IE41838B1 - 4-substituted quinazoline cardiac stimulants - Google Patents
4-substituted quinazoline cardiac stimulantsInfo
- Publication number
- IE41838B1 IE41838B1 IE1658/75A IE165875A IE41838B1 IE 41838 B1 IE41838 B1 IE 41838B1 IE 1658/75 A IE1658/75 A IE 1658/75A IE 165875 A IE165875 A IE 165875A IE 41838 B1 IE41838 B1 IE 41838B1
- Authority
- IE
- Ireland
- Prior art keywords
- group
- compound
- lower alkyl
- hydrogen atom
- alkyl group
- Prior art date
Links
- -1 4-substituted quinazoline Chemical class 0.000 title claims abstract description 32
- 239000000496 cardiotonic agent Substances 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 106
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 83
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 56
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 39
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 34
- 125000003118 aryl group Chemical group 0.000 claims abstract description 32
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 21
- 239000002253 acid Substances 0.000 claims abstract description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
- 239000001257 hydrogen Substances 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 9
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 6
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims abstract description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 25
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 14
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 10
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 8
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 8
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 7
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 5
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 229940095064 tartrate Drugs 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 230000004936 stimulating effect Effects 0.000 claims description 2
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 claims 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 claims 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 1
- 101100311330 Schizosaccharomyces pombe (strain 972 / ATCC 24843) uap56 gene Proteins 0.000 claims 1
- 229940050410 gluconate Drugs 0.000 claims 1
- 150000003840 hydrochlorides Chemical class 0.000 claims 1
- 101150018444 sub2 gene Proteins 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 15
- 125000006239 protecting group Chemical group 0.000 abstract description 10
- 125000001309 chloro group Chemical group Cl* 0.000 abstract description 9
- 239000012948 isocyanate Substances 0.000 abstract description 9
- 150000002513 isocyanates Chemical class 0.000 abstract description 9
- 125000001246 bromo group Chemical group Br* 0.000 abstract description 8
- 150000001412 amines Chemical class 0.000 abstract description 7
- 150000002148 esters Chemical class 0.000 abstract description 7
- 125000001424 substituent group Chemical group 0.000 abstract description 6
- PHPSLBMIXITAGH-UHFFFAOYSA-N 1-(6,7-dimethoxyquinazolin-4-yl)piperidin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1N1CCC(N)CC1 PHPSLBMIXITAGH-UHFFFAOYSA-N 0.000 abstract description 5
- PZHWXCGXKMISHV-UHFFFAOYSA-N 1-(6,7-dimethoxyquinazolin-4-yl)piperidin-4-one Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1N1CCC(=O)CC1 PZHWXCGXKMISHV-UHFFFAOYSA-N 0.000 abstract description 5
- LLLHRNQLGUOJHP-UHFFFAOYSA-N 4-chloro-6,7-dimethoxyquinazoline Chemical compound C1=NC(Cl)=C2C=C(OC)C(OC)=CC2=N1 LLLHRNQLGUOJHP-UHFFFAOYSA-N 0.000 abstract description 5
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 abstract description 5
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 abstract description 5
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 abstract description 5
- 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 abstract description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 abstract description 4
- 150000008064 anhydrides Chemical class 0.000 abstract description 4
- ZFTFAPZRGNKQPU-UHFFFAOYSA-N dicarbonic acid Chemical compound OC(=O)OC(O)=O ZFTFAPZRGNKQPU-UHFFFAOYSA-N 0.000 abstract description 4
- 150000002540 isothiocyanates Chemical class 0.000 abstract description 4
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 abstract description 4
- 239000011734 sodium Substances 0.000 abstract description 4
- 229910052708 sodium Inorganic materials 0.000 abstract description 4
- 101100295738 Gallus gallus COR3 gene Proteins 0.000 abstract description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 abstract description 3
- 229910052736 halogen Inorganic materials 0.000 abstract description 3
- 150000002367 halogens Chemical class 0.000 abstract description 3
- 230000007062 hydrolysis Effects 0.000 abstract description 3
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 3
- 239000000546 pharmaceutical excipient Substances 0.000 abstract description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 abstract description 3
- 239000012279 sodium borohydride Substances 0.000 abstract description 3
- WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 abstract description 2
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 abstract description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 abstract description 2
- 150000001266 acyl halides Chemical class 0.000 abstract description 2
- 125000003277 amino group Chemical group 0.000 abstract description 2
- 239000012024 dehydrating agents Substances 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 125000002911 monocyclic heterocycle group Chemical group 0.000 abstract description 2
- BDMOFPZFPYIPPK-UHFFFAOYSA-N n-[1-(6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]-2,2,2-trifluoroacetamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1N1CCC(NC(=O)C(F)(F)F)CC1 BDMOFPZFPYIPPK-UHFFFAOYSA-N 0.000 abstract description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 abstract description 2
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 abstract description 2
- FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 abstract 1
- KPKNTUUIEVXMOH-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane Chemical compound O1CCOC11CCNCC1 KPKNTUUIEVXMOH-UHFFFAOYSA-N 0.000 abstract 1
- SOYBJPNBFNGLRY-UHFFFAOYSA-N 1-(6,7-dimethoxyquinazolin-4-yl)-N-(pyridin-2-ylmethyl)piperidin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1N(CC1)CCC1NCC1=CC=CC=N1 SOYBJPNBFNGLRY-UHFFFAOYSA-N 0.000 abstract 1
- SZIYXGXFZZLJSV-UHFFFAOYSA-N 1-(6,7-dimethoxyquinazolin-4-yl)-n-methylpiperidin-4-amine Chemical compound C1CC(NC)CCN1C1=NC=NC2=CC(OC)=C(OC)C=C12 SZIYXGXFZZLJSV-UHFFFAOYSA-N 0.000 abstract 1
- SVIRKOCSSOKHBX-UHFFFAOYSA-N 2,2,2-trifluoro-n-piperidin-4-ylacetamide Chemical compound FC(F)(F)C(=O)NC1CCNCC1 SVIRKOCSSOKHBX-UHFFFAOYSA-N 0.000 abstract 1
- IPXNSGCSALMKCA-UHFFFAOYSA-N 2-bromo-n-[1-(6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]acetamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1N1CCC(NC(=O)CBr)CC1 IPXNSGCSALMKCA-UHFFFAOYSA-N 0.000 abstract 1
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 abstract 1
- 125000003368 amide group Chemical group 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 abstract 1
- 150000003254 radicals Chemical class 0.000 abstract 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 66
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 26
- 238000004458 analytical method Methods 0.000 description 26
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- 239000000047 product Substances 0.000 description 23
- 239000000243 solution Substances 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 15
- 238000001953 recrystallisation Methods 0.000 description 13
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 239000003960 organic solvent Substances 0.000 description 12
- FYMQPWWNOCENRN-UHFFFAOYSA-N 6,7-dimethoxyquinazoline Chemical compound N1=CN=C2C=C(OC)C(OC)=CC2=C1 FYMQPWWNOCENRN-UHFFFAOYSA-N 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
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- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 10
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
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- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
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- 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 description 3
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- RVZMPNMUBCAPQO-UHFFFAOYSA-N 2,4-dimethoxyquinazoline Chemical compound C1=CC=CC2=NC(OC)=NC(OC)=C21 RVZMPNMUBCAPQO-UHFFFAOYSA-N 0.000 description 2
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- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
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- ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- CMLDRMOPXHHMKT-UHFFFAOYSA-N 1,4-dioxa-10-azaspiro[4.5]decane Chemical compound O1CCOC11NCCCC1 CMLDRMOPXHHMKT-UHFFFAOYSA-N 0.000 description 1
- CPZHDDGPHQRMEJ-UHFFFAOYSA-N 1-butyl-3-[1-(6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]urea Chemical compound C1CC(NC(=O)NCCCC)CCN1C1=NC=NC2=CC(OC)=C(OC)C=C12 CPZHDDGPHQRMEJ-UHFFFAOYSA-N 0.000 description 1
- RSAFKRSMGOSHRK-UHFFFAOYSA-N 1-diethoxyphosphorylpropan-2-one Chemical compound CCOP(=O)(CC(C)=O)OCC RSAFKRSMGOSHRK-UHFFFAOYSA-N 0.000 description 1
- OQURWGJAWSLGQG-UHFFFAOYSA-N 1-isocyanatopropane Chemical compound CCCN=C=O OQURWGJAWSLGQG-UHFFFAOYSA-N 0.000 description 1
- DZZPLJJYVMWODK-UHFFFAOYSA-N 2,2,2-trifluoro-n-piperidin-4-ylacetamide;hydrochloride Chemical compound Cl.FC(F)(F)C(=O)NC1CCNCC1 DZZPLJJYVMWODK-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- GYMTUXHRQWJXMW-UHFFFAOYSA-N 2-piperidin-1-ylquinazoline Chemical compound C1CCCCN1C1=NC=C(C=CC=C2)C2=N1 GYMTUXHRQWJXMW-UHFFFAOYSA-N 0.000 description 1
- SHVVSKCXWMEDRW-UHFFFAOYSA-N 3-isocyanatopyridine Chemical compound O=C=NC1=CC=CN=C1 SHVVSKCXWMEDRW-UHFFFAOYSA-N 0.000 description 1
- GVRRXASZZAKBMN-UHFFFAOYSA-N 4-chloroquinazoline Chemical class C1=CC=C2C(Cl)=NC=NC2=C1 GVRRXASZZAKBMN-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- DTTTWAIOPVDNGY-UHFFFAOYSA-N CCO.C=12C=C(OC)C(OC)=CC2=NC=NC=1N1CCC(NC(=O)C(F)(F)F)CC1 Chemical compound CCO.C=12C=C(OC)C(OC)=CC2=NC=NC=1N1CCC(NC(=O)C(F)(F)F)CC1 DTTTWAIOPVDNGY-UHFFFAOYSA-N 0.000 description 1
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 1
- 239000004150 EU approved colour Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 1
- 101001047746 Homo sapiens Lamina-associated polypeptide 2, isoform alpha Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102100023981 Lamina-associated polypeptide 2, isoform alpha Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000009298 Trigla lyra Species 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000002057 chronotropic effect Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000006631 isobutoxycarbonylamino group Chemical group 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- HNHVTXYLRVGMHD-UHFFFAOYSA-N n-butyl isocyanate Chemical compound CCCCN=C=O HNHVTXYLRVGMHD-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- DPBLXKKOBLCELK-UHFFFAOYSA-N pentan-1-amine Chemical compound CCCCCN DPBLXKKOBLCELK-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- SRWFBFUYENBCGF-UHFFFAOYSA-M sodium;chloride;hydrochloride Chemical compound [Na+].Cl.[Cl-] SRWFBFUYENBCGF-UHFFFAOYSA-M 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 150000003461 sulfonyl halides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB3280574 | 1974-07-25 | ||
| GB41675*[A GB1460389A (en) | 1974-07-25 | 1975-01-06 | 4-substituted quinazoline cardiac stimulants |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE41838L IE41838L (en) | 1976-01-25 |
| IE41838B1 true IE41838B1 (en) | 1980-04-09 |
Family
ID=26235904
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE1658/75A IE41838B1 (en) | 1974-07-25 | 1975-07-24 | 4-substituted quinazoline cardiac stimulants |
Country Status (23)
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN148482B (US06331856-20011218-P00035.png) | 1977-06-03 | 1981-03-07 | Pfizer | |
| CA1086735A (en) * | 1977-11-03 | 1980-09-30 | John C. Danilewicz | Piperidino-quinazolines |
| US4370328A (en) * | 1977-11-03 | 1983-01-25 | Pfizer Inc. | Cardiac stimulant 1-(3- or 4-substituted piperidino)phthalazines |
| US4489075A (en) * | 1982-05-15 | 1984-12-18 | Pfizer Inc. | Cyclic sulfonamidoalkyl substituted 4-piperidinoquinazoline cardiac stimulants |
| JPS61215389A (ja) * | 1985-03-20 | 1986-09-25 | Kyowa Hakko Kogyo Co Ltd | キナゾリン誘導体およびそれを含有する強心剤 |
| US6645969B1 (en) * | 1991-05-10 | 2003-11-11 | Aventis Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit CSF-1R receptor tyrosine kinase |
| FR2802206B1 (fr) * | 1999-12-14 | 2005-04-22 | Sod Conseils Rech Applic | Derives de 4-aminopiperidine et leur utilisation en tant que medicament |
| PE20030417A1 (es) * | 2001-09-13 | 2003-08-06 | Smithkline Beecham Plc | Derivados de urea como antagonistas del receptor vainilloide |
| HUP0200849A2 (hu) * | 2002-03-06 | 2004-08-30 | Sanofi-Synthelabo | N-aminoacetil-2-ciano-pirrolidin-származékok, e vegyületeket tartalmazó gyógyszerkészítmények és eljárás előállításukra |
| US7064211B2 (en) * | 2002-03-22 | 2006-06-20 | Eisai Co., Ltd. | Hemiasterlin derivatives and uses thereof |
| AU2003270199A1 (en) * | 2002-09-13 | 2004-04-30 | Glaxo Group Limited | Urea compounds active as vanilloid receptor antagonists for the treatment of pain |
| TWI350168B (en) | 2004-05-07 | 2011-10-11 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
| EP1758580A4 (en) * | 2004-06-24 | 2008-01-16 | Incyte Corp | N-SUBSTITUTED PIPERIDINE AND ITS USE AS A MEDICAMENT |
| EP1773773A4 (en) * | 2004-06-24 | 2009-07-29 | Incyte Corp | AMID COMPOUNDS AND THEIR USE AS MEDICAMENTS |
| NZ551602A (en) * | 2004-06-24 | 2010-11-26 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
| US7687665B2 (en) * | 2004-06-24 | 2010-03-30 | Incyte Corporation | 2-methylprop anamides and their use as pharmaceuticals |
| US20060019975A1 (en) * | 2004-07-23 | 2006-01-26 | Pfizer Inc | Novel piperidyl derivatives of quinazoline and isoquinoline |
| BRPI0514230A (pt) * | 2004-08-10 | 2008-06-03 | Incyte Corp | compostos de amido e seu uso como produtos farmacêuticos |
| US7825244B2 (en) * | 2005-06-10 | 2010-11-02 | Janssen Pharmaceutica Nv | Intermediates useful in the synthesis of alkylquinoline and alkylquinazoline kinase modulators, and related methods of synthesis |
| US8071768B2 (en) * | 2005-06-10 | 2011-12-06 | Janssen Pharmaceutica, N.V. | Alkylquinoline and alkylquinazoline kinase modulators |
| TW200808807A (en) * | 2006-03-02 | 2008-02-16 | Incyte Corp | Modulators of 11-β hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| US20070208001A1 (en) * | 2006-03-03 | 2007-09-06 | Jincong Zhuo | Modulators of 11- beta hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| EP2013163A1 (en) * | 2006-05-01 | 2009-01-14 | Incyte Corporation | Tetrasubstituted ureas as modulators of 11-beta hydroxyl steroid dehydrogenase type 1 |
| WO2007137066A2 (en) * | 2006-05-17 | 2007-11-29 | Incyte Corporation | HETEROCYCLIC INHIBITORS OF 11-β HYDROXYL STEROID DEHYDROGENASE TYPE I AND METHODS OF USING THE SAME |
| EP1903037A1 (de) * | 2006-09-07 | 2008-03-26 | Bayer Schering Pharma Aktiengesellschaft | 1-(Het)aryl-3-[hetaryl-piperidin-4-yl]-thioharnstoffe als Modulatoren des EP2-Rezeptors |
| EP1903038A1 (de) * | 2006-09-07 | 2008-03-26 | Bayer Schering Pharma Aktiengesellschaft | N-(1-Hetaryl-piperidin-4-yl)-(het)arylamide als EP2-Rezeptor Modulatoren |
| CN113677350A (zh) * | 2019-02-01 | 2021-11-19 | 里兰斯坦福初级大学理事会 | Enpp1抑制剂和调节免疫反应的方法 |
| EP3941459A4 (en) * | 2019-03-19 | 2022-11-30 | Stingray Therapeutics, Inc. | QUINOLINE AND QUINAZOLINE COMPOUNDS AND METHODS OF USE THEREOF |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1156973A (en) * | 1965-07-06 | 1969-07-02 | Quinazoline Derivatives | |
| US3517005A (en) * | 1967-10-26 | 1970-06-23 | Pfizer & Co C | Certain 2- and 4-substituted quinazolines |
| US3511836A (en) * | 1967-12-13 | 1970-05-12 | Pfizer & Co C | 2,4,6,7-tetra substituted quinazolines |
| US3637701A (en) * | 1969-03-03 | 1972-01-25 | Sandoz Ag | Certain nitrate derivatives of 4-aminoquinazolines |
| DE2121031A1 (en) * | 1971-04-29 | 1972-11-02 | Dr. Karl Thomae Gmbh, 7950 Biberach | Base-substd quinazolines - thrombocyte aggregation inhibitors |
| BE793371A (fr) * | 1971-12-27 | 1973-06-27 | Sandoz Sa | Nouveaux derives de la 4-amino-quinazoline, leur preparation etmedicaments contenant ces |
| US3819628A (en) * | 1972-07-31 | 1974-06-25 | Sandoz Ag | 2-phenyl-4-substituted amino-quinazolines and nitrates thereof |
| US3838127A (en) * | 1972-10-19 | 1974-09-24 | Sandoz Ag | 4-(4-(hydroxyalkyl)-1-piperazino)-quinazoline benzoates |
| GB1417029A (en) * | 1973-03-07 | 1975-12-10 | Pfizer Ltd | Quinazoline-derived amines |
-
1975
- 1975-01-06 GB GB41675*[A patent/GB1460389A/en not_active Expired
- 1975-07-02 IL IL47625A patent/IL47625A/xx unknown
- 1975-07-08 PH PH17358A patent/PH14190A/en unknown
- 1975-07-10 DE DE2530894A patent/DE2530894C2/de not_active Expired
- 1975-07-15 CA CA231,570A patent/CA1060445A/en not_active Expired
- 1975-07-15 SE SE7508101A patent/SE420921B/xx unknown
- 1975-07-17 BG BG030568A patent/BG27086A3/xx unknown
- 1975-07-17 BG BG035524A patent/BG27744A3/xx unknown
- 1975-07-19 RO RO7589560A patent/RO71840A/ro unknown
- 1975-07-19 RO RO7589559A patent/RO71841A/ro unknown
- 1975-07-19 RO RO7582903A patent/RO69296A/ro unknown
- 1975-07-21 YU YU1842/75A patent/YU37155B/xx unknown
- 1975-07-21 AR AR259676A patent/AR216046A1/es active
- 1975-07-21 JP JP8911975A patent/JPS5527062B2/ja not_active Expired
- 1975-07-21 DD DD187385A patent/DD119046A5/xx unknown
- 1975-07-22 FI FI752104A patent/FI66182C/fi not_active IP Right Cessation
- 1975-07-24 US US05/598,723 patent/US4001422A/en not_active Expired - Lifetime
- 1975-07-24 DK DK337175AA patent/DK138800B/da not_active IP Right Cessation
- 1975-07-24 CH CH711378A patent/CH611616A5/xx not_active IP Right Cessation
- 1975-07-24 IE IE1658/75A patent/IE41838B1/en unknown
- 1975-07-24 CH CH759692A patent/CH608803A5/xx not_active IP Right Cessation
- 1975-07-24 NL NL7508824.A patent/NL159982C/xx not_active IP Right Cessation
- 1975-07-24 FR FR7523218A patent/FR2279406A1/fr active Granted
- 1975-07-25 LU LU73072A patent/LU73072A1/xx unknown
-
1976
- 1976-01-01 AR AR263450A patent/AR207895A1/es active
- 1976-05-31 AR AR263449A patent/AR214050A1/es active
- 1976-05-31 AR AR263447A patent/AR214049A1/es active
- 1976-05-31 AR AR263448A patent/AR213407A1/es active
- 1976-05-31 AR AR263451A patent/AR212447A1/es active
-
1977
- 1977-03-01 AR AR266723A patent/AR215882A1/es active
-
1979
- 1979-08-30 HK HK618/79A patent/HK61879A/xx unknown
- 1979-09-05 KE KE2988A patent/KE2988A/xx unknown
-
1980
- 1980-12-31 MY MY1980108A patent/MY8000108A/xx unknown
-
1981
- 1981-05-14 YU YU01242/81A patent/YU124281A/xx unknown
- 1981-05-14 YU YU01241/81A patent/YU124181A/xx unknown
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