BG102790A - ПИРИМИДО/5,4-d/ПИРИМИДИНИ, ЛЕКАРСТВЕНИ СРЕДСТВА, СЪДЪРЖАЩИ ТЕЗИ СЪЕДИНЕНИЯ, ПРИЛОЖЕНИЕТО ИМ И МЕТОДЗА ТЯХНОТО ПОЛУЧАВАНЕ - Google Patents

ПИРИМИДО/5,4-d/ПИРИМИДИНИ, ЛЕКАРСТВЕНИ СРЕДСТВА, СЪДЪРЖАЩИ ТЕЗИ СЪЕДИНЕНИЯ, ПРИЛОЖЕНИЕТО ИМ И МЕТОДЗА ТЯХНОТО ПОЛУЧАВАНЕ Download PDF

Info

Publication number: BG102790A
Authority: BG; Bulgaria
Prior art keywords: group; substituted; alkyl; piperidinyl; amino
Prior art date: 1996-03-06

Application number

BG102790A

Other languages

Bulgarian (bg)

English (en)

Inventor

Frank Himmelsbach

Georg Dahmann

Rueden Thomas Von

Thomas Metz

Original Assignee

Dr. Karl Thomae Gmbh

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.)

1996-03-06

Filing date

1998-09-24

Publication date

1999-09-30

1998-09-24 Application filed by Dr. Karl Thomae Gmbh filed Critical Dr. Karl Thomae Gmbh

1999-09-30 Publication of BG102790A publication Critical patent/BG102790A/bg

Links

238000002360 preparation method Methods 0.000 title claims abstract description 12
JOZPEVMCAKXSEY-UHFFFAOYSA-N pyrimido[5,4-d]pyrimidine Chemical class N1=CN=CC2=NC=NC=C21 JOZPEVMCAKXSEY-UHFFFAOYSA-N 0.000 title claims abstract description 6
238000000034 method Methods 0.000 title claims description 10
150000001875 compounds Chemical class 0.000 claims abstract description 92
150000003839 salts Chemical class 0.000 claims abstract description 31
206010028980 Neoplasm Diseases 0.000 claims abstract description 7
150000007524 organic acids Chemical class 0.000 claims abstract description 6
150000007522 mineralic acids Chemical class 0.000 claims abstract description 5
235000005985 organic acids Nutrition 0.000 claims abstract description 5
-1 phenoxy- Chemical class 0.000 claims description 1002
125000000217 alkyl group Chemical group 0.000 claims description 167
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 146
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 125
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 111
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 104
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 86
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 79
125000004430 oxygen atom Chemical group O* 0.000 claims description 67
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 62
229910052757 nitrogen Inorganic materials 0.000 claims description 57
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 52
125000003545 alkoxy group Chemical group 0.000 claims description 48
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 43
229910052799 carbon Inorganic materials 0.000 claims description 42
229910052801 chlorine Inorganic materials 0.000 claims description 42
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 41
239000000460 chlorine Chemical group 0.000 claims description 40
125000004434 sulfur atom Chemical group 0.000 claims description 38
125000003282 alkyl amino group Chemical group 0.000 claims description 37
229910052717 sulfur Inorganic materials 0.000 claims description 37
150000001721 carbon Chemical group 0.000 claims description 36
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical group ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 35
238000006243 chemical reaction Methods 0.000 claims description 35
229910052760 oxygen Inorganic materials 0.000 claims description 35
239000001301 oxygen Substances 0.000 claims description 35
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 34
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 34
229910052731 fluorine Inorganic materials 0.000 claims description 33
239000011737 fluorine Chemical group 0.000 claims description 33
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 31
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 31
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
125000004433 nitrogen atom Chemical group N* 0.000 claims description 31
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 30
125000004663 dialkyl amino group Chemical group 0.000 claims description 30
229910052739 hydrogen Inorganic materials 0.000 claims description 30
239000001257 hydrogen Substances 0.000 claims description 30
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 28
125000004432 carbon atom Chemical group C* 0.000 claims description 28
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 25
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 24
125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 24
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 24
125000004093 cyano group Chemical group *C#N 0.000 claims description 23
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 22
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 21
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 21
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
125000002947 alkylene group Chemical group 0.000 claims description 20
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 20
125000004076 pyridyl group Chemical group 0.000 claims description 20
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 20
125000005277 alkyl imino group Chemical group 0.000 claims description 19
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 19
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 16
125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 15
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
125000003277 amino group Chemical group 0.000 claims description 14
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 14
125000001841 imino group Chemical group [H]N=* 0.000 claims description 14
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 14
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical group NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 13
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 12
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 12
125000002619 bicyclic group Chemical group 0.000 claims description 12
229910052794 bromium Inorganic materials 0.000 claims description 12
125000000623 heterocyclic group Chemical group 0.000 claims description 12
229910052740 iodine Inorganic materials 0.000 claims description 12
125000006413 ring segment Chemical group 0.000 claims description 12
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 11
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 10
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 10
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
125000001153 fluoro group Chemical group F* 0.000 claims description 9
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 9
125000001072 heteroaryl group Chemical group 0.000 claims description 9
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 9
125000006239 protecting group Chemical group 0.000 claims description 9
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 8
125000005129 aryl carbonyl group Chemical group 0.000 claims description 8
125000004429 atom Chemical group 0.000 claims description 8
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 8
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 8
125000004193 piperazinyl group Chemical group 0.000 claims description 8
125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 8
125000005493 quinolyl group Chemical group 0.000 claims description 8
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 7
230000035755 proliferation Effects 0.000 claims description 7
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
125000004103 aminoalkyl group Chemical group 0.000 claims description 6
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
125000005243 carbonyl alkyl group Chemical group 0.000 claims description 6
125000002993 cycloalkylene group Chemical group 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
230000003647 oxidation Effects 0.000 claims description 6
238000007254 oxidation reaction Methods 0.000 claims description 6
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 5
PYBUOOBNQZWHQJ-UHFFFAOYSA-N n-(1h-indol-5-yl)-6-morpholin-4-ylpyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1COCCN1C1=NC=C(N=CN=C2NC=3C=C4C=CNC4=CC=3)C2=N1 PYBUOOBNQZWHQJ-UHFFFAOYSA-N 0.000 claims description 5
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
150000003230 pyrimidines Chemical class 0.000 claims description 5
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 4
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 4
125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 4
125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims description 4
125000000304 alkynyl group Chemical group 0.000 claims description 4
150000001408 amides Chemical class 0.000 claims description 4
150000001412 amines Chemical class 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
150000002148 esters Chemical class 0.000 claims description 4
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 4
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
125000005956 isoquinolyl group Chemical group 0.000 claims description 4
125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 4
125000002071 phenylalkoxy group Chemical group 0.000 claims description 4
125000003884 phenylalkyl group Chemical group 0.000 claims description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
OQHQOOLVQDEIGL-UHFFFAOYSA-N 2-methyl-2,7-diazaspiro[4.4]nonane Chemical compound C1N(C)CCC11CNCC1 OQHQOOLVQDEIGL-UHFFFAOYSA-N 0.000 claims description 3
230000010933 acylation Effects 0.000 claims description 3
238000005917 acylation reaction Methods 0.000 claims description 3
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 3
230000029936 alkylation Effects 0.000 claims description 3
238000005804 alkylation reaction Methods 0.000 claims description 3
230000009435 amidation Effects 0.000 claims description 3
238000007112 amidation reaction Methods 0.000 claims description 3
125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 3
201000011510 cancer Diseases 0.000 claims description 3
150000001728 carbonyl compounds Chemical class 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
125000004185 ester group Chemical group 0.000 claims description 3
230000032050 esterification Effects 0.000 claims description 3
238000005886 esterification reaction Methods 0.000 claims description 3
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
238000005932 reductive alkylation reaction Methods 0.000 claims description 3
230000006103 sulfonylation Effects 0.000 claims description 3
238000005694 sulfonylation reaction Methods 0.000 claims description 3
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
239000005977 Ethylene Substances 0.000 claims description 2
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 2
206010027476 Metastases Diseases 0.000 claims description 2
241001024304 Mino Species 0.000 claims description 2
206010029113 Neovascularisation Diseases 0.000 claims description 2
230000002159 abnormal effect Effects 0.000 claims description 2
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
125000005021 aminoalkenyl group Chemical group 0.000 claims description 2
125000005140 aralkylsulfonyl group Chemical group 0.000 claims description 2
125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 2
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
125000005111 carboxyalkoxy group Chemical group 0.000 claims description 2
125000004966 cyanoalkyl group Chemical group 0.000 claims description 2
125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000001041 indolyl group Chemical group 0.000 claims description 2
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims description 2
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
239000000126 substance Substances 0.000 claims description 2
125000000335 thiazolyl group Chemical group 0.000 claims description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
210000003556 vascular endothelial cell Anatomy 0.000 claims description 2
229920002554 vinyl polymer Polymers 0.000 claims description 2
150000001735 carboxylic acids Chemical class 0.000 claims 2
239000000969 carrier Substances 0.000 claims 2
125000004956 cyclohexylene group Chemical group 0.000 claims 2
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
FGRBYDKOBBBPOI-UHFFFAOYSA-N 10,10-dioxo-2-[4-(N-phenylanilino)phenyl]thioxanthen-9-one Chemical compound O=C1c2ccccc2S(=O)(=O)c2ccc(cc12)-c1ccc(cc1)N(c1ccccc1)c1ccccc1 FGRBYDKOBBBPOI-UHFFFAOYSA-N 0.000 claims 1
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 1
125000004948 alkyl aryl alkyl group Chemical group 0.000 claims 1
125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims 1
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 claims 1
125000002843 carboxylic acid group Chemical group 0.000 claims 1
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims 1
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 1
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 1
125000001207 fluorophenyl group Chemical group 0.000 claims 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
239000010802 sludge Substances 0.000 claims 1
125000000547 substituted alkyl group Chemical group 0.000 claims 1
239000000052 vinegar Substances 0.000 claims 1
235000021419 vinegar Nutrition 0.000 claims 1
201000010099 disease Diseases 0.000 abstract description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
229940093915 gynecological organic acid Drugs 0.000 abstract description 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 242
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 225
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 141
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 140
238000002844 melting Methods 0.000 description 91
230000008018 melting Effects 0.000 description 91
239000003208 petroleum Substances 0.000 description 60
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
239000000741 silica gel Substances 0.000 description 58
229910002027 silica gel Inorganic materials 0.000 description 58
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
239000002904 solvent Substances 0.000 description 33
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
239000000203 mixture Substances 0.000 description 27
150000003254 radicals Chemical class 0.000 description 27
239000013543 active substance Substances 0.000 description 26
TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 25
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
210000004027 cell Anatomy 0.000 description 19
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 17
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
239000000243 solution Substances 0.000 description 15
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
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TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
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LZFIOSVZIQOVFW-UHFFFAOYSA-N propyl 2-hydroxybenzoate Chemical compound CCCOC(=O)C1=CC=CC=C1O LZFIOSVZIQOVFW-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 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
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235000011152 sodium sulphate Nutrition 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
239000007921 spray Substances 0.000 description 1
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ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
HMMYZMWDTDJTRR-UHFFFAOYSA-N tert-butyl n-[(4-aminocyclohexyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCC(N)CC1 HMMYZMWDTDJTRR-UHFFFAOYSA-N 0.000 description 1
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JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
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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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- 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
- 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
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Dermatology (AREA)
Immunology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

BG102790A 1996-03-06 1998-09-24 ПИРИМИДО/5,4-d/ПИРИМИДИНИ, ЛЕКАРСТВЕНИ СРЕДСТВА, СЪДЪРЖАЩИ ТЕЗИ СЪЕДИНЕНИЯ, ПРИЛОЖЕНИЕТО ИМ И МЕТОДЗА ТЯХНОТО ПОЛУЧАВАНЕ BG102790A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19608653A DE19608653A1 (de)	1996-03-06	1996-03-06	Pyrimido[5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
PCT/EP1997/001058 WO1997032882A1 (de)	1996-03-06	1997-03-03	PYRIMIDO[5,4-d]PYRIMIDINE, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL, DEREN VERWENDUNG UND VERFAHREN ZU IHRER HERSTELLUNG

Publications (1)

Publication Number	Publication Date
BG102790A true BG102790A (bg)	1999-09-30

Family

ID=7787391

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG102790A BG102790A (bg)	1996-03-06	1998-09-24	ПИРИМИДО/5,4-d/ПИРИМИДИНИ, ЛЕКАРСТВЕНИ СРЕДСТВА, СЪДЪРЖАЩИ ТЕЗИ СЪЕДИНЕНИЯ, ПРИЛОЖЕНИЕТО ИМ И МЕТОДЗА ТЯХНОТО ПОЛУЧАВАНЕ

Country Status (23)

Country	Link
US (1)	US5977102A (de)
EP (1)	EP0885227A1 (de)
JP (1)	JP2000506153A (de)
KR (1)	KR19990087551A (de)
CN (1)	CN1212696A (de)
AR (1)	AR009937A1 (de)
AU (1)	AU712072B2 (de)
BG (1)	BG102790A (de)
BR (1)	BR9708004A (de)
CA (1)	CA2248316A1 (de)
CO (1)	CO4650044A1 (de)
CZ (1)	CZ281698A3 (de)
DE (1)	DE19608653A1 (de)
EE (1)	EE9800289A (de)
HU (1)	HUP9901750A2 (de)
IL (1)	IL125341A0 (de)
NO (1)	NO984081D0 (de)
NZ (1)	NZ331382A (de)
PL (1)	PL328776A1 (de)
SK (1)	SK120498A3 (de)
TR (1)	TR199801753T2 (de)
WO (1)	WO1997032882A1 (de)
ZA (1)	ZA971886B (de)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE69720965T2 (de)	1996-02-13	2004-02-05	Astrazeneca Ab	Chinazolinderivate und deren verwendung als vegf hemmer
NZ331191A (en)	1996-03-05	2000-03-27	Zeneca Ltd	4-anilinoquinazoline derivatives and pharmaceutical compositions thereof
JP3270834B2 (ja) *	1999-01-27	2002-04-02	ファイザー・プロダクツ・インク	抗がん剤として有用なヘテロ芳香族二環式誘導体
UA71945C2 (en) *	1999-01-27	2005-01-17	Pfizer Prod Inc	Substituted bicyclic derivatives being used as anticancer agents
DE19911510A1 (de) *	1999-03-15	2000-09-21	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
CZ20013608A3 (cs)	1999-04-09	2002-05-15	Astrazeneca Ab	Adamantanové deriváty
AU5003200A (en)	1999-05-14	2000-12-05	United States Of America As Represented By The Department Of Veterans Affairs, The	Isolation and characterization of epidermal growth factor related protein
US7049410B2 (en) *	1999-05-14	2006-05-23	Majumdar Adhip P N	Antibodies to a novel EGF-receptor related protein (ERRP)
KR100881105B1 (ko)	1999-11-05	2009-02-02	아스트라제네카 아베	Ｖｅｇｆ 억제제로서의 퀴나졸린 유도체
SE9904505D0 (sv)	1999-12-09	1999-12-09	Astra Pharma Prod	Novel compounds
TWI258462B (en)	1999-12-17	2006-07-21	Astrazeneca Ab	Adamantane derivative compounds, process for preparing the same and pharmaceutical composition comprising the same
EP1318985A2 (de) *	2000-09-20	2003-06-18	MERCK PATENT GmbH	4-amino chinazolinen
JP2004509876A (ja) *	2000-09-20	2004-04-02	メルク　パテント　ゲゼルシャフト　ミット　ベシュレンクテル　ハフトング	４−アミノ−キナゾリン
PE20020958A1 (es) *	2001-03-23	2002-11-14	Bayer Corp	Inhibidores de la rho-quinasa
UY27224A1 (es) *	2001-03-23	2002-10-31	Bayer Corp	Inhibidores de la rho-quinasa
US7829566B2 (en) *	2001-09-17	2010-11-09	Werner Mederski	4-amino-quinazolines
JP4505228B2 (ja) *	2002-01-10	2010-07-21	バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト	Ｒｈｏ−キナーゼ阻害剤
MXPA04007196A (es) *	2002-01-23	2005-06-08	Bayer Pharmaceuticals Corp	Inhibidores de rho-quinasa.
EP1470121B1 (de) *	2002-01-23	2012-07-11	Bayer HealthCare LLC	Pyrimidin-derivate als rho kinase inhibitoren
KR101139038B1 (ko) *	2005-06-28	2012-05-02	삼성전자주식회사	피리미도피리미딘 유도체 및 이를 이용한 유기 박막 트랜지스터
TW201014860A (en) *	2008-09-08	2010-04-16	Boehringer Ingelheim Int	New chemical compounds
EP2398797B1 (de)	2009-02-17	2013-11-06	Boehringer Ingelheim International GmbH	Pyrimido[5,4-d]pyrimidine zur hemmung von tyrosinkinasen
CN102369186B (zh)	2009-04-02	2014-07-09	默克专利有限公司	作为自分泌运动因子抑制剂的哌啶和哌嗪衍生物
US20130023531A1 (en)	2011-01-27	2013-01-24	Boehringer Ingelheim International Gmbh	Pyrimido[5,4-d]pyrimidylamino phenyl sulfonamides as serine/threonine kinase inhibitors
WO2014175370A1 (ja) *	2013-04-25	2014-10-30	塩野義製薬株式会社	ピロリジン誘導体およびそれらを含有する医薬組成物
HUE040133T2 (hu)	2014-07-15	2019-02-28	Gruenenthal Gmbh	Szubsztituált azaspiro(4.5)dekán származékok
TW201607923A (zh)	2014-07-15	2016-03-01	歌林達有限公司	被取代之氮螺環（４．５）癸烷衍生物
CA3195121A1 (en) *	2020-10-09	2022-04-14	Robert A. Volkmann	Heteroaryl amide inhibitors of cd38
TW202309022A (zh)	2021-04-13	2023-03-01	美商努法倫特公司	用於治療具egfr突變之癌症之胺基取代雜環

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3031450A (en) *	1959-04-30	1962-04-24	Thomae Gmbh Dr K	Substituted pyrimido-[5, 4-d]-pyrimidines
EP0023559B1 (de) *	1979-07-03	1984-09-19	Dr. Karl Thomae GmbH	2-(Perhydro-1,4-diazino)-pyrimido(5,4-d)pyrimidine, ihre Herstellung und diese Verbindungen enthaltenden Arzneimittel
DE3049207A1 (de) *	1980-12-27	1982-07-29	Dr. Karl Thomae Gmbh, 7950 Biberach	Neue trisubstituierte pyrimido (5,4-d) pyrimidine, ihre herstellung und ihre verwendung als arzneimittel
DE3423092A1 (de) *	1984-06-22	1986-01-02	Dr. Karl Thomae Gmbh, 7950 Biberach	Neue 8-alkylthio-2-piperazino-pyrimido(5,4-d) pyrimidine, ihre herstellung und diese verbindungen enthaltende arzneimittel
US5034393A (en) *	1989-07-27	1991-07-23	Dowelanco	Fungicidal use of pyridopyrimidine, pteridine, pyrimidopyrimidine, pyrimidopyridazine, and pyrimido-1,2,4-triazine derivatives
DE4325900A1 (de) *	1993-08-02	1995-02-09	Thomae Gmbh Dr K	Trisubstituierte Pyrimido [5,4-d] pyrimidine zur Modulation der Multidrugresistenz, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
IL112249A (en) *	1994-01-25	2001-11-25	Warner Lambert Co	Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds
DE4431867A1 (de) *	1994-09-07	1996-03-14	Thomae Gmbh Dr K	Pyrimido[5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
TW414798B (en) *	1994-09-07	2000-12-11	Thomae Gmbh Dr K	Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation

1996
- 1996-03-06 DE DE19608653A patent/DE19608653A1/de not_active Withdrawn
1997
- 1997-03-03 CN CN97192789A patent/CN1212696A/zh active Pending
- 1997-03-03 AU AU19252/97A patent/AU712072B2/en not_active Ceased
- 1997-03-03 CA CA002248316A patent/CA2248316A1/en not_active Abandoned
- 1997-03-03 EP EP97907067A patent/EP0885227A1/de not_active Withdrawn
- 1997-03-03 WO PCT/EP1997/001058 patent/WO1997032882A1/de not_active Ceased
- 1997-03-03 EE EE9800289A patent/EE9800289A/xx unknown
- 1997-03-03 BR BR9708004A patent/BR9708004A/pt unknown
- 1997-03-03 KR KR1019980706988A patent/KR19990087551A/ko not_active Withdrawn
- 1997-03-03 NZ NZ331382A patent/NZ331382A/xx unknown
- 1997-03-03 IL IL12534197A patent/IL125341A0/xx unknown
- 1997-03-03 HU HU9901750A patent/HUP9901750A2/hu unknown
- 1997-03-03 TR TR1998/01753T patent/TR199801753T2/xx unknown
- 1997-03-03 PL PL97328776A patent/PL328776A1/xx unknown
- 1997-03-03 JP JP9531445A patent/JP2000506153A/ja active Pending
- 1997-03-03 SK SK1204-98A patent/SK120498A3/sk unknown
- 1997-03-03 CZ CZ982816A patent/CZ281698A3/cs unknown
- 1997-03-05 US US08/812,002 patent/US5977102A/en not_active Expired - Fee Related
- 1997-03-05 ZA ZA971886A patent/ZA971886B/xx unknown
- 1997-03-05 AR ARP970100874A patent/AR009937A1/es unknown
- 1997-03-06 CO CO97012273A patent/CO4650044A1/es unknown
1998
- 1998-09-04 NO NO984081A patent/NO984081D0/no unknown
- 1998-09-24 BG BG102790A patent/BG102790A/bg unknown

Also Published As

Publication number	Publication date
DE19608653A1 (de)	1997-09-11
NZ331382A (en)	1999-08-30
US5977102A (en)	1999-11-02
AR009937A1 (es)	2000-05-17
NO984081L (no)	1998-09-04
WO1997032882A1 (de)	1997-09-12
CO4650044A1 (es)	1998-09-03
HUP9901750A2 (hu)	1999-09-28
ZA971886B (en)	1998-09-07
EP0885227A1 (de)	1998-12-23
BR9708004A (pt)	1999-07-27
SK120498A3 (en)	1999-04-13
PL328776A1 (en)	1999-02-15
KR19990087551A (ko)	1999-12-27
NO984081D0 (no)	1998-09-04
JP2000506153A (ja)	2000-05-23
CN1212696A (zh)	1999-03-31
IL125341A0 (en)	1999-03-12
AU712072B2 (en)	1999-10-28
TR199801753T2 (xx)	1998-12-21
EE9800289A (et)	1999-02-15
CZ281698A3 (cs)	1999-02-17
AU1925297A (en)	1997-09-22
CA2248316A1 (en)	1997-09-12

Publication	Publication Date	Title
BG102790A (bg)	1999-09-30	ПИРИМИДО/5,4-d/ПИРИМИДИНИ, ЛЕКАРСТВЕНИ СРЕДСТВА, СЪДЪРЖАЩИ ТЕЗИ СЪЕДИНЕНИЯ, ПРИЛОЖЕНИЕТО ИМ И МЕТОДЗА ТЯХНОТО ПОЛУЧАВАНЕ
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CN103958512B (zh)	2016-01-20	3,5-双取代炔基苯化合物及其盐
RU2318826C2 (ru)	2008-03-10	Производные 4-амино-6-фенилпирроло[2,3] пиримидина, обладающие ингибирующим действием в отношении действия тирозинкиназы, их применение и способы получения (варианты)
CA2387013C (en)	2009-12-29	6-position substituted indolinones, the preparation thereof and their use as pharmaceutical compositions
AU2013343550B2 (en)	2016-09-22	Substituted tricyclic benzimidazoles as kinase inhibitors
BG63163B1 (bg)	2001-05-31	Пиримидо/5,4-d/пиримидини, лекарствени средства, съдържащи тези съединения, приложението им и методза тяхното получаване
NZ292909A (en)	1998-09-24	Pyrimido[5,4-d]pyrimidines; medicaments
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TW200808325A (en)	2008-02-16	Novel compounds
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AU673814B2 (en)	1996-11-28	Imidazoquinazoline compounds and their preparation and use
IL110509A (en)	1998-01-04	2, 4, 8-TRISUBSTITUTED PYRIMIDO £5, 4-d\| PYRIMIDINE COMPOUNDS, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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