SK2142003A3 - Quinazoline derivatives, process for their preparation, pharmaceutical composition comprising same and their use - Google Patents

Quinazoline derivatives, process for their preparation, pharmaceutical composition comprising same and their use Download PDF

Info

Publication number: SK2142003A3
Authority: SK; Slovakia
Prior art keywords: group; carbon atoms; ethoxy; propoxy; alkyl
Prior art date: 2000-08-21

Application number

SK214-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Laurent Francois And Hennequin

Patrick Ple

Christine Marie Paul Lambert

Original Assignee

Astrazeneca Ab

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-08-21

Filing date

2001-08-15

Publication date

2003-07-01

2001-08-15 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2003-07-01 Publication of SK2142003A3 publication Critical patent/SK2142003A3/sk

Links

238000000034 method Methods 0.000 title claims abstract description 59
238000002360 preparation method Methods 0.000 title claims abstract description 41
230000008569 process Effects 0.000 title claims abstract description 9
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 5
125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract description 6
206010028980 Neoplasm Diseases 0.000 claims abstract description 32
239000003795 chemical substances by application Substances 0.000 claims abstract description 9
239000003814 drug Substances 0.000 claims abstract description 9
230000001740 anti-invasion Effects 0.000 claims abstract description 8
-1 nitro, hydroxy , mercapto, amino, formyl Chemical group 0.000 claims description 806
125000004432 carbon atom Chemical group C* 0.000 claims description 281
125000000217 alkyl group Chemical group 0.000 claims description 173
125000001424 substituent group Chemical group 0.000 claims description 116
150000001875 compounds Chemical class 0.000 claims description 111
150000003246 quinazolines Chemical class 0.000 claims description 60
239000001257 hydrogen Substances 0.000 claims description 58
229910052739 hydrogen Inorganic materials 0.000 claims description 58
150000003839 salts Chemical class 0.000 claims description 58
125000000623 heterocyclic group Chemical group 0.000 claims description 50
229910052757 nitrogen Inorganic materials 0.000 claims description 45
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 42
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 36
238000006243 chemical reaction Methods 0.000 claims description 34
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 34
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 32
125000003545 alkoxy group Chemical group 0.000 claims description 31
229910052801 chlorine Inorganic materials 0.000 claims description 29
229910052760 oxygen Inorganic materials 0.000 claims description 29
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 29
125000001072 heteroaryl group Chemical group 0.000 claims description 27
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
239000002253 acid Substances 0.000 claims description 25
229910052731 fluorine Inorganic materials 0.000 claims description 24
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 23
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
125000006239 protecting group Chemical group 0.000 claims description 21
125000003118 aryl group Chemical group 0.000 claims description 20
229910052799 carbon Inorganic materials 0.000 claims description 20
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 19
229910052736 halogen Inorganic materials 0.000 claims description 19
150000002367 halogens Chemical class 0.000 claims description 19
239000000460 chlorine Substances 0.000 claims description 18
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 16
125000005236 alkanoylamino group Chemical group 0.000 claims description 16
125000000753 cycloalkyl group Chemical group 0.000 claims description 16
125000003710 aryl alkyl group Chemical group 0.000 claims description 15
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 14
241000282414 Homo sapiens Species 0.000 claims description 14
125000002947 alkylene group Chemical group 0.000 claims description 14
239000011737 fluorine Substances 0.000 claims description 14
241001465754 Metazoa Species 0.000 claims description 13
125000003342 alkenyl group Chemical group 0.000 claims description 13
125000001589 carboacyl group Chemical group 0.000 claims description 13
125000001309 chloro group Chemical group Cl* 0.000 claims description 13
238000003776 cleavage reaction Methods 0.000 claims description 13
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 13
238000003780 insertion Methods 0.000 claims description 13
230000037431 insertion Effects 0.000 claims description 13
125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 12
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
230000007017 scission Effects 0.000 claims description 12
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 11
125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 11
229910002091 carbon monoxide Inorganic materials 0.000 claims description 11
229910052717 sulfur Inorganic materials 0.000 claims description 11
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 10
125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 10
125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 10
125000000392 cycloalkenyl group Chemical group 0.000 claims description 10
125000001153 fluoro group Chemical group F* 0.000 claims description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
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 10
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 9
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 9
125000004423 acyloxy group Chemical group 0.000 claims description 9
150000001335 aliphatic alkanes Chemical class 0.000 claims description 9
125000000304 alkynyl group Chemical group 0.000 claims description 9
125000004103 aminoalkyl group Chemical group 0.000 claims description 9
125000004429 atom Chemical group 0.000 claims description 9
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 9
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 9
125000005843 halogen group Chemical group 0.000 claims description 9
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
125000003282 alkyl amino group Chemical group 0.000 claims description 8
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 8
125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 8
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 8
150000003852 triazoles Chemical group 0.000 claims description 8
125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 7
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 7
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 7
125000006766 (C2-C6) alkynyloxy group Chemical group 0.000 claims description 7
125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 7
150000001412 amines Chemical class 0.000 claims description 7
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 7
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 7
229920002554 vinyl polymer Polymers 0.000 claims description 7
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 6
125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 6
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 6
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
125000003302 alkenyloxy group Chemical group 0.000 claims description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
125000004966 cyanoalkyl group Chemical group 0.000 claims description 5
125000000524 functional group Chemical group 0.000 claims description 5
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 5
125000001425 triazolyl group Chemical group 0.000 claims description 5
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 4
XHOHVIKZCDXJNK-UHFFFAOYSA-N 2-piperazin-1-ylacetonitrile Chemical compound N#CCN1CCNCC1 XHOHVIKZCDXJNK-UHFFFAOYSA-N 0.000 claims description 4
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 4
125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 4
125000003277 amino group Chemical group 0.000 claims description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
238000002560 therapeutic procedure Methods 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
150000001721 carbon Chemical group 0.000 claims description 3
239000012024 dehydrating agents‎ Substances 0.000 claims description 3
125000001188 haloalkyl group Chemical group 0.000 claims description 3
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
MWCIFBSDQJFWIE-UHFFFAOYSA-N n-(5-bromo-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C(=CC=C4OCOC4=3)Br)N=CN=C2C=C1OCCCN1CCCCC1 MWCIFBSDQJFWIE-UHFFFAOYSA-N 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
125000000168 pyrrolyl group Chemical group 0.000 claims description 3
FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 2
GDKVKFPZULERFV-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-4-ylamino)-6-methoxyquinazolin-7-yl]oxy-3-pyrrolidin-1-ylpropan-2-ol Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCC(O)CN1CCCC1 GDKVKFPZULERFV-UHFFFAOYSA-N 0.000 claims description 2
QTDVHHYSYHHNBA-UHFFFAOYSA-N 2-[4-[3-[4-[(5-chloro-1,3-benzodioxol-4-yl)amino]-6-methoxyquinazolin-7-yl]oxypropyl]piperazin-1-yl]acetonitrile Chemical compound COC1=CC2=C(NC=3C(=CC=C4OCOC4=3)Cl)N=CN=C2C=C1OCCCN1CCN(CC#N)CC1 QTDVHHYSYHHNBA-UHFFFAOYSA-N 0.000 claims description 2
DLSRIJJGQIAZHW-UHFFFAOYSA-N 4-[[4-[(5-chloro-1,3-benzodioxol-4-yl)amino]-6-methoxyquinazolin-7-yl]oxymethyl]pyridine-2-carbonitrile Chemical compound COC1=CC2=C(NC=3C(=CC=C4OCOC4=3)Cl)N=CN=C2C=C1OCC1=CC=NC(C#N)=C1 DLSRIJJGQIAZHW-UHFFFAOYSA-N 0.000 claims description 2
230000029936 alkylation Effects 0.000 claims description 2
238000005804 alkylation reaction Methods 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
125000004663 dialkyl amino group Chemical group 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
DNWPHHNJIJAHJZ-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-(2-pyridin-4-yloxyethoxy)quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCCOC1=CC=NC=C1 DNWPHHNJIJAHJZ-UHFFFAOYSA-N 0.000 claims description 2
FQYJMIYZRDNWFL-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCCCN1CCCCC1 FQYJMIYZRDNWFL-UHFFFAOYSA-N 0.000 claims description 2
QGPNNNIDDPCLOP-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-(pyridin-3-ylmethoxy)quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCC1=CC=CN=C1 QGPNNNIDDPCLOP-UHFFFAOYSA-N 0.000 claims description 2
RMCMKWWPSMSMQU-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-[2-(4-methylpiperazin-1-yl)ethoxy]quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCCN1CCN(C)CC1 RMCMKWWPSMSMQU-UHFFFAOYSA-N 0.000 claims description 2
WACGGXLWSGDPHZ-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCCCN1CCN(C)CC1 WACGGXLWSGDPHZ-UHFFFAOYSA-N 0.000 claims description 2
ULKTVLPBTPXRFB-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C(=CC=C4OCOC4=3)Cl)N=CN=C2C=C1OCCCN1CCCC1 ULKTVLPBTPXRFB-UHFFFAOYSA-N 0.000 claims description 2
UYKYCBACTCRLLP-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C(=CC=C4OCOC4=3)Cl)N=CN=C2C=C1OCC1CCN(C)CC1 UYKYCBACTCRLLP-UHFFFAOYSA-N 0.000 claims description 2
125000004043 oxo group Chemical group O=* 0.000 claims description 2
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
125000000547 substituted alkyl group Chemical group 0.000 claims description 2
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 2
125000005115 alkyl carbamoyl group Chemical group 0.000 claims 2
QCEYSUFQHXTGTC-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-4-ylamino)-6-methoxyquinazolin-7-yl]oxy-3-[methyl(propan-2-yl)amino]propan-2-ol Chemical compound N1=CN=C2C=C(OCC(O)CN(C)C(C)C)C(OC)=CC2=C1NC1=CC=CC2=C1OCO2 QCEYSUFQHXTGTC-UHFFFAOYSA-N 0.000 claims 1
VJXBEBMWTIRUQU-UHFFFAOYSA-N 2-[4-[3-[4-(1,3-benzodioxol-4-ylamino)-6-methoxyquinazolin-7-yl]oxy-2-hydroxypropyl]piperazin-1-yl]acetonitrile Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCC(O)CN1CCN(CC#N)CC1 VJXBEBMWTIRUQU-UHFFFAOYSA-N 0.000 claims 1
235000007119 Ananas comosus Nutrition 0.000 claims 1
244000099147 Ananas comosus Species 0.000 claims 1
AYVXLBYVMHZUFF-UHFFFAOYSA-N COC(C(=O)NC(C(=O)N(OCCCC)OC(C)C)(C(N(C)C)(NCC)NC)N(CC)CC)(OCCC)OCC Chemical compound COC(C(=O)NC(C(=O)N(OCCCC)OC(C)C)(C(N(C)C)(NCC)NC)N(CC)CC)(OCCC)OCC AYVXLBYVMHZUFF-UHFFFAOYSA-N 0.000 claims 1
125000005117 dialkylcarbamoyl group Chemical group 0.000 claims 1
125000004438 haloalkoxy group Chemical group 0.000 claims 1
JANJZCFEDLKWOM-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCC1CCN(C)CC1 JANJZCFEDLKWOM-UHFFFAOYSA-N 0.000 claims 1
IFKVYXZTVIFTQM-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-[2-(1-methylpiperidin-4-yl)ethoxy]quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCCC1CCN(C)CC1 IFKVYXZTVIFTQM-UHFFFAOYSA-N 0.000 claims 1
125000003386 piperidinyl group Chemical group 0.000 claims 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
238000004519 manufacturing process Methods 0.000 abstract description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 342
239000000203 mixture Substances 0.000 description 288
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 251
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 168
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 165
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 147
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 130
238000001819 mass spectrum Methods 0.000 description 116
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 114
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 109
239000000243 solution Substances 0.000 description 107
150000002431 hydrogen Chemical class 0.000 description 100
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 98
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 96
239000007787 solid Substances 0.000 description 73
239000007858 starting material Substances 0.000 description 69
239000000047 product Substances 0.000 description 68
239000000463 material Substances 0.000 description 66
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 62
238000004440 column chromatography Methods 0.000 description 56
239000000377 silicon dioxide Substances 0.000 description 52
229910052943 magnesium sulfate Inorganic materials 0.000 description 49
235000019341 magnesium sulphate Nutrition 0.000 description 49
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 48
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
239000011541 reaction mixture Substances 0.000 description 48
238000001914 filtration Methods 0.000 description 47
239000012267 brine Substances 0.000 description 45
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 45
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 43
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 41
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 38
DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 38
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 31
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 31
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 30
239000012074 organic phase Substances 0.000 description 30
238000005481 NMR spectroscopy Methods 0.000 description 29
102000001332 SRC Human genes 0.000 description 29
108060006706 SRC Proteins 0.000 description 29
239000000706 filtrate Substances 0.000 description 28
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
210000004027 cell Anatomy 0.000 description 27
229920006395 saturated elastomer Polymers 0.000 description 26
238000012360 testing method Methods 0.000 description 26
235000017557 sodium bicarbonate Nutrition 0.000 description 23
229910000030 sodium bicarbonate Inorganic materials 0.000 description 23
239000003480 eluent Substances 0.000 description 21
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WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
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VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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FRLRKOBIHDUBMS-UHFFFAOYSA-N tributylazanium;iodide Chemical compound [I-].CCCC[NH+](CCCC)CCCC FRLRKOBIHDUBMS-UHFFFAOYSA-N 0.000 description 1
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JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 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
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238000005292 vacuum distillation Methods 0.000 description 1
WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 1
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239000003981 vehicle Substances 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
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
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- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pulmonology (AREA)
Diabetes (AREA)
Rheumatology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Cardiology (AREA)
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Biomedical Technology (AREA)
Endocrinology (AREA)
Oncology (AREA)
Ophthalmology & Optometry (AREA)
Pain & Pain Management (AREA)
Hematology (AREA)
Vascular Medicine (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Obesity (AREA)
Emergency Medicine (AREA)
Gastroenterology & Hepatology (AREA)
Immunology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

SK214-2003A 2000-08-21 2001-08-15 Quinazoline derivatives, process for their preparation, pharmaceutical composition comprising same and their use SK2142003A3 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP00402320		2000-08-21
EP01401006		2001-04-19
PCT/GB2001/003649 WO2002016352A1 (en)	2000-08-21	2001-08-15	Quinazoline derivatives

Publications (1)

Publication Number	Publication Date
SK2142003A3 true SK2142003A3 (en)	2003-07-01

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ID=26073540

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK214-2003A SK2142003A3 (en)	2000-08-21	2001-08-15	Quinazoline derivatives, process for their preparation, pharmaceutical composition comprising same and their use

Country Status (21)

Country	Link
US (1)	US7115615B2 (zh)
EP (1)	EP1313727A1 (zh)
JP (1)	JP2004506732A (zh)
KR (2)	KR20080027400A (zh)
CN (1)	CN100347169C (zh)
AR (1)	AR033560A1 (zh)
AU (2)	AU7860901A (zh)
BR (1)	BR0113358A (zh)
CA (1)	CA2419301C (zh)
CZ (1)	CZ2003486A3 (zh)
EE (1)	EE05387B1 (zh)
IL (2)	IL154131A0 (zh)
MX (1)	MXPA03001332A (zh)
MY (1)	MY129809A (zh)
NO (1)	NO326515B1 (zh)
NZ (1)	NZ523702A (zh)
PL (1)	PL202812B1 (zh)
RU (1)	RU2267489C2 (zh)
SK (1)	SK2142003A3 (zh)
TW (1)	TWI280960B (zh)
WO (1)	WO2002016352A1 (zh)

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UA73993C2 (uk)	2000-06-06	2005-10-17	Астразенека Аб	Хіназолінові похідні для лікування пухлин та фармацевтична композиція
WO2002030926A1 (en)	2000-10-13	2002-04-18	Astrazeneca Ab	Quinazoline derivatives
US6849625B2 (en)	2000-10-13	2005-02-01	Astrazeneca Ab	Quinazoline derivatives with anti-tumour activity
DE60144284D1 (de)	2000-11-01	2011-05-05	Millennium Pharm Inc	Stickstoffhaltige heterozyklische verbindungen und verfahren zu deren herstellung
ES2312557T3 (es) *	2001-04-19	2009-03-01	Astrazeneca Ab	Derivados de quinazolina.
JP4326328B2 (ja)	2001-07-16	2009-09-02	アストラゼネカアクチボラグ	キノリン誘導体及びそれらのチロシンキナーゼ阻害薬としての使用
GB0128109D0 (en)	2001-11-23	2002-01-16	Astrazeneca Ab	Therapeutic use
AU2002365664A1 (en) *	2001-12-05	2003-06-17	Astrazeneca Ab	Quinoline derivatives as antitumour agents
MXPA04007459A (es) *	2002-02-01	2005-09-08	Astrazeneca Ab	Compuestos de quinazolina.
TWI324597B (en) *	2002-03-28	2010-05-11	Astrazeneca Ab	Quinazoline derivatives
US6924285B2 (en)	2002-03-30	2005-08-02	Boehringer Ingelheim Pharma Gmbh & Co.	Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them
GB0215823D0 (en)	2002-07-09	2002-08-14	Astrazeneca Ab	Quinazoline derivatives
WO2004004732A1 (en) *	2002-07-09	2004-01-15	Astrazeneca Ab	Quinazoline derivatives for use in the treatment of cancer
EP2277867B1 (en)	2002-07-15	2012-12-05	Symphony Evolution, Inc.	Compounds, pharmaceutical compositions thereof and their use in treating cancer
GB0225579D0 (en)	2002-11-02	2002-12-11	Astrazeneca Ab	Chemical compounds
CN100354278C (zh) *	2002-11-04	2007-12-12	阿斯利康(瑞典)有限公司	作为src酪氨酸激酶抑制剂的喹唑啉衍生物
RU2350618C2 (ru)	2002-11-04	2009-03-27	Астразенека Аб	ПРОИЗВОДНЫЕ ХИНАЗОЛИНА В КАЧЕСТВЕ ИНГИБИТОРОВ Src ТИРОЗИНКИНАЗЫ
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CA2529611C (en)	2002-12-20	2009-12-15	Pfizer Products Inc.	Pyrimidine derivatives for the treatment of abnormal cell growth
GB0307333D0 (en) *	2003-03-29	2003-05-07	Astrazeneca Ab	Therapeutic agent
GB0310401D0 (en) *	2003-05-07	2003-06-11	Astrazeneca Ab	Therapeutic agent
GB0317665D0 (en)	2003-07-29	2003-09-03	Astrazeneca Ab	Qinazoline derivatives
ES2371383T3 (es)	2003-09-26	2011-12-30	Exelixis, Inc.	N-[3-fluoro-4-({6-(metiloxi)-7-[(3-morfolin-4-ilpropil)oxi]quinolin-4-il}oxi)fenil]-n'-(4-fluorofenil)ciclopropan-1,1-dicarboxamida para el tratamiento del cáncer.
ES2315834T3 (es)	2004-02-03	2009-04-01	Astrazeneca Ab	Derivados de quinazolina.
WO2005111016A1 (en)	2004-05-14	2005-11-24	Pfizer Products Inc.	Pyrimidine derivatives for the treatment of abnormal cell growth
BRPI0510980A (pt)	2004-05-14	2007-11-27	Pfizer Prod Inc	derivados de pirimidina para o tratamento do crescimento anormal de células
BRPI0511132A (pt)	2004-05-14	2007-11-27	Pfizer Prod Inc	derivados de pirimidina e composição farmacêutica compreendendo os mesmos
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2001
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- 2001-08-15 PL PL360591A patent/PL202812B1/pl not_active IP Right Cessation
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- 2001-08-15 JP JP2002521453A patent/JP2004506732A/ja not_active Ceased
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Publication number	Publication date
AR033560A1 (es)	2003-12-26
KR100821446B1 (ko)	2008-04-10
WO2002016352A1 (en)	2002-02-28
CN100347169C (zh)	2007-11-07
US7115615B2 (en)	2006-10-03
EP1313727A1 (en)	2003-05-28
MXPA03001332A (es)	2004-07-08
NO20030795L (no)	2003-04-04
NO20030795D0 (no)	2003-02-20
IL154131A (en)	2010-04-15
CN1471527A (zh)	2004-01-28
KR20030022416A (ko)	2003-03-15
RU2267489C2 (ru)	2006-01-10
EE05387B1 (et)	2011-02-15
PL202812B1 (pl)	2009-07-31
KR20080027400A (ko)	2008-03-26
AU7860901A (en)	2002-03-04
TWI280960B (en)	2007-05-11
CA2419301A1 (en)	2002-02-28
NZ523702A (en)	2004-08-27
PL360591A1 (en)	2004-09-06
IL154131A0 (en)	2003-07-31
BR0113358A (pt)	2003-07-01
NO326515B1 (no)	2008-12-22
CA2419301C (en)	2009-12-08
MY129809A (en)	2007-05-31
EE200300071A (et)	2004-12-15
JP2004506732A (ja)	2004-03-04
AU2001278609B2 (en)	2005-04-14
US20040034046A1 (en)	2004-02-19
CZ2003486A3 (cs)	2003-05-14

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Publication	Publication Date	Title
CA2419301C (en)	2009-12-08	Quinazoline derivatives
CA2407371C (en)	2009-10-20	Quinazoline derivatives for the treatment of tumours
US6849625B2 (en)	2005-02-01	Quinazoline derivatives with anti-tumour activity
AU2001278609A1 (en)	2002-05-30	Quinazoline derivatives
AU2001260482A1 (en)	2002-03-07	Quinazoline derivatives for the treatment of tumours
JP4307843B2 (ja)	2009-08-05	キナゾリン誘導体
JP2004512335A (ja)	2004-04-22	キナゾリン誘導体
WO2002092577A1 (en)	2002-11-21	Quinazoline derivatives
JP2004511480A (ja)	2004-04-15	キナゾリン誘導体
RU2276151C2 (ru)	2006-05-10	Хиназолиновые производные для лечения опухолей