CA1121816A - Cyanocarboxamidines and quinazoline process - Google Patents
Cyanocarboxamidines and quinazoline processInfo
- Publication number
- CA1121816A CA1121816A CA000311878A CA311878A CA1121816A CA 1121816 A CA1121816 A CA 1121816A CA 000311878 A CA000311878 A CA 000311878A CA 311878 A CA311878 A CA 311878A CA 1121816 A CA1121816 A CA 1121816A
- Authority
- CA
- Canada
- Prior art keywords
- carbon atoms
- atoms inclusive
- formula
- group
- lower alkyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims abstract description 65
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 title description 10
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 40
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 18
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 17
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 13
- 239000004202 carbamide Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 230000029936 alkylation Effects 0.000 claims description 7
- 238000005804 alkylation reaction Methods 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 230000002152 alkylating effect Effects 0.000 claims description 3
- 239000007810 chemical reaction solvent Substances 0.000 claims description 3
- CCAFPWNGIUBUSD-UHFFFAOYSA-N diethyl sulfoxide Chemical compound CCS(=O)CC CCAFPWNGIUBUSD-UHFFFAOYSA-N 0.000 claims description 3
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical group 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- CNJLMVZFWLNOEP-UHFFFAOYSA-N 4,7,7-trimethylbicyclo[4.1.0]heptan-5-one Chemical group O=C1C(C)CCC2C(C)(C)C12 CNJLMVZFWLNOEP-UHFFFAOYSA-N 0.000 claims 1
- -1 4-amino-2-(4-substituted-piperazine-1-yl)-quinazolines Chemical class 0.000 abstract description 33
- 239000000543 intermediate Substances 0.000 abstract description 10
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 230000003276 anti-hypertensive effect Effects 0.000 abstract description 3
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 22
- 238000007363 ring formation reaction Methods 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 7
- 150000003246 quinazolines Chemical class 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229910052698 phosphorus Inorganic materials 0.000 description 6
- 239000011574 phosphorus Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- LHPZZVZPOZPDDB-UHFFFAOYSA-N 4-isothiocyanato-1,2-dimethoxybenzene Chemical compound COC1=CC=C(N=C=S)C=C1OC LHPZZVZPOZPDDB-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- NFKMPKOGCRBAJF-UHFFFAOYSA-N $l^{1}-azanylformonitrile Chemical compound [N]C#N NFKMPKOGCRBAJF-UHFFFAOYSA-N 0.000 description 3
- NYTBFFZQIRSGLL-UHFFFAOYSA-N 4-isocyanato-1,2-dimethoxybenzene Chemical compound COC1=CC=C(N=C=O)C=C1OC NYTBFFZQIRSGLL-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- 239000002026 chloroform extract Substances 0.000 description 3
- 150000001912 cyanamides Chemical class 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- VBUBADWLHFZFDK-UHFFFAOYSA-N quinazoline;hydrochloride Chemical compound Cl.N1=CN=CC2=CC=CC=C21 VBUBADWLHFZFDK-UHFFFAOYSA-N 0.000 description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- SDTBJQANMVJMSP-UHFFFAOYSA-N 1,4-diazepan-1-yl(furan-2-yl)methanone Chemical compound C=1C=COC=1C(=O)N1CCCNCC1 SDTBJQANMVJMSP-UHFFFAOYSA-N 0.000 description 2
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 2
- OGFAWKRXZLGJSK-UHFFFAOYSA-N 1-(2,4-dihydroxyphenyl)-2-(4-nitrophenyl)ethanone Chemical compound OC1=CC(O)=CC=C1C(=O)CC1=CC=C([N+]([O-])=O)C=C1 OGFAWKRXZLGJSK-UHFFFAOYSA-N 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- TUQSVSYUEBNNKQ-UHFFFAOYSA-N 2,4-dichloroquinazoline Chemical class C1=CC=CC2=NC(Cl)=NC(Cl)=C21 TUQSVSYUEBNNKQ-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 2
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- SADPINFEWFPMEA-UHFFFAOYSA-N furan-2-yl(piperazin-1-yl)methanone Chemical compound C=1C=COC=1C(=O)N1CCNCC1 SADPINFEWFPMEA-UHFFFAOYSA-N 0.000 description 2
- 239000011968 lewis acid catalyst Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 1
- BEBULARNHRENRL-UHFFFAOYSA-N (2-hydroxy-2-methylpropyl) piperazine-1-carboxylate Chemical compound CC(C)(O)COC(=O)N1CCNCC1 BEBULARNHRENRL-UHFFFAOYSA-N 0.000 description 1
- OWGLDSMXRVOALN-UHFFFAOYSA-N (5-methylsulfanyl-1,3,4-oxadiazol-2-yl)-piperazin-1-ylmethanone;hydrochloride Chemical compound Cl.O1C(SC)=NN=C1C(=O)N1CCNCC1 OWGLDSMXRVOALN-UHFFFAOYSA-N 0.000 description 1
- OGEPTCLSVFACRT-UHFFFAOYSA-N 1-isothiocyanato-2,3,4-trimethoxybenzene Chemical compound COC1=CC=C(N=C=S)C(OC)=C1OC OGEPTCLSVFACRT-UHFFFAOYSA-N 0.000 description 1
- FSKSRCFNVZOYLO-UHFFFAOYSA-N 1-isothiocyanato-2,3-dimethoxybenzene Chemical compound COC1=CC=CC(N=C=S)=C1OC FSKSRCFNVZOYLO-UHFFFAOYSA-N 0.000 description 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- UDMYVIOIQWIDRY-UHFFFAOYSA-N 6,7-dimethoxy-2-(4-methylpiperazin-1-yl)quinazolin-4-amine pentachloro-lambda5-phosphane dihydrochloride Chemical compound P(Cl)(Cl)(Cl)(Cl)Cl.Cl.Cl.NC1=NC(=NC2=CC(=C(C=C12)OC)OC)N1CCN(CC1)C UDMYVIOIQWIDRY-UHFFFAOYSA-N 0.000 description 1
- LENSZUVXOXHZTL-UHFFFAOYSA-N 6,7-dimethoxy-2-(4-methylpiperazin-1-yl)quinazolin-4-amine;dihydrochloride Chemical compound Cl.Cl.N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N1CCN(C)CC1 LENSZUVXOXHZTL-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- NBXCMJBSSNLVJK-UHFFFAOYSA-N Cl.Cl.NC1=NC(=NC2=CC(=C(C=C12)OC)OC)N1CCN(CC1)C(=O)C=1OC=CC1 Chemical compound Cl.Cl.NC1=NC(=NC2=CC(=C(C=C12)OC)OC)N1CCN(CC1)C(=O)C=1OC=CC1 NBXCMJBSSNLVJK-UHFFFAOYSA-N 0.000 description 1
- 229910015400 FeC13 Inorganic materials 0.000 description 1
- 102100039401 Gap junction beta-6 protein Human genes 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- 230000009858 acid secretion Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- PQLAYKMGZDUDLQ-UHFFFAOYSA-K aluminium bromide Chemical compound Br[Al](Br)Br PQLAYKMGZDUDLQ-UHFFFAOYSA-K 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 description 1
- 150000003931 anilides Chemical class 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- RYTLGWCJESCDMY-UHFFFAOYSA-N carbamimidoyl chloride Chemical class NC(Cl)=N RYTLGWCJESCDMY-UHFFFAOYSA-N 0.000 description 1
- YDVJBLJCSLVMSY-UHFFFAOYSA-N carbamoyl cyanide Chemical class NC(=O)C#N YDVJBLJCSLVMSY-UHFFFAOYSA-N 0.000 description 1
- 150000001723 carbon free-radicals Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- CJQGSTFFFNJNMC-UHFFFAOYSA-N cyclopentyl(piperazin-1-yl)methanone Chemical compound C1CNCCN1C(=O)C1CCCC1 CJQGSTFFFNJNMC-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 150000004050 homopiperazines Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- SLALWQDKKDPPEX-UHFFFAOYSA-N n-(3,4-dimethoxyphenyl)-4-(5-methylsulfanyl-1,3,4-oxadiazole-2-carbonyl)piperazine-1-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)N1CCN(C(=O)C=2OC(SC)=NN=2)CC1 SLALWQDKKDPPEX-UHFFFAOYSA-N 0.000 description 1
- WXJRCMMPKPGSGC-UHFFFAOYSA-N n-(3,4-dimethoxyphenyl)-4-(furan-2-carbonyl)piperazine-1-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)N1CCN(C(=O)C=2OC=CC=2)CC1 WXJRCMMPKPGSGC-UHFFFAOYSA-N 0.000 description 1
- GNTXMSCWTRRBCZ-UHFFFAOYSA-N n-(3,4-dimethoxyphenyl)-4-methylpiperazine-1-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)N1CCN(C)CC1 GNTXMSCWTRRBCZ-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical class O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical class S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- MCZFAEXAOKERQF-UHFFFAOYSA-N quinazoline-4-carboximidamide Chemical class C1=CC=C2C(C(=N)N)=NC=NC2=C1 MCZFAEXAOKERQF-UHFFFAOYSA-N 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- YNZXWQJZEDLQEG-UHFFFAOYSA-N trimazosin Chemical compound N1=C2C(OC)=C(OC)C(OC)=CC2=C(N)N=C1N1CCN(C(=O)OCC(C)(C)O)CC1 YNZXWQJZEDLQEG-UHFFFAOYSA-N 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C07D271/113—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
-
- 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
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/21—Radicals derived from sulfur analogues of carbonic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000365159A CA1121817A (en) | 1977-09-30 | 1980-11-20 | Cyanocarboxamidines and quinazoline process |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US838,417 | 1977-09-30 | ||
| US05/838,417 US4138561A (en) | 1977-09-30 | 1977-09-30 | Cyanocarboxamidines and quinazoline process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1121816A true CA1121816A (en) | 1982-04-13 |
Family
ID=25277044
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000311878A Expired CA1121816A (en) | 1977-09-30 | 1978-09-22 | Cyanocarboxamidines and quinazoline process |
Country Status (13)
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4101548A (en) * | 1977-02-22 | 1978-07-18 | Bristol-Myers Company | 1,2,3-Thiadiazole amides |
| FI57751C (fi) * | 1977-10-25 | 1980-10-10 | Fermion Oy | Foerfarande foer framstaellning av 6,7-dimetoxi- eller 6,7,8-trimetoxi-4-amino-2-(4-substituerade-piperazin-1-yl)-kinazoliner med blodtryckssaenkande verkan |
| EP0022481A1 (en) * | 1979-06-21 | 1981-01-21 | Mitsubishi Yuka Pharmaceutical Co., Ltd. | 5,6-Alkylenepyrimidine derivatives, processes for preparing the same and pharmaceutical compositions |
| DE3014353A1 (de) * | 1980-04-15 | 1982-01-21 | Bayer Ag, 5090 Leverkusen | Trisubstituierte cyanguanidine, verfahren zu ihrer herstellung sowie ihre verwendung als fungizide |
| JPS5791987A (en) * | 1980-11-26 | 1982-06-08 | Sankyo Co Ltd | Aminoquinazoline derivative and its preparation |
| US4367335A (en) * | 1981-08-03 | 1983-01-04 | Mead Johnson & Company | Thiazolidinylalkylene piperazine derivatives |
| DE3336409A1 (de) * | 1983-10-06 | 1985-04-18 | Ludwig Heumann & Co GmbH, 8500 Nürnberg | Chinazolinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE3375395D1 (en) * | 1983-11-22 | 1988-02-25 | Heumann Ludwig & Co Gmbh | Process for the preparation of 4-amino-6,7-dimethoxy-2-(4-(furoyl-2)-piperazin-1-yl)-quinazoline and its physiologically acceptable salt |
| US4713382A (en) * | 1985-05-30 | 1987-12-15 | Syntex (U.S.A.) Inc. | N-phenyl-4-phenyl-1-piperazinecarboxamidines and related compounds as antiarrhythmic agents |
| AT384218B (de) * | 1985-12-04 | 1987-10-12 | Gerot Pharmazeutika | Verfahren zur herstellung von neuen chinazolin-derivaten |
| YU70890A (en) * | 1989-04-21 | 1992-05-28 | Egyt Gyogyszervegyeszeti Gyar | Process for obtaining quinazoline derivatives |
| CA2077252C (en) * | 1992-08-31 | 2001-04-10 | Khashayar Karimian | Methods of making ureas and guanidines, and intermediates therefor |
| US5776962A (en) * | 1994-08-03 | 1998-07-07 | Cell Pathways, Inc. | Lactone compounds for treating patient with precancerous lesions |
| US5696159A (en) * | 1994-08-03 | 1997-12-09 | Cell Pathways, Inc. | Lactone compounds for treating patients with precancerous lesions |
| US6232312B1 (en) | 1995-06-07 | 2001-05-15 | Cell Pathways, Inc. | Method for treating patient having precancerous lesions with a combination of pyrimidopyrimidine derivatives and esters and amides of substituted indenyl acetic acides |
| US6200980B1 (en) | 1995-06-07 | 2001-03-13 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with phenyl purinone derivatives |
| US6060477A (en) * | 1995-06-07 | 2000-05-09 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with phenyl cycloamino pyrimidinone derivatives |
| US6046216A (en) * | 1995-06-07 | 2000-04-04 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with phenyl pyridinone derivatives |
| US5874440A (en) * | 1995-06-07 | 1999-02-23 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with phenyl pyrimidinone derivatives |
| US6262059B1 (en) | 1995-06-07 | 2001-07-17 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with quinazoline derivatives |
| US6046206A (en) * | 1995-06-07 | 2000-04-04 | Cell Pathways, Inc. | Method of treating a patient having a precancerous lesions with amide quinazoline derivatives |
| CA2238283C (en) | 1997-05-30 | 2002-08-20 | Cell Pathways, Inc. | Method for identifying compounds for inhibition of neoplastic lesions, pharmaceutical compositions from such compounds and uses of such compounds and compositions for treating neoplastic lesions |
| US5858694A (en) * | 1997-05-30 | 1999-01-12 | Cell Pathways, Inc. | Method for identifying compounds for inhibition of cancerous lesions |
| US5852035A (en) * | 1997-12-12 | 1998-12-22 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure to substituted N- arylmethyl and heterocyclmethyl-1H-pyrazolo (3,4-B) quinolin-4-amines |
| US6410584B1 (en) * | 1998-01-14 | 2002-06-25 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells with indole derivatives |
| US6046199A (en) * | 1998-01-14 | 2000-04-04 | Cell Pathways, Inc. | Method of inhibiting neoplastic cells with tetracyclic pyrido[3,4-B]indole derivatives |
| US5942520A (en) * | 1998-01-27 | 1999-08-24 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells by exposure to substituted N-cycloalkylmethyl-1-H-pyrazolo (3,4-B) quinolone-4 amines |
| US6313294B1 (en) | 1998-02-04 | 2001-11-06 | Development Center For Biotechnology | Process for preparing amides |
| US5990117A (en) * | 1998-04-15 | 1999-11-23 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure to quinazoline derivatives |
| US6180629B1 (en) | 1998-08-14 | 2001-01-30 | Cell Pathways, Inc. | [4,5]-Fused-1,3-disubstituted-1,2-diazine-6-one derivatives with nitrogen containing substitutents in position one for the treatment of neoplasia |
| US6124303A (en) * | 1998-09-11 | 2000-09-26 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure to 9-substituted 2-(2-N-aloxyphenyl) purin-6-ones |
| US6268372B1 (en) | 1998-09-11 | 2001-07-31 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure to 2,9-disubstituted purin-6-ones |
| US6200771B1 (en) | 1998-10-15 | 2001-03-13 | Cell Pathways, Inc. | Method of using a novel phosphodiesterase in pharmaceutical screeing to identify compounds for treatment of neoplasia |
| US6130053A (en) * | 1999-08-03 | 2000-10-10 | Cell Pathways, Inc. | Method for selecting compounds for inhibition of neoplastic lesions |
| US6133271A (en) * | 1998-11-19 | 2000-10-17 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure thienopyrimidine derivatives |
| US6187779B1 (en) | 1998-11-20 | 2001-02-13 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure to 2,8-disubstituted quinazoline derivatives |
| US6369092B1 (en) | 1998-11-23 | 2002-04-09 | Cell Pathways, Inc. | Method for treating neoplasia by exposure to substituted benzimidazole derivatives |
| US6486155B1 (en) | 1998-11-24 | 2002-11-26 | Cell Pathways Inc | Method of inhibiting neoplastic cells with isoquinoline derivatives |
| US6077842A (en) * | 1998-11-24 | 2000-06-20 | Cell Pathways, Inc. | Method of inhibiting neoplastic cells with pyrazolopyridylpyridazinone derivatives |
| US6034099A (en) * | 1998-11-24 | 2000-03-07 | Cell Pathways, Inc. | Method for inhibiting neoplastic lesions by administering 4-(arylmethylene)- 2, 3- dihydro-pyrazol-3-ones |
| US6025394A (en) | 1999-01-29 | 2000-02-15 | Cell Pathways, Inc. | Method for treating patients with acne by administering substituted sulfonyl indenyl acetic acids, amides and alcohols |
| US6020379A (en) * | 1999-02-19 | 2000-02-01 | Cell Pathways, Inc. | Position 7 substituted indenyl-3-acetic acid derivatives and amides thereof for the treatment of neoplasia |
| US6555547B1 (en) | 2000-02-28 | 2003-04-29 | Cell Pathways, Inc. | Method for treating a patient with neoplasia by treatment with a vinca alkaloid derivative |
| US6569638B1 (en) | 2000-03-03 | 2003-05-27 | Cell Pathways, Inc | Method for screening compounds for the treatment of neoplasia |
| US20070087061A1 (en) * | 2005-10-14 | 2007-04-19 | Medafor, Incorporated | Method and composition for creating and/or activating a platelet-rich gel by contact with a porous particulate material, for use in wound care, tissue adhesion, or as a matrix for delivery of therapeutic components |
| US20070086958A1 (en) * | 2005-10-14 | 2007-04-19 | Medafor, Incorporated | Formation of medically useful gels comprising microporous particles and methods of use |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3935213A (en) * | 1973-12-05 | 1976-01-27 | Pfizer Inc. | Process for hypotensive 4-amino-2-(piperazin-1-yl) quinazoline derivatives |
-
1977
- 1977-09-30 US US05/838,417 patent/US4138561A/en not_active Expired - Lifetime
-
1978
- 1978-09-18 WO PCT/US1978/000083 patent/WO1979000166A1/en unknown
- 1978-09-18 GB GB7906214A patent/GB2036001B/en not_active Expired
- 1978-09-18 CH CH511879A patent/CH641172A5/de not_active IP Right Cessation
- 1978-09-22 CA CA000311878A patent/CA1121816A/en not_active Expired
- 1978-09-26 BE BE190708A patent/BE870763A/xx not_active IP Right Cessation
- 1978-09-27 NL NL7809799A patent/NL7809799A/xx unknown
- 1978-09-27 DK DK429378A patent/DK429378A/da not_active Application Discontinuation
- 1978-09-27 FR FR7827628A patent/FR2404633A1/fr active Granted
- 1978-09-29 IT IT51318/78A patent/IT1107496B/it active
- 1978-09-29 JP JP11930778A patent/JPS5459292A/ja active Pending
- 1978-09-29 IE IE1958/78A patent/IE47569B1/en unknown
-
1979
- 1979-05-29 SE SE7904690A patent/SE7904690L/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BE870763A (fr) | 1979-03-26 |
| IT1107496B (it) | 1985-11-25 |
| IT7851318A0 (it) | 1978-09-29 |
| FR2404633B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1983-05-13 |
| SE7904690L (sv) | 1979-05-29 |
| WO1979000166A1 (en) | 1979-04-05 |
| IE47569B1 (en) | 1984-05-02 |
| JPS5459292A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1979-05-12 |
| IE781958L (en) | 1979-03-30 |
| GB2036001A (en) | 1980-06-25 |
| DK429378A (da) | 1979-03-31 |
| FR2404633A1 (fr) | 1979-04-27 |
| NL7809799A (nl) | 1979-04-03 |
| US4138561A (en) | 1979-02-06 |
| CH641172A5 (de) | 1984-02-15 |
| GB2036001B (en) | 1982-07-07 |
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| MKEX | Expiry |