 claims description 17
150000002367 halogens Chemical class 0.000 claims description 17
125000003710 aryl alkyl group Chemical group 0.000 claims description 14
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 14
150000002431 hydrogen Chemical class 0.000 claims description 14
206010028980 Neoplasm Diseases 0.000 claims description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 11
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 11
230000003197 catalytic effect Effects 0.000 claims description 9
125000004093 cyano group Chemical group *C#N 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 7
239000003112 inhibitor Substances 0.000 claims description 7
125000000304 alkynyl group Chemical group 0.000 claims description 6
206010003246 arthritis Diseases 0.000 claims description 6
201000011510 cancer Diseases 0.000 claims description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
201000010099 disease Diseases 0.000 claims description 5
125000005843 halogen group Chemical group 0.000 claims description 5
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206010006187 Breast cancer Diseases 0.000 claims description 4
208000026310 Breast neoplasm Diseases 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 4
125000003302 alkenyloxy group Chemical group 0.000 claims description 4
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230000001668 ameliorated effect Effects 0.000 claims description 4
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125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 4
208000027866 inflammatory disease Diseases 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
206010009944 Colon cancer Diseases 0.000 claims description 3
208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
201000004624 Dermatitis Diseases 0.000 claims description 3
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
201000004681 Psoriasis Diseases 0.000 claims description 3
208000015634 Rectal Neoplasms Diseases 0.000 claims description 3
206010039085 Rhinitis allergic Diseases 0.000 claims description 3
208000024770 Thyroid neoplasm Diseases 0.000 claims description 3
201000010105 allergic rhinitis Diseases 0.000 claims description 3
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239000003937 drug carrier Substances 0.000 claims description 3
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206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
206010010744 Conjunctivitis allergic Diseases 0.000 claims description 2
206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
206010060862 Prostate cancer Diseases 0.000 claims description 2
201000001263 Psoriatic Arthritis Diseases 0.000 claims description 2
208000036824 Psoriatic arthropathy Diseases 0.000 claims description 2
229910052770 Uranium Inorganic materials 0.000 claims description 2
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206010038038 rectal cancer Diseases 0.000 claims description 2
201000001275 rectum cancer Diseases 0.000 claims description 2
201000005404 rubella Diseases 0.000 claims description 2
208000017520 skin disease Diseases 0.000 claims description 2
125000003107 substituted aryl group Chemical group 0.000 claims description 2
201000002510 thyroid cancer Diseases 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 3
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims 2
206010010741 Conjunctivitis Diseases 0.000 claims 1
206010011686 Cutaneous vasculitis Diseases 0.000 claims 1
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206010047124 Vasculitis necrotising Diseases 0.000 claims 1
230000000172 allergic effect Effects 0.000 claims 1
201000000849 skin cancer Diseases 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
238000011282 treatment Methods 0.000 abstract description 29
150000001204 N-oxides Chemical class 0.000 abstract 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 76
239000000243 solution Substances 0.000 description 49
230000003993 interaction Effects 0.000 description 47
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 42
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 36
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
230000000052 comparative effect Effects 0.000 description 32
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
230000002829 reductive effect Effects 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
238000010992 reflux Methods 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
108091000080 Phosphotransferase Proteins 0.000 description 18
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
102000020233 phosphotransferase Human genes 0.000 description 18
229910052943 magnesium sulfate Inorganic materials 0.000 description 17
235000019341 magnesium sulphate Nutrition 0.000 description 17
125000004432 carbon atom Chemical group C* 0.000 description 16
239000012074 organic phase Substances 0.000 description 16
239000007787 solid Substances 0.000 description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 15
230000008569 process Effects 0.000 description 15
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
239000002585 base Substances 0.000 description 14
239000000377 silicon dioxide Substances 0.000 description 14
238000003818 flash chromatography Methods 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
210000004027 cell Anatomy 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
239000012312 sodium hydride Substances 0.000 description 12
229910000104 sodium hydride Inorganic materials 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
229910052740 iodine Inorganic materials 0.000 description 11
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
102000001253 Protein Kinase Human genes 0.000 description 10
230000000694 effects Effects 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
239000002904 solvent Substances 0.000 description 10
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
239000007864 aqueous solution Substances 0.000 description 9
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 9
108060006633 protein kinase Proteins 0.000 description 9
235000017557 sodium bicarbonate Nutrition 0.000 description 9
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ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
239000011630 iodine Substances 0.000 description 8
229910052763 palladium Inorganic materials 0.000 description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 7
230000029936 alkylation Effects 0.000 description 7
238000005804 alkylation reaction Methods 0.000 description 7
239000000460 chlorine Substances 0.000 description 7
229910052801 chlorine Inorganic materials 0.000 description 7
239000012458 free base Substances 0.000 description 7
239000012442 inert solvent Substances 0.000 description 7
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
241000282414 Homo sapiens Species 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 6
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150000001450 anions Chemical class 0.000 description 6
239000000427 antigen Substances 0.000 description 6
108091007433 antigens Proteins 0.000 description 6
102000036639 antigens Human genes 0.000 description 6
239000012298 atmosphere Substances 0.000 description 6
210000003630 histaminocyte Anatomy 0.000 description 6
150000004677 hydrates Chemical class 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 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
229910052757 nitrogen Inorganic materials 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
125000004076 pyridyl group Chemical group 0.000 description 6
230000004044 response Effects 0.000 description 6
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 6
239000000126 substance Substances 0.000 description 6
ZXUCBXRTRRIBSO-UHFFFAOYSA-L tetrabutylazanium;sulfate Chemical compound [O-]S([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC ZXUCBXRTRRIBSO-UHFFFAOYSA-L 0.000 description 6
238000002560 therapeutic procedure Methods 0.000 description 6
230000004913 activation Effects 0.000 description 5
125000001931 aliphatic group Chemical group 0.000 description 5
210000003719 b-lymphocyte Anatomy 0.000 description 5
239000012267 brine Substances 0.000 description 5
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238000005859 coupling reaction Methods 0.000 description 5
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INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
230000008018 melting Effects 0.000 description 5
238000002844 melting Methods 0.000 description 5
125000002950 monocyclic group Chemical group 0.000 description 5
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239000003826 tablet Substances 0.000 description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
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WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
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150000001412 amines Chemical class 0.000 description 4
CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 4
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238000001704 evaporation Methods 0.000 description 4
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125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 4
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RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
YMQRPXBBBOXHNZ-UHFFFAOYSA-N 2-chloro-1-morpholin-4-ylethanone Chemical compound ClCC(=O)N1CCOCC1 YMQRPXBBBOXHNZ-UHFFFAOYSA-N 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
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GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
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125000000392 cycloalkenyl group Chemical group 0.000 description 3
238000010828 elution Methods 0.000 description 3
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238000002347 injection Methods 0.000 description 3
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239000007858 starting material Substances 0.000 description 3
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125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
239000013641 positive control Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 description 1
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
125000005554 pyridyloxy group Chemical group 0.000 description 1
238000000611 regression analysis Methods 0.000 description 1
208000037803 restenosis Diseases 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-N sodium;hydron;carbonate Chemical compound [Na+].OC(O)=O UIIMBOGNXHQVGW-UHFFFAOYSA-N 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
230000020347 spindle assembly Effects 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
201000004595 synovitis Diseases 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
201000000596 systemic lupus erythematosus Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
230000002463 transducing effect Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
LGQXXHMEBUOXRP-UHFFFAOYSA-N tributyl borate Chemical compound CCCCOB(OCCCC)OCCCC LGQXXHMEBUOXRP-UHFFFAOYSA-N 0.000 description 1
125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
230000005747 tumor angiogenesis Effects 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
230000005748 tumor development Effects 0.000 description 1
150000003668 tyrosines Chemical class 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
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
230000002792 vascular Effects 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
238000005406 washing Methods 0.000 description 1
210000005253 yeast cell Anatomy 0.000 description 1
UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
229910021511 zinc hydroxide Inorganic materials 0.000 description 1
229940007718 zinc hydroxide Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- 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
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pulmonology (AREA)
Rheumatology (AREA)
Immunology (AREA)
Dermatology (AREA)
Cardiology (AREA)
Pain & Pain Management (AREA)
Ophthalmology & Optometry (AREA)
Heart & Thoracic Surgery (AREA)
Otolaryngology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

UA2004010502A 2001-06-23 2002-06-21 Піролопіримідини як інгібітори протеїнкінази UA76760C2 (uk)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GBGB0115393.1A GB0115393D0 (en)	2001-06-23	2001-06-23	Chemical compounds
US30167801P	2001-06-28	2001-06-28
PCT/GB2002/002835 WO2003000695A1 (en)	2001-06-23	2002-06-21	Pyrrolopyrimidines as protein kinase inhibitors

Publications (1)

Publication Number	Publication Date
UA76760C2 true UA76760C2 (uk)	2006-09-15

Family

ID=9917225

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2004010502A UA76760C2 (uk)	2001-06-23	2002-06-21	Піролопіримідини як інгібітори протеїнкінази

Country Status (22)

Country	Link
EP (1)	EP1404676A1 (sr)
JP (1)	JP4344607B2 (sr)
CN (1)	CN1294135C (sr)
AU (1)	AU2002314325B8 (sr)
BR (1)	BR0210652A (sr)
CA (1)	CA2451932C (sr)
CZ (1)	CZ20033443A3 (sr)
EA (1)	EA007415B1 (sr)
EC (1)	ECSP034922A (sr)
EE (1)	EE05432B1 (sr)
GB (1)	GB0115393D0 (sr)
HU (1)	HUP0400300A3 (sr)
ME (1)	MEP19308A (sr)
NZ (1)	NZ529766A (sr)
OA (1)	OA12632A (sr)
PL (1)	PL374096A1 (sr)
RS (1)	RS51698B (sr)
SK (1)	SK15882003A3 (sr)
TN (1)	TNSN03144A1 (sr)
TR (1)	TR200302242T2 (sr)
UA (1)	UA76760C2 (sr)
WO (1)	WO2003000695A1 (sr)

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Publication number	Publication date
BR0210652A (pt)	2004-08-10
ECSP034922A (es)	2004-04-28
TR200302242T2 (tr)	2004-12-21
AU2002314325B8 (en)	2009-01-29
EA200400073A1 (ru)	2004-08-26
HUP0400300A2 (en)	2007-08-28
GB0115393D0 (en)	2001-08-15
EE200400003A (et)	2004-02-16
CA2451932A1 (en)	2003-01-03
RS51698B (sr)	2011-10-31
AU2002314325B2 (en)	2009-01-08
CN1294135C (zh)	2007-01-10
RS99203A (sr)	2006-12-15
TNSN03144A1 (en)	2005-12-23
CZ20033443A3 (en)	2004-03-17
EE05432B1 (et)	2011-06-15
WO2003000695A1 (en)	2003-01-03
JP4344607B2 (ja)	2009-10-14
WO2003000695A8 (en)	2004-03-11
MEP19308A (en)	2010-06-10
OA12632A (en)	2006-06-14
PL374096A1 (en)	2005-09-19
SK15882003A3 (sk)	2004-07-07
EA007415B1 (ru)	2006-10-27
EP1404676A1 (en)	2004-04-07
HUP0400300A3 (en)	2010-12-28
NZ529766A (en)	2008-11-28
CN1518552A (zh)	2004-08-04
CA2451932C (en)	2009-12-29
JP2005508300A (ja)	2005-03-31

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