CS160591A3 - Quinazoline derivatives, process for their manufacture and their application as medicaments - Google Patents

Quinazoline derivatives, process for their manufacture and their application as medicaments Download PDF

Info

Publication number: CS160591A3
Authority: CS; Czechoslovakia
Prior art keywords: group; carbon atoms; amino; methyl; formula
Prior art date: 1990-05-30

Application number

CS911605A

Other languages

Czech (cs)

English (en)

Inventor

Robert George Andrew

Andrew John Barker

Francis Thomas Boyle

James Michael Wardleworth

Original Assignee

Ici Plc

Nat Res Dev

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.)

1990-05-30

Filing date

1991-05-29

Publication date

1992-01-15

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=10676728&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CS160591(A3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1991-05-29 Application filed by Ici Plc, Nat Res Dev filed Critical Ici Plc

1992-01-15 Publication of CS160591A3 publication Critical patent/CS160591A3/cs

Links

238000000034 method Methods 0.000 title claims description 69
125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title claims description 53
239000003814 drug Substances 0.000 title claims description 8
238000004519 manufacturing process Methods 0.000 title description 3
-1 hydroxymethylene group Chemical group 0.000 claims description 415
125000004432 carbon atom Chemical group C* 0.000 claims description 214
125000001424 substituent group Chemical group 0.000 claims description 87
150000001875 compounds Chemical class 0.000 claims description 85
125000003118 aryl group Chemical group 0.000 claims description 75
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 67
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 59
150000003839 salts Chemical class 0.000 claims description 44
125000006239 protecting group Chemical group 0.000 claims description 43
125000000217 alkyl group Chemical group 0.000 claims description 39
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 38
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 37
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 35
229910052786 argon Inorganic materials 0.000 claims description 34
239000002253 acid Substances 0.000 claims description 32
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
229910052727 yttrium Inorganic materials 0.000 claims description 32
125000003277 amino group Chemical group 0.000 claims description 31
125000001072 heteroaryl group Chemical group 0.000 claims description 31
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 30
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 26
238000002360 preparation method Methods 0.000 claims description 25
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 24
125000003545 alkoxy group Chemical group 0.000 claims description 23
125000003282 alkyl amino group Chemical group 0.000 claims description 22
125000004093 cyano group Chemical group *C#N 0.000 claims description 22
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 19
230000000259 anti-tumor effect Effects 0.000 claims description 18
238000006243 chemical reaction Methods 0.000 claims description 18
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 17
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
229910052801 chlorine Inorganic materials 0.000 claims description 16
125000001153 fluoro group Chemical group F* 0.000 claims description 16
125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 16
229910052757 nitrogen Inorganic materials 0.000 claims description 16
125000002947 alkylene group Chemical group 0.000 claims description 15
125000005110 aryl thio group Chemical group 0.000 claims description 15
125000005843 halogen group Chemical group 0.000 claims description 15
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 13
125000001188 haloalkyl group Chemical group 0.000 claims description 13
125000005368 heteroarylthio group Chemical group 0.000 claims description 13
125000005135 aryl sulfinyl group Chemical group 0.000 claims description 12
125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 11
125000004414 alkyl thio group Chemical group 0.000 claims description 11
125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 10
125000004429 atom Chemical group 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 10
125000005842 heteroatom Chemical group 0.000 claims description 10
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 10
125000005449 2-fluoro-1,4-phenylene group Chemical group [H]C1=C([*:2])C([H])=C(F)C([*:1])=C1[H] 0.000 claims description 9
241001465754 Metazoa Species 0.000 claims description 9
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 9
125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 8
229910052739 hydrogen Inorganic materials 0.000 claims description 8
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 8
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 7
239000001257 hydrogen Substances 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 7
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
125000004423 acyloxy group Chemical group 0.000 claims description 6
239000000460 chlorine Substances 0.000 claims description 6
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 6
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
125000004149 thio group Chemical group *S* 0.000 claims description 6
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 6
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 5
125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 5
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 5
125000000464 thioxo group Chemical group S=* 0.000 claims description 5
125000000304 alkynyl group Chemical group 0.000 claims description 4
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
125000004663 dialkyl amino group Chemical group 0.000 claims description 4
125000000623 heterocyclic group Chemical group 0.000 claims description 4
125000003884 phenylalkyl group Chemical group 0.000 claims description 4
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 3
238000005917 acylation reaction Methods 0.000 claims description 3
150000001408 amides Chemical class 0.000 claims description 3
125000004966 cyanoalkyl group Chemical group 0.000 claims description 3
125000001841 imino group Chemical group [H]N=* 0.000 claims description 3
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 3
125000003831 tetrazolyl group Chemical group 0.000 claims description 3
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
239000005977 Ethylene Substances 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
230000010933 acylation Effects 0.000 claims description 2
230000003301 hydrolyzing effect Effects 0.000 claims description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
150000003246 quinazolines Chemical class 0.000 claims 14
230000001681 protective effect Effects 0.000 claims 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
CMVNWVONJDMTSH-UHFFFAOYSA-N 7-bromo-2-methyl-1h-quinazolin-4-one Chemical compound C1=CC(Br)=CC2=NC(C)=NC(O)=C21 CMVNWVONJDMTSH-UHFFFAOYSA-N 0.000 claims 1
125000005153 alkyl sulfamoyl group Chemical group 0.000 claims 1
239000008280 blood Substances 0.000 claims 1
230000001590 oxidative effect Effects 0.000 claims 1
239000000203 mixture Substances 0.000 description 309
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 213
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 131
239000000243 solution Substances 0.000 description 128
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 120
229910001868 water Inorganic materials 0.000 description 113
239000000047 product Substances 0.000 description 109
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 94
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 85
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 78
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 76
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 66
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 53
239000000741 silica gel Substances 0.000 description 53
229910002027 silica gel Inorganic materials 0.000 description 53
239000007858 starting material Substances 0.000 description 50
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
238000004587 chromatography analysis Methods 0.000 description 35
229910052943 magnesium sulfate Inorganic materials 0.000 description 33
235000019341 magnesium sulphate Nutrition 0.000 description 33
239000007787 solid Substances 0.000 description 31
238000002844 melting Methods 0.000 description 30
230000008018 melting Effects 0.000 description 30
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 28
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
229940086542 triethylamine Drugs 0.000 description 26
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 23
238000012360 testing method Methods 0.000 description 23
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 21
150000001412 amines Chemical class 0.000 description 20
238000000921 elemental analysis Methods 0.000 description 20
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 18
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
239000012074 organic phase Substances 0.000 description 17
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 16
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
238000001819 mass spectrum Methods 0.000 description 15
239000002244 precipitate Substances 0.000 description 15
206010028980 Neoplasm Diseases 0.000 description 14
125000001309 chloro group Chemical group Cl* 0.000 description 13
239000003480 eluent Substances 0.000 description 13
150000002500 ions Chemical class 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
239000012044 organic layer Substances 0.000 description 12
239000012267 brine Substances 0.000 description 11
239000000706 filtrate Substances 0.000 description 11
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
239000005711 Benzoic acid Substances 0.000 description 10
229910052731 fluorine Inorganic materials 0.000 description 10
239000003921 oil Substances 0.000 description 10
229920006395 saturated elastomer Polymers 0.000 description 10
239000011734 sodium Substances 0.000 description 10
239000002904 solvent Substances 0.000 description 10
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 9
201000011510 cancer Diseases 0.000 description 9
238000010265 fast atom bombardment Methods 0.000 description 9
238000010992 reflux Methods 0.000 description 9
229910052708 sodium Inorganic materials 0.000 description 9
125000000335 thiazolyl group Chemical group 0.000 description 9
125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 8
XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
229960000583 acetic acid Drugs 0.000 description 8
239000007864 aqueous solution Substances 0.000 description 8
238000003556 assay Methods 0.000 description 8
239000002585 base Substances 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 8
239000012071 phase Substances 0.000 description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
239000012265 solid product Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 7
235000010233 benzoic acid Nutrition 0.000 description 7
238000004949 mass spectrometry Methods 0.000 description 7
230000002441 reversible effect Effects 0.000 description 7
239000012047 saturated solution Substances 0.000 description 7
125000001544 thienyl group Chemical group 0.000 description 7
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 7
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 6
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 6
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
239000004471 Glycine Substances 0.000 description 6
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
229910052794 bromium Inorganic materials 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
239000006260 foam Substances 0.000 description 6
238000002347 injection Methods 0.000 description 6
239000007924 injection Substances 0.000 description 6
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 6
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
125000004076 pyridyl group Chemical group 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
229910052717 sulfur Chemical group 0.000 description 6
239000011593 sulfur Chemical group 0.000 description 6
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 6
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
QMNUDYFKZYBWQX-UHFFFAOYSA-N 3H-quinazolinyl-4-one Natural products C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 description 5
ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 5
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
239000012359 Methanesulfonyl chloride Substances 0.000 description 5
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
150000001540 azides Chemical class 0.000 description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
GYOZYWVXFNDGLU-XLPZGREQSA-N dTMP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 GYOZYWVXFNDGLU-XLPZGREQSA-N 0.000 description 5
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 5
DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 5
125000006125 ethylsulfonyl group Chemical group 0.000 description 5
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 5
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 5
125000004043 oxo group Chemical group O=* 0.000 description 5
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BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000005557 thiazolylene group Chemical group 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
125000002480 thymidyl group Chemical group 0.000 description 1
239000003734 thymidylate synthase inhibitor Substances 0.000 description 1
229940044693 topoisomerase inhibitor Drugs 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
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
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
229910052724 xenon Inorganic materials 0.000 description 1
FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (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)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CS911605A 1990-05-30 1991-05-29 Quinazoline derivatives, process for their manufacture and their application as medicaments CS160591A3 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB9011989		1990-05-30

Publications (1)

Publication Number	Publication Date
CS160591A3 true CS160591A3 (en)	1992-01-15

Family

ID=10676728

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS911605A CS160591A3 (en)	1990-05-30	1991-05-29	Quinazoline derivatives, process for their manufacture and their application as medicaments

Country Status (15)

Country	Link
US (1)	US5280027A (fr)
EP (1)	EP0459730A3 (fr)
JP (1)	JPH04235173A (fr)
AU (1)	AU640016B2 (fr)
CA (1)	CA2042922A1 (fr)
CS (1)	CS160591A3 (fr)
FI (1)	FI912600A7 (fr)
GB (1)	GB2244708B (fr)
HU (1)	HUT57739A (fr)
IE (1)	IE64085B1 (fr)
IL (1)	IL98167A0 (fr)
NO (1)	NO912071L (fr)
NZ (1)	NZ238259A (fr)
PT (1)	PT97799A (fr)
ZA (1)	ZA913730B (fr)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9105771D0 (en) *	1991-03-19	1991-05-01	Cancer Res Inst Royal	Anti-cancer compounds
GB9205320D0 (en) *	1992-03-11	1992-04-22	Ici Plc	Anti-tumour compounds
GB9205907D0 (en) *	1992-03-18	1992-04-29	Cancer Res Inst Royal	Anti-cancer compounds
US5430148A (en) *	1992-03-31	1995-07-04	Agouron Pharmaceuticals, Inc.	Antiproliferative quinazolines
GB9220571D0 (en) *	1992-09-30	1992-11-11	Ici Plc	Quinazoline derivatives
US6174887B1 (en)	1995-08-22	2001-01-16	Japan Tobacco Inc.	Amide compounds and use of the same
US5786358A (en) *	1995-09-08	1998-07-28	The Trustees Of Princeton University	Pyridopyrimidines as nonclassical antifolates
GB9904275D0 (en) *	1999-02-24	1999-04-21	Cancer Res Campaign Tech	Anti-cancer compounds
US6518292B1 (en) *	1999-03-12	2003-02-11	Bristol-Myers Squibb Co.	Heterocyclic aromatic compounds usefuls as growth hormone secretagogues
US6545004B1 (en)	1999-10-27	2003-04-08	Cytokinetics, Inc.	Methods and compositions utilizing quinazolinones
US7230000B1 (en) *	1999-10-27	2007-06-12	Cytokinetics, Incorporated	Methods and compositions utilizing quinazolinones
AU2002346471A1 (en) *	2001-11-20	2003-06-10	Cytokinetics, Inc.	Process for the racemization of chiral quinazolinones
AU2003213092A1 (en) *	2002-02-15	2003-09-09	Smithkline Beecham Corporation	Syntheses of quinazolinones
US7214800B2 (en) *	2002-05-09	2007-05-08	Cytokinetics, Inc.	Compounds, compositions, and methods
WO2003094839A2 (fr) *	2002-05-09	2003-11-20	Cytokinetics, Inc.	Composes, compositions et procedes
AU2003265242A1 (en) *	2002-05-23	2003-12-22	Cytokinetics, Inc.	Compounds, compositions, and methods
WO2003106426A1 (fr) *	2002-06-14	2003-12-24	Cytokinetics, Inc.	Composes, compositions et procedes
WO2004009036A2 (fr) *	2002-07-23	2004-01-29	Cytokinetics, Inc.	Composes, compositions et procedes
AU2003262747A1 (en) *	2002-08-21	2004-03-11	Cytokinetics, Inc.	Compounds, compositions, and methods
US7557115B2 (en)	2002-09-30	2009-07-07	Cytokinetics, Inc.	Compounds, compositions, and methods
WO2005041888A2 (fr) *	2003-11-03	2005-05-12	Cytokinetics, Inc.	Composes, compositions et methodes
JP2007510660A (ja) *	2003-11-07	2007-04-26	サイトキネティクス・インコーポレーテッド	化合物、組成物及び方法
US7439254B2 (en) *	2003-12-08	2008-10-21	Cytokinetics, Inc.	Compounds, compositions, and methods
MX2009013815A (es) *	2007-06-22	2010-03-01	Arqule Inc	Compuestos de quinazolinona y metodos de uso para los mismos.
DE102010001064A1 (de) *	2009-03-18	2010-09-23	Bayer Schering Pharma Aktiengesellschaft	Substituierte 2-Acetamido-5-Aryl-1,2,4-triazolone und deren Verwendung
CN103906733A (zh)	2011-06-24	2014-07-02	安姆根有限公司	Trpm8拮抗剂及其在治疗中的用途
WO2012177896A1 (fr)	2011-06-24	2012-12-27	Amgen Inc.	Antagonistes de trpm8 et leur utilisation dans le cadre thérapeutique
US8952009B2 (en)	2012-08-06	2015-02-10	Amgen Inc.	Chroman derivatives as TRPM8 inhibitors
US10413583B2 (en) *	2016-11-30	2019-09-17	The University Of Chicago	Synthetic substrates for enzymes that catalyze reactions of modified cysteines and related methods
AU2024277518A1 (en) *	2023-05-25	2025-11-27	Allorion Therapeutics Inc	N-(1h-indol-2-yl)methyl)-4-ethynyl-picolinamide derivatives as egfr inhibitors for the treatment of cancer

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB2065653B (en) *	1979-12-19	1983-03-09	Nat Res Dev	Anti-cancer quinazoline derivatives
GB8607683D0 (en) *	1986-03-27	1986-04-30	Ici Plc	Anti-tumor agents
GB8707053D0 (en) *	1987-03-25	1987-04-29	Ici Plc	Anti-tumour agents
US4857530A (en) *	1987-11-03	1989-08-15	Warner-Lambert Company	Substituted quinazolinones as anticancer agents
GB8809978D0 (en) *	1988-04-27	1988-06-02	Ici Plc	Anti-tumour agents
EP0365763A1 (fr) *	1988-09-30	1990-05-02	Agouron Pharmaceuticals, Inc.	Composés cycliques antiproléfératifs
GB8829296D0 (en) *	1988-12-15	1989-01-25	Ici Plc	Anti-tumour compounds

1991
- 1991-05-16 IL IL98167A patent/IL98167A0/xx unknown
- 1991-05-16 AU AU77075/91A patent/AU640016B2/en not_active Ceased
- 1991-05-16 ZA ZA913730A patent/ZA913730B/xx unknown
- 1991-05-21 CA CA002042922A patent/CA2042922A1/fr not_active Abandoned
- 1991-05-22 IE IE175791A patent/IE64085B1/en not_active IP Right Cessation
- 1991-05-24 NZ NZ238259A patent/NZ238259A/en unknown
- 1991-05-24 EP EP19910304757 patent/EP0459730A3/en not_active Withdrawn
- 1991-05-27 HU HU911768A patent/HUT57739A/hu unknown
- 1991-05-29 CS CS911605A patent/CS160591A3/cs unknown
- 1991-05-29 JP JP3124260A patent/JPH04235173A/ja active Pending
- 1991-05-29 NO NO91912071A patent/NO912071L/no unknown
- 1991-05-29 PT PT97799A patent/PT97799A/pt not_active Application Discontinuation
- 1991-05-30 US US07/708,046 patent/US5280027A/en not_active Expired - Fee Related
- 1991-05-30 GB GB9111656A patent/GB2244708B/en not_active Expired - Fee Related
- 1991-05-30 FI FI912600A patent/FI912600A7/fi not_active Application Discontinuation

Also Published As

Publication number	Publication date
GB9111656D0 (en)	1991-07-24
IE911757A1 (en)	1991-12-04
US5280027A (en)	1994-01-18
FI912600A0 (fi)	1991-05-30
GB2244708A (en)	1991-12-11
IL98167A0 (en)	1992-06-21
IE64085B1 (en)	1995-07-12
NZ238259A (en)	1993-07-27
EP0459730A2 (fr)	1991-12-04
CA2042922A1 (fr)	1991-12-01
ZA913730B (en)	1992-02-26
NO912071D0 (no)	1991-05-29
JPH04235173A (ja)	1992-08-24
GB2244708B (en)	1993-12-08
FI912600A7 (fi)	1991-12-01
AU640016B2 (en)	1993-08-12
HUT57739A (en)	1991-12-30
PT97799A (pt)	1992-02-28
NO912071L (no)	1991-12-02
AU7707591A (en)	1991-12-05
EP0459730A3 (en)	1993-01-20

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